U.S. patent application number 16/493986 was filed with the patent office on 2022-03-17 for broad spectrum influenza virus vaccine.
This patent application is currently assigned to ModernaTX, Inc.. The applicant listed for this patent is ModernaTX, Inc.. Invention is credited to Kerim Babaoglu, Giuseppe Ciaramella, Jessica Anne Flynn, Eric Yi-Chun Huang, David Nickle, Lan Zhang.
Application Number | 20220080038 16/493986 |
Document ID | / |
Family ID | |
Filed Date | 2022-03-17 |
United States Patent
Application |
20220080038 |
Kind Code |
A9 |
Ciaramella; Giuseppe ; et
al. |
March 17, 2022 |
BROAD SPECTRUM INFLUENZA VIRUS VACCINE
Abstract
The disclosure relates to broad spectrum influenza virus
ribonucleic acid (RNA) vaccines, as well as methods of using the
vaccines and compositions comprising the vaccine. In a preferred
embodiment, the vaccine is formulated as a lipid nanoparticle
comprising at least one cationic lipid.
Inventors: |
Ciaramella; Giuseppe;
(Sudbury, MA) ; Huang; Eric Yi-Chun; (Boston,
MA) ; Babaoglu; Kerim; (Lansdale, PA) ; Flynn;
Jessica Anne; (Lansdale, PA) ; Zhang; Lan;
(Chalfont, PA) ; Nickle; David; (Seattle,
WA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
ModernaTX, Inc. |
Cambridge |
MA |
US |
|
|
Assignee: |
ModernaTX, Inc.
Cambridge
MA
|
Prior
Publication: |
|
Document Identifier |
Publication Date |
|
US 20210187097 A1 |
June 24, 2021 |
|
|
Appl. No.: |
16/493986 |
Filed: |
March 15, 2018 |
PCT Filed: |
March 15, 2018 |
PCT NO: |
PCT/US2018/022605 PCKC 00 |
371 Date: |
September 13, 2019 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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62490057 |
Apr 26, 2017 |
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62471771 |
Mar 15, 2017 |
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International
Class: |
A61K 39/145 20060101
A61K039/145 |
Claims
1. A vaccine comprising at least one ribonucleic acid (RNA)
polynucleotide having an open reading frame encoding at least one
influenza virus antigenic polypeptide formulated in a lipid
nanoparticle comprising compounds of Formula (I): ##STR00048## or a
salt or isomer thereof, wherein: R.sub.1 is selected from the group
consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; R.sub.2 and R.sub.3 are independently
selected from the group consisting of H, C.sub.1-14 alkyl,
C.sub.2-14 alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and
R.sub.3, together with the atom to which they are attached, form a
heterocycle or carbocycle; R.sub.4 is selected from the group
consisting of a C.sub.3-6 carbocycle, --(CH.sub.2).sub.nQ,
--(CH.sub.2).sub.nCHQR, --CHQR, --CQ(R).sub.2, and unsubstituted
C.sub.1-6 alkyl, where Q is selected from a carbocycle,
heterocycle, --OR, --O(CH.sub.2).sub.nN(R).sub.2, --C(O)OR,
--OC(O)R, --CX.sub.3, --CX.sub.2H, --CXH.sub.2, --CN, --N(R).sub.2,
--C(O)N(R).sub.2, --N(R)C(O)R, --N(R)S(O).sub.2R,
--N(R)C(O)N(R).sub.2, --N(R)C(S)N(R).sub.2, --N(R)R.sub.8,
--O(CH.sub.2).sub.nOR, --N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)N(R).sub.2,
--C(.dbd.NR.sub.9)R, --C(O)N(R)OR, and --C(R)N(R).sub.2C(O)OR, and
each n is independently selected from 1, 2, 3, 4, and 5; each
R.sub.5 is independently selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each R.sub.6 is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; M and M' are independently
selected from --C(O)O--, --OC(O)--, --C(O)N(R')--, --N(R')C(O)--,
--C(O)--, --C(S)--, --C(S)S--, --SC(S)--, --CH(OH)--,
--P(O)(OR')O--, --S(O).sub.2--, --S--S--, an aryl group, and a
heteroaryl group; R.sub.7 is selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; R.sub.8 is selected from
the group consisting of C.sub.3-6 carbocycle and heterocycle;
R.sub.9 is selected from the group consisting of H, CN, NO.sub.2,
C.sub.1-6 alkyl, --OR, --S(O).sub.2R, --S(O).sub.2N(R).sub.2,
C.sub.2-6 alkenyl, C.sub.3-6 carbocycle and heterocycle; each R is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; each R' is independently selected
from the group consisting of C.sub.1-18 alkyl, C.sub.2-18 alkenyl,
--R*YR'', --YR'', and H; each R'' is independently selected from
the group consisting of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
each R* is independently selected from the group consisting of
C.sub.1-12 alkyl and C.sub.2-12 alkenyl; each Y is independently a
C.sub.3-6 carbocycle; each X is independently selected from the
group consisting of F, Cl, Br, and I; and m is selected from 5, 6,
7, 8, 9, 10, 11, 12, and 13.
2. The vaccine of claim 1, wherein a subset of compounds of Formula
(I) includes those in which when R.sub.4 is --(CH.sub.2).sub.nQ,
--(CH.sub.2).sub.nCHQR, --CHQR, or --CQ(R).sub.2, then (i) Q is not
--N(R).sub.2 when n is 1, 2, 3, 4 or 5, or (ii) Q is not 5, 6, or
7-membered heterocycloalkyl when n is 1 or 2.
3. The vaccine of claim 1, wherein a subset of compounds of Formula
(I) includes those in which R.sub.1 is selected from the group
consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; R.sub.2 and R.sub.3 are independently
selected from the group consisting of H, C.sub.1-14 alkyl,
C.sub.2-14 alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and
R.sub.3, together with the atom to which they are attached, form a
heterocycle or carbocycle; R.sub.4 is selected from the group
consisting of a C.sub.3-6 carbocycle, --(CH.sub.2).sub.nQ,
--(CH.sub.2).sub.nCHQR, --CHQR, --CQ(R).sub.2, and unsubstituted
C.sub.1-6 alkyl, where Q is selected from a C.sub.3-6 carbocycle, a
5- to 14-membered heteroaryl having one or more heteroatoms
selected from N, O, and S, --OR, --O(CH.sub.2).sub.nN(R).sub.2,
--C(O)OR, --OC(O)R, --CX.sub.3, --CX.sub.2H, --CXH.sub.2, --CN,
--C(O)N(R).sub.2, --N(R)C(O)R, --N(R)S(O).sub.2R,
--N(R)C(O)N(R).sub.2, --N(R)C(S)N(R).sub.2, --CRN(R).sub.2C(O)OR,
--N(R)R.sub.8, --O(CH.sub.2).sub.nOR,
--N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)N(R).sub.2,
--C(.dbd.NR.sub.9)R, --C(O)N(R)OR, and a 5- to 14-membered
heterocycloalkyl having one or more heteroatoms selected from N, O,
and S which is substituted with one or more substituents selected
from oxo (.dbd.O), OH, amino, mono- or di-alkylamino, and C.sub.1-3
alkyl, and each n is independently selected from 1, 2, 3, 4, and 5;
each R.sub.5 is independently selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each R.sub.6 is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; M and M' are independently
selected from --C(O)O--, --OC(O)--, --C(O)N(R')--, --N(R')C(O)--,
--C(O)--, --C(S)--, --C(S)S--, --SC(S)--, --CH(OH)--,
--P(O)(OR')O--, --S(O).sub.2--, --S--S--, an aryl group, and a
heteroaryl group; R.sub.7 is selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; R.sub.8 is selected from
the group consisting of C.sub.3-6 carbocycle and heterocycle;
R.sub.9 is selected from the group consisting of H, CN, NO.sub.2,
C.sub.1-6 alkyl, --OR, --S(O).sub.2R, --S(O).sub.2N(R).sub.2,
C.sub.2-6 alkenyl, C.sub.3-6 carbocycle and heterocycle; each R is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; each R' is independently selected
from the group consisting of C.sub.1-18 alkyl, C.sub.2-18 alkenyl,
--R*YR'', --YR'', and H; each R'' is independently selected from
the group consisting of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
each R* is independently selected from the group consisting of
C.sub.1-12 alkyl and C.sub.2-12 alkenyl; each Y is independently a
C.sub.3-6 carbocycle; each X is independently selected from the
group consisting of F, Cl, Br, and I; and m is selected from 5, 6,
7, 8, 9, 10, 11, 12, and 13, or salts or isomers thereof.
4. The vaccine of claim 1, wherein a subset of compounds of Formula
(I) includes those in which R.sub.1 is selected from the group
consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; R.sub.2 and R.sub.3 are independently
selected from the group consisting of H, C.sub.1-14 alkyl,
C.sub.2-14 alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and
R.sub.3, together with the atom to which they are attached, form a
heterocycle or carbocycle; R.sub.4 is selected from the group
consisting of a C.sub.3-6 carbocycle, --(CH.sub.2).sub.nQ,
--(CH.sub.2).sub.nCHQR, --CHQR, --CQ(R).sub.2, and unsubstituted
C.sub.1-6 alkyl, where Q is selected from a C.sub.3-6 carbocycle, a
5- to 14-membered heterocycle having one or more heteroatoms
selected from N, O, and S, --OR, --O(CH.sub.2).sub.nN(R).sub.2,
--C(O)OR, --OC(O)R, --CX.sub.3, --CX.sub.2H, --CXH.sub.2, --CN,
--C(O)N(R).sub.2, --N(R)C(O)R, --N(R)S(O).sub.2R,
--N(R)C(O)N(R).sub.2, --N(R)C(S)N(R).sub.2, --CRN(R).sub.2C(O)OR,
--N(R)R.sub.8, --O(CH.sub.2).sub.nOR,
--N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)R,
--C(O)N(R)OR, and --C(.dbd.NR.sub.9)N(R).sub.2, and each n is
independently selected from 1, 2, 3, 4, and 5; and when Q is a 5-
to 14-membered heterocycle and (i) R.sub.4 is --(CH.sub.2).sub.nQ
in which n is 1 or 2, or (ii) R.sub.4 is --(CH.sub.2).sub.nCHQR in
which n is 1, or (iii) R.sub.4 is --CHQR, and --CQ(R).sub.2, then Q
is either a 5- to 14-membered heteroaryl or 8- to 14-membered
heterocycloalkyl; each R.sub.5 is independently selected from the
group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each
R.sub.6 is independently selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; M and M' are
independently selected from --C(O)O--, --OC(O)--, --C(O)N(R')--,
--N(R')C(O)--, --C(O)--, --C(S)--, --C(S)S--, --SC(S)--,
--CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--, --S--S--, an aryl
group, and a heteroaryl group; R.sub.7 is selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; R.sub.8 is
selected from the group consisting of C.sub.3-6 carbocycle and
heterocycle; R.sub.9 is selected from the group consisting of H,
CN, NO.sub.2, C.sub.1-6 alkyl, --OR, --S(O).sub.2R,
--S(O).sub.2N(R).sub.2, C.sub.2-6 alkenyl, C.sub.3-6 carbocycle and
heterocycle; each R is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each R' is
independently selected from the group consisting of C.sub.1-18
alkyl, C.sub.2-18 alkenyl, --R*YR'', --YR'', and H; each R'' is
independently selected from the group consisting of C.sub.3-14
alkyl and C.sub.3-14 alkenyl; each R* is independently selected
from the group consisting of C.sub.1-12 alkyl and C.sub.2-12
alkenyl; each Y is independently a C.sub.3-6 carbocycle; each X is
independently selected from the group consisting of F, Cl, Br, and
I; and m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13, or
salts or isomers thereof.
5. The vaccine of claim 1, wherein a subset of compounds of Formula
(I) includes those in which R.sub.1 is selected from the group
consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; R.sub.2 and R.sub.3 are independently
selected from the group consisting of H, C.sub.1-14 alkyl,
C.sub.2-14 alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and
R.sub.3, together with the atom to which they are attached, form a
heterocycle or carbocycle; R.sub.4 is selected from the group
consisting of a C.sub.3-6 carbocycle, --(CH.sub.2).sub.nQ,
--(CH.sub.2).sub.nCHQR, --CHQR, --CQ(R).sub.2, and unsubstituted
C.sub.1-6 alkyl, where Q is selected from a C.sub.3-6 carbocycle, a
5- to 14-membered heteroaryl having one or more heteroatoms
selected from N, O, and S, --OR, --O(CH.sub.2).sub.nN(R).sub.2,
--C(O)OR, --OC(O)R, --CX.sub.3, --CX.sub.2H, --CXH.sub.2, --CN,
--C(O)N(R).sub.2, --N(R)C(O)R, --N(R)S(O).sub.2R,
--N(R)C(O)N(R).sub.2, --N(R)C(S)N(R).sub.2, --CRN(R).sub.2C(O)OR,
--N(R)R.sub.8 --O(CH.sub.2).sub.nOR,
--N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)R,
--C(O)N(R)OR, and --C(.dbd.NR.sub.9)N(R).sub.2, and each n is
independently selected from 1, 2, 3, 4, and 5; each R.sub.5 is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; each R.sub.6 is independently
selected from the group consisting of C.sub.1-3 alkyl, C.sub.2-3
alkenyl, and H; M and M' are independently selected from --C(O)O--,
--OC(O)--, --C(O)N(R')--, --N(R')C(O)--, --C(O)--, --C(S)--,
--C(S)S--, --SC(S)--, --CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--,
--S--S--, an aryl group, and a heteroaryl group; R.sub.7 is
selected from the group consisting of C.sub.1-3 alkyl, C.sub.2-3
alkenyl, and H; R.sub.8 is selected from the group consisting of
C.sub.3-6 carbocycle and heterocycle; R.sub.9 is selected from the
group consisting of H, CN, NO.sub.2, C.sub.1-6 alkyl, --OR,
--S(O).sub.2R, --S(O).sub.2N(R).sub.2, C.sub.2-6 alkenyl, C.sub.3-6
carbocycle and heterocycle; each R is independently selected from
the group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
each R' is independently selected from the group consisting of
C.sub.1-18 alkyl, C.sub.2-18 alkenyl, --R*YR'', --YR'', and H; each
R'' is independently selected from the group consisting of
C.sub.3-14 alkyl and C.sub.3-14 alkenyl; each R* is independently
selected from the group consisting of C.sub.1-12 alkyl and
C.sub.2-12 alkenyl; each Y is independently a C.sub.3-6 carbocycle;
each X is independently selected from the group consisting of F,
Cl, Br, and I; and m is selected from 5, 6, 7, 8, 9, 10, 11, 12,
and 13, or salts or isomers thereof.
6. The vaccine of claim 1, wherein subset of compounds of Formula
(I) includes those in which R.sub.1 is selected from the group
consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; R.sub.2 and R.sub.3 are independently
selected from the group consisting of H, C.sub.2-14 alkyl,
C.sub.2-14 alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and
R.sub.3, together with the atom to which they are attached, form a
heterocycle or carbocycle; R.sub.4 is --(CH.sub.2).sub.nQ or
--(CH.sub.2).sub.nCHQR, where Q is --N(R).sub.2, and n is selected
from 3, 4, and 5; each R.sub.5 is independently selected from the
group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each
R.sub.6 is independently selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; M and M' are
independently selected from --C(O)O--, --OC(O)--, --C(O)N(R')--,
--N(R')C(O)--, --C(O)--, --C(S)--, --C(S)S--, --SC(S)--,
--CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--, --S--S--, an aryl
group, and a heteroaryl group; R.sub.7 is selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each R is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; each R' is independently selected
from the group consisting of C.sub.1-18 alkyl, C.sub.2-18 alkenyl,
--R*YR'', --YR'', and H; each R'' is independently selected from
the group consisting of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
each R* is independently selected from the group consisting of
C.sub.1-12 alkyl and C.sub.1-12 alkenyl; each Y is independently a
C.sub.3-6 carbocycle; each X is independently selected from the
group consisting of F, Cl, Br, and I; and m is selected from 5, 6,
7, 8, 9, 10, 11, 12, and 13, or salts or isomers thereof.
7. The vaccine of claim 1, wherein a subset of compounds of Formula
(I) includes those in which R.sub.1 is selected from the group
consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; R.sub.2 and R.sub.3 are independently
selected from the group consisting of C.sub.1-14 alkyl, C.sub.2-14
alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and R.sub.3,
together with the atom to which they are attached, form a
heterocycle or carbocycle; R.sub.4 is selected from the group
consisting of --(CH.sub.2).sub.nQ, --(CH.sub.2).sub.nCHQR, --CHQR,
and --CQ(R).sub.2, where Q is --N(R).sub.2, and n is selected from
1, 2, 3, 4, and 5; each R.sub.5 is independently selected from the
group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each
R.sub.6 is independently selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; M and M' are
independently selected from --C(O)O--, --OC(O)--, --C(O)N(R')--,
--N(R')C(O)--, --C(O)--, --C(S)--, --C(S)S--, --SC(S)--,
--CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--, --S--S--, an aryl
group, and a heteroaryl group; R.sub.7 is selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each R is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; each R' is independently selected
from the group consisting of C.sub.1-18 alkyl, C.sub.2-18 alkenyl,
--R*YR'', --YR'', and H; each R'' is independently selected from
the group consisting of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
each R* is independently selected from the group consisting of
C.sub.1-12 alkyl and C.sub.1-12 alkenyl; each Y is independently a
C.sub.3-6 carbocycle; each X is independently selected from the
group consisting of F, Cl, Br, and I; and m is selected from 5, 6,
7, 8, 9, 10, 11, 12, and 13, or salts or isomers thereof.
8. The vaccine of claim 1, wherein a subset of compounds of Formula
(I) includes those of Formula (IA): ##STR00049## or a salt or
isomer thereof, wherein l is selected from 1, 2, 3, 4, and 5; m is
selected from 5, 6, 7, 8, and 9; M.sub.1 is a bond or M'; R.sub.4
is unsubstituted C.sub.1-3 alkyl, or --(CH.sub.2).sub.nQ, in which
Q is OH, --NHC(S)N(R).sub.2, --NHC(O)N(R).sub.2, --N(R)C(O)R,
--N(R)S(O).sub.2R, --N(R)R.sub.8, --NHC(.dbd.NR.sub.9)N(R).sub.2,
--NHC(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
heteroaryl or heterocycloalkyl; M and M' are independently selected
from --C(O)O--, --OC(O)--, --C(O)N(R')--, --P(O)(OR')O--, --S--S--,
an aryl group, and a heteroaryl group; and R.sub.2 and R.sub.3 are
independently selected from the group consisting of H, C.sub.1-14
alkyl, and C.sub.2-14 alkenyl.
9. The vaccine of any one of claims 1-8, wherein the at least one
antigenic polypeptide is influenza hemagglutinin 1 (HA1) and/or
hemagglutinin 2 (HA2).
10. The vaccine of any one of claims 1-8, wherein at least one
antigenic polypeptide is HA1, HA2, or a combination of HA1 and HA2,
and at least one antigenic polypeptide is selected from the group
consisting of neuraminidase (NA), nucleoprotein (NP), matrix
protein 1 (M1), matrix protein 2 (M2), non-structural protein 1
(NS1) and non-structural protein 2 (NS2).
11. The vaccine of claim 10, wherein at least one antigenic
polypeptide is HA2 and at least one antigenic polypeptide is
selected from the group consisting of NA, NP, M1, M2, NS1 and
NS2.
12. The vaccine of claim 11, wherein at least one antigenic
polypeptide is HA2 and at least one antigenic polypeptides is
selected from the group consisting of NA, NP, M1, M2, NS1 and
NS2.
13. The vaccine of any one of claims 1-12, wherein the at least one
antigenic polypeptide is from influenza virus strain
H1/PuertoRico/8/1934, H1/New Caledonia/20/1999,
H1/California/04/2009, H5/Vietnam/1194/2004, H2/Japan/305/1957,
H9/Hong Kong/1073/99, H3/Aichi/2/1968, H3/Brisbane/10/2007,
H7/Anhui/1/2013, H10/Jiangxi-Donghu/346/2013, H3/Wisconsin/67/2005,
H1/Vietnam/850/2009, or a combination thereof.
14. The vaccine of any one of claims 1-13, wherein the at least one
antigenic polypeptide comprises an amino acid sequence identified
by any one of SEQ ID NO: 1-444, 458, 460, 462-479, or 543-565.
15. The vaccine of any one of claims 1-14, wherein the at least one
RNA polypeptide is encoded by a nucleic acid sequence identified by
any one of SEQ ID NO: 447-457, 459, 461, or 505-523, and/or wherein
the at least one RNA polypeptide comprises a nucleic acid sequence
identified by any one of SEQ ID NO: 491-503 or 524-542.
16. The vaccine of any one of claims 1-15, wherein the at least one
antigenic polypeptide has an amino acid sequence that has at least
95% identity to an amino acid sequence identified by any one of SEQ
ID NO: 1-444, 458, 460, 462-479, or 543-565.
17. The vaccine of any one of claims 1-16, wherein the at least one
antigenic polypeptide has an amino acid sequence that is 95%-99%
identical to an amino acid sequence identified by any one of SEQ ID
NO: 1-444, 458, 460, 462-479, or 543-565.
18. The vaccine of any one of claims 1-17, wherein the at least one
antigenic polypeptide has an amino acid sequence that has at least
90% identity to an amino acid sequence of SEQ ID NO: 1-444, 458,
460, 462-479, or 543-565 and wherein the antigenic polypeptide has
membrane fusion activity, attaches to cell receptors, causes fusion
of viral and cellular membranes, and/or is responsible for binding
of the virus to a cell being infected.
19. The vaccine of any one of claims 1-18, wherein the at least one
antigenic polypeptide has an amino acid sequence that has 90%-99%
identity to an amino acid sequence of SEQ ID NO: 1-444, 458, 460,
462-479, or 543-565 and wherein the antigenic polypeptide has
membrane fusion activity, attaches to cell receptors, causes fusion
of viral and cellular membranes, and/or is responsible for binding
of the virus to a cell being infected.
20. The vaccine of any one of claims 1-19, wherein the open reading
frame is codon-optimized.
21. An influenza virus vaccine, comprising: at least one
ribonucleic acid polynucleotide having an open reading frame
encoding at least one influenza virus antigenic polypeptide or an
immunogenic fragment thereof, formulated in a lipid nanoparticle,
wherein (i) the at least one RNA polypeptide is encoded by a
nucleic acid sequence identified by any one of SEQ ID NO: 505-523
or 570-573, and/or (ii) the at least one RNA polypeptide comprises
a nucleic acid sequence identified by any one of SEQ ID NO: 524-542
or 566-569, and/or (iii) the at least one antigenic polypeptide
comprises an amino acid sequence identified by any one of SEQ ID
NO: 543-565.
22. The vaccine of any one of claims 1-21, wherein the vaccine is
multivalent.
23. The vaccine of any one of claims 1-22 formulated in an
effective amount to produce an antigen-specific immune
response.
24. A multiple consensus subtype vaccine comprising at least one
ribonucleic acid (RNA) polynucleotide having an open reading frame
encoding at least one influenza virus antigenic polypeptide,
wherein the vaccine provides cross-reactivity against a variety of
influenza strains, the vaccine comprising at least one consensus
hemagglutinin antigen, formulated in a lipid nanoparticle
comprising compounds of Formula (I): ##STR00050## or a salt or
isomer thereof, wherein: R.sub.1 is selected from the group
consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; R.sub.2 and R.sub.3 are independently
selected from the group consisting of H, C.sub.1-14 alkyl,
C.sub.2-14 alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and
R.sub.3, together with the atom to which they are attached, form a
heterocycle or carbocycle; R.sub.4 is selected from the group
consisting of a C.sub.3-6 carbocycle, --(CH.sub.2).sub.nQ,
--(CH.sub.2).sub.nCHQR, --CHQR, --CQ(R).sub.2, and unsubstituted
C.sub.1-6 alkyl, where Q is selected from a carbocycle,
heterocycle, --OR, --O(CH.sub.2).sub.nN(R).sub.2, --C(O)OR,
--OC(O)R, --CX.sub.3, --CX.sub.2H, --CXH.sub.2, --CN, --N(R).sub.2,
--C(O)N(R).sub.2, --N(R)C(O)R, --N(R)S(O).sub.2R,
--N(R)C(O)N(R).sub.2, --N(R)C(S)N(R).sub.2, --N(R)R.sub.8,
--O(CH.sub.2).sub.nOR, --N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)N(R).sub.2,
--C(.dbd.NR.sub.9)R, --C(O)N(R)OR, and --C(R)N(R).sub.2C(O)OR, and
each n is independently selected from 1, 2, 3, 4, and 5; each
R.sub.5 is independently selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each R.sub.6 is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; M and M' are independently
selected from --C(O)O--, --OC(O)--, --C(O)N(R')--, --N(R')C(O)--,
--C(O)--, --C(S)--, --C(S)S--, --SC(S)--, --CH(OH)--,
--P(O)(OR')O--, --S(O).sub.2--, --S--S--, an aryl group, and a
heteroaryl group; R.sub.7 is selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; R.sub.8 is selected from
the group consisting of C.sub.3-6 carbocycle and heterocycle;
R.sub.9 is selected from the group consisting of H, CN, NO.sub.2,
C.sub.1-6 alkyl, --OR, --S(O).sub.2R, --S(O).sub.2N(R).sub.2,
C.sub.2-6 alkenyl, C.sub.3-6 carbocycle and heterocycle; each R is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; each R' is independently selected
from the group consisting of C.sub.1-18 alkyl, C.sub.2-18 alkenyl,
--R*YR'', --YR'', and H; each R'' is independently selected from
the group consisting of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
each R* is independently selected from the group consisting of
C.sub.1-12 alkyl and C.sub.2-12 alkenyl; each Y is independently a
C.sub.3-6 carbocycle; each X is independently selected from the
group consisting of F, Cl, Br, and I; and m is selected from 5, 6,
7, 8, 9, 10, 11, 12, and 13.
25. The vaccine of claim 24, wherein a subset of compounds of
Formula (I) includes those in which when R.sub.4 is
--(CH.sub.2).sub.nQ, --(CH.sub.2).sub.nCHQR, --CHQR, or
--CQ(R).sub.2, then (i) Q is not --N(R).sub.2 when n is 1, 2, 3, 4
or 5, or (ii) Q is not 5, 6, or 7-membered heterocycloalkyl when n
is 1 or 2.
26. The vaccine of claim 24, wherein a subset of compounds of
Formula (I) includes those in which R.sub.1 is selected from the
group consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; R.sub.2 and R.sub.3 are independently
selected from the group consisting of H, C.sub.1-14 alkyl,
C.sub.2-14 alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and
R.sub.3, together with the atom to which they are attached, form a
heterocycle or carbocycle; R.sub.4 is selected from the group
consisting of a C.sub.3-6 carbocycle, --(CH.sub.2).sub.nQ,
--(CH.sub.2).sub.nCHQR, --CHQR, --CQ(R).sub.2, and unsubstituted
C.sub.1-6 alkyl, where Q is selected from a C.sub.3-6 carbocycle, a
5- to 14-membered heteroaryl having one or more heteroatoms
selected from N, O, and S, --OR, --O(CH.sub.2).sub.nN(R).sub.2,
--C(O)OR, --OC(O)R, --CX.sub.3, --CX.sub.2H, --CXH.sub.2, --CN,
--C(O)N(R).sub.2, --N(R)C(O)R, --N(R)S(O).sub.2R,
--N(R)C(O)N(R).sub.2, --N(R)C(S)N(R).sub.2, --CRN(R).sub.2C(O)OR,
--N(R)R.sub.8, --O(CH.sub.2).sub.nOR,
--N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)N(R).sub.2,
--C(.dbd.NR.sub.9)R, --C(O)N(R)OR, and a 5- to 14-membered
heterocycloalkyl having one or more heteroatoms selected from N, O,
and S which is substituted with one or more substituents selected
from oxo (.dbd.O), OH, amino, mono- or di-alkylamino, and C.sub.1-3
alkyl, and each n is independently selected from 1, 2, 3, 4, and 5;
each R.sub.5 is independently selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each R.sub.6 is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; M and M' are independently
selected from --C(O)O--, --OC(O)--, --C(O)N(R')--, --N(R')C(O)--,
--C(O)--, --C(S)--, --C(S)S--, --SC(S)--, --CH(OH)--,
--P(O)(OR')O--, --S(O).sub.2--, --S--S--, an aryl group, and a
heteroaryl group; R.sub.7 is selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; R.sub.8 is selected from
the group consisting of C.sub.3-6 carbocycle and heterocycle;
R.sub.9 is selected from the group consisting of H, CN, NO.sub.2,
C.sub.1-6 alkyl, --OR, --S(O).sub.2R, --S(O).sub.2N(R).sub.2,
C.sub.2-6 alkenyl, C.sub.3-6 carbocycle and heterocycle; each R is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; each R' is independently selected
from the group consisting of C.sub.1-18 alkyl, C.sub.2-18 alkenyl,
--R*YR'', --YR'', and H; each R'' is independently selected from
the group consisting of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
each R* is independently selected from the group consisting of
C.sub.1-12 alkyl and C.sub.2-12 alkenyl; each Y is independently a
C.sub.3-6 carbocycle; each X is independently selected from the
group consisting of F, Cl, Br, and I; and m is selected from 5, 6,
7, 8, 9, 10, 11, 12, and 13, or salts or isomers thereof.
27. The vaccine of claim 24, wherein a subset of compounds of
Formula (I) includes those in which R.sub.1 is selected from the
group consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; R.sub.2 and R.sub.3 are independently
selected from the group consisting of H, C.sub.1-14 alkyl,
C.sub.2-14 alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and
R.sub.3, together with the atom to which they are attached, form a
heterocycle or carbocycle; R.sub.4 is selected from the group
consisting of a C.sub.3-6 carbocycle, --(CH.sub.2).sub.nQ,
--(CH.sub.2).sub.nCHQR, --CHQR, --CQ(R).sub.2, and unsubstituted
C.sub.1-6 alkyl, where Q is selected from a C.sub.3-6 carbocycle, a
5- to 14-membered heterocycle having one or more heteroatoms
selected from N, O, and S, --OR, --O(CH.sub.2).sub.nN(R).sub.2,
--C(O)OR, --OC(O)R, --CX.sub.3, --CX.sub.2H, --CXH.sub.2, --CN,
--C(O)N(R).sub.2, --N(R)C(O)R, --N(R)S(O).sub.2R,
--N(R)C(O)N(R).sub.2, --N(R)C(S)N(R).sub.2, --CRN(R).sub.2C(O)OR,
--N(R)R.sub.8, --O(CH.sub.2).sub.nOR,
--N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)R,
--C(O)N(R)OR, and --C(.dbd.NR.sub.9) N(R).sub.2, and each n is
independently selected from 1, 2, 3, 4, and 5; and when Q is a 5-
to 14-membered heterocycle and (i) R.sub.4 is --(CH.sub.2).sub.nQ
in which n is 1 or 2, or (ii) R.sub.4 is --(CH.sub.2).sub.nCHQR in
which n is 1, or (iii) R.sub.4 is --CHQR, and --CQ(R).sub.2, then Q
is either a 5- to 14-membered heteroaryl or 8- to 14-membered
heterocycloalkyl; each R.sub.5 is independently selected from the
group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each
R.sub.6 is independently selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; M and M' are
independently selected from --C(O)O--, --OC(O)--, --C(O)N(R')--,
--N(R')C(O)--, --C(O)--, --C(S)--, --C(S)S--, --SC(S)--,
--CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--, --S--S--, an aryl
group, and a heteroaryl group; R.sub.7 is selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; R.sub.8 is
selected from the group consisting of C.sub.3-6 carbocycle and
heterocycle; R.sub.9 is selected from the group consisting of H,
CN, NO.sub.2, C.sub.1-6 alkyl, --OR, --S(O).sub.2R,
--S(O).sub.2N(R).sub.2, C.sub.2-6 alkenyl, C.sub.3-6 carbocycle and
heterocycle; each R is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each R' is
independently selected from the group consisting of C.sub.1-18
alkyl, C.sub.2-18 alkenyl, --R*YR'', --YR'', and H; each R'' is
independently selected from the group consisting of C.sub.3-14
alkyl and C.sub.3-14 alkenyl; each R* is independently selected
from the group consisting of C.sub.1-12 alkyl and C.sub.2-12
alkenyl; each Y is independently a C.sub.3-6 carbocycle; each X is
independently selected from the group consisting of F, Cl, Br, and
I; and m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13, or
salts or isomers thereof.
28. The vaccine of claim 24, wherein a subset of compounds of
Formula (I) includes those in which R.sub.1 is selected from the
group consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; R.sub.2 and R.sub.3 are independently
selected from the group consisting of H, C.sub.1-14 alkyl,
C.sub.2-14 alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and
R.sub.3, together with the atom to which they are attached, form a
heterocycle or carbocycle; R.sub.4 is selected from the group
consisting of a C.sub.3-6 carbocycle, --(CH.sub.2).sub.nQ,
--(CH.sub.2).sub.nCHQR, --CHQR, --CQ(R).sub.2, and unsubstituted
C.sub.1-6 alkyl, where Q is selected from a C.sub.3-6 carbocycle, a
5- to 14-membered heteroaryl having one or more heteroatoms
selected from N, O, and S, --OR, --O(CH.sub.2).sub.nN(R).sub.2,
--C(O)OR, --OC(O)R, --CX.sub.3, --CX.sub.2H, --CXH.sub.2, --CN,
--C(O)N(R).sub.2, --N(R)C(O)R, --N(R)S(O).sub.2R,
--N(R)C(O)N(R).sub.2, --N(R)C(S)N(R).sub.2, --CRN(R).sub.2C(O)OR,
--N(R)R.sub.8, --O(CH.sub.2).sub.nOR,
--N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)R,
--C(O)N(R)OR, and --C(.dbd.NR.sub.9)N(R).sub.2, and each n is
independently selected from 1, 2, 3, 4, and 5; each R.sub.5 is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; each R.sub.6 is independently
selected from the group consisting of C.sub.1-3 alkyl, C.sub.2-3
alkenyl, and H; M and M' are independently selected from --C(O)O--,
--OC(O)--, --C(O)N(R')--, --N(R')C(O)--, --C(O)--, --C(S)--,
--C(S)S--, --SC(S)--, --CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--,
--S--S--, an aryl group, and a heteroaryl group; R.sub.7 is
selected from the group consisting of C.sub.1-3 alkyl, C.sub.2-3
alkenyl, and H; R.sub.8 is selected from the group consisting of
C.sub.3-6 carbocycle and heterocycle; R.sub.9 is selected from the
group consisting of H, CN, NO.sub.2, C.sub.1-6 alkyl, --OR,
--S(O).sub.2R, --S(O).sub.2N(R).sub.2, C.sub.2-6 alkenyl, C.sub.3-6
carbocycle and heterocycle; each R is independently selected from
the group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
each R' is independently selected from the group consisting of
C.sub.1-18 alkyl, C.sub.2-18 alkenyl, --R*YR'', --YR'', and H; each
R'' is independently selected from the group consisting of
C.sub.3-14 alkyl and C.sub.3-14 alkenyl; each R* is independently
selected from the group consisting of C.sub.1-12 alkyl and
C.sub.2-12 alkenyl; each Y is independently a C.sub.3-6 carbocycle;
each X is independently selected from the group consisting of F,
Cl, Br, and I; and m is selected from 5, 6, 7, 8, 9, 10, 11, 12,
and 13, or salts or isomers thereof.
29. The vaccine of claim 24, wherein subset of compounds of Formula
(I) includes those in which R.sub.1 is selected from the group
consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; R.sub.2 and R.sub.3 are independently
selected from the group consisting of H, C.sub.2-14 alkyl,
C.sub.2-14 alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and
R.sub.3, together with the atom to which they are attached, form a
heterocycle or carbocycle; R.sub.4 is --(CH.sub.2).sub.nQ or
--(CH.sub.2).sub.nCHQR, where Q is --N(R).sub.2, and n is selected
from 3, 4, and 5; each R.sub.5 is independently selected from the
group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each
R.sub.6 is independently selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; M and M' are
independently selected from --C(O)O--, --OC(O)--, --C(O)N(R')--,
--N(R')C(O)--, --C(O)--, --C(S)--, --C(S)S--, --SC(S)--,
--CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--, --S--S--, an aryl
group, and a heteroaryl group; R.sub.7 is selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each R is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; each R' is independently selected
from the group consisting of C.sub.1-18 alkyl, C.sub.2-18 alkenyl,
--R*YR'', --YR'', and H; each R'' is independently selected from
the group consisting of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
each R* is independently selected from the group consisting of
C.sub.1-12 alkyl and C.sub.1-12 alkenyl; each Y is independently a
C.sub.3-6 carbocycle; each X is independently selected from the
group consisting of F, Cl, Br, and I; and m is selected from 5, 6,
7, 8, 9, 10, 11, 12, and 13, or salts or isomers thereof.
30. The vaccine of claim 24, wherein a subset of compounds of
Formula (I) includes those in which R.sub.1 is selected from the
group consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; R.sub.2 and R.sub.3 are independently
selected from the group consisting of C.sub.1-14 alkyl, C.sub.2-14
alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and R.sub.3,
together with the atom to which they are attached, form a
heterocycle or carbocycle; R.sub.4 is selected from the group
consisting of --(CH.sub.2).sub.nQ, --(CH.sub.2).sub.nCHQR, --CHQR,
and --CQ(R).sub.2, where Q is --N(R).sub.2, and n is selected from
1, 2, 3, 4, and 5; each R.sub.5 is independently selected from the
group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each
R.sub.6 is independently selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; M and M' are
independently selected from --C(O)O--, --OC(O)--, --C(O)N(R')--,
--N(R')C(O)--, --C(O)--, --C(S)--, --C(S)S--, --SC(S)--,
--CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--, --S--S--, an aryl
group, and a heteroaryl group; R.sub.7 is selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each R is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; each R' is independently selected
from the group consisting of C.sub.1-18 alkyl, C.sub.2-18 alkenyl,
--R*YR'', --YR'', and H; each R'' is independently selected from
the group consisting of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
each R* is independently selected from the group consisting of
C.sub.1-12 alkyl and C.sub.1-12 alkenyl; each Y is independently a
C.sub.3-6 carbocycle; each X is independently selected from the
group consisting of F, Cl, Br, and I; and m is selected from 5, 6,
7, 8, 9, 10, 11, 12, and 13, or salts or isomers thereof.
31. The vaccine of claim 24, wherein a subset of compounds of
Formula (I) includes those of Formula (IA): ##STR00051## or a salt
or isomer thereof, wherein l is selected from 1, 2, 3, 4, and 5; m
is selected from 5, 6, 7, 8, and 9; M.sub.1 is a bond or M';
R.sub.4 is unsubstituted C.sub.1-3 alkyl, or --(CH.sub.2).Q, in
which Q is OH, --NHC(S)N(R).sub.2, --NHC(O)N(R).sub.2, --N(R)C(O)R,
--N(R)S(O).sub.2R, --N(R)R.sub.8, --NHC(.dbd.NR.sub.9)N(R).sub.2,
--NHC(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
heteroaryl or heterocycloalkyl; M and M' are independently selected
from --C(O)O--, --OC(O)--, --C(O)N(R')--, --P(O)(OR')O--, --S--S--,
an aryl group, and a heteroaryl group; and R.sub.2 and R.sub.3 are
independently selected from the group consisting of H, C.sub.1-14
alkyl, and C.sub.2-14 alkenyl.
32. The vaccine of any one of claims 24-31, wherein the consensus
hemagglutinin antigen is selected from the group consisting of
influenza hemagglutinin 1 (HA1) and/or hemagglutinin 2 (HA2).
33. The vaccine of any one of claims 24-31, wherein at least one
antigenic polypeptide is HA1, HA2, or a combination of HA1 and HA2,
and at least one antigenic polypeptide is selected from the group
consisting of neuraminidase (NA), nucleoprotein (NP), matrix
protein 1 (M1), matrix protein 2 (M2), non-structural protein 1
(NS1) and non-structural protein 2 (NS2).
34. The vaccine of claim 33, wherein at least one antigenic
polypeptide is HA1 and at least one antigenic polypeptide is
selected from the group consisting of NA, NP, M1, M2, NS1 and
NS2.
35. The vaccine of claim 34, wherein at least one antigenic
polypeptide is HA2 and at least one antigenic polypeptides is
selected from the group consisting of NA, NP, M1, M2, NS1 and
NS2.
36. The vaccine of any one of claims 24-35, wherein the at least
one antigenic polypeptide is from influenza virus strain
H1/PuertoRico/8/1934, H1/New Caledonia/20/1999,
H1/California/04/2009, H5/Vietnam/1194/2004, H2/Japan/305/1957,
H9/Hong Kong/1073/99, H3/Aichi/2/1968, H3/Brisbane/10/2007,
H7/Anhui/1/2013, H10/Jiangxi-Donghu/346/2013, H3/Wisconsin/67/2005,
H1/Vietnam/850/2009, or a combination thereof.
37. The vaccine of any one of claims 1-36, wherein the nanoparticle
has a mean diameter of 50-200 nm.
38. The vaccine of any one of claims 1-37 or any one of claims
1-15, wherein the lipid nanoparticle further comprises a
PEG-modified lipid, a sterol, and a non-cationic lipid.
39. The vaccine of claim 38, wherein the lipid nanoparticle
comprises a molar ratio of about 20-60% cationic lipid, 0.5-15%
PEG-modified lipid, 25-55% sterol, and 5-25% non-cationic
lipid.
40. The vaccine of claim 39, wherein the non-cationic lipid is a
neutral lipid and the sterol is a cholesterol.
41. The vaccine of any one of claims 1-40, wherein the nanoparticle
has a polydispersity value of less than 0.4.
42. The vaccine of any one of claims 1-41, wherein the nanoparticle
has a net neutral charge at a neutral pH value.
43. The vaccine of any one of claims 1-42, wherein the at least one
RNA polynucleotide comprises at least one chemical
modification.
44. The vaccine of claim 43, wherein the chemical modification is
selected from pseudouridine, N1-methylpseudouridine,
N1-ethylpseudouridine, 2-thiouridine, 4'-thiouridine,
5-methylcytosine, 5-methyluridine,
2-thio-1-methyl-1-deaza-pseudouridine,
2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine ,
2-thio-dihydropseudouridine, 2-thio-dihydrouridine,
2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine,
4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine,
4-thio-pseudouridine, 5-aza-uridine, dihydropseudouridine,
5-methoxyuridine and 2'-O-methyl uridine.
45. A method of inducing an immune response in a subject, the
method comprising administering to the subject the vaccine of any
one of claims 1-44 in an amount effective to produce an
antigen-specific immune response in the subject.
46. The method of claim 45, wherein the antigen specific immune
response comprises a T cell response or a B cell response.
47. The method of claim 45 or 46, wherein the subject is
administered a single dose of the vaccine.
48. The method of claim 45 or 46, wherein the subject is
administered a booster dose of the vaccine.
49. The method of any one of claims 45-48, wherein the vaccine is
administered to the subject by intradermal injection or
intramuscular injection.
50. The method of any one of claims 45-49, wherein an
anti-antigenic polypeptide antibody titer produced in the subject
is increased by at least 1 log relative to a control.
51. The method of any one of claims 45-50, wherein an
anti-antigenic polypeptide antibody titer produced in the subject
is increased by 1-3 log relative to a control.
52. The method of any one of claims 45-51, wherein the
anti-antigenic polypeptide antibody titer produced in the subject
is increased at least 2 times relative to a control.
53. The method of any one of claims 45-52, wherein the
anti-antigenic polypeptide antibody titer produced in the subject
is increased 2-10 times relative to a control.
54. The method of any one of claims 50-53, wherein the control is
an anti-antigenic polypeptide antibody titer produced in a subject
who has not been administered a vaccine against the virus.
55. The method of any one of claims 50-53, wherein the control is
an anti-antigenic polypeptide antibody titer produced in a subject
who has been administered a live attenuated vaccine or an
inactivated vaccine against the virus.
56. The method of any one of claims 50-53, wherein the control is
an anti-antigenic polypeptide antibody titer produced in a subject
who has been administered a recombinant protein vaccine or purified
protein vaccine against the virus.
57. The method of any one of claims 50-53, wherein the control is
an anti-antigenic polypeptide antibody titer produced in a subject
who has been administered a VLP vaccine against the virus.
58. The method of any one of claims 45-57, wherein the effective
amount is a dose equivalent to an at least 2-fold reduction in the
standard of care dose of a recombinant protein vaccine or a
purified protein vaccine against the virus, and wherein an
anti-antigenic polypeptide antibody titer produced in the subject
is equivalent to an anti-antigenic polypeptide antibody titer
produced in a control subject administered the standard of care
dose of a recombinant protein vaccine or a purified protein vaccine
against the virus, respectively.
59. The method of any one of claims 45-57, wherein the effective
amount is a dose equivalent to an at least 2-fold reduction in the
standard of care dose of a live attenuated vaccine or an
inactivated vaccine against the virus, and wherein an
anti-antigenic polypeptide antibody titer produced in the subject
is equivalent to an anti-antigenic polypeptide antibody titer
produced in a control subject administered the standard of care
dose of a live attenuated vaccine or an inactivated vaccine against
the virus, respectively.
60. The method of any one of claims 45-57, wherein the effective
amount is a dose equivalent to an at least 2-fold reduction in the
standard of care dose of a VLP vaccine against the virus, and
wherein an anti-antigenic polypeptide antibody titer produced in
the subject is equivalent to an anti-antigenic polypeptide antibody
titer produced in a control subject administered the standard of
care dose of a VLP vaccine against the virus.
61. The method of any one of claims 45-57, wherein the effective
amount is a total dose of 50 .mu.g-1000 .mu.g.
62. The method of claim 61, wherein the effective amount is a dose
of 25 .mu.g, 100 .mu.g, 400 .mu.g, or 500 .mu.g administered to the
subject a total of two times.
63. The method of any one of claims 45-62, wherein the efficacy of
the vaccine against the virus is greater than 65%.
64. The method of any one of claims 45-63, wherein the vaccine
immunizes the subject against the virus for up to 2 years.
65. The method of any one of claims 45-63, wherein the vaccine
immunizes the subject against the virus for more than 2 years.
66. The method of any one of claims 45-65, wherein the subject has
been exposed to the virus, wherein the subject is infected with the
virus, or wherein the subject is at risk of infection by the
virus.
67. The method of any one of claims 45-66, wherein the subject is
immunocompromised.
68. The vaccine of any one of claims 1-44 for use in a method of
inducing an antigen specific immune response in a subject, the
method comprising administering to the subject the vaccine in an
amount effective to produce an antigen specific immune response in
the subject.
69. Use of the vaccine of any one of claims 1-44 in the manufacture
of a medicament for use in a method of inducing an antigen specific
immune response in a subject, the method comprising administering
to the subject the vaccine in an amount effective to produce an
antigen specific immune response in the subject.
70. A method of inducing cross-reactivity against a variety of
influenza strains in a mammal, the method comprising administering
to the mammal in need thereof the vaccine of any one of claims
1-44.
71. The method of claim 70, wherein at least two ribonucleic acid
(RNA) polynucleotides having an open reading frame each encoding a
consensus hemagglutinin antigen are administered to the mammal
separately.
72. The method of claim 70, wherein at least two ribonucleic acid
(RNA) polynucleotides having an open reading frame each encoding a
consensus hemagglutinin antigen are administered to the mammal
simultaneously.
73. A pharmaceutical composition for use in vaccination of a
subject comprising the vaccine of any one of claims 1-44, wherein
the effective dose is sufficient to produce detectable levels of
antigen as measured in serum of the subject at 1-72 hours post
administration.
74. The composition of claim 73, wherein the cut off index of the
antigen is 1-2.
75. A pharmaceutical composition for use in vaccination of a
subject comprising an effective dose of the vaccine of any one of
claims 1-44, wherein the effective dose is sufficient to produce a
1,000-10,000 neutralization titer produced by neutralizing antibody
against said antigen as measured in serum of the subject at 1-72
hours post administration.
Description
RELATED APPLICATIONS
[0001] This application claims the benefit under 35 U.S.C. .sctn.
119(e) of U.S. provisional application No. 62/471,771, filed Mar.
15, 2017, and U.S. provisional application No. 62/490,057, filed
Apr. 26, 2017, each of which is incorporated by reference herein in
its entirety.
BACKGROUND
[0002] Influenza viruses are members of the orthomyxoviridae
family, and are classified into three distinct types (A, B, and C),
based on antigenic differences between their nucleoprotein (NP) and
matrix (M) protein. The orthomyxoviruses are enveloped animal
viruses of approximately 100 nm in diameter. The influenza virions
consist of an internal ribonucleoprotein core (a helical
nucleocapsid) containing a single-stranded RNA genome, and an outer
lipoprotein envelope lined inside by a matrix protein (M1). The
segmented genome of influenza A virus consists of eight molecules
(seven for influenza C virus) of linear, negative polarity,
single-stranded RNAs, which encode several polypeptides including:
the RNA-directed RNA polymerase proteins (PB2, PB1 and PA) and
nucleoprotein (NP), which form the nucleocapsid; the matrix
proteins (M1, M2, which is also a surface-exposed protein embedded
in the virus membrane); two surface glycoproteins, which project
from the lipoprotein envelope: hemagglutinin (HA) and neuraminidase
(NA); and nonstructural proteins (NS1 and NS2). Transcription and
replication of the genome takes place in the nucleus and assembly
takes place at the plasma membrane.
[0003] Hemagglutinin is the major envelope glycoprotein of
influenza A and B viruses, and hemagglutinin-esterase (HE) of
influenza C viruses is a protein homologous to HA. The rapid
evolution of the HA protein of the influenza virus results in the
constant emergence of new strains, rendering the adaptive immune
response of the host only partially protective to new infections.
The biggest challenge for therapy and prophylaxis against influenza
and other infections using traditional vaccines is the limitation
of vaccines in breadth, providing protection only against closely
related subtypes. In addition, the length of time required to
complete current standard influenza virus vaccine production
processes inhibits the rapid development and production of an
adapted vaccine in a pandemic situation.
[0004] Deoxyribonucleic acid (DNA) vaccination is one technique
used to stimulate humoral and cellular immune responses to foreign
antigens, such as influenza antigens. The direct injection of
genetically engineered DNA (e.g., naked plasmid DNA) into a living
host results in a small number of its cells directly producing an
antigen, resulting in a protective immunological response. With
this technique, however, come potential problems, including the
possibility of insertional mutagenesis, which could lead to the
activation of oncogenes or the inhibition of tumor suppressor
genes.
SUMMARY
[0005] Provided herein is a ribonucleic acid (RNA) vaccine (or a
composition or an immunogenic composition) that builds on the
knowledge that RNA (e.g., messenger RNA (mRNA)) can safely direct
the body's cellular machinery to produce nearly any protein of
interest, from native proteins to antibodies and other entirely
novel protein constructs that can have therapeutic activity inside
and outside of cells. The RNA vaccines of the present disclosure
may be used to induce a balanced immune response against influenza
virus, comprising both cellular and humoral immunity, without
risking the possibility of insertional mutagenesis, for
example.
[0006] The RNA (e.g., mRNA) vaccines may be utilized in various
settings depending on the prevalence of the infection or the degree
or level of unmet medical need. The RNA vaccines may be utilized to
treat and/or prevent an influenza virus of various genotypes,
strains, and isolates. The RNA vaccines typically have superior
properties in that they produce much larger antibody titers and
produce responses earlier than commercially available anti-viral
therapeutic treatments. While not wishing to be bound by theory, it
is believed that the RNA vaccines, as mRNA polynucleotides, are
better designed to produce the appropriate protein conformation
upon translation as the RNA vaccines co-opt natural cellular
machinery. Unlike traditional vaccines, which are manufactured ex
vivo and may trigger unwanted cellular responses, RNA (e.g., mRNA)
vaccines are presented to the cellular system in a more native
fashion.
[0007] There may be situations where persons are at risk for
infection with more than one strain of influenza virus. RNA (e.g.,
mRNA) therapeutic vaccines are particularly amenable to combination
vaccination approaches due to a number of factors including, but
not limited to, speed of manufacture, ability to rapidly tailor
vaccines to accommodate perceived geographical threat, and the
like. Moreover, because the vaccines utilize the human body to
produce the antigenic protein, the vaccines are amenable to the
production of larger, more complex antigenic proteins, allowing for
proper folding, surface expression, antigen presentation, etc. in
the human subject. To protect against more than one strain of
influenza, a combination vaccine can be administered that includes
RNA (e.g., mRNA) encoding at least one antigenic polypeptide
protein (or antigenic portion thereof) of a first influenza virus
or organism and further includes RNA encoding at least one
antigenic polypeptide protein (or antigenic portion thereof) of a
second influenza virus or organism. RNA (e.g., mRNA) can be
co-formulated, for example, in a single lipid nanoparticle (LNP) or
can be formulated in separate LNPs for co-administration.
[0008] Some embodiments of the present disclosure provide influenza
virus (influenza) vaccines (or compositions or immunogenic
compositions) that include at least one RNA polynucleotide having
an open reading frame encoding at least one influenza antigenic
polypeptide.
[0009] In some embodiments, the at least one antigenic polypeptide
is one of the defined antigenic subdomains of HA, termed HA1, HA2,
or a combination of HA1 and HA2, and at least one antigenic
polypeptide selected from neuraminidase (NA), nucleoprotein (NP),
matrix protein 1 (M1), matrix protein 2 (M2), non-structural
protein 1 (NS1) and non-structural protein 2 (NS2).
[0010] In some embodiments, the at least one antigenic polypeptide
is HA or derivatives thereof comprising antigenic sequences from
HA1 and/or HA2, and at least one antigenic polypeptide selected
from NA, NP, M1, M2, NS1 and NS2.
[0011] In some embodiments, the at least one antigenic polypeptide
is HA or derivatives thereof comprising antigenic sequences from
HA1 and/or HA2 and at least two antigenic polypeptides selected
from NA, NP, M1, M2, NS1 and NS2.
[0012] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
an influenza virus protein.
[0013] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
multiple influenza virus proteins.
[0014] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (e.g., at least one HA1, HA2, or a combination of
both).
[0015] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (e.g., at least one HA1, HA2, or a combination of both,
of any one of or a combination of any or all of H1, H2, H3, H4, H5,
H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, and/or H18)
and at least one other RNA (e.g., mRNA) polynucleotide having an
open reading frame encoding a protein selected from a NP protein, a
NA protein, a M1 protein, a M2 protein, a NS1 protein and a NS2
protein obtained from influenza virus.
[0016] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (e.g., at least one any one of or a combination of any
or all of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13,
H14, H15, H16, H17, and/or H18) and at least two other RNAs (e.g.,
mRNAs) polynucleotides having two open reading frames encoding two
proteins selected from a NP protein, a NA protein, a M1 protein, a
M2 protein, a NS1 protein and a NS2 protein obtained from influenza
virus.
[0017] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (e.g., at least one of any one of or a combination of
any or all of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12,
H13, H14, H15, H16, H17, and/or H18) and at least three other RNAs
(e.g., mRNAs) polynucleotides having three open reading frames
encoding three proteins selected from a NP protein, a NA protein, a
M1 protein, a M2 protein, a NS1 protein and a NS2 protein obtained
from influenza virus.
[0018] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (e.g., at least one of any one of or a combination of
any or all of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12,
H13, H14, H15, H16, H17, and/or H18) and at least four other RNAs
(e.g., mRNAs) polynucleotides having four open reading frames
encoding four proteins selected from a NP protein, a NA protein, a
M1 protein, a M2 protein, a NS1 protein and a NS2 protein obtained
from influenza virus.
[0019] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (e.g., at least one of any one of or a combination of
any or all of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12,
H13, H14, H15, H16, H17, and/or H18) and at least five other RNAs
(e.g., mRNAs) polynucleotides having five open reading frames
encoding five proteins selected from a NP protein, a NA protein, a
M1 protein, a M2 protein, a NS1 protein and a NS2 protein obtained
from influenza virus.
[0020] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (e.g., at least one of any one of or a combination of
any or all of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12,
H13, H14, H15, H16, H17, and/or H18), a NP protein, a NA protein, a
M1 protein, a M2 protein, a NS1 protein and a NS2 protein obtained
from influenza virus.
[0021] Some embodiments of the present disclosure provide the
following novel influenza virus polypeptide sequences:
H1HA10-Foldon_.DELTA.Ngly1; H1HA10TM-PR8 (H1 A/Puerto Rico/8/34
HA); H1HA10-PR8-DS (H1 A/Puerto Rico/8/34 HA; pH1HA10-Cal04-DS (H1
A/California/04/2009 HA); Pandemic H1HA10 from California 04;
pH1HA10-ferritin; HA10; Pandemic H1HA10 from California 04;
Pandemic H1HA10 from California 04 strain/without foldon and with
K68C/R76C mutation for trimerization; H1HA10 from A/Puerto
Rico/8/34 strain, without foldon and with Y94D/N95L mutation for
trimerization; H1HA10 from A/Puerto Rico/8/34 strain, without
foldon and with K68C/R76C mutation for trimerization; H1N1 A/Viet
Nam/850/2009; H3N2 A/Wisconsin/67/2005; H7N9 (A/Anhui/1/2013); H9N2
A/Hong Kong/1073/99; H10N8 A/JX346/2013.
[0022] Some embodiments of the present disclosure provide influenza
virus (influenza) vaccines that include at least one RNA
polynucleotide having an open reading frame encoding at least one
influenza antigenic polypeptide. In some embodiments, an influenza
vaccine comprises at least one RNA (e.g., mRNA) polynucleotide
having an open reading frame encoding at least one influenza
antigenic polypeptide comprising a modified sequence that is at
least 75% (e.g., any number between 75% and 100%, inclusive, e.g.,
70%, 80%, 85%, 90%, 95%, 99%, and 100%) identity to an amino acid
sequence of the novel influenza virus sequences described above.
The modified sequence can be at least 75% (e.g., any number between
75% and 100%, inclusive, e.g., 70%, 80%, 85%, 90%, 95%, 99%, and
100%) identical to an amino acid sequence of the novel influenza
virus sequences described above.
[0023] Some embodiments of the present disclosure provide an
isolated nucleic acid comprising a sequence encoding the novel
influenza virus polypeptide sequences described above; an
expression vector comprising the nucleic acid; and a host cell
comprising the nucleic acid. The present disclosure also provides a
method of producing a polypeptide of any of the novel influenza
virus sequences described above. A method may include culturing the
host cell in a medium under conditions permitting nucleic acid
expression of the novel influenza virus sequences described above,
and purifying from the cultured cell or the medium of the cell a
novel influenza virus polypeptide. The present disclosure also
provides antibody molecules, including full length antibodies and
antibody derivatives, directed against the novel influenza virus
sequences.
[0024] In some embodiments, an open reading frame of a RNA (e.g.,
mRNA) vaccine is codon-optimized. In some embodiments, at least one
RNA polynucleotide encodes at least one antigenic polypeptide
comprising an amino acid sequence identified by any one of SEQ ID
NO: 1-444, 458, 460, 462-479, or 543-565 (see also Tables 7-13 and
26) and is codon optimized mRNA.
[0025] In some embodiments, a RNA (e.g., mRNA) vaccine further
comprising an adjuvant.
[0026] Tables 7-13 provide National Center for Biotechnology
Information (NCBI) accession numbers of interest. It should be
understood that the phrase "an amino acid sequence of Tables 7-13"
refers to an amino acid sequence identified by one or more NCBI
accession numbers listed in 7-13. Each of the amino acid sequences,
and variants having greater than 95% identity or greater than 98%
identity to each of the amino acid sequences encompassed by the
accession numbers of Tables 7-13 are included within the constructs
(polynucleotides/polypeptides) of the present disclosure.
[0027] In some embodiments, at least one mRNA polynucleotide is
encoded by a nucleic acid comprising a sequence identified by any
one of SEQ ID NO: 447-457, 459, 461, 505-523, or 570-573 and having
less than 80% identity to wild-type mRNA sequence. In some
embodiments, at least one mRNA polynucleotide is encoded by a
nucleic acid comprising a sequence identified by any one SEQ ID NO:
447-457, 459, 461, 505-523, or 570-573 and having less than 75%,
85% or 95% identity to a wild-type mRNA sequence. In some
embodiments, at least one mRNA polynucleotide is encoded by nucleic
acid comprising a sequence identified by any one of SEQ ID NO:
447-457, 459, 461, 505-523, or 570-573 and having less than 50-80%,
60-80%, 40-80%, 30-80%, 70-80%, 75-80% or 78-80% identity to
wild-type mRNA sequence. In some embodiments, at least one mRNA
polynucleotide is encoded by a nucleic acid comprising a sequence
identified by any one of SEQ ID NO: 447-457, 459, 461, 505-523, or
570-573 and having less than 40-85%, 50-85%, 60-85%, 30-85%,
70-85%, 75-85% or 80-85% identity to wild-type mRNA sequence. In
some embodiments, at least one mRNA polynucleotide is encoded by a
nucleic acid comprising a sequence identified by any one of SEQ ID
NO: 447-457, 459, 461, 505-523, or 570-573 and having less than
40-90%, 50-90%, 60-90%, 30-90%, 70-90%, 75-90%, 80-90%, or 85-90%
identity to wild-type mRNA sequence.
[0028] In some embodiments, at least one mRNA polynucleotide
comprises a sequence identified by any one of SEQ ID NO: 491-503 or
566-569 and has less than 80% identity to wild-type mRNA sequence.
In some embodiments, at least one mRNA polynucleotide is encoded by
a nucleic acid comprising a sequence identified by any one SEQ ID
NO: 491-503 or 566-569and has less than 75%, 85% or 95% identity to
a wild-type mRNA sequence. In some embodiments, at least one mRNA
polynucleotide is encoded by nucleic acid comprising a sequence
identified by any one of SEQ ID NO: 491-503 or 566-569and has less
than 50-80%, 60-80%, 40-80%, 30-80%, 70-80%, 75-80% or 78-80%
identity to wild-type mRNA sequence. In some embodiments, at least
one mRNA polynucleotide is encoded by a nucleic acid comprising a
sequence identified by any one of SEQ ID NO: 491-503 or 566-569and
has less than 40-85%, 50-85%, 60-85%, 30-85%, 70-85%, 75-85% or
80-85% identity to wild-type mRNA sequence. In some embodiments, at
least one mRNA polynucleotide is encoded by a nucleic acid
comprising a sequence identified by any one of SEQ ID NO: 491-503
or 566-569and has less than 40-90%, 50-90%, 60-90%, 30-90%, 70-90%,
75-90%, 80-90%, or 85-90% identity to wild-type mRNA sequence.
[0029] In some embodiments, at least one RNA polynucleotide encodes
at least one antigenic polypeptide comprising an amino acid
sequence identified by any one of SEQ ID NO: 1-444, 458, 460,
462-479, or 543-565 (see also Tables 7-13 and 26) and having at
least 80% (e.g., 85%, 90%, 95%, 98%, 99%) identity to wild-type
mRNA sequence, but does not include wild-type mRNA sequence.
[0030] In some embodiments, at least one RNA polynucleotide encodes
at least one antigenic polypeptide comprising an amino acid
sequence identified by any one of SEQ ID NO: 1-444, 458, 460,
462-479, or 543-565 (see also Tables 7-13 and 26) and has less than
95%, 90%, 85%, 80% or 75% identity to wild-type mRNA sequence. In
some embodiments, at least one RNA polynucleotide encodes at least
one antigenic polypeptide comprising an amino acid sequence
identified by any one of SEQ ID NO: 1-444, 458, 460, 462-479, or
543-565 (see also Tables 7-13 and 26) and has 30-80%, 40-80%,
50-80%, 60-80%, 70-80%, 75-80% or 78-80%, 30-85%, 40-85%, 50-805%,
60-85%, 70-85%, 75-85% or 78-85%, 30-90%, 40-90%, 50-90%, 60-90%,
70-90%, 75-90%, 80-90% or 85-90% identity to wild-type mRNA
sequence.
[0031] In some embodiments, at least one RNA polynucleotide encodes
at least one antigenic polypeptide having at least 90%, at least
95%, at least 96%, at least 97%, at least 98%, or at least 99%
identity to an amino acid sequence identified by any one of SEQ ID
NO: 1-444, 458, 460, 462-479, or 543-565 (see also Tables 7-13 and
26). In some embodiments, at least one RNA polynucleotide encodes
at least one antigenic polypeptide having 95%-99% identity to an
amino acid sequence identified by any one of 1-444, 458, 460,
462-479, or 543-565 (see also Tables 7-13 and 26).
[0032] In some embodiments, at least one RNA polynucleotide encodes
at least one antigenic polypeptide having at least 90%, at least
95%, at least 96%, at least 97%, at least 98%, or at least 99%
identity to amino acid sequence identified by any one of SEQ ID NO:
1-444, 458, 460, 462-479, or 543-565 (see also Tables 7-13 and 26)
and having membrane fusion activity. In some embodiments, at least
one RNA polynucleotide encodes at least one antigenic polypeptide
having 95%-99% identity to amino acid sequence identified by any
one of SEQ ID NO: 1-444, 458, 460, 462-479, or 543-565 (see also
Tables 7-13 and 26) and having membrane fusion activity.
[0033] In some embodiments, at least one RNA polynucleotide encodes
at least one influenza antigenic polypeptide that attaches to cell
receptors.
[0034] In some embodiments, at least one RNA polynucleotide encodes
at least one influenza antigenic polypeptide that causes fusion of
viral and cellular membranes.
[0035] In some embodiments, at least one RNA polynucleotide encodes
at least one influenza antigenic polypeptide that is responsible
for binding of the virus to a cell being infected.
[0036] Some embodiments of the present disclosure provide a vaccine
that includes at least one ribonucleic acid (RNA) (e.g., mRNA)
polynucleotide having an open reading frame encoding at least one
influenza antigenic polypeptide, at least one 5' terminal cap and
at least one chemical modification, formulated within a lipid
nanoparticle.
[0037] In some embodiments, a 5' terminal cap is
7mG(5')ppp(5')NlmpNp.
[0038] In some embodiments, at least one chemical modification is
selected from pseudouridine, N1-methylpseudouridine,
N1-ethylpseudouridine, 2-thiouridine, 4'-thiouridine,
5-methylcytosine, 5-methyluridine,
2-thio-1-methyl-1-deaza-pseudouridine,
2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine ,
2-thio-dihydropseudouridine, 2-thio-dihydrouridine,
2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine,
4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine,
4-thio-pseudouridine, 5-aza-uridine, dihydropseudouridine,
5-methoxyuridine and 2'-O-methyl uridine. In some embodiments, the
chemical modification is in the 5-position of the uracil. In some
embodiments, the chemical modification is a N1-methylpseudouridine.
In some embodiments, the chemical modification is a
N1-ethylpseudouridine.
[0039] In some embodiments, a lipid nanoparticle comprises a
cationic lipid, a PEG-modified lipid, a sterol and a non-cationic
lipid. In some embodiments, a cationic lipid is an ionizable
cationic lipid and the non-cationic lipid is a neutral lipid, and
the sterol is a cholesterol. In some embodiments, a cationic lipid
is selected from the group consisting of
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA),
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate,
(12Z,15Z)-N,N-dimethyl-2-nonylhenicosa-12,15-dien-1-amine, and
N,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]heptadecan-8-amine. In
some embodiments, the cationic lipid is
##STR00001##
[0040] In some embodiments, the cationic lipid is
##STR00002##
[0041] In some embodiments, at least one cationic lipid selected
from compounds of Formula (I):
##STR00003## [0042] or a salt or isomer thereof, wherein: [0043]
R.sub.1 is selected from the group consisting of C.sub.5-30 alkyl,
C.sub.5-20 alkenyl, --R*YR'', --YR'', and --R''M'R'; [0044] R.sub.2
and R.sub.3 are independently selected from the group consisting of
H, C.sub.1-14 alkyl, C.sub.2-14 alkenyl, --R*YR'', --YR'', and
--R*OR'', or R.sub.2 and R.sub.3, together with the atom to which
they are attached, form a heterocycle or carbocycle; [0045] R.sub.4
is selected from the group consisting of a C.sub.3-6 carbocycle,
--(CH.sub.2).sub.nQ, --(CH.sub.2).sub.nCHQR, --CHQR, --CQ(R).sub.2,
and unsubstituted C.sub.1-6 alkyl, where Q is selected from a
carbocycle, heterocycle, --OR, --O(CH.sub.2).sub.nN(R).sub.2,
--C(O)OR, --OC(O)R, --CX.sub.3, --CX.sub.2H, --CXH.sub.2, --CN,
--N(R).sub.2, --C(O)N(R).sub.2, --N(R)C(O)R, --N(R)S(O).sub.2R,
--N(R)C(O)N(R).sub.2, --N(R)C(S)N(R).sub.2, --N(R)R.sub.8,
--O(CH.sub.2).sub.nOR, --N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)N(R).sub.2,
--C(.dbd.NR.sub.9)R, --C(O)N(R)OR, and --C(R)N(R).sub.2C(O)OR, and
each n is independently selected from 1, 2, 3, 4, and 5; [0046]
each R.sub.5 is independently selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; [0047] each R.sub.6 is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; [0048] M and M' are independently
selected from --C(O)O--, --OC(O)--, --C(O)N(R')--, --N(R')C(O)--,
--C(O)--, --C(S)--, --C(S)S--, --SC(S)--, --CH(OH)--,
--P(O)(OR')O--, --S(O).sub.2--, --S--S--, an aryl group, and a
heteroaryl group; [0049] R.sub.7 is selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; [0050]
R.sub.8 is selected from the group consisting of C.sub.3-6
carbocycle and heterocycle; [0051] R.sub.9 is selected from the
group consisting of H, CN, NO.sub.2, C.sub.1-6 alkyl, --OR,
--S(O).sub.2R, --S(O).sub.2N(R).sub.2, C.sub.2-6 alkenyl, C.sub.3-6
carbocycle and heterocycle; [0052] each R is independently selected
from the group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl,
and H; [0053] each R' is independently selected from the group
consisting of C.sub.1-18 alkyl, C.sub.2-18 alkenyl, --R*YR'',
--YR'', and H; [0054] each R'' is independently selected from the
group consisting of C.sub.3-14 alkyl and C.sub.3-14 alkenyl; [0055]
each R* is independently selected from the group consisting of
C.sub.1-12 alkyl and C.sub.2-12 alkenyl; [0056] each Y is
independently a C.sub.3-6 carbocycle; [0057] each X is
independently selected from the group consisting of F, Cl, Br, and
I; and [0058] m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and
13.
[0059] In some embodiments, a subset of compounds of Formula (I)
includes those in which when R.sub.4 is --(CH.sub.2).sub.nQ,
--(CH.sub.2).sub.nCHQR, --CHQR, or --CQ(R).sub.2, then (i) Q is not
--N(R).sub.2 when n is 1, 2, 3, 4 or 5, or (ii) Q is not 5, 6, or
7-membered heterocycloalkyl when n is 1 or 2.
[0060] In some embodiments, a subset of compounds of Formula (I)
includes those in which [0061] R.sub.1 is selected from the group
consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; [0062] R.sub.2 and R.sub.3 are independently
selected from the group consisting of H, C.sub.1-14 alkyl,
C.sub.2-14 alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and
R.sub.3, together with the atom to which they are attached, form a
heterocycle or carbocycle; [0063] R.sub.4 is selected from the
group consisting of a C.sub.3-6 carbocycle, --(CH.sub.2).sub.nQ,
--(CH.sub.2).sub.nCHQR, --CHQR, --CQ(R).sub.2, and unsubstituted
C.sub.1-6 alkyl, where Q is selected from a C.sub.3-6 carbocycle, a
5- to 14-membered heteroaryl having one or more heteroatoms
selected from N, O, and S, --OR, --O(CH.sub.2).sub.nN(R).sub.2,
--C(O)OR, --OC(O)R, --CX.sub.3, --CX.sub.2H, --CXH.sub.2, --CN,
--C(O)N(R).sub.2, --N(R)C(O)R, --N(R)S(O).sub.2R,
--N(R)C(O)N(R).sub.2, --N(R)C(S)N(R).sub.2, --CRN(R).sub.2C(O)OR,
--N(R)R.sub.8, --O(CH.sub.2).sub.nOR,
--N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)N(R).sub.2,
--C(.dbd.NR.sub.9)R, --C(O)N(R)OR, and a 5- to 14-membered
heterocycloalkyl having one or more heteroatoms selected from N, O,
and S which is substituted with one or more substituents selected
from oxo (.dbd.O), OH, amino, mono- or di-alkylamino, and C.sub.1-3
alkyl, and each n is independently selected from 1, 2, 3, 4, and 5;
[0064] each R.sub.5 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; [0065]
each R.sub.6 is independently selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; [0066] M and M' are
independently selected from --C(O)O--, --OC(O)--, --C(O)N(R')--,
--N(R')C(O)--, --C(O)--, --C(S)--, --C(S)S--, --SC(S)--,
--CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--, --S--S--, an aryl
group, and a heteroaryl group; [0067] R.sub.7 is selected from the
group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0068] R.sub.8 is selected from the group consisting of C.sub.3-6
carbocycle and heterocycle; [0069] R.sub.9 is selected from the
group consisting of H, CN, NO.sub.2, C.sub.1-6 alkyl, --OR,
--S(O).sub.2R, --S(O).sub.2N(R).sub.2, C.sub.2-6 alkenyl, C.sub.3-6
carbocycle and heterocycle; [0070] each R is independently selected
from the group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl,
and H; [0071] each R' is independently selected from the group
consisting of C.sub.1-18 alkyl, C.sub.2-18 alkenyl, --R*YR'',
--YR'', and H; [0072] each R'' is independently selected from the
group consisting of C.sub.3-14 alkyl and C.sub.3-14 alkenyl; [0073]
each R* is independently selected from the group consisting of
C.sub.1-12 alkyl and C.sub.2-12 alkenyl; [0074] each Y is
independently a C.sub.3-6 carbocycle; [0075] each X is
independently selected from the group consisting of F, Cl, Br, and
I; and [0076] m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,
[0077] or salts or isomers thereof.
[0078] In some embodiments, a subset of compounds of Formula (I)
includes those in which R.sub.1 is selected from the group
consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; [0079] R.sub.2 and R.sub.3 are independently
selected from the group consisting of H, C.sub.1-14 alkyl,
C.sub.2-14 alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and
R.sub.3, together with the atom to which they are attached, form a
heterocycle or carbocycle; [0080] R.sub.4 is selected from the
group consisting of a C.sub.3-6 carbocycle, --(CH.sub.2).sub.nQ,
--(CH.sub.2).sub.nCHQR, --CHQR, --CQ(R).sub.2, and unsubstituted
C.sub.1-6 alkyl, where Q is selected from a C.sub.3-6 carbocycle, a
5- to 14-membered heterocycle having one or more heteroatoms
selected from N, O, and S, --OR, --O(CH.sub.2).sub.nN(R).sub.2,
--C(O)OR, --OC(O)R, --CX.sub.3, --CX.sub.2H, --CXH.sub.2, --CN,
--C(O)N(R).sub.2, --N(R)C(O)R, --N(R)S(O).sub.2R,
--N(R)C(O)N(R).sub.2, --N(R)C(S)N(R).sub.2, --CRN(R).sub.2C(O)OR,
--N(R)R.sub.8, --O(CH.sub.2).sub.nOR,
--N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)R,
--C(O)N(R)OR, and --C(.dbd.NR.sub.9)N(R).sub.2, and each n is
independently selected from 1, 2, 3, 4, and 5; and when Q is a 5-
to 14-membered heterocycle and (i) R.sub.4 is --(CH.sub.2).sub.nQ
in which n is 1 or 2, or (ii) R.sub.4 is --(CH.sub.2).sub.nCHQR in
which n is 1, or (iii) R.sub.4 is --CHQR, and --CQ(R).sub.2, then Q
is either a 5- to 14-membered heteroaryl or 8- to 14-membered
heterocycloalkyl; [0081] each R.sub.5 is independently selected
from the group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl,
and H; [0082] each R.sub.6 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; [0083] M
and M' are independently selected from --C(O)O--, --OC(O)--,
--C(O)N(R')--, --N(R')C(O)--, --C(O)--, --C(S)--, --C(S)S--,
--SC(S)--, --CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--, --S--S--, an
aryl group, and a heteroaryl group; [0084] R.sub.7 is selected from
the group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0085] R.sub.8 is selected from the group consisting of C.sub.3-6
carbocycle and heterocycle; [0086] R.sub.9 is selected from the
group consisting of H, CN, NO.sub.2, C.sub.1-6 alkyl, --OR,
--S(O).sub.2R, --S(O).sub.2N(R).sub.2, C.sub.2-6 alkenyl, C.sub.3-6
carbocycle and heterocycle; [0087] each R is independently selected
from the group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl,
and H; [0088] each R' is independently selected from the group
consisting of C.sub.1-18 alkyl, C.sub.2-18 alkenyl, --R*YR'',
--YR'', and H; [0089] each R'' is independently selected from the
group consisting of C.sub.3-14 alkyl and C.sub.3-14 alkenyl; [0090]
each R* is independently selected from the group consisting of
C.sub.1-12 alkyl and C.sub.2-12 alkenyl; [0091] each Y is
independently a C.sub.3-6 carbocycle; [0092] each X is
independently selected from the group consisting of F, Cl, Br, and
I; and [0093] m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,
[0094] or salts or isomers thereof.
[0095] In some embodiments, a subset of compounds of Formula (I)
includes those in which R.sub.1 is selected from the group
consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; [0096] R.sub.2 and R.sub.3 are independently
selected from the group consisting of H, C.sub.1-14 alkyl,
C.sub.2-14 alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and
R.sub.3, together with the atom to which they are attached, form a
heterocycle or carbocycle; [0097] R.sub.4 is selected from the
group consisting of a C.sub.3-6 carbocycle, --(CH.sub.2).sub.nQ,
--(CH.sub.2).sub.nCHQR, --CHQR, --CQ(R).sub.2, and unsubstituted
C.sub.1-6 alkyl, where Q is selected from a C.sub.3-6 carbocycle, a
5- to 14-membered heteroaryl having one or more heteroatoms
selected from N, O, and S, --OR, --O(CH.sub.2).sub.nN(R).sub.2,
--C(O)OR, --OC(O)R, --CX.sub.3, --CX.sub.2H, --CXH.sub.2, --CN,
--C(O)N(R).sub.2, --N(R)C(O)R, --N(R)S(O).sub.2R,
--N(R)C(O)N(R).sub.2, --N(R)C(S)N(R).sub.2, --CRN(R).sub.2C(O)OR,
--N(R)R.sub.8, --O(CH.sub.2).sub.nOR,
--N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)R,
--C(O)N(R)OR, and --C(.dbd.NR.sub.9)N(R).sub.2, and each n is
independently selected from 1, 2, 3, 4, and 5; [0098] each R.sub.5
is independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; [0099] each R.sub.6 is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; [0100] M and M' are independently
selected from --C(O)O--, --OC(O)--, --C(O)N(R')--, --N(R')C(O)--,
--C(O)--, --C(S)--, --C(S)S--, --SC(S)--, --CH(OH)--,
--P(O)(OR')O--, --S(O).sub.2--, --S--S--, an aryl group, and a
heteroaryl group; [0101] R.sub.7 is selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; [0102]
R.sub.8 is selected from the group consisting of C.sub.3-6
carbocycle and heterocycle; [0103] R.sub.9 is selected from the
group consisting of H, CN, NO.sub.2, C.sub.1-6 alkyl, --OR,
--S(O).sub.2R, --S(O).sub.2N(R).sub.2, C.sub.2-6 alkenyl, C.sub.3-6
carbocycle and heterocycle; [0104] each R is independently selected
from the group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl,
and H; [0105] each R' is independently selected from the group
consisting of C.sub.1-18 alkyl, C.sub.2-18 alkenyl, --R*YR'',
--YR'', and H; [0106] each R'' is independently selected from the
group consisting of C.sub.3-14 alkyl and C.sub.3-14 alkenyl; [0107]
each R* is independently selected from the group consisting of
C.sub.1-12 alkyl and C.sub.2-12 alkenyl; [0108] each Y is
independently a C.sub.3-6 carbocycle; [0109] each X is
independently selected from the group consisting of F, Cl, Br, and
I; and [0110] m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,
[0111] or salts or isomers thereof.
[0112] In some embodiments, a subset of compounds of Formula (I)
includes those in which R.sub.1 is selected from the group
consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; [0113] R.sub.2 and R.sub.3 are independently
selected from the group consisting of H, C.sub.2-14 alkyl,
C.sub.2-14 alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and
R.sub.3, together with the atom to which they are attached, form a
heterocycle or carbocycle; [0114] R.sub.4 is --(CH.sub.2).sub.nQ or
--(CH.sub.2).sub.nCHQR, where Q is --N(R).sub.2, and n is selected
from 3, 4, and 5; [0115] each R.sub.5 is independently selected
from the group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl,
and H; [0116] each R.sub.6 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; [0117] M
and M' are independently selected from --C(O)O--, --OC(O)--,
--C(O)N(R')--, --N(R')C(O)--, --C(O)--, --C(S)--, --C(S)S--,
--SC(S)--, --CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--, --S--S--, an
aryl group, and a heteroaryl group; [0118] R.sub.7 is selected from
the group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0119] each R is independently selected from the group consisting
of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; [0120] each R' is
independently selected from the group consisting of C.sub.1-18
alkyl, C.sub.2-18 alkenyl, --R*YR'', --YR'', and H; [0121] each R''
is independently selected from the group consisting of C.sub.3-14
alkyl and C.sub.3-14 alkenyl; [0122] each R* is independently
selected from the group consisting of C.sub.1-12 alkyl and
C.sub.1-12 alkenyl; [0123] each Y is independently a C.sub.3-6
carbocycle; [0124] each X is independently selected from the group
consisting of F, Cl, Br, and I; and [0125] m is selected from 5, 6,
7, 8, 9, 10, 11, 12, and 13, [0126] or salts or isomers
thereof.
[0127] In some embodiments, a subset of compounds of Formula (I)
includes those in which R.sub.1 is selected from the group
consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; [0128] R.sub.2 and R.sub.3 are independently
selected from the group consisting of C.sub.1-14 alkyl, C.sub.2-14
alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and R.sub.3,
together with the atom to which they are attached, form a
heterocycle or carbocycle; [0129] R.sub.4 is selected from the
group consisting of --(CH.sub.2).sub.nQ, --(CH.sub.2).sub.nCHQR,
--CHQR, and --CQ(R).sub.2, where Q is --N(R).sub.2, and n is
selected from 1, 2, 3, 4, and 5; [0130] each R.sub.5 is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; [0131] each R.sub.6 is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; [0132] M and M' are independently
selected from --C(O)O--, --OC(O)--, --C(O)N(R')--, --N(R')C(O)--,
--C(O)--, --C(S)--, --C(S)S--, --SC(S)--, --CH(OH)--,
--P(O)(OR')O--, --S(O).sub.2--, --S--S--, an aryl group, and a
heteroaryl group; [0133] R.sub.7 is selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; [0134]
each R is independently selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; [0135] each R' is
independently selected from the group consisting of C.sub.1-18
alkyl, C.sub.2-18 alkenyl, --R*YR'', --YR'', and H; [0136] each R''
is independently selected from the group consisting of C.sub.3-14
alkyl and C.sub.3-14 alkenyl; [0137] each R* is independently
selected from the group consisting of C.sub.1-12 alkyl and
C.sub.1-12 alkenyl; [0138] each Y is independently a C.sub.3-6
carbocycle; [0139] each X is independently selected from the group
consisting of F, Cl, Br, and I; and [0140] m is selected from 5, 6,
7, 8, 9, 10, 11, 12, and 13, [0141] or salts or isomers
thereof.
[0142] In some embodiments, a subset of compounds of Formula (I)
includes those of Formula (IA):
##STR00004## [0143] or a salt or isomer thereof, wherein 1 is
selected from 1, 2, 3, 4, and 5; m is selected from 5, 6, 7, 8, and
9; M.sub.1 is a bond or M'; R.sub.4 is unsubstituted C.sub.1-3
alkyl, or --(CH.sub.2).sub.nQ, in which Q is OH,
--NHC(S)N(R).sub.2, --NHC(O)N(R).sub.2, --N(R)C(O)R,
--N(R)S(O).sub.2R, --N(R)R.sub.8, --NHC(.dbd.NR.sub.9)N(R).sub.2,
--NHC(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
heteroaryl or heterocycloalkyl; M and M' are independently selected
from --C(O)O--, --OC(O)--, --C(O)N(R')--, --P(O)(OR')O--, --S--S--,
an aryl group, and a heteroaryl group; and R.sub.2 and R.sub.3 are
independently selected from the group consisting of H, C.sub.1-14
alkyl, and C.sub.2-14 alkenyl.
[0144] Some embodiments of the present disclosure provide a vaccine
that includes at least one RNA (e.g., mRNA) polynucleotide having
an open reading frame encoding at least one influenza antigenic
polypeptide, wherein at least 80% (e.g., 85%, 90%, 95%, 98%, 99%)
of the uracil in the open reading frame have a chemical
modification, optionally wherein the vaccine is formulated in a
lipid nanoparticle (e.g., a lipid nanoparticle comprises a cationic
lipid, a PEG-modified lipid, a sterol and a non-cationic
lipid).
[0145] In some embodiments, 100% of the uracil in the open reading
frame have a chemical modification. In some embodiments, a chemical
modification is in the 5-position of the uracil. In some
embodiments, a chemical modification is a N1-methyl pseudouridine.
In some embodiments, 100% of the uracil in the open reading frame
have a N1-methyl pseudouridine in the 5-position of the uracil.
[0146] In some embodiments, an open reading frame of a RNA (e.g.,
mRNA) polynucleotide encodes at least two influenza antigenic
polypeptides. In some embodiments, the open reading frame encodes
at least five or at least ten antigenic polypeptides. In some
embodiments, the open reading frame encodes at least 100 antigenic
polypeptides. In some embodiments, the open reading frame encodes
2-100 antigenic polypeptides.
[0147] In some embodiments, a vaccine comprises at least two RNA
(e.g., mRNA) polynucleotides, each having an open reading frame
encoding at least one influenza antigenic polypeptide. In some
embodiments, the vaccine comprises at least five or at least ten
RNA (e.g., mRNA) polynucleotides, each having an open reading frame
encoding at least one antigenic polypeptide. In some embodiments,
the vaccine comprises at least 100 RNA (e.g., mRNA)
polynucleotides, each having an open reading frame encoding at
least one antigenic polypeptide. In some embodiments, the vaccine
comprises 2-100 RNA (e.g., mRNA) polynucleotides, each having an
open reading frame encoding at least one antigenic polypeptide.
[0148] In some embodiments, at least one influenza antigenic
polypeptide is fused to a signal peptide. In some embodiments, the
signal peptide is selected from: a HuIgGk signal peptide
(METPAQLLFLLLLWLPDTTG; SEQ ID NO: 480); IgE heavy chain epsilon-1
signal peptide (MDWTWILFLVAAATRVHS; SEQ ID NO: 481); Japanese
encephalitis PRM signal sequence (MLGSNSGQRVVFTILLLLVAPAYS; SEQ ID
NO: 482), VSVg protein signal sequence (MKCLLYLAFLFIGVNCA; SEQ ID
NO: 483) and Japanese encephalitis JEV signal sequence
(MWLVSLAIVTACAGA; SEQ ID NO: 484).
[0149] In some embodiments, the signal peptide is fused to the
N-terminus of at least one antigenic polypeptide. In some
embodiments, a signal peptide is fused to the C-terminus of at
least one antigenic polypeptide.
[0150] In some embodiments, at least one influenza antigenic
polypeptide comprises a mutated N-linked glycosylation site.
[0151] Also provided herein is an influenza RNA (e.g., mRNA)
vaccine of any one of the foregoing paragraphs formulated in a
nanoparticle (e.g., a lipid nanoparticle).
[0152] In some embodiments, the nanoparticle has a mean diameter of
50-200 nm. In some embodiments, the nanoparticle is a lipid
nanoparticle. In some embodiments, the lipid nanoparticle comprises
a cationic lipid, a PEG-modified lipid, a sterol and a non-cationic
lipid. In some embodiments, the lipid nanoparticle comprises a
molar ratio of about 20-60% cationic lipid, 0.5-15% PEG-modified
lipid, 25-55% sterol, and 25% non-cationic lipid. In some
embodiments, the cationic lipid is an ionizable cationic lipid and
the non-cationic lipid is a neutral lipid, and the sterol is a
cholesterol. In some embodiments, the cationic lipid is selected
from 2,2-dilinoleyl-4-dimethylaminoethyl[1,3]-dioxolane
(DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate
(DLin-MC3-DMA), and di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate.
[0153] In some embodiments, the nanoparticle has a polydispersity
value of less than 0.4 (e.g., less than 0.3, 0.2 or 0.1).
[0154] In some embodiments, the nanoparticle has a net neutral
charge at a neutral pH value.
[0155] In some embodiments, the RNA (e.g., mRNA) vaccine is
multivalent.
[0156] Some embodiments of the present disclosure provide methods
of inducing an antigen specific immune response in a subject,
comprising administering to the subject any of the
[0157] RNA (e.g., mRNA) vaccine as provided herein in an amount
effective to produce an antigen-specific immune response. In some
embodiments, the RNA (e.g., mRNA) vaccine is an influenza vaccine.
In some embodiments, the RNA (e.g., mRNA) vaccine is a combination
vaccine comprising a combination of influenza vaccines (a broad
spectrum influenza vaccine).
[0158] In some embodiments, an antigen-specific immune response
comprises a T cell response or a B cell response.
[0159] In some embodiments, a method of producing an
antigen-specific immune response comprises administering to a
subject a single dose (no booster dose) of an influenza RNA (e.g.,
mRNA) vaccine of the present disclosure.
[0160] In some embodiments, a method further comprises
administering to the subject a second (booster) dose of an
influenza RNA (e.g., mRNA) vaccine. Additional doses of an
influenza RNA (e.g., mRNA) vaccine may be administered.
[0161] In some embodiments, the subjects exhibit a seroconversion
rate of at least 80% (e.g., at least 85%, at least 90%, or at least
95%) following the first dose or the second (booster) dose of the
vaccine. Seroconversion is the time period during which a specific
antibody develops and becomes detectable in the blood. After
seroconversion has occurred, a virus can be detected in blood tests
for the antibody. During an infection or immunization, antigens
enter the blood, and the immune system begins to produce antibodies
in response. Before seroconversion, the antigen itself may or may
not be detectable, but antibodies are considered absent. During
seroconversion, antibodies are present but not yet detectable. Any
time after seroconversion, the antibodies can be detected in the
blood, indicating a prior or current infection.
[0162] In some embodiments, an influenza RNA (e.g., mRNA) vaccine
is administered to a subject by intradermal injection,
intramuscular injection, or by intranasal administration. In some
embodiments, an influenza RNA (e.g., mRNA) vaccine is administered
to a subject by intramuscular injection.
[0163] Some embodiments, of the present disclosure provide methods
of inducing an antigen specific immune response in a subject,
including administering to a subject an influenza RNA (e.g., mRNA)
vaccine in an effective amount to produce an antigen specific
immune response in a subject. Antigen-specific immune responses in
a subject may be determined, in some embodiments, by assaying for
antibody titer (for titer of an antibody that binds to an influenza
antigenic polypeptide) following administration to the subject of
any of the influenza RNA (e.g., mRNA) vaccines of the present
disclosure. In some embodiments, the anti-antigenic polypeptide
antibody titer produced in the subject is increased by at least 1
log relative to a control. In some embodiments, the anti-antigenic
polypeptide antibody titer produced in the subject is increased by
1-3 log relative to a control.
[0164] In some embodiments, the anti-antigenic polypeptide antibody
titer produced in a subject is increased at least 2 times relative
to a control. In some embodiments, the anti-antigenic polypeptide
antibody titer produced in the subject is increased at least 5
times relative to a control. In some embodiments, the
anti-antigenic polypeptide antibody titer produced in the subject
is increased at least 10 times relative to a control. In some
embodiments, the anti-antigenic polypeptide antibody titer produced
in the subject is increased 2-10 times relative to a control.
[0165] In some embodiments, the control is an anti-antigenic
polypeptide antibody titer produced in a subject who has not been
administered a RNA (e.g., mRNA) vaccine of the present disclosure.
In some embodiments, the control is an anti-antigenic polypeptide
antibody titer produced in a subject who has been administered a
live attenuated or inactivated influenza, or wherein the control is
an anti-antigenic polypeptide antibody titer produced in a subject
who has been administered a recombinant or purified influenza
protein vaccine. In some embodiments, the control is an
anti-antigenic polypeptide antibody titer produced in a subject who
has been administered an influenza virus-like particle (VLP)
vaccine (see, e.g., Cox RG et al., J Virol. 2014 June; 88(11):
6368-6379).
[0166] A RNA (e.g., mRNA) vaccine of the present disclosure is
administered to a subject in an effective amount (an amount
effective to induce an immune response). In some embodiments, the
effective amount is a dose equivalent to an at least 2-fold, at
least 4-fold, at least 10-fold, at least 100-fold, at least
1000-fold reduction in the standard of care dose of a recombinant
influenza protein vaccine, wherein the anti-antigenic polypeptide
antibody titer produced in the subject is equivalent to an
anti-antigenic polypeptide antibody titer produced in a control
subject administered the standard of care dose of a recombinant
influenza protein vaccine, a purified influenza protein vaccine, a
live attenuated influenza vaccine, an inactivated influenza
vaccine, or an influenza VLP vaccine. In some embodiments, the
effective amount is a dose equivalent to 2-1000-fold reduction in
the standard of care dose of a recombinant influenza protein
vaccine, wherein the anti-antigenic polypeptide antibody titer
produced in the subject is equivalent to an anti-antigenic
polypeptide antibody titer produced in a control subject
administered the standard of care dose of a recombinant influenza
protein vaccine, a purified influenza protein vaccine, a live
attenuated influenza vaccine, an inactivated influenza vaccine, or
an influenza VLP vaccine.
[0167] In some embodiments, the control is an anti-antigenic
polypeptide antibody titer produced in a subject who has been
administered a virus-like particle (VLP) vaccine comprising
structural proteins of influenza.
[0168] In some embodiments, the RNA (e.g., mRNA) vaccine is
formulated in an effective amount to produce an antigen specific
immune response in a subject.
[0169] In some embodiments, the effective amount is a total dose of
25 .mu.g to 1000 .mu.g, or 50 .mu.g to 1000 .mu.g. In some
embodiments, the effective amount is a total dose of 100 .mu.g. In
some embodiments, the effective amount is a dose of 25 .mu.g
administered to the subject a total of two times. In some
embodiments, the effective amount is a dose of 100 .mu.g
administered to the subject a total of two times. In some
embodiments, the effective amount is a dose of 400 .mu.g
administered to the subject a total of two times. In some
embodiments, the effective amount is a dose of 500 .mu.g
administered to the subject a total of two times.
[0170] In some embodiments, the efficacy (or effectiveness) of a
RNA (e.g., mRNA) vaccine is greater than 60%. In some embodiments,
the RNA (e.g., mRNA) polynucleotide of the vaccine at least one
Influenza antigenic polypeptide.
[0171] Vaccine efficacy may be assessed using standard analyses
(see, e.g., Weinberg et al., J Infect Dis. 2010 Jun. 1;
201(11):1607-10). For example, vaccine efficacy may be measured by
double-blind, randomized, clinical controlled trials. Vaccine
efficacy may be expressed as a proportionate reduction in disease
attack rate (AR) between the unvaccinated (ARU) and vaccinated
(ARV) study cohorts and can be calculated from the relative risk
(RR) of disease among the vaccinated group with use of the
following formulas:
Efficacy=(ARU-ARV)/ARU.times.100; and
Efficacy=(1-RR).times.100.
[0172] Likewise, vaccine effectiveness may be assessed using
standard analyses (see, e.g., Weinberg et al., J Infect Dis. 2010
Jun. 1; 201(11):1607-10). Vaccine effectiveness is an assessment of
how a vaccine (which may have already proven to have high vaccine
efficacy) reduces disease in a population. This measure can assess
the net balance of benefits and adverse effects of a vaccination
program, not just the vaccine itself, under natural field
conditions rather than in a controlled clinical trial. Vaccine
effectiveness is proportional to vaccine efficacy (potency) but is
also affected by how well target groups in the population are
immunized, as well as by other non-vaccine-related factors that
influence the `real-world` outcomes of hospitalizations, ambulatory
visits, or costs. For example, a retrospective case control
analysis may be used, in which the rates of vaccination among a set
of infected cases and appropriate controls are compared. Vaccine
effectiveness may be expressed as a rate difference, with use of
the odds ratio (OR) for developing infection despite
vaccination:
Effectiveness=(1-OR).times.100.
[0173] In some embodiments, the efficacy (or effectiveness) of a
RNA (e.g., mRNA) vaccine is at least 65%, at least 70%, at least
75%, at least 80%, at least 85%, or at least 90%.
[0174] In some embodiments, the vaccine immunizes the subject
against Influenza for up to 2 years. In some embodiments, the
vaccine immunizes the subject against Influenza for more than 2
years, more than 3 years, more than 4 years, or for 5-10 years.
[0175] In some embodiments, the subject is about 5 years old or
younger. For example, the subject may be between the ages of about
1 year and about 5 years (e.g., about 1, 2, 3, 5 or 5 years), or
between the ages of about 6 months and about 1 year (e.g., about 6,
7, 8, 9, 10, 11 or 12 months). In some embodiments, the subject is
about 12 months or younger (e.g., 12, 11, 10, 9, 8, 7, 6, 5, 4, 3,
2 months or 1 month). In some embodiments, the subject is about 6
months or younger.
[0176] In some embodiments, the subject was born full term (e.g.,
about 37-42 weeks). In some embodiments, the subject was born
prematurely, for example, at about 36 weeks of gestation or earlier
(e.g., about 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26 or 25
weeks). For example, the subject may have been born at about 32
weeks of gestation or earlier. In some embodiments, the subject was
born prematurely between about 32 weeks and about 36 weeks of
gestation. In such subjects, a RNA (e.g., mRNA) vaccine may be
administered later in life, for example, at the age of about 6
months to about 5 years, or older.
[0177] In some embodiments, the subject is a young adult between
the ages of about 20 years and about 50 years (e.g., about 20, 25,
30, 35, 40, 45 or 50 years old).
[0178] In some embodiments, the subject is an elderly subject about
60 years old, about 70 years old, or older (e.g., about 60, 65, 70,
75, 80, 85 or 90 years old).
[0179] In some embodiments, the subject has been exposed to
influenza (e.g., C. trachomatis); the subject is infected with
influenza (e.g., C. trachomatis); or subject is at risk of
infection by influenza (e.g., C. trachomatis).
[0180] In some embodiments, the subject is immunocompromised (has
an impaired immune system, e.g., has an immune disorder or
autoimmune disorder).
[0181] In some embodiments the nucleic acid vaccines described
herein are chemically modified. In other embodiments the nucleic
acid vaccines are unmodified.
[0182] Yet other aspects provide compositions for and methods of
vaccinating a subject comprising administering to the subject a
nucleic acid vaccine comprising one or more RNA polynucleotides
having an open reading frame encoding a first virus antigenic
polypeptide, wherein the RNA polynucleotide does not include a
stabilization element, and wherein an adjuvant is not coformulated
or co-administered with the vaccine.
[0183] In other aspects the invention is a composition for or
method of vaccinating a subject comprising administering to the
subject a nucleic acid vaccine comprising one or more RNA
polynucleotides having an open reading frame encoding a first
antigenic polypeptide wherein a dosage of between 10 .mu.g/kg and
400 .mu.g/kg of the nucleic acid vaccine is administered to the
subject. In some embodiments the dosage of the RNA polynucleotide
is 1-5 .mu.g, 5-10 .mu.g, 10-15 .mu.g, 15-20 .mu.g, 10-25 .mu.g,
20-25 .mu.g, 20-50 .mu.g, 30-50 .mu.g, 40-50 .mu.g, 40-60 .mu.g,
60-80 .mu.g, 60-100 .mu.g, 50-100 .mu.g, 80-120 .mu.g, 40-120
.mu.g, 40-150 .mu.g, 50-150 .mu.g, 50-200 .mu.g, 80-200 .mu.g,
100-200 .mu.g, 120-250 .mu.g, 150-250 .mu.g, 180-280 .mu.g, 200-300
.mu.g, 50-300 .mu.g, 80-300 .mu.g, 100-300 .mu.g, 40-300 .mu.g,
50-350 .mu.g, 100-350 .mu.g, 200-350 .mu.g, 300-350 .mu.g, 320-400
.mu.g, 40-380 .mu.g, 40-100 .mu.g, 100-400 .mu.g, 200-400 .mu.g, or
300-400 .mu.g per dose. In some embodiments, the nucleic acid
vaccine is administered to the subject by intradermal or
intramuscular injection. In some embodiments, the nucleic acid
vaccine is administered to the subject on day zero. In some
embodiments, a second dose of the nucleic acid vaccine is
administered to the subject on day twenty one.
[0184] In some embodiments, a dosage of 25 micrograms of the RNA
polynucleotide is included in the nucleic acid vaccine administered
to the subject. In some embodiments, a dosage of 100 micrograms of
the RNA polynucleotide is included in the nucleic acid vaccine
administered to the subject. In some embodiments, a dosage of 50
micrograms of the RNA polynucleotide is included in the nucleic
acid vaccine administered to the subject. In some embodiments, a
dosage of 75 micrograms of the RNA polynucleotide is included in
the nucleic acid vaccine administered to the subject. In some
embodiments, a dosage of 150 micrograms of the RNA polynucleotide
is included in the nucleic acid vaccine administered to the
subject. In some embodiments, a dosage of 400 micrograms of the RNA
polynucleotide is included in the nucleic acid vaccine administered
to the subject. In some embodiments, a dosage of 200 micrograms of
the RNA polynucleotide is included in the nucleic acid vaccine
administered to the subject. In some embodiments, the RNA
polynucleotide accumulates at a 100 fold higher level in the local
lymph node in comparison with the distal lymph node. In other
embodiments the nucleic acid vaccine is chemically modified and in
other embodiments the nucleic acid vaccine is not chemically
modified.
[0185] Aspects of the invention provide a nucleic acid vaccine
comprising one or more RNA polynucleotides having an open reading
frame encoding a first antigenic polypeptide, wherein the RNA
polynucleotide does not include a stabilization element, and a
pharmaceutically acceptable carrier or excipient, wherein an
adjuvant is not included in the vaccine. In some embodiments, the
stabilization element is a histone stem-loop. In some embodiments,
the stabilization element is a nucleic acid sequence having
increased GC content relative to wild type sequence.
[0186] Aspects of the invention provide nucleic acid vaccines
comprising one or more RNA polynucleotides having an open reading
frame encoding a first antigenic polypeptide, wherein the RNA
polynucleotide is present in the formulation for in vivo
administration to a host, which confers an antibody titer superior
to the criterion for seroprotection for the first antigen for an
acceptable percentage of human subjects. In some embodiments, the
antibody titer produced by the mRNA vaccines of the invention is a
neutralizing antibody titer. In some embodiments the neutralizing
antibody titer is greater than a protein vaccine. In other
embodiments the neutralizing antibody titer produced by the mRNA
vaccines of the invention is greater than an adjuvanted protein
vaccine. In yet other embodiments the neutralizing antibody titer
produced by the mRNA vaccines of the invention is 1,000-10,000,
1,200-10,000, 1,400-10,000, 1,500-10,000, 1,000-5,000, 1,000-4,000,
1,800-10,000, 2000-10,000, 2,000-5,000, 2,000-3,000, 2,000-4,000,
3,000-5,000, 3,000-4,000, or 2,000-2,500. A neutralization titer is
typically expressed as the highest serum dilution required to
achieve a 50% reduction in the number of plaques.
[0187] Also provided are nucleic acid vaccines comprising one or
more RNA polynucleotides having an open reading frame encoding a
first antigenic polypeptide, wherein the RNA polynucleotide is
present in a formulation for in vivo administration to a host for
eliciting a longer lasting high antibody titer than an antibody
titer elicited by an mRNA vaccine having a stabilizing element or
formulated with an adjuvant and encoding the first antigenic
polypeptide. In some embodiments, the RNA polynucleotide is
formulated to produce a neutralizing antibodies within one week of
a single administration. In some embodiments, the adjuvant is
selected from a cationic peptide and an immunostimulatory nucleic
acid. In some embodiments, the cationic peptide is protamine.
[0188] Aspects provide nucleic acid vaccines comprising one or more
RNA polynucleotides having an open reading frame comprising at
least one chemical modification or optionally no modified
nucleotides, the open reading frame encoding a first antigenic
polypeptide, wherein the RNA polynucleotide is present in the
formulation for in vivo administration to a host such that the
level of antigen expression in the host significantly exceeds a
level of antigen expression produced by an mRNA vaccine having a
stabilizing element or formulated with an adjuvant and encoding the
first antigenic polypeptide.
[0189] Other aspects provide nucleic acid vaccines comprising one
or more RNA polynucleotides having an open reading frame comprising
at least one chemical modification or optionally no modified
nucleotides, the open reading frame encoding a first antigenic
polypeptide, wherein the vaccine has at least 10 fold less RNA
polynucleotide than is required for an unmodified mRNA vaccine to
produce an equivalent antibody titer. In some embodiments, the RNA
polynucleotide is present in a dosage of 25-100 micrograms.
[0190] Aspects of the invention also provide a unit of use vaccine,
comprising between bug and 400 .mu.g of one or more RNA
polynucleotides having an open reading frame comprising at least
one chemical modification or optionally no modified nucleotides,
the open reading frame encoding a first antigenic polypeptide, and
a pharmaceutically acceptable carrier or excipient, formulated for
delivery to a human subject. In some embodiments, the vaccine
further comprises a cationic lipid nanoparticle.
[0191] Aspects of the invention provide methods of creating,
maintaining or restoring antigenic memory to a virus strain in an
individual or population of individuals comprising administering to
said individual or population an antigenic memory booster nucleic
acid vaccine comprising (a) at least one RNA polynucleotide, said
polynucleotide comprising at least one chemical modification or
optionally no modified nucleotides and two or more codon-optimized
open reading frames, said open reading frames encoding a set of
reference antigenic polypeptides, and (b) optionally a
pharmaceutically acceptable carrier or excipient.
[0192] In some embodiments, the vaccine is administered to the
individual via a route selected from the group consisting of
intramuscular administration, intradermal administration and
subcutaneous administration. In some embodiments, the administering
step comprises contacting a muscle tissue of the subject with a
device suitable for injection of the composition. In some
embodiments, the administering step comprises contacting a muscle
tissue of the subject with a device suitable for injection of the
composition in combination with electroporation.
[0193] Aspects of the invention provide methods of vaccinating a
subject comprising administering to the subject a single dosage of
between 25 .mu.g/kg and 400 .mu.g/kg of a nucleic acid vaccine
comprising one or more RNA polynucleotides having an open reading
frame encoding a first antigenic polypeptide in an effective amount
to vaccinate the subject.
[0194] Other aspects provide nucleic acid vaccines comprising one
or more RNA polynucleotides having an open reading frame comprising
at least one chemical modification, the open reading frame encoding
a first antigenic polypeptide, wherein the vaccine has at least 10
fold less RNA polynucleotide than is required for an unmodified
mRNA vaccine to produce an equivalent antibody titer. In some
embodiments, the RNA polynucleotide is present in a dosage of
25-100 micrograms.
[0195] Other aspects provide nucleic acid vaccines comprising an
LNP formulated RNA polynucleotide having an open reading frame
comprising no nucleotide modifications (unmodified), the open
reading frame encoding a first antigenic polypeptide, wherein the
vaccine has at least 10 fold less RNA polynucleotide than is
required for an unmodified mRNA vaccine not formulated in a LNP to
produce an equivalent antibody titer. In some embodiments, the RNA
polynucleotide is present in a dosage of 25-100 micrograms.
[0196] The data presented in the Examples demonstrate significant
enhanced immune responses using the formulations of the invention.
Both chemically modified and unmodified RNA vaccines are useful
according to the invention. Surprisingly, in contrast to prior art
reports that it was preferable to use chemically unmodified mRNA
formulated in a carrier for the production of vaccines, it is
described herein that chemically modified mRNA-LNP vaccines
required a much lower effective mRNA dose than unmodified mRNA,
i.e., tenfold less than unmodified mRNA when formulated in carriers
other than LNP. Both the chemically modified and unmodified RNA
vaccines of the invention produce better immune responses than mRNA
vaccines formulated in a different lipid carrier.
[0197] In other aspects the invention encompasses a method of
treating an elderly subject age 60 years or older comprising
administering to the subject a nucleic acid vaccine comprising one
or more RNA polynucleotides having an open reading frame encoding
an virus antigenic polypeptide in an effective amount to vaccinate
the subject.
[0198] In other aspects the invention encompasses a method of
treating a young subject age 17 years or younger comprising
administering to the subject a nucleic acid vaccine comprising one
or more RNA polynucleotides having an open reading frame encoding
an virus antigenic polypeptide in an effective amount to vaccinate
the subject.
[0199] In other aspects the invention encompasses a method of
treating an adult subject comprising administering to the subject a
nucleic acid vaccine comprising one or more RNA polynucleotides
having an open reading frame encoding an virus antigenic
polypeptide in an effective amount to vaccinate the subject.
[0200] In some aspects the invention is a method of vaccinating a
subject with a combination vaccine including at least two nucleic
acid sequences encoding antigens wherein the dosage for the vaccine
is a combined therapeutic dosage wherein the dosage of each
individual nucleic acid encoding an antigen is a sub therapeutic
dosage. In some embodiments, the combined dosage is 25 micrograms
of the RNA polynucleotide in the nucleic acid vaccine administered
to the subject. In some embodiments, the combined dosage is 100
micrograms of the RNA polynucleotide in the nucleic acid vaccine
administered to the subject. In some embodiments the combined
dosage is 50 micrograms of the RNA polynucleotide in the nucleic
acid vaccine administered to the subject. In some embodiments, the
combined dosage is 75 micrograms of the RNA polynucleotide in the
nucleic acid vaccine administered to the subject. In some
embodiments, the combined dosage is 150 micrograms of the RNA
polynucleotide in the nucleic acid vaccine administered to the
subject. In some embodiments, the combined dosage is 400 micrograms
of the RNA polynucleotide in the nucleic acid vaccine administered
to the subject. In some embodiments, the sub therapeutic dosage of
each individual nucleic acid encoding an antigen is 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20
micrograms. In other embodiments the nucleic acid vaccine is
chemically modified and in other embodiments the nucleic acid
vaccine is not nucleotide modified.
[0201] In some embodiments, the RNA polynucleotide is one of SEQ ID
NO: 447-457, 459, 461, 491-503, 524-542, or 566-569 and includes at
least one chemical modification. In other embodiments, the RNA
polynucleotide is one of SEQ ID NO: 447-457, 459, 461, 491-503,
524-542, or 566-569 and does not include any nucleotide
modifications, or is unmodified. In yet other embodiments the at
least one RNA polynucleotide encodes an antigenic protein of any of
SEQ ID NO: 1-444, 458, 460, 462-479, 543-565, or 566-569 and
includes at least one chemical modification. In other embodiments
the RNA polynucleotide encodes an antigenic protein of any of SEQ
ID NO: 1-444, 458, 460, 462-479,543-565, or 566-569 and does not
include any nucleotide modifications, or is unmodified.
[0202] In preferred aspects, vaccines of the invention (e.g.,
LNP-encapsulated mRNA vaccines) produce prophylactically- and/or
therapeutically-efficacious levels, concentrations and/or titers of
antigen-specific antibodies in the blood or serum of a vaccinated
subject. As defined herein, the term antibody titer refers to the
amount of antigen-specific antibody produces in s subject, e.g., a
human subject. In exemplary embodiments, antibody titer is
expressed as the inverse of the greatest dilution (in a serial
dilution) that still gives a positive result. In exemplary
embodiments, antibody titer is determined or measured by
enzyme-linked immunosorbent assay (ELISA). In exemplary
embodiments, antibody titer is determined or measured by
neutralization assay, e.g., by microneutralization assay. In
certain aspects, antibody titer measurement is expressed as a
ratio, such as 1:40, 1:100, etc.
[0203] In exemplary embodiments of the invention, an efficacious
vaccine produces an antibody titer of greater than 1:40, greater
that 1:100, greater than 1:400, greater than 1:1000, greater than
1:2000, greater than 1:3000, greater than 1:4000, greater than
1:500, greater than 1:6000, greater than 1:7500, greater than
1:10000. In exemplary embodiments, the antibody titer is produced
or reached by 10 days following vaccination, by 20 days following
vaccination, by 30 days following vaccination, by 40 days following
vaccination, or by 50 or more days following vaccination. In
exemplary embodiments, the titer is produced or reached following a
single dose of vaccine administered to the subject. In other
embodiments, the titer is produced or reached following multiple
doses, e.g., following a first and a second dose (e.g., a booster
dose).
[0204] In exemplary aspects of the invention, antigen-specific
antibodies are measured in units of .mu.g/ml or are measured in
units of IU/L (International Units per liter) or mIU/ml (milli
International Units per ml). In exemplary embodiments of the
invention, an efficacious vaccine produces >0.5 .mu.g/ml,
>0.1 .mu.g/ml, >0.2 .mu.g/ml, >0.35 .mu.g/ml, >0.5
.mu.g/ml, >1 .mu.g/ml, >2 .mu.g/ml, >5 .mu.g/ml or >10
.mu.g/ml. In exemplary embodiments of the invention, an efficacious
vaccine produces >10 mIU/ml, >20 mIU/ml, >50 mIU/ml,
>100 mIU/ml, >200 mIU/ml, >500 mIU/ml or >1000 mIU/ml.
In exemplary embodiments, the antibody level or concentration is
produced or reached by 10 days following vaccination, by 20 days
following vaccination, by 30 days following vaccination, by 40 days
following vaccination, or by 50 or more days following vaccination.
In exemplary embodiments, the level or concentration is produced or
reached following a single dose of vaccine administered to the
subject. In other embodiments, the level or concentration is
produced or reached following multiple doses, e.g., following a
first and a second dose (e.g., a booster dose.) In exemplary
embodiments, antibody level or concentration is determined or
measured by enzyme-linked immunosorbent assay (ELISA). In exemplary
embodiments, antibody level or concentration is determined or
measured by neutralization assay, e.g., by microneutralization
assay.
[0205] The details of various embodiments of the disclosure are set
forth in the description below. Other features, objects, and
advantages of the disclosure will be apparent from the description
and from the claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0206] The foregoing and other objects, features and advantages
will be apparent from the following description of particular
embodiments of the invention, as illustrated in the accompanying
drawings in which like reference characters refer to the same parts
throughout the different views. The drawings are not necessarily to
scale, emphasis instead being placed upon illustrating the
principles of various embodiments of the invention.
[0207] FIG. 1 shows data obtained from an ELISA, demonstrating that
vaccination with RNA encoding HA stem protein sequences from
different strains induces serum antibodies that bind to diverse
panel of recombinant HA (rHA) proteins.
[0208] FIG. 2 shows data demonstrating that serum antibody titers
obtained from mice vaccinated with a second set of mRNA vaccine
antigens induces serum antibodies that bind to a diverse panel of
recombinant HA (rHA) proteins.
[0209] FIG. 3 shows combining mRNAs encoding HA stem protein from
an H1 strain with mRNA encoding HA stem protein from an H3 strain
did not result in interference in the immune response to either
HA.
[0210] FIGS. 4A-4B depict endpoint titers of the pooled serum from
animals vaccinated with the test vaccines. In FIG. 4A, the vaccines
tested are shown on the x-axis and the binding to HA from each of
the different strains of influenza is plotted as an endpoint titer.
In FIG. 4B, the vaccines tested are shown on the x-axis, and the
endpoint titer to NP protein is plotted.
[0211] FIG. 5 shows an examination of functional antibody response
through an assessment of the ability of serum to neutralize a panel
of HA-pseudotyped viruses.
[0212] FIG. 6 shows data plotted as fold induction (sample
luminescence/background luminescence) versus serum
concentration.
[0213] FIG. 7 is a representation of cell-mediated immune responses
following mRNA vaccination. Splenocytes were harvested from
vaccinated mice and stimulated with a pool of overlapping NP
peptides. The % of CD4 or CD8 T cells secreting one of the three
cytokines (IFN-.gamma., IL-2, or TNF-.alpha.) is plotted.
[0214] FIG. 8 is a representation of cell-mediated immune responses
following mRNA vaccination. Splenocytes were harvested from
vaccinated mice and stimulated with a pool of overlapping HA
peptides. The % of CD4 or CD8 T cells secreting one of the three
cytokines (IFN-.gamma., IL-2, or TNF-.alpha.) is plotted.
[0215] FIG. 9 shows murine weight loss following challenge with a
lethal dose of mouse-adapted H1N1 A/Puerto Rico/8/1934. The
percentage of weight lost as compared to baseline was calculated
for each animal and was averaged across the group. The group
average was plotted over time in days. Error bars represent
standard error of the mean. Efficacy of the NIHGen6HASS-foldon+NP
combination vaccine was better than that of either the
NIHGen6HASS-foldon or NP mRNA vaccine alone.
[0216] FIG. 10 shows vaccine efficacy was similar at all vaccine
doses, as well as with all co-formulation and co-delivery methods
assessed. Following challenge with a lethal dose of mouse-adapted
H1N1 A/Puerto Rico/8/1934, the percentage of weight lost as
compared to baseline was calculated for each animal and was
averaged across the group. The group average was plotted over time
in days. Error bars represent standard error of the mean.
[0217] FIG. 11A depicts the endpoint titers of the pooled serum
from animals vaccinated with the test vaccines. FIG. 11B shows
efficacy of the test vaccines (NIHGen6HASS-foldon and
NIHGen6HASS-TM2) is similar. Following challenge with a lethal dose
of mouse-adapted H1N1 A/Puerto Rico/8/1934, the percentage of group
weight lost as compared to baseline was calculated and plotted over
time in days.
[0218] FIG. 12A shows that serum from mice immunized with mRNA
encoding consensus HA antigens from the H1 subtype was able to
detectably neutralize the PR8 luciferase virus. FIG. 12B shows that
serum from mice immunized with mRNA encoding H1 subtype consensus
HA antigens with a ferritin fusion sequence was able to detectably
neutralize the PR8 luciferase virus, except for the Merck_pH1
Con_ferritin mRNA, while serum from mice vaccinated with an mRNA
encoding the consensus H3 antigen with a ferritin fusion sequence
was not able to neutralize the PR8 luciferase virus.
[0219] FIGS. 13A-13B show murine weight loss following challenge
with a lethal dose of mouse-adapted H1N1 A/Puerto Rico/8/1934. The
percentage of group weight lost as compared to baseline was
calculated and plotted over time in days.
[0220] FIG. 14 shows the results of neutralization assays performed
on a panel of pseudoviruses to assess the breadth of the
serum-neutralizing activity elicited by the consensus HA
antigens.
[0221] FIG. 15A depicts the ELISA endpoint anti-HA antibody titers
of the pooled serum from animals vaccinated with the test vaccines.
FIG. 15B shows murine survival (left) and weight loss (right)
following challenge with a lethal dose of mouse-adapted B/Ann
Arbor/1954. The percentage of group survival and weight loss as
compared to baseline was calculated and plotted over time in
days.
[0222] FIGS. 16A-16C show data depicting the NIHGen6HASS-foldon
vaccine's robust antibody response as measured by ELISA assay
(plates coated with recombinantly-expressed NIHGen6HASS-foldon [HA
stem] or NP proteins). FIG. 16A shows titers to HA stem, over time,
for four rhesus macaques previously vaccinated with FLUZONE.RTM.
and boosted a single time with NIHGen6HASS-foldon mRNA vaccine.
FIG. 16B depicts titers to HA stem, over time, from four rhesus
macaques vaccinated at days 0, 28 and 56 with the same
NIHGen6HASS-foldon RNA vaccine. FIG. 16C illustrates antibody
titers to NP, over time, for four rhesus macaques vaccinated at
days 0, 28 and 56 with the NP mRNA vaccine and shows that the
vaccine elicited a robust antibody response to NP.
[0223] FIGS. 17A-17B show the results of ELISAs examining the
presence of antibody capable of binding to recombinant
hemagglutinin (rHA) from a wide variety of influenza strains. FIG.
17A shows the results of rhesus macaques previously vaccinated with
FLUZONE.RTM. and boosted a single time with NIHGen6HASS-foldon mRNA
vaccine, and FIG. 17B shows the results of naive rhesus macaques
vaccinated at days 0, 28 and 56 with the same NIHGen6HASS-foldon
RNA vaccine.
[0224] FIG. 18 is a representation of cell-mediated immune
responses following mRNA vaccination. Peripheral blood mononuclear
cells were harvested from vaccinated macaques and stimulated with a
pool of overlapping NP peptides. The % of CD4 or CD8 T cells
secreting one of the three cytokines (IFN-.gamma., IL-2, or
TNF-.alpha.) is plotted.
[0225] FIG. 19 shows the results of hemagglutination inhibition
(HAI) tests. Placebo subjects (targeted to be 25% of each cohort)
are included. The data is shown per protocol, and excludes those
that did not receive the day 22 injection.
[0226] FIG. 20 shows the HAI test kinetics per subject, including
the placebo subjects (targeted to be 25% of each cohort).
[0227] FIG. 21 shows the results of microneutralization (MN) tests,
including placebo subjects (targeted to be 25% of each cohort). The
data shown is per protocol, and excludes those that did not receive
a day 22 injection.
[0228] FIG. 22 shows the MN test kinetics per subject, including
the placebo subjects (targeted to be 25% of each cohort).
[0229] FIG. 23 is a graph depicting the very strong correlation
between HAI and MN. The data includes placebo subjects (targeted to
be 25% of each cohort).
[0230] FIG. 24A shows murine survival following challenge with a
lethal dose of mouse-adapted influenza virus strain H1N1 A/Puerto
Rico/8/1934 (PR8) or H3 A/Hong Kong/1/1968 (HK68). FIG. 24B shows
murine weight loss following challenge with a lethal dose of
mouse-adapted influenza virus strain H1N1 A/Puerto Rico/8/1934
(PR8) or H3 A/Hong Kong/1/1968 (HK68). FIG. 24C shows murine
survival following challenge with a lethal dose of HK68 virus. FIG.
24D shows murine weight loss following challenge with a lethal dose
of HK68 virus. The percentage of group survival and weight loss as
compared to baseline was calculated and plotted over time in
days.
DETAILED DESCRIPTION
[0231] Embodiments of the present disclosure provide RNA (e.g.,
mRNA) vaccines that include polynucleotide encoding an influenza
virus antigen. Influenza virus RNA vaccines, as provided herein may
be used to induce a balanced immune response, comprising both
cellular and humoral immunity, without many of the risks associated
with DNA vaccination.
[0232] In some embodiments, the virus is a strain of Influenza A or
Influenza B or combinations thereof. In some embodiments, the
strain of Influenza A or Influenza B is associated with birds,
pigs, horses, dogs, humans or non-human primates. In some
embodiments, the antigenic polypeptide encodes a hemagglutinin
protein. In some embodiments, the hemagglutinin protein is H1, H2,
H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17,
H18. In some embodiments, the hemagglutinin protein does not
comprise a head domain. In some embodiments, the hemagglutinin
protein comprises a portion of the head domain. In some
embodiments, the hemagglutinin protein does not comprise a
cytoplasmic domain. In some embodiments, the hemagglutinin protein
comprises a portion of the cytoplasmic domain. In some embodiments,
the truncated hemagglutinin protein comprises a portion of the
transmembrane domain. In some embodiments, the amino acid sequence
of the hemagglutinin protein comprises at least 90%, 91%, 92%, 93%,
94%, 95%, 96%, 97% 98%, or 99% identify with any of the amino acid
sequences having an amino acid sequence identified by any one of
SEQ ID NO: 1-444, 458, 460, 462-479, or 543-561 (see also Tables
7-13 and 26). In some embodiments, the virus is selected from the
group consisting of H1N1, H3N2, H7N9, and H10N8. In some
embodiments, the antigenic polypeptide is selected from those
proteins having an amino acid sequences identified by any one of
SEQ ID NO: 1-444, 458, 460, 462-479, or 543-561 (see also Tables
7-13 and 26).
[0233] Some embodiments provide influenza vaccines comprising one
or more RNA polynucleotides having an open reading frame encoding a
hemagglutinin protein and a pharmaceutically acceptable carrier or
excipient, formulated within a cationic lipid nanoparticle. In some
embodiments, the hemagglutinin protein is selected from H1, H7 and
H10. In some embodiments, the RNA polynucleotide further encodes
neuraminidase protein. In some embodiments, the hemagglutinin
protein is derived from a strain of Influenza A virus or Influenza
B virus or combinations thereof. In some embodiments, the Influenza
virus is selected from H1N1, H3N2, H7N9, and H10N8.
[0234] Some embodiments provide methods of preventing or treating
influenza viral infection comprising administering to a subject any
of the vaccines described herein. In some embodiments, the antigen
specific immune response comprises a T cell response. In some
embodiments, the antigen specific immune response comprises a B
cell response. In some embodiments, the antigen specific immune
response comprises both a T cell response and a B cell response. In
some embodiments, the method of producing an antigen specific
immune response involves a single administration of the vaccine. In
some embodiments, the vaccine is administered to the subject by
intradermal, intramuscular injection, subcutaneous injection,
intranasal inoculation, or oral administration.
[0235] In some embodiments, the RNA (e.g., mRNA) polynucleotides or
portions thereof may encode one or more polypeptides of an
influenza strain as an antigen. Such antigens include, but are not
limited to, those antigens encoded by the polynucleotides or
portions thereof of the polynucleotides listed in the Tables
presented herein. In the Tables, the GenBank Accession Number or GI
Accession Number represents either the complete or partial CDS of
the encoded antigen. The RNA (e.g., mRNA) polynucleotides may
comprise a region of any of the sequences listed in the Tables or
entire coding region of the mRNA listed. They may comprise hybrid
or chimeric regions, or mimics or variants.
[0236] In the following embodiments, when referring to at least one
RNA (e.g., mRNA) polynucleotide having an open reading frame
encoding for a specific influenza virus protein, the
polynucleotides may comprise a coding region of the specific
influenza virus protein sequence or the entire coding region of the
mRNA for that specific influenza virus protein sequence.
[0237] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (e.g., at least one HA1, HA2, or a combination of both,
of H1-H18).
[0238] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (e.g., at least one HA1, HA2, or a combination of both,
of H1-H18) and at least one protein selected from a NP protein, a
NA protein, a M1 protein, a M2 protein, a NS1 protein and a NS2
protein obtained from influenza virus.
[0239] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (e.g., at least one of H1-H18) and at least two proteins
selected from a NP protein, a NA protein, a M1 protein, a M2
protein, a NS1 protein and a NS2 protein obtained from influenza
virus.
[0240] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (e.g., at least one of H1-H18) and at least three
proteins selected from a NP protein, a NA protein, a M1 protein, a
M2 protein, a NS1 protein and a NS2 protein obtained from influenza
virus.
[0241] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (e.g., at least one of H1-H18) and at least four
proteins selected from a NP protein, a NA protein, a M1 protein, a
M2 protein, a NS1 protein and a NS2 protein obtained from influenza
virus.
[0242] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (e.g., at least one of H1-H18) and at least five
proteins selected from a NP protein, a NA protein, a M1 protein, a
M2 protein, a NS1 protein and a NS2 protein obtained from influenza
virus.
[0243] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (e.g., at least one of H1-H18), a NP protein, a NA
protein, a M1 protein, a M2 protein, a NS1 protein, and a NS2
protein obtained from influenza virus.
[0244] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein and a NA protein obtained from influenza virus.
[0245] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein and a M1 protein obtained from influenza virus.
[0246] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein and a M2 protein obtained from influenza virus.
[0247] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein and a NS1 protein obtained from influenza virus.
[0248] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein and a NS2 protein obtained from influenza virus.
[0249] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein, a NP protein and a NA protein obtained from influenza
virus.
[0250] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein, a NP protein, and a M1 protein obtained from influenza
virus.
[0251] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein, a NP protein, and a M2 protein obtained from influenza
virus.
[0252] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein, a NP protein, and a NS1 protein obtained from influenza
virus.
[0253] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein, a NP protein, and a NS2 protein, obtained from
influenza virus.
[0254] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein, a NA protein, and a M1 protein, obtained from influenza
virus.
[0255] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein, a NA protein, and a M2 protein, obtained from influenza
virus.
[0256] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein, a NA protein, and a NS1 protein, obtained from
influenza virus.
[0257] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein, a NA protein, and a NS2 protein, obtained from
influenza virus.
[0258] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein, a M1 protein, and a M2 protein, obtained from influenza
virus.
[0259] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein, a M1 protein, and a NS1 protein, obtained from
influenza virus.
[0260] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein, a M1 protein, and a NS2 protein, obtained from
influenza virus.
[0261] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein, a M2 protein, and a NS1 protein, obtained from
influenza virus.
[0262] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein, a M2 protein, and a NS2 protein, obtained from
influenza virus.
[0263] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein, a NS1 protein, and a NS2 protein, obtained from
influenza virus.
[0264] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA1 protein, and a NA protein, obtained from influenza virus.
[0265] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA1 protein and a M1 protein, obtained from influenza virus.
[0266] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA1 protein and a M2 protein, obtained from influenza virus.
[0267] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA1 protein and a NS1 protein, obtained from influenza virus.
[0268] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA1 protein and a NS2 protein, obtained from influenza virus.
[0269] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA1 protein, a NP protein, and a NA protein, obtained from
influenza virus.
[0270] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA1 protein, a NP protein, and a M1 protein, obtained from
influenza virus.
[0271] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA1 protein, a NP protein, and a M2 protein, obtained from
influenza virus.
[0272] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA1 protein, a NP protein, and a NS1 protein, obtained from
influenza virus.
[0273] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA1 protein, a NP protein, and a NS2 protein, obtained from
influenza virus.
[0274] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA1 protein, a NA protein, and a M1 protein, obtained from
influenza virus.
[0275] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA1 protein, a NA protein, and a
[0276] M2 protein, obtained from influenza virus.
[0277] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA1 protein, a NA protein and a NS1 protein, obtained from
influenza virus.
[0278] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA1 protein, a NA protein, and a NS2 protein, obtained from
influenza virus.
[0279] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA1 protein, a M1 protein, and a M2 protein, obtained from
influenza virus.
[0280] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA1 protein, a M1 protein, and a NS1 protein, obtained from
influenza virus.
[0281] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA1 protein, a M1 protein, and a NS2 protein, obtained from
influenza virus.
[0282] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA1 protein, a M2 protein, and a NS1 protein, obtained from
influenza virus.
[0283] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA1 protein, a M2 protein, and a NS2 protein, obtained from
influenza virus.
[0284] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA1 protein, a NS1 protein, and a NS2 protein, obtained from
influenza virus.
[0285] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (HA or derivatives thereof comprising antigenic
sequences from HA1 and/or HA2), and a NA protein, obtained from
influenza virus.
[0286] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (HA or derivatives thereof comprising antigenic
sequences from HA1 and/or HA2) and a M1 protein, obtained from
influenza virus.
[0287] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (HA or derivatives thereof comprising antigenic
sequences from HA1 and/or HA2) and a M2 protein, obtained from
influenza virus.
[0288] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (HA or derivatives thereof comprising antigenic
sequences from HA1 and/or HA2) and a NS1 protein obtained from
influenza virus.
[0289] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (HA or derivatives thereof comprising antigenic
sequences from HA1 and/or HA2) and a NS2 protein, obtained from
influenza virus.
[0290] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (HA or derivatives thereof comprising antigenic
sequences from HA1 and/or HA2), a NP protein, and a NA protein,
obtained from influenza virus.
[0291] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (HA or derivatives thereof comprising antigenic
sequences from HA1 and/or HA2), a NP protein, and a M1 protein,
obtained from influenza virus.
[0292] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (HA or derivatives thereof comprising antigenic
sequences from HA1 and/or HA2), a NP protein, and a M2 protein,
obtained from influenza virus.
[0293] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (HA or derivatives thereof comprising antigenic
sequences from HA1 and/or HA2), a NP protein, and a NS1 protein,
obtained from influenza virus.
[0294] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (HA or derivatives thereof comprising antigenic
sequences from HA1 and/or HA2), a NP protein and a NS2 protein,
obtained from influenza virus.
[0295] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (HA or derivatives thereof comprising antigenic
sequences from HA1 and/or HA2), a NA protein, and a M1 protein,
obtained from influenza virus.
[0296] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (HA or derivatives thereof comprising antigenic
sequences from HA1 and/or HA2), a NA protein, and a M2 protein,
obtained from influenza virus.
[0297] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (HA or derivatives thereof comprising antigenic
sequences from HA1 and/or HA2), a NA protein, and a NS1 protein,
obtained from influenza virus.
[0298] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (HA or derivatives thereof comprising antigenic
sequences from HA1 and/or HA2), a NA protein, and a NS2 protein,
obtained from influenza virus.
[0299] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (HA or derivatives thereof comprising antigenic
sequences from HA1 and/or HA2), a M1 protein, and a M2 protein,
obtained from influenza virus.
[0300] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (HA or derivatives thereof comprising antigenic
sequences from HA1 and/or HA2), a M1 protein, and a NS1 protein,
obtained from influenza virus.
[0301] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (HA or derivatives thereof comprising antigenic
sequences from HA1 and/or HA2), a M1 protein, and a NS2 protein,
obtained from influenza virus.
[0302] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (HA or derivatives thereof comprising antigenic
sequences from HA1 and/or HA2), a M2 protein, and a NS1 protein,
obtained from influenza virus.
[0303] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
H HA protein (HA or derivatives thereof comprising antigenic
sequences from HA1 and/or HA2), a M2 protein, and a NS2 protein,
obtained from influenza virus.
[0304] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
HA protein (HA or derivatives thereof comprising antigenic
sequences from HA1 and/or HA2), a NS1 protein, and a NS2 protein,
obtained from influenza virus.
[0305] It should be understood that the present disclosure is not
intended to be limited by a particular strain of influenza virus.
The strain of influenza virus used, as provided herein, may be any
strain of influenza virus. Examples of preferred strains of
influenza virus and preferred influenza antigens are provided in
Tables 7-13 below.
[0306] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
an influenza antigenic polypeptide (e.g., a HA protein, a NP
protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a
NS2 protein, an immunogenic fragment of any of the foregoing
influenza antigens, a variant or homolog of any of the foregoing
influenza antigens, or any combination of two or more of the
foregoing influenza antigens, variants or homologs) obtained from
H1/PuertoRico/8/1934.
[0307] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
an influenza antigenic polypeptide (e.g., a HA protein, a NP
protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a
NS2 protein, an immunogenic fragment of any of the foregoing
influenza antigens, a variant or homolog of any of the foregoing
influenza antigens, or any combination of two or more of the
foregoing influenza antigens, variants or homologs) obtained from
H1/New Caledonia/20/1999.
[0308] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
an influenza antigenic polypeptide (e.g., a HA protein, a NP
protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a
NS2 protein, an immunogenic fragment of any of the foregoing
influenza antigens, a variant or homolog of any of the foregoing
influenza antigens, or any combination of two or more of the
foregoing influenza antigens, variants or homologs) obtained from
H1/California/04/2009.
[0309] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
an influenza antigenic polypeptide (e.g., a HA protein, a NP
protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a
NS2 protein, an immunogenic fragment of any of the foregoing
influenza antigens, a variant or homolog of any of the foregoing
influenza antigens, or any combination of two or more of the
foregoing influenza antigens, variants or homologs) obtained from
H5/Vietnam/1194/2004.
[0310] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
an influenza antigenic polypeptide (e.g., a HA protein, a NP
protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a
NS2 protein, an immunogenic fragment of any of the foregoing
influenza antigens, a variant or homolog of any of the foregoing
influenza antigens, or any combination of two or more of the
foregoing influenza antigens, variants or homologs) obtained from
H2/Japan/305/1957.
[0311] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
an influenza antigenic polypeptide (e.g., a HA protein, a NP
protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein,
a
[0312] NS2 protein, an immunogenic fragment of any of the foregoing
influenza antigens, a variant or homolog of any of the foregoing
influenza antigens, or any combination of two or more of the
foregoing influenza antigens, variants or homologs) obtained from
H9/Hong Kong/1073/99.
[0313] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
an influenza antigenic polypeptide (e.g., a HA protein, a NP
protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a
NS2 protein, an immunogenic fragment of any of the foregoing
influenza antigens, a variant or homolog of any of the foregoing
influenza antigens, or any combination of two or more of the
foregoing influenza antigens, variants or homologs) obtained from
H3/Aichi/2/1968.
[0314] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
an influenza antigenic polypeptide (e.g., a HA protein, a NP
protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a
NS2 protein, an immunogenic fragment of any of the foregoing
influenza antigens, a variant or homolog of any of the foregoing
influenza antigens, or any combination of two or more of the
foregoing influenza antigens, variants or homologs) obtained from
H3/Brisbane/10/2007.
[0315] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
an influenza antigenic polypeptide (e.g., a HA protein, a NP
protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a
NS2 protein, an immunogenic fragment of any of the foregoing
influenza antigens, a variant or homolog of any of the foregoing
influenza antigens, or any combination of two or more of the
foregoing influenza antigens, variants or homologs) obtained from
H7/Anhui/1/2013.
[0316] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
an influenza antigenic polypeptide (e.g., a HA protein, a NP
protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a
NS2 protein, an immunogenic fragment of any of the foregoing
influenza antigens, a variant or homolog of any of the foregoing
influenza antigens, or any combination of two or more of the
foregoing influenza antigens, variants or homologs) obtained from
H10/Jiangxi-Donghu/346/2013.
[0317] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
an influenza antigenic polypeptide (e.g., a HA protein, a NP
protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a
NS2 protein, an immunogenic fragment of any of the foregoing
influenza antigens, a variant or homolog of any of the foregoing
influenza antigens, or any combination of two or more of the
foregoing influenza antigens, variants or homologs) obtained from
H3/Wisconsin/67/2005.
[0318] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
an influenza antigenic polypeptide (e.g., a HA protein, a NP
protein, a NA protein, a M1 protein, a M2 protein, a NS1 protein, a
NS2 protein, an immunogenic fragment of any of the foregoing
influenza antigens, a variant or homolog of any of the foregoing
influenza antigens, or any combination of two or more of the
foregoing influenza antigens, variants or homologs) obtained from
H1/Vietnam/850/2009.
[0319] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
influenza H7N9 HA1 protein, ferritin and a dendritic cell targeting
peptide (see, e.g., Ren X et al. Emerg Infect Dis 2013;
19(11):1881-84; Steel J et al. mBio 2010; 1(1):e00018-10; Kanekiyo
M. et al. Nature 2013; 499:102-6, each of which is incorporated
herein by reference).
[0320] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
an avian influenza H7 HA protein.
[0321] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
influenza H7 HA1 protein (see, e.g., Steel Jet al. mBio 2010;
1(1):e00018-10).
[0322] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
influenza H7N9 HAI protein and ferritin (see, e.g., Kanekiyo M. et
al. Nature 2013; 499:102-6).
[0323] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
an influenza H5N1 protein. In some embodiments, the influenza H5N1
protein is from a human strain.
[0324] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
an influenza H1N1 protein.
[0325] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
an influenza protein from an influenza A strain, such as human
H1N1, H5N1, H9N2 or H3N2.
[0326] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
an influenza H1N1 HA having a nanoscaffold (see, e.g., Walker A et
al. Sci Rep 2011:1(5):1-8, incorporated herein by reference).
[0327] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding a
glycosylated influenza H1N1 HA (see, e.g., Chen J et al. PNAS USA
2014; 111(7):2476-81, incorporated herein by reference).
[0328] An influenza vaccine may comprise, for example, at least one
RNA (e.g., mRNA) polynucleotide having an open reading frame
encoding at least one influenza HA2 stem antigen selected from the
influenza HA2 stem antigens, provided herein, for example, those
listed in Table 16, comprising an amino acid sequence identified by
any one of SEQ ID NO: 394-412.
[0329] The present disclosure also encompasses an influenza vaccine
comprising, for example, at least one RNA (e.g., mRNA)
polynucleotide having a nucleic acid sequence selected from the
influenza sequences listed in SEQ ID NO: 491-503 or 566-569 (see
also: Mallajosyula V V et al., Front Immunol. 2015 Jun 26; 6:329.;
Mallajosyula V V et al., Proc Natl Acad Sci USA. 2014 Jun. 24;
111(25):E2514-23.; Bommakanti G, et al., J Virol. 2012 December;
86(24):13434-44; Bommakanti G et al., Proc Natl Acad Sci USA. 2010
Aug. 3; 107(31):13701-6 and Yassine et al., Nat Med. 2015 Sep;
21(9):1065-70; Impagliazzo et al., Science, 2015 Sep 18;
349(6254)).
[0330] The entire contents of International Application No.
PCT/US2015/027400, International Publication No. WO2015/164674A, is
incorporated herein by reference.
[0331] In some embodiments the vaccines described herein are
consensus sequences. A "consensus sequence" as used herein refers
to a polypeptide sequence based on analysis of an alignment of
multiple subtypes of a particular influenza antigen. mRNA sequences
that encode a consensus polypeptide sequence may be prepared and
used to induce broad immunity against multiple subtypes or
serotypes of a particular influenza antigen.
[0332] The mRNA encoding influenza antigens provided herein can be
arranged as a vaccine that causes seroconversion in vaccinated
mammals and provides cross-reactivity against a broad range of
seasonal strains of influenza and also pandemic strains of
influenza. The seroconversion and broad cross-reactivity can be
determined by measuring inhibiting titers against different
hemagglutinin strains of influenza. Preferred combinations include
at least two antigens from each of the influenza antigens described
herein.
[0333] It has been discovered that the mRNA vaccines described
herein are superior to current vaccines in several ways. First, the
lipid nanoparticle (LNP) delivery is superior to other formulations
including a protamine base approach described in the literature and
no additional adjuvants are to be necessary. The use of LNPs
enables the effective delivery of chemically modified or unmodified
mRNA vaccines. Additionally it has been demonstrated herein that
both modified and unmodified LNP formulated mRNA vaccines were
superior to conventional vaccines by a significant degree. In some
embodiments the mRNA vaccines of the invention are superior to
conventional vaccines by a factor of at least 10 fold, 20 fold, 40
fold, 50 fold, 100 fold, 500 fold or 1,000 fold.
[0334] Although attempts have been made to produce functional RNA
vaccines, including mRNA vaccines and self-replicating RNA
vaccines, the therapeutic efficacy of these RNA vaccines have not
yet been fully established. Quite surprisingly, the inventors have
discovered, according to aspects of the invention a class of
formulations for delivering mRNA vaccines in vivo that results in
significantly enhanced, and in many respects synergistic, immune
responses including enhanced antigen generation and functional
antibody production with neutralization capability. These results
can be achieved even when significantly lower doses of the mRNA are
administered in comparison with mRNA doses used in other classes of
lipid based formulations. The formulations of the invention have
demonstrated significant unexpected in vivo immune responses
sufficient to establish the efficacy of functional mRNA vaccines as
prophylactic and therapeutic agents. Additionally, self-replicating
RNA vaccines rely on viral replication pathways to deliver enough
RNA to a cell to produce an immunogenic response. The formulations
of the invention do not require viral replication to produce enough
protein to result in a strong immune response. Thus, the mRNA of
the invention are not self-replicating RNA and do not include
components necessary for viral replication.
[0335] The invention involves, in some aspects, the surprising
finding that lipid nanoparticle (LNP) formulations significantly
enhance the effectiveness of mRNA vaccines, including chemically
modified and unmodified mRNA vaccines. The efficacy of mRNA
vaccines formulated in LNP was examined in vivo using several
distinct antigens. The results presented herein demonstrate the
unexpected superior efficacy of the mRNA vaccines formulated in LNP
over other commercially available vaccines.
[0336] In addition to providing an enhanced immune response, the
formulations of the invention generate a more rapid immune response
with fewer doses of antigen than other vaccines tested. The
mRNA-LNP formulations of the invention also produce quantitatively
and qualitatively better immune responses than vaccines formulated
in a different carriers.
[0337] The data described herein demonstrate that the formulations
of the invention produced significant unexpected improvements over
existing antigen vaccines. Additionally, the mRNA-LNP formulations
of the invention are superior to other vaccines even when the dose
of mRNA is lower than other vaccines. mRNA encoding HA protein
sequences such as HA stem sequences from different strains have
been demonstrated to induce serum antibodies that bind to diverse
panel of recombinant HA (rHA) proteins. The vaccine efficacy in
mice was similar at all vaccine doses, as well as with all
co-formulation and co-delivery methods assessed.
[0338] The LNP used in the studies described herein has been used
previously to deliver siRNA in various animal models as well as in
humans. In view of the observations made in association with the
siRNA delivery of LNP formulations, the fact that LNP is useful in
vaccines is quite surprising. It has been observed that therapeutic
delivery of siRNA formulated in LNP causes an undesirable
inflammatory response associated with a transient IgM response,
typically leading to a reduction in antigen production and a
compromised immune response. In contrast to the findings observed
with siRNA, the LNP-mRNA formulations of the invention are
demonstrated herein to generate enhanced IgG levels, sufficient for
prophylactic and therapeutic methods rather than transient IgM
responses.
Nucleic Acids/Polynucleotides
[0339] Influenza virus vaccines, as provided herein, comprise at
least one (one or more) ribonucleic acid (RNA) (e.g., mRNA)
polynucleotide having an open reading frame encoding at least one
Influenza antigenic polypeptide. The term "nucleic acid" includes
any compound and/or substance that comprises a polymer of
nucleotides (nucleotide monomer). These polymers are referred to as
polynucleotides. Thus, the terms "nucleic acid" and
"polynucleotide" are used interchangeably.
[0340] Nucleic acids may be or may include, for example,
ribonucleic acids (RNAs), deoxyribonucleic acids (DNAs), threose
nucleic acids (TNAs), glycol nucleic acids (GNAs), peptide nucleic
acids (PNAs), locked nucleic acids (LNAs, including LNA having a
.beta.-D-ribo configuration, .alpha.-LNA having an .alpha.-L-ribo
configuration (a diastereomer of LNA), 2'-amino-LNA having a
2'-amino functionalization, and 2'-amino-.alpha.-LNA having a
2'-amino functionalization), ethylene nucleic acids (ENA),
cyclohexenyl nucleic acids (CeNA) or chimeras or combinations
thereof.
[0341] In some embodiments, polynucleotides of the present
disclosure function as messenger RNA (mRNA). "Messenger RNA" (mRNA)
refers to any polynucleotide that encodes a (at least one)
polypeptide (a naturally-occurring, non-naturally-occurring, or
modified polymer of amino acids) and can be translated to produce
the encoded polypeptide in vitro, in vivo, in situ or ex vivo. The
skilled artisan will appreciate that, except where otherwise noted,
polynucleotide sequences set forth in the instant application will
recite "T"s in a representative DNA sequence but where the sequence
represents RNA (e.g., mRNA), the "T"s would be substituted for
"U"s. Thus, any of the RNA polynucleotides encoded by a DNA
identified by a particular sequence identification number may also
comprise the corresponding RNA (e.g., mRNA) sequence encoded by the
DNA, where each "T" of the DNA sequence is substituted with
"U."
[0342] It should be understood that the mRNA polynucleotides of the
vaccines as provided herein are synthetic molecules, i.e., they are
not naturally-occurring molecules. That is, the mRNA
polynucleotides of the present disclosure are isolated mRNA
polynucleotides. As is known in the art, "isolated polynucleotides"
refer to polynucleotides that are substantially physically
separated from other cellular material (e.g., separated from cells
and/or systems that produce the polynucleotides) or from other
material that hinders their use in the vaccines of the present
disclosure. Isolated polynucleotides are substantially pure in that
they have been substantially separated from the substances with
which they may be associated in living or viral systems. Thus, mRNA
polynucleotide vaccines are not associated with living or viral
systems, such as cells or viruses. The mRNA polynucleotide vaccines
do not include viral components (e.g., viral capsids, viral
enzymes, or other viral proteins, for example, those needed for
viral-based replication), and the mRNA polynucleotide vaccines are
not packaged within, encapsulated within, linked to, or otherwise
associated with a virus or viral particle. In some embodiments, the
mRNA vaccines comprise a lipid nanoparticle that consists of, or
consists essentially of, one or more mRNA polynucleotides (e.g.,
mRNA polynucleotides encoding one or more influenza
antigen(s)).
[0343] The basic components of an mRNA molecule typically include
at least one coding region, a 5' untranslated region (UTR), a 3'
UTR, a 5' cap and a poly-A tail. Polynucleotides of the present
disclosure may function as mRNA but can be distinguished from
wild-type mRNA in their functional and/or structural design
features, which serve to overcome existing problems of effective
polypeptide expression using nucleic-acid based therapeutics. In
some embodiments, the RNA is a mRNA having an open reading frame
encoding at least one influenza virus antigen. In some embodiments,
the RNA (e.g., mRNA) further comprises a (at least one) 5' UTR, 3'
UTR, a polyA tail and/or a 5' cap.
[0344] In some embodiments, a RNA polynucleotide of an RNA (e.g.,
mRNA) vaccine encodes 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3,
3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5,
5-10, 5-9, 5-8, 5-7, 5-6, 6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8,
8-10, 8-9 or 9-10 antigenic polypeptides. In some embodiments, a
RNA (e.g., mRNA) polynucleotide of an influenza vaccine encodes at
least 10, 20, 30, 40, 50 , 60, 70, 80, 90 or 100 antigenic
polypeptides. In some embodiments, a RNA (e.g., mRNA)
polynucleotide of an influenza vaccine encodes at least 100 or at
least 200 antigenic polypeptides. In some embodiments, a RNA
polynucleotide of an influenza vaccine encodes 1-10, 5-15, 10-20,
15-25, 20-30, 25-35, 30-40, 35-45, 40-50, 1-50, 1-100, 2-50 or
2-100 antigenic polypeptides.
[0345] Polynucleotides of the present disclosure, in some
embodiments, are codon optimized. Codon optimization methods are
known in the art and may be used as provided herein. Codon
optimization, in some embodiments, may be used to match codon
frequencies in target and host organisms to ensure proper folding;
bias GC content to increase mRNA stability or reduce secondary
structures; minimize tandem repeat codons or base runs that may
impair gene construction or expression; customize transcriptional
and translational control regions; insert or remove protein
trafficking sequences; remove/add post translation modification
sites in encoded protein (e.g. glycosylation sites); add, remove or
shuffle protein domains; insert or delete restriction sites; modify
ribosome binding sites and mRNA degradation sites; adjust
translational rates to allow the various domains of the protein to
fold properly; or to reduce or eliminate problem secondary
structures within the polynucleotide. Codon optimization tools,
algorithms and services are known in the art--non-limiting examples
include services from GeneArt (Life Technologies), DNA2.0 (Menlo
Park Calif.) and/or proprietary methods. In some embodiments, the
open reading frame (ORF) sequence is optimized using optimization
algorithms.
[0346] In some embodiments, a codon optimized sequence shares less
than 95% sequence identity, less than 90% sequence identity, less
than 85% sequence identity, less than 80% sequence identity, or
less than 75% sequence identity to a naturally-occurring or
wild-type sequence (e.g., a naturally-occurring or wild-type mRNA
sequence encoding a polypeptide or protein of interest (e.g., an
antigenic protein or antigenic polypeptide)).
[0347] In some embodiments, a codon-optimized sequence shares
between 65% and 85% (e.g., between about 67% and about 85%, or
between about 67% and about 80%) sequence identity to a
naturally-occurring sequence or a wild-type sequence (e.g., a
naturally-occurring or wild-type mRNA sequence encoding a
polypeptide or protein of interest (e.g., an antigenic protein or
polypeptide)). In some embodiments, a codon-optimized sequence
shares between 65% and 75%, or about 80% sequence identity to a
naturally-occurring sequence or wild-type sequence (e.g., a
naturally-occurring or wild-type mRNA sequence encoding a
polypeptide or protein of interest (e.g., an antigenic protein or
polypeptide)).
[0348] In some embodiments a codon-optimized RNA (e.g., mRNA) may,
for instance, be one in which the levels of G/C are enhanced. The
G/C-content of nucleic acid molecules may influence the stability
of the RNA. RNA having an increased amount of guanine (G) and/or
cytosine (C) residues may be functionally more stable than nucleic
acids containing a large amount of adenine (A) and thymine (T) or
uracil (U) nucleotides. WO2002/098443 discloses a pharmaceutical
composition containing an mRNA stabilized by sequence modifications
in the translated region. Due to the degeneracy of the genetic
code, the modifications work by substituting existing codons for
those that promote greater RNA stability without changing the
resulting amino acid. The approach is limited to coding regions of
the RNA.
Antigens/Antigenic Polypeptides
[0349] In some embodiments, an antigenic polypeptide (e.g., at
least one Influenza antigenic polypeptide) is longer than 25 amino
acids and shorter than 50 amino acids. The term "antigenic
polypeptides" and "antigenic proteins" includes immunogenic
fragments and epitopes thereof (e.g., an immunogenic fragment
capable of inducing an immune response to influenza). Polypeptides
include gene products, naturally occurring polypeptides, synthetic
polypeptides, homologs, orthologs, paralogs, fragments and other
equivalents, variants, and analogs of the foregoing. A polypeptide
may be a single molecule or may be a multi-molecular complex such
as a dimer, trimer or tetramer. Polypeptides may also comprise
single chain polypeptides or multichain polypeptides, such as
antibodies or insulin, and may be associated or linked to each
other. Most commonly, disulfide linkages are found in multichain
polypeptides. The term "polypeptide" may also apply to amino acid
polymers in which at least one amino acid residue is an artificial
chemical analogue of a corresponding naturally-occurring amino
acid.
[0350] A "polypeptide variant" is a molecule that differs in its
amino acid sequence relative to a native sequence or a reference
sequence. Amino acid sequence variants may possess substitutions,
deletions, insertions, or a combination of any two or three of the
foregoing, at certain positions within the amino acid sequence, as
compared to a native sequence or a reference sequence. Ordinarily,
variants possess at least 50% identity to a native sequence or a
reference sequence. In some embodiments, variants share at least
80% identity or at least 90% identity with a native sequence or a
reference sequence.
[0351] In some embodiments "variant mimics" are provided. A
"variant mimic" contains at least one amino acid that would mimic
an activated sequence. For example, glutamate may serve as a mimic
for phosphoro-threonine and/or phosphoro-serine. Alternatively,
variant mimics may result in deactivation or in an inactivated
product containing the mimic. For example, phenylalanine may act as
an inactivating substitution for tyrosine, or alanine may act as an
inactivating substitution for serine.
[0352] "Orthologs" refers to genes in different species that
evolved from a common ancestral gene by speciation. Normally,
orthologs retain the same function in the course of evolution.
Identification of orthologs is important for reliable prediction of
gene function in newly sequenced genomes.
[0353] "Analogs" is meant to include polypeptide variants that
differ by one or more amino acid alterations, for example,
substitutions, additions or deletions of amino acid residues that
still maintain one or more of the properties of the parent or
starting polypeptide.
[0354] The present disclosure provides several types of
compositions that are polynucleotide or polypeptide based,
including variants and derivatives. These include, for example,
substitutional, insertional, deletion and covalent variants and
derivatives. The term "derivative" is synonymous with the term
"variant" and generally refers to a molecule that has been modified
and/or changed in any way relative to a reference molecule or a
starting molecule.
[0355] As such, polynucleotides encoding peptides or polypeptides
containing substitutions, insertions and/or additions, deletions
and covalent modifications with respect to reference sequences, in
particular the polypeptide sequences disclosed herein, are included
within the scope of this disclosure. For example, sequence tags or
amino acids, such as one or more lysines, can be added to peptide
sequences (e.g., at the N-terminal or C-terminal ends). Sequence
tags can be used for peptide detection, purification or
localization. Lysines can be used to increase peptide solubility or
to allow for biotinylation. Alternatively, amino acid residues
located at the carboxy and amino terminal regions of the amino acid
sequence of a peptide or protein may optionally be deleted
providing for truncated sequences. Certain amino acids (e.g.,
C-terminal residues or N-terminal residues) alternatively may be
deleted depending on the use of the sequence, as for example,
expression of the sequence as part of a larger sequence that is
soluble, or linked to a solid support.
[0356] "Substitutional variants" when referring to polypeptides are
those that have at least one amino acid residue in a native or
starting sequence removed and a different amino acid inserted in
its place at the same position. Substitutions may be single, where
only one amino acid in the molecule has been substituted, or they
may be multiple, where two or more (e.g., 3, 4 or 5) amino acids
have been substituted in the same molecule.
[0357] As used herein the term "conservative amino acid
substitution" refers to the substitution of an amino acid that is
normally present in the sequence with a different amino acid of
similar size, charge, or polarity. Examples of conservative
substitutions include the substitution of a non-polar (hydrophobic)
residue such as isoleucine, valine and leucine for another
non-polar residue. Likewise, examples of conservative substitutions
include the substitution of one polar (hydrophilic) residue for
another such as between arginine and lysine, between glutamine and
asparagine, and between glycine and serine. Additionally, the
substitution of a basic residue such as lysine, arginine or
histidine for another, or the substitution of one acidic residue
such as aspartic acid or glutamic acid for another acidic residue
are additional examples of conservative substitutions. Examples of
non-conservative substitutions include the substitution of a
non-polar (hydrophobic) amino acid residue such as isoleucine,
valine, leucine, alanine, methionine for a polar (hydrophilic)
residue such as cysteine, glutamine, glutamic acid or lysine and/or
a polar residue for a non-polar residue.
[0358] "Features" when referring to polypeptide or polynucleotide
are defined as distinct amino acid sequence-based or
nucleotide-based components of a molecule respectively. Features of
the polypeptides encoded by the polynucleotides include surface
manifestations, local conformational shape, folds, loops,
half-loops, domains, half-domains, sites, termini and any
combination(s) thereof.
[0359] As used herein when referring to polypeptides the term
"domain" refers to a motif of a polypeptide having one or more
identifiable structural or functional characteristics or properties
(e.g., binding capacity, serving as a site for protein-protein
interactions).
[0360] As used herein when referring to polypeptides the terms
"site" as it pertains to amino acid based embodiments is used
synonymously with "amino acid residue" and "amino acid side chain."
As used herein when referring to polynucleotides the terms "site"
as it pertains to nucleotide based embodiments is used synonymously
with "nucleotide." A site represents a position within a peptide or
polypeptide or polynucleotide that may be modified, manipulated,
altered, derivatized or varied within the polypeptide-based or
polynucleotide-based molecules.
[0361] As used herein the terms "termini" or "terminus" when
referring to polypeptides or polynucleotides refers to an extremity
of a polypeptide or polynucleotide respectively. Such extremity is
not limited only to the first or final site of the polypeptide or
polynucleotide but may include additional amino acids or
nucleotides in the terminal regions. Polypeptide-based molecules
may be characterized as having both an N-terminus (terminated by an
amino acid with a free amino group (NH2)) and a C-terminus
(terminated by an amino acid with a free carboxyl group (COOH)).
Proteins are in some cases made up of multiple polypeptide chains
brought together by disulfide bonds or by non-covalent forces
(multimers, oligomers). These proteins have multiple N- and
C-termini. Alternatively, the termini of the polypeptides may be
modified such that they begin or end, as the case may be, with a
non-polypeptide based moiety such as an organic conjugate.
[0362] As recognized by those skilled in the art, protein
fragments, functional protein domains, and homologous proteins are
also considered to be within the scope of polypeptides of interest.
For example, provided herein is any protein fragment (meaning a
polypeptide sequence at least one amino acid residue shorter than a
reference polypeptide sequence but otherwise identical) of a
reference protein having a length of 10, 20, 30, 40, 50, 60, 70,
80, 90, 100 or longer than 100 amino acids. In another example, any
protein that includes a stretch of 20, 30, 40, 50, or 100
(contiguous) amino acids that are 40%, 50%, 60%, 70%, 80%, 90%,
95%, or 100% identical to any of the sequences described herein can
be utilized in accordance with the disclosure. In some embodiments,
a polypeptide includes 2, 3, 4, 5, 6, 7, 8, 9, 10, or more
mutations as shown in any of the sequences provided herein or
referenced herein. In another example, any protein that includes a
stretch of 20, 30, 40, 50, or 100 amino acids that are greater than
80%, 90%, 95%, or 100% identical to any of the sequences described
herein, wherein the protein has a stretch of 5, 10, 15, 20, 25, or
30 amino acids that are less than 80%, 75%, 70%, 65% to 60%
identical to any of the sequences described herein can be utilized
in accordance with the disclosure.
[0363] Polypeptide or polynucleotide molecules of the present
disclosure may share a certain degree of sequence similarity or
identity with the reference molecules (e.g., reference polypeptides
or reference polynucleotides), for example, with art-described
molecules (e.g., engineered or designed molecules or wild-type
molecules). The term "identity," as known in the art, refers to a
relationship between the sequences of two or more polypeptides or
polynucleotides, as determined by comparing the sequences. In the
art, identity also means the degree of sequence relatedness between
two sequences as determined by the number of matches between
strings of two or more amino acid residues or nucleic acid
residues. Identity measures the percent of identical matches
between the smaller of two or more sequences with gap alignments
(if any) addressed by a particular mathematical model or computer
program (e.g.,"algorithms"). Identity of related peptides can be
readily calculated by known methods. "% identity" as it applies to
polypeptide or polynucleotide sequences is defined as the
percentage of residues (amino acid residues or nucleic acid
residues) in the candidate amino acid or nucleic acid sequence that
are identical with the residues in the amino acid sequence or
nucleic acid sequence of a second sequence after aligning the
sequences and introducing gaps, if necessary, to achieve the
maximum percent identity. Methods and computer programs for the
alignment are well known in the art. Identity depends on a
calculation of percent identity but may differ in value due to gaps
and penalties introduced in the calculation. Generally, variants of
a particular polynucleotide or polypeptide have at least 40%, 45%,
50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%,
95%, 96%, 97%, 98%, 99% but less than 100% sequence identity to
that particular reference polynucleotide or polypeptide as
determined by sequence alignment programs and parameters described
herein and known to those skilled in the art. Such tools for
alignment include those of the BLAST suite (Stephen F. Altschul, et
al. (1997). "Gapped BLAST and PSI-BLAST: a new generation of
protein database search programs," Nucleic Acids Res.
25:3389-3402). Another popular local alignment technique is based
on the Smith-Waterman algorithm (Smith, T. F. & Waterman, M. S.
(1981) "Identification of common molecular subsequences." J. Mol.
Biol. 147:195-197). A general global alignment technique based on
dynamic programming is the Needleman-Wunsch algorithm (Needleman,
S. B. & Wunsch, C. D. (1970) "A general method applicable to
the search for similarities in the amino acid sequences of two
proteins." J. Mol. Biol. 48:443-453). More recently, a Fast Optimal
Global Sequence Alignment Algorithm (FOGSAA) was developed that
purportedly produces global alignment of nucleotide and protein
sequences faster than other optimal global alignment methods,
including the Needleman-Wunsch algorithm. Other tools are described
herein, specifically in the definition of "identity" below.
[0364] As used herein, the term "homology" refers to the overall
relatedness between polymeric molecules, e.g. between nucleic acid
molecules (e.g. DNA molecules and/or RNA molecules) and/or between
polypeptide molecules. Polymeric molecules (e.g. nucleic acid
molecules (e.g. DNA molecules and/or RNA molecules) and/or
polypeptide molecules) that share a threshold level of similarity
or identity determined by alignment of matching residues are termed
homologous. Homology is a qualitative term that describes a
relationship between molecules and can be based upon the
quantitative similarity or identity. Similarity or identity is a
quantitative term that defines the degree of sequence match between
two compared sequences. In some embodiments, polymeric molecules
are considered to be "homologous" to one another if their sequences
are at least 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%,
80%, 85%, 90%, 95%, or 99% identical or similar. The term
"homologous" necessarily refers to a comparison between at least
two sequences (polynucleotide or polypeptide sequences). Two
polynucleotide sequences are considered homologous if the
polypeptides they encode are at least 50%, 60%, 70%, 80%, 90%, 95%,
or even 99% for at least one stretch of at least 20 amino acids. In
some embodiments, homologous polynucleotide sequences are
characterized by the ability to encode a stretch of at least 4-5
uniquely specified amino acids. For polynucleotide sequences less
than 60 nucleotides in length, homology is determined by the
ability to encode a stretch of at least 4-5 uniquely specified
amino acids. Two protein sequences are considered homologous if the
proteins are at least 50%, 60%, 70%, 80%, or 90% identical for at
least one stretch of at least 20 amino acids.
[0365] Homology implies that the compared sequences diverged in
evolution from a common origin. The term "homolog" refers to a
first amino acid sequence or nucleic acid sequence (e.g., gene (DNA
or RNA) or protein sequence) that is related to a second amino acid
sequence or nucleic acid sequence by descent from a common
ancestral sequence. The term "homolog" may apply to the
relationship between genes and/or proteins separated by the event
of speciation or to the relationship between genes and/or proteins
separated by the event of genetic duplication. "Orthologs" are
genes (or proteins) in different species that evolved from a common
ancestral gene (or protein) by speciation. Typically, orthologs
retain the same function in the course of evolution. "Paralogs" are
genes (or proteins) related by duplication within a genome.
Orthologs retain the same function in the course of evolution,
whereas paralogs evolve new functions, even if these are related to
the original one.
[0366] The term "identity" refers to the overall relatedness
between polymeric molecules, for example, between polynucleotide
molecules (e.g. DNA molecules and/or RNA molecules) and/or between
polypeptide molecules. Calculation of the percent identity of two
polynucleic acid sequences, for example, can be performed by
aligning the two sequences for optimal comparison purposes (e.g.,
gaps can be introduced in one or both of a first and a second
nucleic acid sequences for optimal alignment and non-identical
sequences can be disregarded for comparison purposes). In certain
embodiments, the length of a sequence aligned for comparison
purposes is at least 30%, at least 40%, at least 50%, at least 60%,
at least 70%, at least 80%, at least 90%, at least 95%, or 100% of
the length of the reference sequence. The nucleotides at
corresponding nucleotide positions are then compared. When a
position in the first sequence is occupied by the same nucleotide
as the corresponding position in the second sequence, then the
molecules are identical at that position. The percent identity
between the two sequences is a function of the number of identical
positions shared by the sequences, taking into account the number
of gaps, and the length of each gap, which needs to be introduced
for optimal alignment of the two sequences. The comparison of
sequences and determination of percent identity between two
sequences can be accomplished using a mathematical algorithm. For
example, the percent identity between two nucleic acid sequences
can be determined using methods such as those described in
Computational Molecular Biology, Lesk, A. M., ed., Oxford
University Press, New York, 1988; Biocomputing: Informatics and
Genome Projects, Smith, D. W., ed., Academic Press, New York, 1993;
Sequence Analysis in Molecular Biology, von Heinje, G., Academic
Press, 1987; Computer Analysis of Sequence Data, Part I, Griffin,
A. M., and Griffin, H. G., eds., Humana Press, New Jersey, 1994;
and Sequence Analysis Primer, Gribskov, M. and Devereux, J., eds.,
M Stockton Press, New York, 1991; each of which is incorporated
herein by reference. For example, the percent identity between two
nucleic acid sequences can be determined using the algorithm of
Meyers and Miller (CABIOS, 1989, 4:11-17), which has been
incorporated into the ALIGN program (version 2.0) using a PAM120
weight residue table, a gap length penalty of 12 and a gap penalty
of 4. The percent identity between two nucleic acid sequences can,
alternatively, be determined using the GAP program in the GCG
software package using an NWSgapdna.CMP matrix. Methods commonly
employed to determine percent identity between sequences include,
but are not limited to those disclosed in Carillo, H., and Lipman,
D., SIAM J Applied Math., 48:1073 (1988); incorporated herein by
reference. Techniques for determining identity are codified in
publicly available computer programs. Exemplary computer software
to determine homology between two sequences include, but are not
limited to, GCG program package, Devereux, J., et al., Nucleic
Acids Research, 12, 387 (1984)), BLASTP, BLASTN, and FASTA
Altschul, S. F. et al., J. Molec. Biol., 215, 403 (1990)).
Multiprotein and Multicomponent Vaccines
[0367] The present disclosure encompasses influenza vaccines
comprising multiple RNA (e.g., mRNA) polynucleotides, each encoding
a single antigenic polypeptide, as well as influenza vaccines
comprising a single RNA polynucleotide encoding more than one
antigenic polypeptide (e.g., as a fusion polypeptide). Thus, a
vaccine composition comprising a RNA (e.g., mRNA) polynucleotide
having an open reading frame encoding a first antigenic polypeptide
and a RNA (e.g., mRNA) polynucleotide having an open reading frame
encoding a second antigenic polypeptide encompasses (a) vaccines
that comprise a first RNA polynucleotide encoding a first antigenic
polypeptide and a second RNA polynucleotide encoding a second
antigenic polypeptide, and (b) vaccines that comprise a single RNA
polynucleotide encoding a first and second antigenic polypeptide
(e.g., as a fusion polypeptide). RNA (e.g., mRNA) vaccines of the
present disclosure, in some embodiments, comprise 2-10 (e.g., 2, 3,
4, 5, 6, 7, 8, 9 or 10), or more, RNA polynucleotides having an
open reading frame, each of which encodes a different antigenic
polypeptide (or a single RNA polynucleotide encoding 2-10, or more,
different antigenic polypeptides). The antigenic polypeptides may
be selected from any of the influenza antigenic polypeptides
described herein.
[0368] In some embodiments, a multicomponent vaccine comprises at
least one RNA (e.g., mRNA) polynucleotide encoding at least one
influenza antigenic polypeptide fused to a signal peptide (e.g.,
SEQ ID NO: 488-490). The signal peptide may be fused at the
N-terminus or the C-terminus of an antigenic polypeptide.
Signal Peptides
[0369] In some embodiments, antigenic polypeptides encoded by
influenza RNA (e.g., mRNA) polynucleotides comprise a signal
peptide. Signal peptides, comprising the N-terminal 15-60 amino
acids of proteins, are typically needed for the translocation
across the membrane on the secretory pathway and, thus, universally
control the entry of most proteins both in eukaryotes and
prokaryotes to the secretory pathway. Signal peptides generally
include three regions: an N-terminal region of differing length,
which usually comprises positively charged amino acids; a
hydrophobic region; and a short carboxy-terminal peptide region. In
eukaryotes, the signal peptide of a nascent precursor protein
(pre-protein) directs the ribosome to the rough endoplasmic
reticulum (ER) membrane and initiates the transport of the growing
peptide chain across it for processing. ER processing produces
mature proteins, wherein the signal peptide is cleaved from
precursor proteins, typically by a ER-resident signal peptidase of
the host cell, or they remain uncleaved and function as a membrane
anchor. A signal peptide may also facilitate the targeting of the
protein to the cell membrane. The signal peptide, however, is not
responsible for the final destination of the mature protein.
Secretory proteins devoid of additional address tags in their
sequence are by default secreted to the external environment.
During recent years, a more advanced view of signal peptides has
evolved, showing that the functions and immunodominance of certain
signal peptides are much more versatile than previously
anticipated.
[0370] Influenza vaccines of the present disclosure may comprise,
for example, RNA (e.g., mRNA) polynucleotides encoding an
artificial signal peptide, wherein the signal peptide coding
sequence is operably linked to and is in frame with the coding
sequence of the antigenic polypeptide. Thus, influenza vaccines of
the present disclosure, in some embodiments, produce an antigenic
polypeptide fused to a signal peptide. In some embodiments, a
signal peptide is fused to the N-terminus of the antigenic
polypeptide. In some embodiments, a signal peptide is fused to the
C-terminus of the antigenic polypeptide.
[0371] In some embodiments, the signal peptide fused to the
antigenic polypeptide is an artificial signal peptide. In some
embodiments, an artificial signal peptide fused to the antigenic
polypeptide encoded by the RNA (e.g., mRNA) vaccine is obtained
from an immunoglobulin protein, e.g., an IgE signal peptide or an
IgG signal peptide. In some embodiments, a signal peptide fused to
the antigenic polypeptide encoded by a RNA (e.g., mRNA) vaccine is
an Ig heavy chain epsilon-1 signal peptide (IgE HC SP) having the
sequence of: MDWTWILFLVAAATRVHS; SEQ ID NO: 481. In some
embodiments, a signal peptide fused to the antigenic polypeptide
encoded by the (e.g., mRNA) RNA (e.g., mRNA) vaccine is an IgGk
chain V-III region HAH signal peptide (IgGk SP) having the sequence
of METPAQLLFLLLLWLPDTTG; SEQ ID NO: 480. In some embodiments, the
signal peptide is selected from: Japanese encephalitis PRM signal
sequence (MLGSNSGQRVVFTILLLLVAPAYS; SEQ ID NO: 482), VSVg protein
signal sequence (MKCLLYLAFLFIGVNCA; SEQ ID NO: 483) and Japanese
encephalitis JEV signal sequence (MWLVSLAIVTACAGA; SEQ ID NO:
484).
[0372] In some embodiments, the antigenic polypeptide encoded by a
RNA (e.g., mRNA) vaccine comprises an amino acid sequence
identified by any one of SEQ ID NO: 1-444, 458, 460, 462-479, or
543-565 (see also Tables 7-13 and 26) fused to a signal peptide
identified by any one of SEQ ID NO: 480-484. The examples disclosed
herein are not meant to be limiting and any signal peptide that is
known in the art to facilitate targeting of a protein to ER for
processing and/or targeting of a protein to the cell membrane may
be used in accordance with the present disclosure.
[0373] A signal peptide may have a length of 15-60 amino acids. For
example, a signal peptide may have a length of 15, 16, 17, 18, 19,
20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36,
37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,
54, 55, 56, 57, 58, 59, or 60 amino acids. In some embodiments, a
signal peptide has a length of 20-60, 25-60, 30-60, 35-60, 40-60,
45-60, 50-60, 55-60, 15-55, 20-55, 25-55, 30-55, 35-55, 40-55,
45-55, 50-55, 15-50, 20-50, 25-50, 30-50, 35-50, 40-50, 45-50,
15-45, 20-45, 25-45, 30-45, 35-45, 40-45, 15-40, 20-40, 25-40,
30-40, 35-40, 15-35, 20-35, 25-35, 30-35, 15-30, 20-30, 25-30,
15-25, 20-25, or 15-20 amino acids.
[0374] A signal peptide is typically cleaved from the nascent
polypeptide at the cleavage junction during ER processing. The
mature antigenic polypeptide produce by an influenza RNA (e.g.,
mRNA) vaccine of the present disclosure typically does not comprise
a signal peptide.
Chemical Modifications
[0375] Influenza vaccines of the present disclosure, in some
embodiments, comprise at least RNA (e.g. mRNA) polynucleotide
having an open reading frame encoding at least one antigenic
polypeptide that comprises at least one chemical modification.
[0376] The terms "chemical modification" and "chemically modified"
refer to modification with respect to adenosine (A), guanosine (G),
uridine (U), thymidine (T) or cytidine (C) ribonucleosides or
deoxyribnucleosides in at least one of their position, pattern,
percent or population. Generally, these terms do not refer to the
ribonucleotide modifications in naturally occurring 5'-terminal
mRNA cap moieties. With respect to a polypeptide, the term
"modification" refers to a modification relative to the canonical
set 20 amino acids. Polypeptides, as provided herein, are also
considered "modified" of they contain amino acid substitutions,
insertions or a combination of substitutions and insertions.
[0377] Polynucleotides (e.g., RNA polynucleotides, such as mRNA
polynucleotides), in some embodiments, comprise various (more than
one) different modifications. In some embodiments, a particular
region of a polynucleotide contains one, two or more (optionally
different) nucleoside or nucleotide modifications. In some
embodiments, a modified RNA polynucleotide (e.g., a modified mRNA
polynucleotide), introduced to a cell or organism, exhibits reduced
degradation in the cell or organism, respectively, relative to an
unmodified polynucleotide. In some embodiments, a modified RNA
polynucleotide (e.g., a modified mRNA polynucleotide), introduced
into a cell or organism, may exhibit reduced immunogenicity in the
cell or organism, respectively (e.g., a reduced innate
response).
[0378] Modifications of polynucleotides include, without
limitation, those described herein. Polynucleotides (e.g., RNA
polynucleotides, such as mRNA polynucleotides) may comprise
modifications that are naturally-occurring, non-naturally-occurring
or the polynucleotide may comprise a combination of
naturally-occurring and non-naturally-occurring modifications.
Polynucleotides may include any useful modification, for example,
of a sugar, a nucleobase, or an internucleoside linkage (e.g., to a
linking phosphate, to a phosphodiester linkage or to the
phosphodiester backbone).
[0379] Polynucleotides (e.g., RNA polynucleotides, such as mRNA
polynucleotides), in some embodiments, comprise non-natural
modified nucleotides that are introduced during synthesis or
post-synthesis of the polynucleotides to achieve desired functions
or properties. The modifications may be present on an
internucleotide linkages, purine or pyrimidine bases, or sugars.
The modification may be introduced with chemical synthesis or with
a polymerase enzyme at the terminal of a chain or anywhere else in
the chain. Any of the regions of a polynucleotide may be chemically
modified.
[0380] The present disclosure provides for modified nucleosides and
nucleotides of a polynucleotide (e.g., RNA polynucleotides, such as
mRNA polynucleotides). A "nucleoside" refers to a compound
containing a sugar molecule (e.g., a pentose or ribose) or a
derivative thereof in combination with an organic base (e.g., a
purine or pyrimidine) or a derivative thereof (also referred to
herein as "nucleobase"). A nucleotide" refers to a nucleoside,
including a phosphate group. Modified nucleotides may by
synthesized by any useful method, such as, for example, chemically,
enzymatically, or recombinantly, to include one or more modified or
non-natural nucleosides. Polynucleotides may comprise a region or
regions of linked nucleosides. Such regions may have variable
backbone linkages. The linkages may be standard phosphodioester
linkages, in which case the polynucleotides would comprise regions
of nucleotides.
[0381] Modified nucleotide base pairing encompasses not only the
standard adenosine-thymine, adenosine-uracil, or guanosine-cytosine
base pairs, but also base pairs formed between nucleotides and/or
modified nucleotides comprising non-standard or modified bases,
wherein the arrangement of hydrogen bond donors and hydrogen bond
acceptors permits hydrogen bonding between a non-standard base and
a standard base or between two complementary non-standard base
structures. One example of such non-standard base pairing is the
base pairing between the modified nucleotide inosine and adenine,
cytosine or uracil. Any combination of base/sugar or linker may be
incorporated into polynucleotides of the present disclosure.
[0382] Modifications of polynucleotides (e.g., RNA polynucleotides,
such as mRNA polynucleotides) that are useful in the vaccines of
the present disclosure include, but are not limited to the
following: 2-methylthio-N6-(cis-hydroxyisopentenyl)adenosine;
2-methylthio-N6-methyl adenosine; 2-methylthio-N6-threonyl
carbamoyladenosine; N6-glycinylcarb amoyladenosine;
N6-isopentenyladenosine; N6-methyl adenosine; N6-threonylcarb
amoyladenosine; 1,2'-O-dimethyl adenosine; 1-methyladenosine;
2'-O-methyladenosine; 2'-O-ribosyladenosine (phosphate); 2-methyl
adenosine; 2-methylthio-N6 isopentenyladenosine;
2-methylthio-N6-hydroxynorvalyl carbamoyladenosine;
2'-O-methyladenosine; 2'-O-ribosyladenosine (phosphate);
Isopentenyladenosine; N6-(cis-hydroxyisopentenyl)adenosine;
N6,2'-O-dimethyladenosine; N6,2'-O-dimethyladenosine;
N6,N6,2'-O-trimethyladenosine; N6,N6-dimethyladenosine;
N6-acetyladenosine; N6-hydroxynorvalylcarbamoyladenosine;
N6-methyl-N6-threonylcarbamoyladenosine; 2-methyladenosine;
2-methylthio-N6-isopentenyladenosine; 7-deaza-adenosine;
N1-methyl-adenosine; N6, N6 (dimethyl)adenine;
N6-cis-hydroxy-isopentenyl-adenosine; .alpha.-thio-adenosine; 2
(amino)adenine; 2 (aminopropyl)adenine; 2 (methylthio) N6 (i
sopentenyl)adenine; 2-(alkyl)adenine; 2-(aminoalkyl)adenine;
2-(aminopropyl)adenine; 2-(halo)adenine; 2-(halo)adenine;
2-(propyl)adenine; 2'-Amino-2'-deoxy-ATP; 2'-Azido-2'-deoxy-ATP;
2'-Deoxy-2'-a-aminoadenosine TP; 2'-Deoxy-2'-a-azidoadenosine TP; 6
(alkyl)adenine; 6 (methyl)adenine; 6-(alkyl)adenine;
6-(methyl)adenine; 7 (deaza)adenine; 8 (alkenyl)adenine; 8
(alkynyl)adenine; 8 (amino)adenine; 8 (thioalkyl)adenine;
8-(alkenyl)adenine; 8-(alkyl)adenine; 8-(alkynyl)adenine;
8-(amino)adenine; 8-(halo)adenine; 8-(hydroxyl)adenine;
8-(thioalkyl)adenine; 8-(thiol)adenine; 8-azido-adenosine; aza
adenine; deaza adenine; N6 (methyl)adenine; N6-(isopentyl)adenine;
7-deaza-8-aza-adenosine; 7-methyladenine; 1-Deazaadenosine TP;
2'Fluoro-N6-Bz-deoxyadenosine TP; 2'-OMe-2-Amino-ATP;
2'O-methyl-N6-Bz-deoxyadenosine TP; 2'-a-Ethynyl adenosine TP;
2-aminoadenine; 2-Aminoadenosine TP; 2-Amino-ATP;
2'-a-Trifluoromethyladenosine TP; 2-Azidoadenosine TP;
2'-b-Ethynyladenosine TP; 2-Bromoadenosine TP;
2'-b-Trifluoromethyladenosine TP; 2-Chloroadenosine TP;
2'-Deoxy-2',2'-difluoroadenosine TP;
2'-Deoxy-2'-a-mercaptoadenosine TP;
2'-Deoxy-2'-a-thiomethoxyadenosine TP; 2'-Deoxy-2'-b-aminoadenosine
TP; 2'-Deoxy-2'-b-azidoadenosine TP; 2'-Deoxy-2'-b-bromoadenosine
TP; 2'-Deoxy-2'-b-chloroadenosine TP; 2'-Deoxy-2'-b-fluoroadenosine
TP; 2'-Deoxy-2'-b-iodoadenosine TP; 2'-Deoxy-2'-b-mercaptoadenosine
TP; 2'-Deoxy-2'-b-thiomethoxyadenosine TP; 2-Fluoroadenosine TP;
2-Iodoadenosine TP; 2-Mercaptoadenosine TP; 2-methoxy-adenine;
2-methylthio-adenine; 2-Trifluoromethyladenosine TP;
3-Deaza-3-bromoadenosine TP; 3-Deaza-3-chloroadenosine TP;
3-Deaza-3-fluoroadenosine TP; 3-Deaza-3-iodoadenosine TP;
3-Deazaadenosine TP; 4'-Azidoadenosine TP; 4'-Carbocyclic adenosine
TP; 4'-Ethynyladenosine TP; 5'-Homo-adenosine TP; 8-Aza-ATP;
8-bromo-adenosine TP; 8-Trifluoromethyladenosine TP;
9-Deazaadenosine TP; 2-aminopurine; 7-deaza-2,6-diaminopurine;
7-deaza-8-aza-2,6-diaminopurine; 7-deaza-8-aza-2-aminopurine;
2,6-diaminopurine; 7-deaza-8-aza-adenine, 7-deaza-2-aminopurine;
2-thiocytidine; 3-methylcytidine; 5-formyl cytidine;
5-hydroxymethylcytidine; 5-methylcytidine; N4-acetylcytidine;
2'-O-methyl cytidine; 2'-O-methylcytidine; 5,2'-O-dimethylcytidine;
5-formyl-2'-O-methylcytidine; Lysidine; N4,2'-O-dimethylcytidine;
N4-acetyl-2'-O-methylcytidine; N4-methylcytidine;
N4,N4-Dimethyl-2'-OMe-Cytidine TP; 4-methylcytidine;
5-aza-cytidine; Pseudo-iso-cytidine; pyrrolo-cytidine;
a-thio-cytidine; 2-(thio)cytosine; 2'-Amino-2'-deoxy-CTP;
2'-Azido-2'-deoxy-CTP; 2'-Deoxy-2'-a-aminocytidine TP;
2'-Deoxy-2'-a-azidocytidine TP; 3 (deaza) 5 (aza)cytosine; 3
(methyl)cytosine; 3-(alkyl)cytosine; 3-(deaza) 5 (aza)cytosine;
3-(methyl)cytidine; 4,2'-O-dimethylcytidine; 5 (halo)cytosine; 5
(methyl)cytosine; 5 (propynyl)cytosine; 5
(trifluoromethyl)cytosine; 5-(alkyl)cytosine; 5-(alkynyl)cytosine;
5-(halo)cytosine; 5-(propynyl)cytosine;
5-(trifluoromethyl)cytosine; 5-bromo-cytidine; 5-iodo-cytidine;
5-propynyl cytosine; 6-(azo)cytosine; 6-aza-cytidine; aza cytosine;
deaza cytosine; N4 (acetyl)cytosine;
1-methyl-1-deaza-pseudoisocytidine; 1-methyl-pseudoisocytidine;
2-methoxy-5-methyl-cytidine; 2-methoxy-cytidine;
2-thio-5-methyl-cytidine; 4-methoxy-1-methyl-pseudoisocytidine;
4-methoxy-pseudoisocytidine;
4-thio-1-methyl-1-deaza-pseudoisocytidine;
4-thio-1-methyl-pseudoisocytidine; 4-thio-pseudoisocytidine;
5-aza-zebularine; 5-methyl-zebularine; pyrrolo-pseudoisocytidine;
Zebularine; (E)-5-(2-Bromo-vinyl)cytidine TP; 2,2'-anhydro-cytidine
TP hydrochloride; 2'Fluor-N4-Bz-cytidine TP;
2'Fluoro-N4-Acetyl-cytidine TP; 2'-O-Methyl-N4-Acetyl-cytidine TP;
2'0-methyl-N4-Bz-cytidine TP; 2'-a-Ethynylcytidine TP;
2'-a-Trifluoromethylcytidine TP; 2'-b-Ethynylcytidine TP;
2'-b-Trifluoromethylcytidine TP; 2'-Deoxy-2',2'-difluorocytidine
TP; 2'-Deoxy-2'-a-mercaptocytidine TP;
2'-Deoxy-2'-a-thiomethoxycytidine TP; 2'-Deoxy-2'-b-aminocytidine
TP; 2'-Deoxy-2'-b-azidocytidine TP; 2'-Deoxy-2'-b-bromocytidine TP;
2'-Deoxy-2'-b-chlorocytidine TP; 2'-Deoxy-2'-b-fluorocytidine TP;
2'-Deoxy-2'-b-iodocytidine TP; 2'-Deoxy-2'-b-mercaptocytidine TP;
2'-Deoxy-2'-b-thiomethoxycytidine TP;
2'-O-Methyl-5-(1-propynyl)cytidine TP; 3'-Ethynylcytidine TP;
4'-Azidocytidine TP; 4'-Carbocyclic cytidine TP; 4'-Ethynylcytidine
TP; 5-(1-Propynyl)ara-cytidine TP;
5-(2-Chloro-phenyl)-2-thiocytidine TP;
5-(4-Amino-phenyl)-2-thiocytidine TP; 5-Aminoallyl-CTP;
5-Cyanocytidine TP; 5-Ethynylara-cytidine TP; 5-Ethynylcytidine TP;
5'-Homo-cytidine TP; 5-Methoxycytidine TP;
5-Trifluoromethyl-Cytidine TP; N4-Amino-cytidine TP;
N4-Benzoyl-cytidine TP; Pseudoisocytidine; 7-methylguanosine;
N2,2'-O-dimethylguanosine; N2-methylguanosine; Wyosine;
1,2'-O-dimethylguanosine; 1-methylguanosine; 2'-O-methylguanosine;
2'-O-ribosylguanosine (phosphate); 2'-O-methylguanosine;
2'-O-ribosylguanosine (phosphate); 7-aminomethyl-7-deazaguanosine;
7-cyano-7-deazaguanosine; Archaeosine; Methylwyosine;
N2,7-dimethylguanosine; N2,N2,2'-O-trimethylguanosine;
N2,N2,7-trimethylguanosine; N2,N2-dimethylguanosine;
N2,7,2'-O-trimethylguanosine; 6-thio-guanosine; 7-deaza-guanosine;
8-oxo-guanosine; N1-methyl-guanosine; .alpha.-thio-guanosine; 2
(propyl)guanine; 2-(alkyl)guanine; 2'-Amino-2'-deoxy-GTP;
2'-Azido-2'-deoxy-GTP; 2'-Deoxy-2'-a-aminoguanosine TP;
2'-Deoxy-2'-a-azidoguanosine TP; 6 (methyl)guanine;
6-(alkyl)guanine; 6-(methyl)guanine; 6-methyl-guanosine; 7
(alkyl)guanine; 7 (deaza)guanine; 7 (methyl)guanine;
7-(alkyl)guanine; 7-(deaza)guanine; 7-(methyl)guanine; 8
(alkyl)guanine; 8 (alkynyl)guanine; 8 (halo)guanine; 8
(thioalkyl)guanine; 8-(alkenyl)guanine; 8-(alkyl)guanine;
8-(alkynyl)guanine; 8-(amino)guanine; 8-(halo)guanine;
8-(hydroxyl)guanine; 8-(thioalkyl)guanine; 8-(thiol)guanine; aza
guanine; deaza guanine; N (methyl)guanine; N-(methyl)guanine;
1-methyl-6-thio-guanosine; 6-methoxy-guanosine;
6-thio-7-deaza-8-aza-guanosine; 6-thio-7-deaza-guanosine;
6-thio-7-methyl-guanosine; 7-deaza-8-aza-guanosine;
7-methyl-8-oxo-guanosine; N2,N2-dimethyl-6-thio-guanosine;
N2-methyl-6-thio-guanosine; 1-Me-GTP;
2'Fluoro-N2-isobutyl-guanosine TP; 2'0-methyl-N2-isobutyl-guanosine
TP; 2'-a-Ethynylguanosine TP; 2'-a-Trifluoromethylguanosine TP;
2'-b-Ethynylguanosine TP; 2'-b-Trifluoromethylguanosine TP;
2'-Deoxy-2',2'-difluoroguanosine TP;
2'-Deoxy-2'-a-mercaptoguanosine TP;
2'-Deoxy-2'-a-thiomethoxyguanosine TP; 2'-Deoxy-2'-b-aminoguanosine
TP; 2'-Deoxy-2'-b-azidoguanosine TP; 2'-Deoxy-2'-b-bromoguanosine
TP; 2'-Deoxy-2'-b-chloroguanosine TP; 2'-Deoxy-2'-b-fluoroguanosine
TP; 2'-Deoxy-2'-b-iodoguanosine TP; 2'-Deoxy-2'-b-mercaptoguanosine
TP; 2'-Deoxy-2'-b-thiomethoxyguanosine TP; 4'-Azidoguanosine TP;
4'-Carbocyclic guanosine TP; 4'-Ethynylguanosine TP;
5'-Homo-guanosine TP; 8-bromo-guanosine TP; 9-Deazaguanosine TP;
N2-isobutyl-guanosine TP; 1-methylinosine; Inosine;
1,2'-O-dimethylinosine; 2'-O-methylinosine; 7-methylinosine;
2'-O-methylinosine; Epoxyqueuosine; galactosyl-queuosine;
Mannosylqueuosine; Queuosine; allyamino-thymidine; aza thymidine;
deaza thymidine; deoxy-thymidine; 2'-O-methyluridine;
2-thiouridine; 3-methyluridine; 5-carboxymethyluridine;
5-hydroxyuridine; 5-methyluridine; 5-taurinomethyl-2-thiouridine;
5-taurinomethyluridine; Dihydrouridine; Pseudouridine;
(3-(3-amino-3-carboxypropyl)uridine;
1-methyl-3-(3-amino-5-carboxypropyl)pseudouridine;
1-methylpseduouridine; 1-methyl-pseudouridine; 2'-O-methyluridine;
2'-O-methylpseudouridine; 2'-O-methyluridine;
2-thio-2'-O-methyluridine; 3-(3-amino-3-carboxypropyl)uridine;
3,2'-O-dimethyluri dine; 3-Methyl-pseudo-Uridine TP; 4-thiouridine;
5-(carboxyhydroxymethyl)uridine; 5-(carboxyhydroxymethyl)uridine
methyl ester; 5,2'-O-dimethyluridine; 5,6-dihydro-uridine;
5-aminomethyl-2-thiouridine; 5-carbamoylmethyl-2'-O-methyluridine;
5-carbamoylmethyluridine; 5-carboxyhydroxymethyluridine;
5-carboxyhydroxymethyluridine methyl ester;
5-carboxymethylaminomethyl-2'-O-methyluridine;
5-carboxymethylaminomethyl-2-thiouridine;
5-carboxymethylaminomethyl-2-thiouridine;
5-carboxymethylaminomethyluridine;
5-carboxymethylaminomethyluridine; 5-Carbamoylmethyluridine TP;
5-methoxycarbonylmethyl-2'-O-methyluridine;
5-methoxycarbonylmethyl-2-thiouridine;
5-methoxycarbonylmethyluridine; 5-methoxyuridine;
5-methyl-2-thiouridine; 5-methylaminomethyl-2-selenouridine;
5-methylaminomethyl-2-thiouridine; 5-methylaminomethyluridine;
5-Methyldihydrouridine; 5-Oxyacetic acid-Uridine TP; 5-Oxyacetic
acid-methyl ester-Uridine TP; N1-methyl-pseudo-uridine; uridine
5-oxyacetic acid; uridine 5-oxyacetic acid methyl ester;
3-(3-Amino-3-carboxypropyl)-Uridine TP;
5-(iso-Pentenylaminomethyl)-2-thiouridine TP;
5-(iso-Pentenylaminomethyl)-2'-O-methyluridine TP;
5-(iso-Pentenylaminomethyl)uridine TP; 5-propynyl uracil;
.alpha.-thio-uridine; 1
(aminoalkylamino-carbonylethylenyl)-2(thio)-pseudouracil; 1
(aminoalkylaminocarbonylethylenyl)-2,4-(dithio)pseudouracil; 1
(aminoalkylaminocarbonylethylenyl)-4 (thio)pseudouracil; 1
(aminoalkylaminocarbonylethylenyl)-pseudouracil; 1
(aminocarbonylethylenyl)-2(thio)-pseudouracil; 1
(aminocarbonylethylenyl)-2,4-(dithio)pseudouracil; 1
(aminocarbonylethylenyl)-4 (thio)pseudouracil; 1
(aminocarbonylethylenyl)-p seudouracil; 1 substituted
2(thio)-pseudouracil; 1 substituted 2,4-(dithio)pseudouracil; 1
substituted 4 (thio)pseudouracil; 1 substituted pseudouracil;
1-(aminoalkylamino-carbonylethylenyl)-2-(thio)-pseudouracil;
1-Methyl-3-(3-amino-3-carboxypropyl) pseudouridine TP;
1-Methyl-3-(3-amino-3-carboxypropyl)pseudo-UTP;
1-Methyl-pseudo-UTP; 2 (thio)pseudouracil; 2' deoxy uridine; 2'
fluorouridine; 2-(thio)uracil; 2,4-(dithio)psuedouracil; 2' methyl,
2' amino, 2'azido, 2'fluro-guanosine; 2'-Amino-2'-deoxy-UTP;
2'-Azido-2'-deoxy-UTP; 2'-Azido-deoxyuridine TP;
2'-O-methylpseudouridine; 2' deoxy uridine; 2' fluorouridine;
2'-Deoxy-2'-a-aminouridine TP; 2'-Deoxy-2'-a-azidouridine TP;
2-methylpseudouridine; 3 (3 amino-3 carboxypropyl)uracil; 4
(thio)pseudouracil; 4-(thio)pseudouracil; 4-(thio)uracil;
4-thiouracil; 5 (1,3-diazole-1-alkyl)uracil; 5
(2-aminopropyl)uracil; 5 (aminoalkyl)uracil; 5
(dimethylaminoalkyl)uracil; 5 (guanidiniumalkyl)uracil; 5
(methoxycarbonylmethyl)-2-(thio)uracil; 5
(methoxycarbonyl-methyl)uracil; 5 (methyl) 2 (thio)uracil; 5
(methyl) 2,4 (dithio)uracil; 5 (methyl) 4 (thio)uracil; 5
(methylaminomethyl)-2 (thio)uracil; 5 (methylaminomethyl)-2,4
(dithio)uracil; 5 (methylaminomethyl)-4 (thio)uracil; 5
(propynyl)uracil; 5 (trifluoromethyl)uracil;
5-(2-aminopropyl)uracil; 5-(alkyl)-2-(thio)pseudouracil;
5-(alkyl)-2,4 (dithio)pseudouracil; 5-(alkyl)-4 (thio)pseudouracil;
5-(alkyl)pseudouracil; 5-(alkyl)uracil; 5-(alkynyl)uracil;
5-(allylamino)uracil; 5-(cyanoalkyl)uracil;
5-(dialkylaminoalkyl)uracil; 5-(dimethylaminoalkyl)uracil;
5-(guanidiniumalkyl)uracil; 5-(halo)uracil;
5-(1,3-diazole-1-alkyl)uracil; 5-(methoxy)uracil;
5-(methoxycarbonylmethyl)-2-(thio)uracil;
5-(methoxycarbonyl-methyl)uracil; 5-(methyl) 2(thio)uracil;
5-(methyl) 2,4 (dithio)uracil; 5-(methyl) 4 (thio)uracil;
5-(methyl)-2-(thio)pseudouracil; 5-(methyl)-2,4
(dithio)pseudouracil; 5-(methyl)-4 (thio)pseudouracil;
5-(methyl)pseudouracil; 5-(methylaminomethyl)-2 (thio)uracil;
5-(methylaminomethyl)-2,4(dithio)uracil;
5-(methylaminomethyl)-4-(thio)uracil; 5-(propynyl)uracil;
5-(trifluoromethyl)uracil; 5-aminoallyl-uridine; 5-bromo-uridine;
5-iodo-uridine; 5-uracil; 6 (azo)uracil; 6-(azo)uracil;
6-aza-uridine; allyamino-uracil; aza uracil; deaza uracil; N3
(methyl)uracil; Pseudo-UTP-1-2-ethanoic acid; Pseudouracil;
4-Thio-pseudo-UTP; 1-carboxymethyl-pseudouridine;
1-methyl-1-deaza-pseudouridine; 1-propynyl -uridine;
1-taurinomethyl-1-methyl -uridine; 1-taurinomethyl -4-thio-uridine;
1-taurinomethyl-pseudouridine; 2-methoxy-4-thio-pseudouridine;
2-thio-1-methyl-1-deaza-pseudouridine;
2-thio-1-methyl-pseudouridine; 2-thio-5-aza-uridine;
2-thio-dihydropseudouridine; 2-thio-dihydrouridine;
2-thio-pseudouridine; 4-methoxy-2-thio-pseudouridine;
4-methoxy-pseudouridine; 4-thio-1-methyl-pseudouridine;
4-thio-pseudouridine; 5-aza-uridine; Dihydropseudouridine;
(.+-.)1-(2-Hydroxypropyl)pseudouridine TP;
(2R)-1-(2-Hydroxypropyl)pseudouridine TP;
(2S)-1-(2-Hydroxypropyl)pseudouridine TP;
(E)-5-(2-Bromo-vinyl)ara-uridine TP; (E)-5-(2-Bromo-vinyl)uridine
TP; (Z)-5-(2-Bromo-vinyl)ara-uridine TP;
(Z)-5-(2-Bromo-vinyl)uridine TP;
1-(2,2,2-Trifluoroethyl)-pseudo-UTP;
1-(2,2,3,3,3-Pentafluoropropyl)pseudouridine TP;
1-(2,2-Diethoxyethyl)pseudouridine TP;
1-(2,4,6-Trimethylbenzyl)pseudouridine TP;
1-(2,4,6-Trimethyl-benzyl)pseudo-UTP;
1-(2,4,6-Trimethyl-phenyl)pseudo-UTP;
1-(2-Amino-2-carboxyethyl)pseudo-UTP; 1-(2-Amino-ethyl)pseudo-UTP;
1-(2-Hydroxyethyl)pseudouridine TP; 1-(2-Methoxyethyl)pseudouridine
TP; 1-(3 ,4-Bis-trifluoromethoxybenzyl)pseudouridine TP;
1-(3,4-Dimethoxybenzyl)pseudouridine TP;
1-(3-Amino-3-carboxypropyl)pseudo-UTP;
1-(3-Amino-propyl)pseudo-UTP;
1-(3-Cyclopropyl-prop-2-ynyl)pseudouridine TP;
1-(4-Amino-4-carboxybutyl)pseudo-UTP; 1-(4-Amino-benzyl)pseudo-UTP;
1-(4-Amino-butyl)pseudo-UTP; 1-(4-Amino-phenyl)pseudo-UTP;
1-(4-Azidobenzyl)pseudouridine TP; 1-(4-Bromobenzyl)pseudouridine
TP; 1-(4-Chlorobenzyl)pseudouridine TP;
1-(4-Fluorobenzyl)pseudouridine TP; 1-(4-Iodobenzyl)pseudouridine
TP; 1-(4-Methanesulfonylbenzyl)pseudouridine TP;
1-(4-Methoxybenzyl)pseudouridine TP;
1-(4-Methoxy-benzyl)pseudo-UTP; 1-(4-Methoxy-phenyl)pseudo-UTP;
1-(4-Methylbenzyl)pseudouridine TP; 1-(4-Methyl-benzyl)pseudo-UTP;
1-(4-Nitrobenzyl)pseudouridine TP; 1-(4-Nitro-benzyl)pseudo-UTP;
1(4-Nitro-phenyl)pseudo-UTP; 1-(4-Thiomethoxybenzyl)pseudouridine
TP; 1-(4-Trifluoromethoxybenzyl)pseudouridine TP;
1-(4-Trifluoromethylbenzyl)pseudouridine TP;
1-(5-Amino-pentyl)pseudo-UTP; 1-(6-Amino-hexyl)pseudo-UTP;
1,6-Dimethyl-pseudo-UTP;
1-[3-(2-{2-[2-(2-Aminoethoxy)-ethoxy]-ethoxy}-ethoxy)-propionyl]pseudouri-
dine TP; 1-{3-[2-(2-Aminoethoxy)-ethoxy]-propionyl}pseudouridine
TP; 1-Acetylpseudouridine TP; 1-Alkyl-6-(1-propynyl)-pseudo-UTP;
1-Alkyl-6-(2-propynyl)-pseudo-UTP; 1-Alkyl-6-allyl-pseudo-UTP;
1-Alkyl-6-ethynyl-pseudo-UTP; 1-Alkyl-6-homoallyl-pseudo-UTP;
1-Alkyl-6-vinyl-pseudo-UTP; 1-Allylpseudouridine TP;
1-Aminomethyl-pseudo-UTP; 1-Benzoylpseudouridine TP;
1-Benzyloxymethylpseudouridine TP; 1-B enzyl-pseudo-UTP;
1-Biotinyl-PEG2-pseudouridine TP; 1-Biotinylpseudouridine TP;
1-Butyl-pseudo-UTP; 1-Cyanomethylpseudouridine TP;
1-Cyclobutylmethyl-pseudo-UTP; 1-Cyclobutyl-pseudo-UTP;
1-Cycloheptylmethyl-pseudo-UTP; 1-Cycloheptyl-pseudo-UTP;
1-Cyclohexylmethyl-pseudo-UTP; 1-Cyclohexyl-pseudo-UTP;
1-Cyclooctylmethyl-pseudo-UTP; 1-Cyclooctyl-pseudo-UTP;
1-Cyclopentylmethyl-pseudo-UTP; 1-Cyclopentyl-pseudo-UTP;
1-Cyclopropylmethyl-pseudo-UTP; 1-Cyclopropyl-pseudo-UTP;
1-Ethyl-pseudo-UTP; 1-Hexyl-pseudo-UTP; 1-Homoallylpseudouridine
TP; 1-Hydroxymethylpseudouridine TP; 1-iso-propyl-pseudo-UTP;
1-Me-2-thio-pseudo-UTP; 1-Me-4-thio-pseudo-UTP;
1-Me-alpha-thio-pseudo-UTP; 1-Methanesulfonylmethylpseudouridine
TP; 1-Methoxymethylpseudouridine TP;
1-Methyl-6-(2,2,2-Trifluoroethyl)pseudo-UTP;
1-Methyl-6-(4-morpholino)-pseudo-UTP;
1-Methyl-6-(4-thiomorpholino)-pseudo-UTP; 1-Methyl-6-(substituted
phenyl)pseudo-UTP; 1-Methyl-6-amino-pseudo-UTP;
1-Methyl-6-azido-pseudo-UTP; 1-Methyl-6-bromo-pseudo-UTP;
1-Methyl-6-butyl-pseudo-UTP; 1-Methyl-6-chloro-pseudo-UTP;
1-Methyl-6-cyano-pseudo-UTP; 1-Methyl-6-dimethylamino-pseudo-UTP;
1-Methyl-6-ethoxy-pseudo-UTP;
1-Methyl-6-ethylcarboxylate-pseudo-UTP;
1-Methyl-6-ethyl-pseudo-UTP; 1-Methyl-6-fluoro-pseudo-UTP;
1-Methyl-6-formyl-pseudo-UTP; 1-Methyl-6-hydroxyamino-pseudo-UTP;
1-Methyl-6-hydroxy-pseudo-UTP; 1-Methyl-6-iodo-pseudo-UTP;
1-Methyl-6-iso-propyl-pseudo-UTP; 1-Methyl-6-methoxy-pseudo-UTP;
1-Methyl-6-methylamino-pseudo-UTP; 1-Methyl-6-phenyl-pseudo-UTP;
1-Methyl-6-propyl-pseudo-UTP; 1-Methyl-6-tert-butyl-pseudo-UTP;
1-Methyl-6-trifluoromethoxy-pseudo-UTP;
1-Methyl-6-trifluoromethyl-pseudo-UTP;
1-Morpholinomethylpseudouridine TP; 1-Pentyl-pseudo-UTP;
1-Phenyl-pseudo-UTP; 1-Pivaloylpseudouridine TP;
1-Propargylpseudouridine TP; 1-Propyl-pseudo-UTP;
1-propynyl-pseudouridine; 1-p-tolyl-pseudo-UTP;
1-tert-Butyl-pseudo-UTP; 1-Thiomethoxymethylpseudouridine TP;
1-Thiomorpholinomethylpseudouridine TP;
1-Trifluoroacetylpseudouridine TP; 1-Trifluoromethyl-pseudo-UTP;
1-Vinylpseudouridine TP; 2,2'-anhydro-uridine TP;
2'-bromo-deoxyuridine TP; 2'-F-5-Methyl-2'-deoxy-UTP;
2'-OMe-5-Me-UTP; 2'-OMe-pseudo-UTP; 2'-a-Ethynyluridine TP;
2'-a-Trifluoromethyluridine TP; 2'-b-Ethynyluridine TP;
2'-b-Trifluoromethyluridine TP; 2'-Deoxy-2',2'-difluorouridine TP;
2'-Deoxy-2'-a-mercaptouridine TP; 2'-Deoxy-2'-a-thiomethoxyuridine
TP; 2'-Deoxy-2'-b-aminouridine TP; 2'-Deoxy-2'-b-azidouridine TP;
2'-Deoxy-2'-b-bromouridine TP; 2'-Deoxy-2'-b-chlorouridine TP;
2'-Deoxy-2'-b-fluorouridine TP; 2'-Deoxy-2'-b-iodouridine TP;
2'-Deoxy-2'-b-mercaptouridine TP; 2'-Deoxy-2'-b-thiomethoxyuridine
TP; 2-methoxy-4-thio-uridine; 2-methoxyuridine;
2'-O-Methyl-5-(1-propynyl)uridine TP; 3-Alkyl-pseudo-UTP;
4'-Azidouridine TP; 4'-Carbocyclic uridine TP; 4'-Ethynyluridine
TP; 5-(1-Propynyl)ara-uridine TP; 5-(2-Furanyl)uridine TP;
5-Cyanouridine TP; 5-Dimethylaminouridine TP; 5'-Homo-uridine TP;
5-iodo-2'-fluoro-deoxyuridine TP; 5-Phenylethynyluridine TP;
5-Trideuteromethyl-6-deuterouridine TP; 5-Trifluoromethyl-Uridine
TP; 5-Vinylarauridine TP; 6-(2,2,2-Trifluoroethyl)-pseudo-UTP;
6-(4-Morpholino)-pseudo-UTP; 6-(4-Thiomorpholino)-pseudo-UTP;
6-(Substituted-Phenyl)-pseudo-UTP; 6-Amino-pseudo-UTP;
6-Azido-pseudo-UTP; 6-Bromo-pseudo-UTP; 6-Butyl-pseudo-UTP;
6-Chloro-pseudo-UTP; 6-Cyano-pseudo-UTP;
6-Dimethylamino-pseudo-UTP; 6-Ethoxy-pseudo-UTP;
6-Ethylcarboxylate-pseudo-UTP; 6-Ethyl-pseudo-UTP;
6-Fluoro-pseudo-UTP; 6-Formyl-pseudo-UTP;
6-Hydroxyamino-pseudo-UTP; 6-Hydroxy-pseudo-UTP; 6-Iodo-pseudo-UTP;
6-iso-Propyl-pseudo-UTP; 6-Methoxy-pseudo-UTP;
6-Methylamino-pseudo-UTP; 6-Methyl-pseudo-UTP; 6-Phenyl-pseudo-UTP;
6-Phenyl-pseudo-UTP; 6-Propyl-pseudo-UTP; 6-tert-Butyl-pseudo-UTP;
6-Trifluoromethoxy-pseudo-UTP; 6-Trifluoromethyl-pseudo-UTP;
Alpha-thio-pseudo-UTP; Pseudouridine 1-(4-methylbenzenesulfonic
acid) TP; Pseudouridine 1-(4-methylbenzoic acid) TP; Pseudouridine
TP 1-[3-(2-ethoxy)]propionic acid; Pseudouridine TP
1-[3-{2-(2-[2-(2-ethoxy)-ethoxy]-ethoxy)-ethoxy}]propionic acid;
Pseudouridine TP
1-[3-{2-(2-[2-{2(2-ethoxy)-ethoxy}-ethoxy]-ethoxy)-ethoxy}]propionic
acid; Pseudouridine TP
1-[3-{2-(2-[2-ethoxy]-ethoxy)-ethoxy}]propionic acid; Pseudouridine
TP 1-[3-{2-(2-ethoxy)-ethoxy}] propionic acid; Pseudouridine TP
1-methylphosphonic acid; Pseudouridine TP 1-methylphosphonic acid
diethyl ester; Pseudo-UTP-N1-3-propionic acid;
Pseudo-UTP-N1-4-butanoic acid; Pseudo-UTP-N1-5-pentanoic acid;
Pseudo-UTP-N1-6-hexanoic acid; Pseudo-UTP-N1-7-heptanoic acid;
Pseudo-UTP-N1-methyl-p-benzoic acid; Pseudo-UTP-N1-p-benzoic acid;
Wybutosine; Hydroxywybutosine; Isowyosine; Peroxywybutosine;
undermodified hydroxywybutosine; 4-demethylwyosine;
2,6-(diamino)purine; 1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl:
1,3-(diaza)-2-(oxo)-phenthiazin-1-yl;
1,3-(diaza)-2-(oxo)-phenoxazin-1-yl;
1,3,5-(triaza)-2,6-(dioxa)-naphthalene; 2(amino)purine;
2,4,5-(trimethyl)phenyl; 2' methyl, 2'amino, 2'azido,
2'fluro-cytidine; 2' methyl, 2'amino, 2'azido, 2'fluro-adenine;
2'methyl, 2'amino, 2'azido, 2'fluro-uridine;
2'-amino-2'-deoxyribose; 2-amino-6-Chloro-purine; 2-aza-inosinyl;
2'-azido-2'-deoxyribose; 2'fluoro-2'-deoxyribose;
2'-fluoro-modified bases; 2'-O-methyl-ribose;
2-oxo-7-aminopyridopyrimidin-3-yl; 2-oxo-pyridopyrimidine-3-yl;
2-pyridinone; 3 nitropyrrole;
3-(methyl)-7-(propynyl)isocarbostyrilyl;
3-(methyl)isocarbostyrilyl; 4-(fluoro)-6-(methyl)benzimidazole;
4-(methyl)benzimidazole; 4-(methyl)indolyl; 4,6-(dimethyl)indolyl;
5 nitroindole; 5 substituted pyrimidines;
5-(methyl)isocarbostyrilyl; 5-nitroindole; 6-(aza)pyrimidine;
6-(azo)thymine; 6-(methyl)-7-(aza)indolyl; 6-chloro-purine;
6-phenyl-pyrrolo-pyrimidin-2-on-3-yl;
7-(aminoalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenthiazin-1-yl;
7-(aminoalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl;
7-(aminoalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenoxazin-1-yl;
7-(aminoalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenthiazin-1-yl;
7-(aminoalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenoxazin-1-yl;
7-(aza)indolyl;
7-(guanidiniumalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenoxazinl-yl;
7-(guanidiniumalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenthiazin-1-yl;
7-(guanidiniumalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl;
7-(guanidiniumalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenoxazin-1-yl;
7-(guanidiniumalkyl-hydroxy)-1,3-(diaza)-2-(oxo)-phenthiazin-1-yl;
7-(guanidiniumalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenoxazin-1-yl;
7-(propynyl)isocarbostyrilyl; 7-(propynyl)isocarbostyrilyl,
propynyl-7-(aza)indolyl; 7-deaza-inosinyl; 7-substituted
1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl; 7-substituted
1,3-(diaza)-2-(oxo)-phenoxazin-1-yl; 9-(methyl)-imidizopyridinyl;
Aminoindolyl; Anthracenyl;
bis-ortho-(aminoalkylhydroxy)-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl;
bis-ortho-substituted-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl;
Difluorotolyl; Hypoxanthine; Imidizopyridinyl; Inosinyl;
Isocarbostyrilyl; Isoguanisine; N2-substituted purines;
N6-methyl-2-amino-purine; N6-substituted purines; N-alkylated
derivative; Napthalenyl; Nitrobenzimidazolyl; Nitroimidazolyl;
Nitroindazolyl; Nitropyrazolyl; Nubularine; O6-substituted purines;
O-alkylated derivative;
ortho-(aminoalkylhydroxy)-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl;
ortho-substituted-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; Oxoformycin
TP; para-(aminoalkylhydroxy)-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl;
para-substituted-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; Pentacenyl;
Phenanthracenyl; Phenyl; propynyl-7-(aza)indolyl; Pyrenyl;
pyridopyrimidin-3-yl; pyridopyrimidin-3-yl,
2-oxo-7-amino-pyridopyrimidin-3-yl; pyrrolo-pyrimidin-2-on-3-yl;
Pyrrolopyrimidinyl; Pyrrolopyrizinyl; Stilbenzyl; substituted
1,2,4-triazoles; Tetracenyl; Tubercidine; Xanthine;
Xanthosine-5'-TP; 2-thio-zebularine; 5-aza-2-thio-zebularine;
7-deaza-2-amino-purine; pyridin-4-one ribonucleoside;
2-Amino-riboside-TP; Formycin A TP; Formycin B TP; Pyrrolosine TP;
2'-OH-ara-adenosine TP; 2'-OH-ara-cytidine TP; 2'-OH-ara-uridine
TP; 2'-OH-ara-guanosine TP; 5-(2-carbomethoxyvinyl)uridine TP; and
N6-(19-Amino-pentaoxanonadecyl)adenosine TP.
[0383] In some embodiments, polynucleotides (e.g., RNA
polynucleotides, such as mRNA polynucleotides) include a
combination of at least two (e.g., 2, 3, 4 or more) of the
aforementioned modified nucleobases.
[0384] In some embodiments, modified nucleobases in polynucleotides
(e.g., RNA polynucleotides, such as mRNA polynucleotides) are
selected from the group consisting of pseudouridine (.psi.),
N1-methylpseudouridine (m.sup.1.psi.), 2-thiouridine,
N1-ethylpseudouridine, 4'-thiouridine, 5-methylcytosine,
2-thio-1-methyl-1-deaza-pseudouridine,
2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine ,
2-thio-dihydropseudouridine, 2-thio-dihydrouridine,
2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine,
4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine,
4-thio-pseudouridine, 5-aza-uridine, dihydropseudouridine,
5-methoxyuridine and 2'-O-methyl uridine. In some embodiments,
polynucleotides (e.g., RNA polynucleotides, such as mRNA
polynucleotides) include a combination of at least two (e.g., 2, 3,
4 or more) of the aforementioned modified nucleobases.
[0385] In some embodiments, modified nucleobases in polynucleotides
(e.g., RNA polynucleotides, such as mRNA polynucleotides) are
selected from the group consisting of 1-methyl-pseudouridine
(m.sup.1.psi.), 5-methoxy-uridine (mo.sup.5U), 5-methyl-cytidine
(m.sup.5C), pseudouridine (.psi.), .alpha.-thio-guanosine and
.alpha.-thio-adenosine. In some embodiments, polynucleotides
includes a combination of at least two (e.g., 2, 3, 4 or more) of
the aforementioned modified nucleobases.
[0386] In some embodiments, polynucleotides (e.g., RNA
polynucleotides, such as mRNA polynucleotides) comprise
pseudouridine (.psi.) and 5-methyl-cytidine (m.sup.5C). In some
embodiments, polynucleotides (e.g., RNA polynucleotides, such as
mRNA polynucleotides) comprise 1-methyl-pseudouridine
(m.sup.1.psi.). In some embodiments, polynucleotides (e.g., RNA
polynucleotides, such as mRNA polynucleotides) comprise
1-methyl-pseudouridine (m.sup.1.psi.) and 5-methyl-cytidine
(m.sup.5C). In some embodiments, polynucleotides (e.g., RNA
polynucleotides, such as mRNA polynucleotides) comprise
2-thiouridine (s.sup.2U). In some embodiments, polynucleotides
(e.g., RNA polynucleotides, such as mRNA polynucleotides) comprise
2-thiouridine and 5-methyl-cytidine (m.sup.5C). In some
embodiments, polynucleotides (e.g., RNA polynucleotides, such as
mRNA polynucleotides) comprise methoxy-uridine (mo.sup.5U). In some
embodiments, polynucleotides (e.g., RNA polynucleotides, such as
mRNA polynucleotides) comprise 5-methoxy-uridine (mo.sup.5U) and
5-methyl-cytidine (m.sup.5C). In some embodiments, polynucleotides
(e.g., RNA polynucleotides, such as mRNA polynucleotides) comprise
2'-O-methyl uridine. In some embodiments polynucleotides (e.g., RNA
polynucleotides, such as mRNA polynucleotides) comprise 2'-O-methyl
uridine and 5-methyl-cytidine (m.sup.5C). In some embodiments,
polynucleotides (e.g., RNA polynucleotides, such as mRNA
polynucleotides) comprise N6-methyl-adenosine (m.sup.6A). In some
embodiments, polynucleotides (e.g., RNA polynucleotides, such as
mRNA polynucleotides) comprise N6-methyl-adenosine (m.sup.6A) and
5-methyl-cytidine (m.sup.5C).
[0387] In some embodiments, polynucleotides (e.g., RNA
polynucleotides, such as mRNA polynucleotides) are uniformly
modified (e.g., fully modified, modified throughout the entire
sequence) for a particular modification. For example, a
polynucleotide can be uniformly modified with 5-methyl-cytidine
(m.sup.5C), meaning that all cytosine residues in the mRNA sequence
are replaced with 5-methyl-cytidine (m.sup.5C). Similarly, a
polynucleotide can be uniformly modified for any type of nucleoside
residue present in the sequence by replacement with a modified
residue such as those set forth above.
[0388] Exemplary nucleobases and nucleosides having a modified
cytosine include N4-acetyl-cytidine (ac4C), 5-methyl-cytidine
(m5C), 5-halo-cytidine (e.g., 5-iodo-cytidine),
5-hydroxymethyl-cytidine (hm5C), 1-methyl-pseudoisocytidine,
2-thio-cytidine (s2C), and 2-thio-5-methyl-cytidine.
[0389] In some embodiments, a modified nucleobase is a modified
uridine. Exemplary nucleobases and In some embodiments, a modified
nucleobase is a modified cytosine. nucleosides having a modified
uridine include 5-cyano uridine, and 4'-thio uridine.
[0390] In some embodiments, a modified nucleobase is a modified
adenine. Exemplary nucleobases and nucleosides having a modified
adenine include 7-deaza-adenine, 1-methyl-adenosine (m1A),
2-methyl-adenine (m2A), and N6-methyl-adenosine (m6A).
[0391] In some embodiments, a modified nucleobase is a modified
guanine. Exemplary nucleobases and nucleosides having a modified
guanine include inosine (I), 1-methyl-inosine (m1I), wyosine (imG),
methylwyosine (mimG), 7-deaza-guanosine, 7-cyano-7-deaza-guanosine
(preQO), 7-aminomethyl-7-deaza-guanosine (preQ1),
7-methyl-guanosine (m7G), 1-methyl-guanosine (m1G),
8-oxo-guanosine, 7-methyl-8-oxo-guanosine.
[0392] The polynucleotides of the present disclosure may be
partially or fully modified along the entire length of the
molecule. For example, one or more or all or a given type of
nucleotide (e.g., purine or pyrimidine, or any one or more or all
of A, G, U, C) may be uniformly modified in a polynucleotide of the
invention, or in a given predetermined sequence region thereof
(e.g., in the mRNA including or excluding the polyA tail). In some
embodiments, all nucleotides X in a polynucleotide of the present
disclosure (or in a given sequence region thereof) are modified
nucleotides, wherein X may any one of nucleotides A, G, U, C, or
any one of the combinations A+G, A+U, A+C, G+U, G+C, U+C, A+G+U,
A+G+C, G+U+C or A+G+C.
[0393] The polynucleotide may contain from about 1% to about 100%
modified nucleotides (either in relation to overall nucleotide
content, or in relation to one or more types of nucleotide, i.e.,
any one or more of A, G, U or C) or any intervening percentage
(e.g., from 1% to 20%, from 1% to 25%, from 1% to 50%, from 1% to
60%, from 1% to 70%, from 1% to 80%, from 1% to 90%, from 1% to
95%, from 10% to 20%, from 10% to 25%, from 10% to 50%, from 10% to
60%, from 10% to 70%, from 10% to 80%, from 10% to 90%, from 10% to
95%, from 10% to 100%, from 20% to 25%, from 20% to 50%, from 20%
to 60%, from 20% to 70%, from 20% to 80%, from 20% to 90%, from 20%
to 95%, from 20% to 100%, from 50% to 60%, from 50% to 70%, from
50% to 80%, from 50% to 90%, from 50% to 95%, from 50% to 100%,
from 70% to 80%, from 70% to 90%, from 70% to 95%, from 70% to
100%, from 80% to 90%, from 80% to 95%, from 80% to 100%, from 90%
to 95%, from 90% to 100%, and from 95% to 100%). Any remaining
percentage is accounted for by the presence of unmodified A, G, U,
or C.
[0394] The polynucleotides may contain at a minimum 1% and at
maximum 100% modified nucleotides, or any intervening percentage,
such as at least 5% modified nucleotides, at least 10% modified
nucleotides, at least 25% modified nucleotides, at least 50%
modified nucleotides, at least 80% modified nucleotides, or at
least 90% modified nucleotides. For example, the polynucleotides
may contain a modified pyrimidine such as a modified uracil or
cytosine. In some embodiments, at least 5%, at least 10%, at least
25%, at least 50%, at least 80%, at least 90% or 100% of the uracil
in the polynucleotide is replaced with a modified uracil (e.g., a
5-substituted uracil). The modified uracil can be replaced by a
compound having a single unique structure, or can be replaced by a
plurality of compounds having different structures (e.g., 2, 3, 4
or more unique structures). n some embodiments, at least 5%, at
least 10%, at least 25%, at least 50%, at least 80%, at least 90%
or 100% of the cytosine in the polynucleotide is replaced with a
modified cytosine (e.g., a 5-substituted cytosine). The modified
cytosine can be replaced by a compound having a single unique
structure, or can be replaced by a plurality of compounds having
different structures (e.g., 2, 3, 4 or more unique structures).
[0395] Thus, in some embodiments, the RNA (e.g., mRNA) vaccines
comprise a 5'UTR element, an optionally codon optimized open
reading frame, and a 3'UTR element, a poly(A) sequence and/or a
polyadenylation signal wherein the RNA is not chemically
modified.
[0396] In some embodiments, the modified nucleobase is a modified
uracil. Exemplary nucleobases and nucleosides having a modified
uracil include pseudouridine (.psi.), pyridin-4-one ribonucleoside,
5-aza-uridine, 6-aza-uridine, 2-thio-5-aza-uridine, 2-thio-uridine
(s.sup.2U), 4-thio-uridine (s.sup.4U), 4-thio-pseudouridine,
2-thio-pseudouridine, 5-hydroxy-uridine (ho.sup.5U),
5-aminoallyl-uridine, 5-halo-uridine (e.g., 5-iodo-uridineor
5-bromo-uridine), 3-methyl-uridine (m.sup.3U), 5-methoxy-uridine
(mo.sup.5U), uridine 5-oxyacetic acid (cmo.sup.5U), uridine
5-oxyacetic acid methyl ester (mcmo.sup.5U),
5-carboxymethyl-uridine (cm.sup.5U), 1-carboxymethyl-pseudouridine,
5-carboxyhydroxymethyl-uridine (chm.sup.5U),
5-carboxyhydroxymethyl-uridine methyl ester (mchm.sup.5U),
5-methoxycarbonylmethyl-uridine (mcm.sup.5U),
5-methoxycarbonylmethyl-2-thio-uridine (mcm.sup.5s.sup.2U),
5-aminomethyl-2-thio-uridine (nm.sup.5s.sup.2U),
5-methylaminomethyl-uridine (mnm.sup.5U),
5-methylaminomethyl-2-thio-uridine (mnm.sup.5s.sup.2U),
5-methylaminomethyl-2-seleno-uridine (mnm.sup.5se.sup.2U),
5-carbamoylmethyl-uridine (ncm.sup.5U),
5-carboxymethylaminomethyl-uridine (cmnm.sup.5U),
5-carboxymethylaminomethyl-2-thio-uridine (cmnm.sup.5s.sup.2U),
5-propynyl-uridine, 1-propynyl-pseudouridine,
5-taurinomethyl-uridine (.tau.m.sup.5U),
1-taurinomethyl-pseudouridine,
5-taurinomethyl-2-thio-uridine(.tau.m.sup.5 s.sup.2U),
1-taurinomethyl-4-thio-pseudouridine, 5-methyl-uridine (m.sup.5U,
i.e., having the nucleobase deoxythymine), 1-methyl-pseudouridine
(m.sup.1.psi.), 5-methyl-2-thio-uridine (m.sup.5 s.sup.2U),
1-methyl-4-thio-pseudouridine (m.sup.1s.sup.4.psi.),
4-thio-1-methyl-pseudouridine, 3-methyl-pseudouridine
(m.sup.3.psi.), 2-thio-1-methyl-pseudouridine, 1-methyl -1-deaza-p
seudouri dine, 2-thio-1-methyl-1-deaza-pseudouridine,
dihydrouridine (D), dihydropseudouridine, 5,6-dihydrouridine,
5-methyl-dihydrouridine (m.sup.5D), 2-thio-dihydrouridine,
2-thio-dihydropseudouridine, 2-methoxy-uridine,
2-methoxy-4-thio-uridine, 4-methoxy-pseudouridine,
4-methoxy-2-thio-pseudouridine, N1-methyl-pseudouridine,
3-(3-amino-3-carboxypropyl)uridine (acp.sup.3U),
1-methyl-3-(3-amino-3-carboxypropyl)pseudouridine (acp.sup.3
.psi.), 5-(isopentenylaminomethyl)uridine (inm.sup.5U),
5-(isopentenylaminomethyl)-2-thio-uridine (inm.sup.5s.sup.2U),
.alpha.-thio-uridine, 2'-O-methyl-uridine (Um),
5,2'-O-dimethyl-uridine (m.sup.5Um), 2'-O-methyl-pseudouridine
(.psi.m), 2-thio-2'-O-methyl-uridine (s.sup.2Um),
5-methoxycarbonylmethyl-2'-O-methyl-uridine (mcm.sup.5Um),
5-carbamoylmethyl-2'-O-methyl-uridine (ncm.sup.5Um),
5-carboxymethylaminomethyl-2'-O-methyl-uridine (cmnm.sup.5Um),
3,2'-O-dimethyl-uridine (m.sup.3Um), and
5-(isopentenylaminomethyl)-2'-O-methyl-uridine (inm.sup.5Um),
1-thio-uridine, deoxythymidine, 2'-F-ara-uridine, 2'-F-uridine,
2'-OH-ara-uridine, 5-(2-carbomethoxyvinyl) uridine, and
5-[3-(1-E-propenylamino)]uridine.
[0397] In some embodiments, the modified nucleobase is a modified
cytosine. Exemplary nucleobases and nucleosides having a modified
cytosine include 5-aza-cytidine, 6-aza-cytidine, pseudoisocytidine,
3-methyl-cytidine (m.sup.3C), N4-acetyl-cytidine (ac.sup.4C),
5-formyl-cytidine (f.sup.5C), N4-methyl-cytidine (m.sup.4C),
5-methyl-cytidine (m.sup.5C), 5-halo-cytidine (e.g.,
5-iodo-cytidine), 5-hydroxymethyl-cytidine (hm.sup.5C),
1-methyl-pseudoisocytidine, pyrrolo-cytidine,
pyrrolo-pseudoisocytidine, 2-thio-cytidine (s.sup.2C),
2-thio-5-methyl-cytidine, 4-thio-pseudoisocytidine,
4-thio-1-methyl-pseudoisocytidine,
4-thio-1-methyl-1-deaza-pseudoisocytidine,
1-methyl-1-deaza-pseudoisocytidine, zebularine, 5-aza-zebularine,
5-methyl-zebularine, 5-aza-2-thio-zebularine, 2-thio-zebularine,
2-methoxy-cytidine, 2-methoxy-5-methyl-cytidine,
4-methoxy-pseudoisocytidine, 4-methoxy-1-methyl-pseudoisocytidine,
lysidine (k.sub.2C), .alpha.-thio-cytidine, 2'-O-methyl-cytidine
(Cm), 5,2'-O-dimethyl-cytidine (m.sup.5Cm),
N4-acetyl-2'-O-methyl-cytidine (ac.sup.4Cm),
N4,2'-O-dimethyl-cytidine (m.sup.4Cm),
5-formyl-2'-O-methyl-cytidine (f.sup.5Cm),
N4,N4,2'-O-trimethyl-cytidine (m.sup.4.sub.2Cm), 1-thio-cytidine,
2'-F-ara-cytidine, 2'-F-cytidine, and 2'-OH-ara-cytidine.
[0398] In some embodiments, the modified nucleobase is a modified
adenine. Exemplary nucleobases and nucleosides having a modified
adenine include 2-amino-purine, 2, 6-diaminopurine,
2-amino-6-halo-purine (e.g., 2-amino-6-chloro-purine),
6-halo-purine (e.g., 6-chloro-purine), 2-amino-6-methyl-purine,
8-azido-adenosine, 7-deaza-adenine, 7-deaza-8-aza-adenine,
7-deaza-2-amino-purine, 7-deaza-8-aza-2-amino-purine,
7-deaza-2,6-diaminopurine, 7-deaza-8-aza-2,6-diaminopurine,
1-methyl-adenosine (m.sup.1A), 2-methyl-adenine (m.sup.2A),
N6-methyl-adenosine (m.sup.6A), 2-methylthio-N6-methyl-adenosine
(ms.sup.2m.sup.6A), N6-isopentenyl-adenosine (i.sup.6A),
2-methylthio-N6-isopentenyl-adenosine (ms.sup.2i.sup.6A),
N6-(cis-hydroxyisopentenyl)adenosine (io.sup.6A),
2-methylthio-N6-(cis-hydroxyisopentenyl)adenosine
(ms.sup.2io.sup.6A), N6-glycinylcarbamoyl-adenosine (g.sup.6A),
N6-threonylcarbamoyl-adenosine (t.sup.6A),
N6-methyl-N6-threonylcarbamoyl-adenosine (m.sup.6t.sup.6A),
2-methylthio-N6-threonylcarbamoyl-adenosine (ms.sup.2g.sup.6A),
N6,N6-dimethyl-adenosine (m.sup.6.sub.2A),
N6-hydroxynorvalylcarbamoyl-adenosine (hn.sup.6A),
2-methylthio-N6-hydroxynorvalylcarbamoyl-adenosine
(ms.sup.2hn.sup.6A), N6-acetyl-adenosine (ac.sup.6A),
7-methyl-adenine, 2-methylthio-adenine, 2-methoxy-adenine,
.alpha.-thio-adenosine, 2'-O-methyl-adenosine (Am),
N6,2'-O-dimethyl-adenosine (m.sup.6Am),
N6,N6,2'-O-trimethyl-adenosine (m.sup.6.sub.2Am),
1,2'-O-dimethyl-adenosine (m'Am), 2'-O-ribosyladenosine (phosphate)
(Ar(p)), 2-amino-N6-methyl-purine, 1-thio-adenosine,
8-azido-adenosine, 2'-F-ara-adenosine, 2'-F-adenosine,
2'-OH-ara-adenosine, and
N6-(19-amino-pentaoxanonadecyl)-adenosine.
[0399] In some embodiments, the modified nucleobase is a modified
guanine. Exemplary nucleobases and nucleosides having a modified
guanine include inosine (I), 1-methyl-inosine (m.sup.1I), wyosine
(imG), methylwyosine (mimG), 4-demethyl-wyosine (imG-14),
isowyosine (imG2), wybutosine (yW), peroxywybutosine (o.sub.2yW),
hydroxywybutosine (OhyW), undermodified hydroxywybutosine (OhyW*),
7-deaza-guanosine, queuosine (Q), epoxyqueuosine (oQ),
galactosyl-queuosine (galQ), mannosyl-queuosine (manQ),
7-cyano-7-deaza-guanosine (preQ.sub.0),
7-aminomethyl-7-deaza-guanosine (preQ.sub.1), archaeosine
(G.sup.+), 7-deaza-8-aza-guanosine, 6-thio-guanosine,
6-thio-7-deaza-guanosine, 6-thio-7-deaza-8-aza-guanosine,
7-methyl-guanosine (m.sup.7G), 6-thio-7-methyl-guanosine,
7-methyl-inosine, 6-methoxy-guanosine, 1-methyl-guanosine
(m.sup.7G), N2-methyl-guanosine (m.sup.2G),
N2,N2-dimethyl-guanosine (m.sup.2.sub.2G), N2,7-dimethyl-guanosine
(m.sup.2'.sup.7G), N2, N2,7-dimethyl-guanosine 8-oxo-guanosine,
7-methyl-8-oxo-guanosine, 1-methyl-6-thio-guanosine,
N2-methyl-6-thio-guanosine, N2,N2-dimethyl-6-thio-guanosine,
.alpha.-thio-guanosine, 2'-O-methyl-guanosine (Gm),
N2-methyl-2'-O-methyl-guanosine (m.sup.2Gm),
N2,N2-dimethyl-2'-O-methyl-guanosine (m.sup.2.sub.2Gm),
1-methyl-2'-O-methyl-guanosine (m.sup.1Gm),
N2,7-dimethyl-2'-O-methyl-guanosine (m.sup.2'.sup.7Gm),
2'-O-methyl-inosine (Im), 1,2'-O-dimethyl-inosine (m.sup.1Im),
2'-O-ribosylguanosine (phosphate) (Gr(p)) , 1-thio-guanosine,
06-methyl-guanosine, 2'-F-ara-guanosine, and 2'-F-guanosine.
In Vitro Transcription of RNA (e.g., mRNA)
[0400] Influenza virus vaccines of the present disclosure comprise
at least one RNA polynucleotide, such as a mRNA (e.g., modified
mRNA). mRNA, for example, is transcribed in vitro from template
DNA, referred to as an "in vitro transcription template." In some
embodiments, an in vitro transcription template encodes a 5'
untranslated (UTR) region, contains an open reading frame, and
encodes a 3' UTR and a polyA tail. The particular nucleic acid
sequence composition and length of an in vitro transcription
template will depend on the mRNA encoded by the template.
[0401] A "5' untranslated region" (5'UTR) refers to a region of an
mRNA that is directly upstream (i.e., 5') from the start codon
(i.e., the first codon of an mRNA transcript translated by a
ribosome) that does not encode a polypeptide.
[0402] A "3' untranslated region" (3'UTR) refers to a region of an
mRNA that is directly downstream (i.e., 3') from the stop codon
(i.e., the codon of an mRNA transcript that signals a termination
of translation) that does not encode a polypeptide.
[0403] An "open reading frame" is a continuous stretch of DNA or
RNA beginning with a start codon (e.g., methionine (ATG or AUG)),
and ending with a stop codon (e.g., TAA, TAG or TGA, or UAA, UAG or
UGA) and typically encodes a polypeptide (e.g., protein).
[0404] A "polyA tail" is a region of mRNA that is downstream, e.g.,
directly downstream (i.e., 3'), from the 3' UTR that contains
multiple, consecutive adenosine monophosphates. A polyA tail may
contain 10 to 300 adenosine monophosphates. For example, a polyA
tail may contain 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120,
130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250,
260, 270, 280, 290 or 300 adenosine monophosphates. In some
embodiments, a polyA tail contains 50 to 250 adenosine
monophosphates. In a relevant biological setting (e.g., in cells,
in vivo) the poly(A) tail functions to protect mRNA from enzymatic
degradation, e.g., in the cytoplasm, and aids in transcription
termination, export of the mRNA from the nucleus and
translation.
[0405] In some embodiments, a polynucleotide includes 200 to 3,000
nucleotides. For example, a polynucleotide may include 200 to 500,
200 to 1000, 200 to 1500, 200 to 3000, 500 to 1000, 500 to 1500,
500 to 2000, 500 to 3000, 1000 to 1500, 1000 to 2000, 1000 to 3000,
1500 to 3000, or 2000 to 3000 nucleotides.
Flagellin Adjuvants
[0406] Flagellin is an approximately 500 amino acid monomeric
protein that polymerizes to form the flagella associated with
bacterial motion. Flagellin is expressed by a variety of
flagellated bacteria (Salmonella typhimurium for example) as well
as non-flagellated bacteria (such as Escherichia coli). Sensing of
flagellin by cells of the innate immune system (dendritic cells,
macrophages, etc.) is mediated by the Toll-like receptor 5 (TLRS)
as well as by Nod-like receptors (NLRs) Ipaf and Naip5. TLRs and
NLRs have been identified as playing a role in the activation of
innate immune response and adaptive immune response.
[0407] As such, flagellin provides an adjuvant effect in a
vaccine.
[0408] The nucleotide and amino acid sequences encoding known
flagellin polypeptides are publicly available in the NCBI GenBank
database. The flagellin sequences from S. Typhimurium, H. Pylori,
V. Cholera, S. marcesens, S. flexneri, T Pallidum, L. pneumophila,
B. burgdorferei, C. difficile, R. meliloti, A. tumefaciens, R.
lupini, B. clarridgeiae, P. Mirabilis, B. subtilus, L.
monocytogenes, P. aeruginosa, and E. coli, among others are
known.
[0409] A flagellin polypeptide, as used herein, refers to a full
length flagellin protein, immunogenic fragments thereof, and
peptides having at least 50% sequence identify to a flagellin
protein or immunogenic fragments thereof. Exemplary flagellin
proteins include flagellin from Salmonella typhi (UniPro Entry
number: Q56086), Salmonella typhimurium (A0A0C9DG09), Salmonella
enteritidis (A0A0C9BAB7), and Salmonella choleraesuis (Q6V2X8), and
proteins having an amino acid sequence identified by any one of SEQ
ID NO 1-444, 458, 460, 462-479, or 543-565 (see also Tables 7-13
and 26). In some embodiments, the flagellin polypeptide has at
least 60%, 70%, 75%, 80%, 90%, 95%, 97%, 98%, or 99% sequence
identify to a flagellin protein or immunogenic fragments
thereof.
[0410] In some embodiments, the flagellin polypeptide is an
immunogenic fragment. An immunogenic fragment is a portion of a
flagellin protein that provokes an immune response. In some
embodiments, the immune response is a TLR5 immune response. An
example of an immunogenic fragment is a flagellin protein in which
all or a portion of a hinge region has been deleted or replaced
with other amino acids. For example, an antigenic polypeptide may
be inserted in the hinge region. Hinge regions are the
hypervariable regions of a flagellin. Hinge regions of a flagellin
are also referred to as "D3 domain or region, "propeller domain or
region," "hypervariable domain or region" and "variable domain or
region." "At least a portion of a hinge region," as used herein,
refers to any part of the hinge region of the flagellin, or the
entirety of the hinge region. In other embodiments an immunogenic
fragment of flagellin is a 20, 25, 30, 35, or 40 amino acid
C-terminal fragment of flagellin.
[0411] The flagellin monomer is formed by domains D0 through D3. D0
and D1, which form the stem, are composed of tandem long alpha
helices and are highly conserved among different bacteria. The D1
domain includes several stretches of amino acids that are useful
for TLR5 activation. The entire D1 domain or one or more of the
active regions within the domain are immunogenic fragments of
flagellin. Examples of immunogenic regions within the D1 domain
include residues 88-114 and residues 411-431 (in Salmonella
typhimurium FliC flagellin. Within the 13 amino acids in the 88-100
region, at least 6 substitutions are permitted between Salmonella
flagellin and other flagellins that still preserve TLR5 activation.
Thus, immunogenic fragments of flagellin include flagellin like
sequences that activate TLR5 and contain a 13 amino acid motif that
is 53% or more identical to the Salmonella sequence in 88-100 of
FliC (LQRVRELAVQSAN; SEQ ID NO: 504).
[0412] In some embodiments, the RNA (e.g., mRNA) vaccine includes
an RNA that encodes a fusion protein of flagellin and one or more
antigenic polypeptides. A "fusion protein" as used herein, refers
to a linking of two components of the construct. In some
embodiments, a carboxy-terminus of the antigenic polypeptide is
fused or linked to an amino terminus of the flagellin polypeptide.
In other embodiments, an amino-terminus of the antigenic
polypeptide is fused or linked to a carboxy-terminus of the
flagellin polypeptide. The fusion protein may include, for example,
one, two, three, four, five, six or more flagellin polypeptides
linked to one, two, three, four, five, six or more antigenic
polypeptides. When two or more flagellin polypeptides and/or two or
more antigenic polypeptides are linked such a construct may be
referred to as a "multimer."
[0413] Each of the components of a fusion protein may be directly
linked to one another or they may be connected through a linker.
For instance, the linker may be an amino acid linker. The amino
acid linker encoded for by the RNA (e.g., mRNA) vaccine to link the
components of the fusion protein may include, for instance, at
least one member selected from the group consisting of a lysine
residue, a glutamic acid residue, a serine residue and an arginine
residue. In some embodiments the linker is 1-30, 1-25, 1-25, 5-10,
5, 15, or 5-20 amino acids in length.
[0414] In other embodiments the RNA (e.g., mRNA) vaccine includes
at least two separate RNA polynucleotides, one encoding one or more
antigenic polypeptides and the other encoding the flagellin
polypeptide. The at least two RNA polynucleotides may be
co-formulated in a carrier such as a lipid nanoparticle.
Methods of Treatment
[0415] Provided herein are compositions (e.g., pharmaceutical
compositions), methods, kits and reagents for prevention and/or
treatment of influenza virus in humans and other mammals. Influenza
virus RNA vaccines can be used as therapeutic or prophylactic
agents. They may be used in medicine to prevent and/or treat
infectious disease. In exemplary aspects, the influenza virus RNA
vaccines of the present disclosure are used to provide prophylactic
protection from influenza virus. Prophylactic protection from
influenza virus can be achieved following administration of an
influenza virus RNA vaccine of the present disclosure. Vaccines can
be administered once, twice, three times, four times or more. It is
possible, although less desirable, to administer the vaccine to an
infected individual to achieve a therapeutic response. Dosing may
need to be adjusted accordingly.
[0416] In some embodiments, the influenza virus vaccines of the
present disclosure can be used as a method of preventing an
influenza virus infection in a subject, the method comprising
administering to said subject at least one influenza virus vaccine
as provided herein. In some embodiments, the influenza virus
vaccines of the present disclosure can be used as a method of
inhibiting a primary influenza virus infection in a subject, the
method comprising administering to said subject at least one
influenza virus vaccine as provided herein. In some embodiments,
the influenza virus vaccines of the present disclosure can be used
as a method of treating an influenza virus infection in a subject,
the method comprising administering to said subject at least one
influenza virus vaccine as provided herein. In some embodiments,
the influenza virus vaccines of the present disclosure can be used
as a method of reducing an incidence of influenza virus infection
in a subject, the method comprising administering to said subject
at least one influenza virus vaccine as provided herein. In come
embodiments, the influenza virus vaccines of the present disclosure
can be used as a method of inhibiting spread of influenza virus
from a first subject infected with influenza virus to a second
subject not infected with influenza virus, the method comprising
administering to at least one of said first subject sand said
second subject at least one influenza virus vaccine as provided
herein.
[0417] A method of eliciting an immune response in a subject
against an influenza virus is provided in aspects of the invention.
The method involves administering to the subject an influenza virus
RNA vaccine comprising at least one RNA polynucleotide having an
open reading frame encoding at least one influenza virus antigenic
polypeptide, thereby inducing in the subject an immune response
specific to influenza virus antigenic polypeptide, wherein
anti-antigenic polypeptide antibody titer in the subject is
increased following vaccination relative to anti-antigenic
polypeptide antibody titer in a subject vaccinated with a
prophylactically effective dose of a traditional vaccine against
the influenza virus. An "anti-antigenic polypeptide antibody" is a
serum antibody the binds specifically to the antigenic
polypeptide.
[0418] A prophylactically effective dose is a therapeutically
effective dose that prevents infection with the virus at a
clinically acceptable level. In some embodiments the
therapeutically effective dose is a dose listed in a package insert
for the vaccine. A traditional vaccine, as used herein, refers to a
vaccine other than the mRNA vaccines of the present disclosure. For
instance, a traditional vaccine includes, but is not limited to,
live microorganism vaccines, killed microorganism vaccines, subunit
vaccines, protein antigen vaccines, DNA vaccines, VLP vaccines,
etc. In exemplary embodiments, a traditional vaccine is a vaccine
that has achieved regulatory approval and/or is registered by a
national drug regulatory body, for example the Food and Drug
Administration (FDA) in the United States or the European Medicines
Agency (EMA).
[0419] In some embodiments the anti-antigenic polypeptide antibody
titer in the subject is increased 1 log to 10 log following
vaccination relative to anti-antigenic polypeptide antibody titer
in a subject vaccinated with a prophylactically effective dose of a
traditional vaccine against the influenza virus.
[0420] In some embodiments the anti-antigenic polypeptide antibody
titer in the subject is increased 1 log, 2 log, 3 log, 5 log or 10
log following vaccination relative to anti-antigenic polypeptide
antibody titer in a subject vaccinated with a prophylactically
effective dose of a traditional vaccine against influenza.
[0421] A method of eliciting an immune response in a subject
against an influenza virus is provided in other aspects of the
present disclosure. The method involves administering to the
subject an influenza virus RNA vaccine comprising at least one RNA
polynucleotide having an open reading frame encoding at least one
influenza virus antigenic polypeptide, thereby inducing in the
subject an immune response specific to influenza virus antigenic
polypeptide, wherein the immune response in the subject is
equivalent to an immune response in a subject vaccinated with a
traditional vaccine against the influenza virus at 2 times to 100
times the dosage level relative to the RNA vaccine.
[0422] In some embodiments, the immune response in the subject is
equivalent to an immune response in a subject vaccinated with a
traditional vaccine at 2, 3, 4, 5, 10, 50, 100 times the dosage
level relative to the influenza vaccine.
[0423] In some embodiments the immune response in the subject is
equivalent to an immune response in a subject vaccinated with a
traditional vaccine at 10-100 times, or 100-1000 times, the dosage
level relative to the influenza vaccine.
[0424] In some embodiments the immune response is assessed by
determining [protein] antibody titer in the subject.
[0425] Some embodiments provide a method of inducing an immune
response in a subject by administering to the subject an influenza
RNA (e.g., mRNA) vaccine comprising at least one RNA (e.g., mRNA)
polynucleotide having an open reading frame encoding at least one
influenza antigenic polypeptide, thereby inducing in the subject an
immune response specific to the antigenic polypeptide, wherein the
immune response in the subject is induced 2 days to 10 weeks
earlier relative to an immune response induced in a subject
vaccinated with a prophylactically effective dose of a traditional
vaccine against influenza. In some embodiments, the immune response
in the subject is induced in a subject vaccinated with a
prophylactically effective dose of a traditional vaccine at 2 times
to 100 times the dosage level relative to the influenza RNA (e.g.,
mRNA) vaccine.
[0426] In some embodiments the immune response in the subject is
equivalent to an immune response in a subject vaccinated with a
traditional vaccine at 2, 3, 4, 5, 10, 50, 100 times the dosage
level relative to the influenza RNA (e.g., mRNA) vaccine.
[0427] In some embodiments, the immune response in the subject is
induced 2 days earlier, or 3 days earlier, relative to an immune
response induced in a subject vaccinated with a prophylactically
effective dose of a traditional vaccine.
[0428] In some embodiments the immune response in the subject is
induced 1 week, 2 weeks, 3 weeks, 5 weeks, or 10 weeks earlier
relative to an immune response induced in a subject vaccinated with
a prophylactically effective dose of a traditional vaccine.
Therapeutic and Prophylactic Compositions
[0429] Provided herein are compositions (e.g., pharmaceutical
compositions), methods, kits and reagents for prevention, treatment
or diagnosis of influenza in humans and other mammals, for example.
Influenza RNA (e.g. mRNA) vaccines can be used as therapeutic or
prophylactic agents. They may be used in medicine to prevent and/or
treat infectious disease. In some embodiments, the respiratory RNA
(e.g., mRNA) vaccines of the present disclosure are used fin the
priming of immune effector cells, for example, to activate
peripheral blood mononuclear cells (PBMCs) ex vivo, which are then
infused (re-infused) into a subject.
[0430] In some embodiments, influenza vaccine containing RNA (e.g.,
mRNA) polynucleotides as described herein can be administered to a
subject (e.g., a mammalian subject, such as a human subject), and
the RNA (e.g., mRNA) polynucleotides are translated in vivo to
produce an antigenic polypeptide.
[0431] The influenza RNA (e.g., mRNA) vaccines may be induced for
translation of a polypeptide (e.g., antigen or immunogen) in a
cell, tissue or organism. In some embodiments, such translation
occurs in vivo, although such translation may occur ex vivo, in
culture or in vitro. In some embodiments, the cell, tissue or
organism is contacted with an effective amount of a composition
containing an influenza RNA (e.g., mRNA) vaccine that contains a
polynucleotide that has at least one a translatable region encoding
an antigenic polypeptide.
[0432] An "effective amount" of an influenza RNA (e.g. mRNA)
vaccine is provided based, at least in part, on the target tissue,
target cell type, means of administration, physical characteristics
of the polynucleotide (e.g., size, and extent of modified
nucleosides) and other components of the vaccine, and other
determinants. In general, an effective amount of the influenza RNA
(e.g., mRNA) vaccine composition provides an induced or boosted
immune response as a function of antigen production in the cell,
preferably more efficient than a composition containing a
corresponding unmodified polynucleotide encoding the same antigen
or a peptide antigen. Increased antigen production may be
demonstrated by increased cell transfection (the percentage of
cells transfected with the RNA, e.g., mRNA, vaccine), increased
protein translation from the polynucleotide, decreased nucleic acid
degradation (as demonstrated, for example, by increased duration of
protein translation from a modified polynucleotide), or altered
antigen specific immune response of the host cell.
[0433] In some embodiments, RNA (e.g. mRNA) vaccines (including
polynucleotides their encoded polypeptides) in accordance with the
present disclosure may be used for treatment of Influenza.
[0434] Influenza RNA (e.g. mRNA) vaccines may be administered
prophylactically or therapeutically as part of an active
immunization scheme to healthy individuals or early in infection
during the incubation phase or during active infection after onset
of symptoms. In some embodiments, the amount of RNA (e.g., mRNA)
vaccine of the present disclosure provided to a cell, a tissue or a
subject may be an amount effective for immune prophylaxis.
[0435] Influenza RNA (e.g. mRNA) vaccines may be administrated with
other prophylactic or therapeutic compounds. As a non-limiting
example, a prophylactic or therapeutic compound may be an adjuvant
or a booster. As used herein, when referring to a prophylactic
composition, such as a vaccine, the term "booster" refers to an
extra administration of the prophylactic (vaccine) composition. A
booster (or booster vaccine) may be given after an earlier
administration of the prophylactic composition. The time of
administration between the initial administration of the
prophylactic composition and the booster may be, but is not limited
to, 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 6
minutes, 7 minutes, 8 minutes, 9 minutes, 10 minutes, 15 minutes,
20 minutes 35 minutes, 40 minutes, 45 minutes, 50 minutes, 55
minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7
hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14
hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours,
21 hours, 22 hours, 23 hours, 1 day, 36 hours, 2 days, 3 days, 4
days, 5 days, 6 days, 1 week, 10 days, 2 weeks, 3 weeks, 1 month, 2
months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months,
9 months, 10 months, 11 months, 1 year, 18 months, 2 years, 3
years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10
years, 11 years, 12 years, 13 years, 14 years, 15 years, 16 years,
17 years, 18 years, 19 years, 20 years, 25 years, 30 years, 35
years, 40 years, 45 years, 50 years, 55 years, 60 years, 65 years,
70 years, 75 years, 80 years, 85 years, 90 years, 95 years or more
than 99 years. In some embodiments, the time of administration
between the initial administration of the prophylactic composition
and the booster may be, but is not limited to, 1 week, 2 weeks, 3
weeks, 1 month, 2 months, 3 months, 6 months or 1 year.
[0436] In some embodiments, influenza RNA (e.g. mRNA) vaccines may
be administered intramuscularly, intradermally, or intranasally,
similarly to the administration of inactivated vaccines known in
the art. In some embodiments, influenza RNA (e.g. mRNA) vaccines
are administered intramuscularly.
[0437] Influenza RNA (e.g. mRNA) vaccines may be utilized in
various settings depending on the prevalence of the infection or
the degree or level of unmet medical need. As a non-limiting
example, the RNA (e.g., mRNA) vaccines may be utilized to treat
and/or prevent a variety of influenzas. RNA (e.g., mRNA) vaccines
have superior properties in that they produce much larger antibody
titers and produce responses early than commercially available
anti-viral agents/compositions.
[0438] Provided herein are pharmaceutical compositions including
influenza RNA (e.g. mRNA) vaccines and RNA (e.g. mRNA) vaccine
compositions and/or complexes optionally in combination with one or
more pharmaceutically acceptable excipients.
[0439] Influenza RNA (e.g. mRNA) vaccines may be formulated or
administered alone or in conjunction with one or more other
components. For instance, Influenza RNA (e.g., mRNA) vaccines
(vaccine compositions) may comprise other components including, but
not limited to, adjuvants.
[0440] In some embodiments, influenza (e.g. mRNA) vaccines do not
include an adjuvant (they are adjuvant free).
[0441] Influenza RNA (e.g. mRNA) vaccines may be formulated or
administered in combination with one or more
pharmaceutically-acceptable excipients. In some embodiments,
vaccine compositions comprise at least one additional active
substances, such as, for example, a therapeutically-active
substance, a prophylactically-active substance, or a combination of
both. Vaccine compositions may be sterile, pyrogen-free or both
sterile and pyrogen-free. General considerations in the formulation
and/or manufacture of pharmaceutical agents, such as vaccine
compositions, may be found, for example, in Remington: The Science
and Practice of Pharmacy 21st ed., Lippincott Williams &
Wilkins, 2005 (incorporated herein by reference in its
entirety).
[0442] In some embodiments, influenza RNA (e.g. mRNA) vaccines are
administered to humans, human patients or subjects. For the
purposes of the present disclosure, the phrase "active ingredient"
generally refers to the RNA (e.g., mRNA) vaccines or the
polynucleotides contained therein, for example, RNA polynucleotides
(e.g., mRNA polynucleotides) encoding antigenic polypeptides.
[0443] Formulations of the influenza vaccine compositions described
herein may be prepared by any method known or hereafter developed
in the art of pharmacology. In general, such preparatory methods
include the step of bringing the active ingredient (e.g., mRNA
polynucleotide) into association with an excipient and/or one or
more other accessory ingredients, and then, if necessary and/or
desirable, dividing, shaping and/or packaging the product into a
desired single- or multi-dose unit.
[0444] Relative amounts of the active ingredient, the
pharmaceutically acceptable excipient, and/or any additional
ingredients in a pharmaceutical composition in accordance with the
disclosure will vary, depending upon the identity, size, and/or
condition of the subject treated and further depending upon the
route by which the composition is to be administered. By way of
example, the composition may comprise between 0.1% and 100%, e.g.,
between 0.5 and 50%, between 1-30%, between 5-80%, at least 80%
(w/w) active ingredient.
[0445] Influenza RNA (e.g. mRNA) vaccines can be formulated using
one or more excipients to: increase stability; increase cell
transfection; permit the sustained or delayed release (e.g., from a
depot formulation); alter the biodistribution (e.g., target to
specific tissues or cell types); increase the translation of
encoded protein in vivo; and/or alter the release profile of
encoded protein (antigen) in vivo. In addition to traditional
excipients such as any and all solvents, dispersion media,
diluents, or other liquid vehicles, dispersion or suspension aids,
surface active agents, isotonic agents, thickening or emulsifying
agents, preservatives, excipients can include, without limitation,
lipidoids, liposomes, lipid nanoparticles, polymers, lipoplexes,
core-shell nanoparticles, peptides, proteins, cells transfected
with influenza RNA (e.g. mRNA)vaccines (e.g., for transplantation
into a subject), hyaluronidase, nanoparticle mimics and
combinations thereof.
Stabilizing Elements
[0446] Naturally-occurring eukaryotic mRNA molecules have been
found to contain stabilizing elements, including, but not limited
to untranslated regions (UTR) at their 5'-end (5'UTR) and/or at
their 3'-end (3'UTR), in addition to other structural features,
such as a 5'-cap structure or a 3'-poly(A) tail. Both the 5'UTR and
the 3'UTR are typically transcribed from the genomic DNA and are
elements of the premature mRNA. Characteristic structural features
of mature mRNA, such as the 5'-cap and the 3'-poly(A) tail are
usually added to the transcribed (premature) mRNA during mRNA
processing. The 3'-poly(A) tail is typically a stretch of adenine
nucleotides added to the 3'-end of the transcribed mRNA. It can
comprise up to about 400 adenine nucleotides. In some embodiments
the length of the 3'-poly(A) tail may be an essential element with
respect to the stability of the individual mRNA.
[0447] In some embodiments the RNA (e.g., mRNA) vaccine may include
one or more stabilizing elements. Stabilizing elements may include
for instance a histone stem-loop. A stem-loop binding protein
(SLBP), a 32 kDa protein has been identified. It is associated with
the histone stem-loop at the 3'-end of the histone messages in both
the nucleus and the cytoplasm. Its expression level is regulated by
the cell cycle; it is peaks during the S-phase, when histone mRNA
levels are also elevated. The protein has been shown to be
essential for efficient 3'-end processing of histone pre-mRNA by
the U7 snRNP. SLBP continues to be associated with the stem-loop
after processing, and then stimulates the translation of mature
histone mRNAs into histone proteins in the cytoplasm. The RNA
binding domain of SLBP is conserved through metazoa and protozoa;
its binding to the histone stem-loop depends on the structure of
the loop. The minimum binding site includes at least three
nucleotides 5' and two nucleotides 3' relative to the
stem-loop.
[0448] In some embodiments, the RNA (e.g., mRNA) vaccines include a
coding region, at least one histone stem-loop, and optionally, a
poly(A) sequence or polyadenylation signal. The poly(A) sequence or
polyadenylation signal generally should enhance the expression
level of the encoded protein. The encoded protein, in some
embodiments, is not a histone protein, a reporter protein (e.g.
Luciferase, GFP, EGFP, .beta.-Galactosidase, EGFP), or a marker or
selection protein (e.g. alpha-Globin, Galactokinase and
Xanthine:guanine phosphoribosyl transferase (GPT)).
[0449] In some embodiments, the combination of a poly(A) sequence
or polyadenylation signal and at least one histone stem-loop, even
though both represent alternative mechanisms in nature, acts
synergistically to increase the protein expression beyond the level
observed with either of the individual elements. It has been found
that the synergistic effect of the combination of poly(A) and at
least one histone stem-loop does not depend on the order of the
elements or the length of the poly(A) sequence.
[0450] In some embodiments, the RNA (e.g., mRNA) vaccine does not
comprise a histone downstream element (HDE). "Histone downstream
element" (HDE) includes a purine-rich polynucleotide stretch of
approximately 15 to 20 nucleotides 3' of naturally occurring
stem-loops, representing the binding site for the U7 snRNA, which
is involved in processing of histone pre-mRNA into mature histone
mRNA. Ideally, the inventive nucleic acid does not include an
intron.
[0451] In some embodiments, the RNA (e.g., mRNA) vaccine may or may
not contain a enhancer and/or promoter sequence, which may be
modified or unmodified or which may be activated or inactivated. In
some embodiments, the histone stem-loop is generally derived from
histone genes, and includes an intramolecular base pairing of two
neighbored partially or entirely reverse complementary sequences
separated by a spacer, including (e.g., consisting of) a short
sequence, which forms the loop of the structure. The unpaired loop
region is typically unable to base pair with either of the stem
loop elements. It occurs more often in RNA, as is a key component
of many RNA secondary structures, but may be present in
single-stranded DNA as well. Stability of the stem-loop structure
generally depends on the length, number of mismatches or bulges,
and base composition of the paired region. In some embodiments,
wobble base pairing (non-Watson-Crick base pairing) may result. In
some embodiments, the at least one histone stem-loop sequence
comprises a length of 15 to 45 nucleotides.
[0452] In other embodiments the RNA (e.g., mRNA) vaccine may have
one or more AU-rich sequences removed. These sequences, sometimes
referred to as AURES are destabilizing sequences found in the
3'UTR. The AURES may be removed from the RNA (e.g., mRNA) vaccines.
Alternatively the AURES may remain in the RNA (e.g., mRNA)
vaccine.
Nanoparticle Formulations
[0453] In some embodiments, influenza RNA (e.g. mRNA) vaccines are
formulated in a nanoparticle. In some embodiments, influenza RNA
(e.g. mRNA) vaccines are formulated in a lipid nanoparticle. In
some embodiments, influenza RNA (e.g. mRNA) vaccines are formulated
in a lipid-polycation complex, referred to as a cationic lipid
nanoparticle. As a non-limiting example, the polycation may include
a cationic peptide or a polypeptide such as, but not limited to,
polylysine, polyornithine and/or polyarginine. In some embodiments,
influenza RNA (e.g., mRNA) vaccines are formulated in a lipid
nanoparticle that includes a non-cationic lipid such as, but not
limited to, cholesterol or dioleoyl phosphatidylethanolamine
(DOPE).
[0454] A lipid nanoparticle formulation may be influenced by, but
not limited to, the selection of the cationic lipid component, the
degree of cationic lipid saturation, the nature of the PEGylation,
ratio of all components and biophysical parameters such as size. In
one example by Semple et al. (Nature Biotech. 2010 28:172-176), the
lipid nanoparticle formulation is composed of 57.1% cationic lipid,
7.1% dipalmitoylphosphatidylcholine, 34.3% cholesterol, and 1.4%
PEG-c-DMA. As another example, changing the composition of the
cationic lipid can more effectively deliver siRNA to various
antigen presenting cells (Basha et al. Mol Ther. 2011
19:2186-2200).
[0455] In some embodiments, lipid nanoparticle formulations may
comprise 35 to 45% cationic lipid, 40% to 50% cationic lipid, 50%
to 60% cationic lipid and/or 55% to 65% cationic lipid. In some
embodiments, the ratio of lipid to RNA (e.g., mRNA) in lipid
nanoparticles maybe 5:1 to 20:1, 10:1 to 25:1, 15:1 to 30:1 and/or
at least 30:1.
[0456] In some embodiments, the ratio of PEG in the lipid
nanoparticle formulations may be increased or decreased and/or the
carbon chain length of the PEG lipid may be modified from C14 to
C18 to alter the pharmacokinetics and/or biodistribution of the
lipid nanoparticle formulations. As a non-limiting example, lipid
nanoparticle formulations may contain 0.5% to 3.0%, 1.0% to 3.5%,
1.5% to 4.0%, 2.0% to 4.5%, 2.5% to 5.0% and/or 3.0% to 6.0% of the
lipid molar ratio of PEG-c-DOMG
(R-3-[(.omega.-methoxy-poly(ethyleneglycol)2000)carbamoyl)]-1,2-dimyristy-
loxypropyl-3-amine) (also referred to herein as PEG-DOMG) as
compared to the cationic lipid, DSPC and cholesterol. In some
embodiments, the PEG-c-DOMG may be replaced with a PEG lipid such
as, but not limited to, PEG-DSG (1,2-Distearoyl-sn-glycerol,
methoxypolyethylene glycol), PEG-DMG (1,2-Dimyristoyl-sn-glycerol)
and/or PEG-DPG (1,2-Dipalmitoyl-sn-glycerol, methoxypolyethylene
glycol). The cationic lipid may be selected from any lipid known in
the art such as, but not limited to, DLin-MC3-DMA, DLin-DMA,
C12-200 and DLin-KC2-DMA.
[0457] In some embodiments, an influenza RNA (e.g. mRNA) vaccine
formulation is a nanoparticle that comprises at least one lipid.
The lipid may be selected from, but is not limited to, DLin-DMA,
DLin-K-DMA, 98N12-5, C12-200, DLin-MC3-DMA, DLin-KC2-DMA, DODMA,
PLGA, PEG, PEG-DMG, PEGylated lipids and amino alcohol lipids. In
some embodiments, the lipid may be a cationic lipid such as, but
not limited to, DLin-DMA, DLin-D-DMA, DLin-MC3-DMA, DLin-KC2-DMA,
DODMA and amino alcohol lipids. The amino alcohol cationic lipid
may be the lipids described in and/or made by the methods described
in U.S. Patent Publication No. US2013/0150625, herein incorporated
by reference in its entirety. As a non-limiting example, the
cationic lipid may be
2-amino-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-2-{[(9Z,2Z)-octadeca-9,12-
-dien-1-yloxy]methyl}propan-1-ol (Compound 1 in US2013/0150625);
2-amino-3-[(9Z)-octadec-9-en-1-yloxy]-2-{[(9Z)-octadec-9-en-1-yloxy]methy-
l}propan-1-ol (Compound 2 in US2013/0150625);
2-amino-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-2-[(octyloxy)methyl]propa-
n-1-ol (Compound 3 in US2013/0150625); and
2-(dimethylamino)-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-2-{[(9Z,12Z)-oc-
tadeca-9,12-dien-1-yloxy]methyl}propan-1-ol (Compound 4 in
US2013/0150625); or any pharmaceutically acceptable salt or
stereoisomer thereof.
[0458] Lipid nanoparticle formulations typically comprise a lipid,
in particular, an ionizable cationic lipid, for example,
2,2-dilinoleyl-4-dimethylaminoethyl[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), or
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, and further
comprise a neutral lipid, a sterol and a molecule capable of
reducing particle aggregation, for example a PEG or PEG-modified
lipid.
[0459] In some embodiments, a lipid nanoparticle formulation
consists essentially of (i) at least one lipid selected from the
group consisting of
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate; (ii) a neutral
lipid selected from DSPC, DPPC, POPC, DOPE and SM; (iii) a sterol,
e.g., cholesterol; and (iv) a PEG-lipid, e.g., PEG-DMG or PEG-cDMA,
in a molar ratio of 20-60% cationic lipid: 5-25% neutral lipid:
25-55% sterol; 0.5-15% PEG-lipid.
[0460] In some embodiments, a lipid nanoparticle formulation
includes 25% to 75% on a molar basis of a cationic lipid selected
from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane
(DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate
(DLin-MC3-DMA), and di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, e.g., 35 to
65%, 45 to 65%, 60%, 57.5%, 50% or 40% on a molar basis.
[0461] In some embodiments, a lipid nanoparticle formulation
includes 0.5% to 15% on a molar basis of the neutral lipid, e.g., 3
to 12%, 5 to 10% or 15%, 10%, or 7.5% on a molar basis. Examples of
neutral lipids include, without limitation, DSPC, POPC, DPPC, DOPE
and SM. In some embodiments, the formulation includes 5% to 50% on
a molar basis of the sterol (e.g., 15 to 45%, 20 to 40%, 40%,
38.5%, 35%, or 31% on a molar basis. A non-limiting example of a
sterol is cholesterol. In some embodiments, a lipid nanoparticle
formulation includes 0.5% to 20% on a molar basis of the PEG or
PEG-modified lipid (e.g., 0.5 to 10%, 0.5 to 5%, 1.5%, 0.5%, 1.5%,
3.5%, or 5% on a molar basis. In some embodiments, a PEG or PEG
modified lipid comprises a PEG molecule of an average molecular
weight of 2,000 Da. In some embodiments, a PEG or PEG modified
lipid comprises a PEG molecule of an average molecular weight of
less than 2,000, for example around 1,500 Da, around 1,000 Da, or
around 500 Da. Non-limiting examples of PEG-modified lipids include
PEG-distearoyl glycerol (PEG-DMG) (also referred herein as PEG-C14
or C14-PEG), PEG-cDMA (further discussed in Reyes et al. J.
Controlled Release, 107, 276-287 (2005) the contents of which are
herein incorporated by reference in their entirety).
[0462] In some embodiments, lipid nanoparticle formulations include
25-75% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 0.5-15% of the
neutral lipid, 5-50% of the sterol, and 0.5-20% of the PEG or
PEG-modified lipid on a molar basis.
[0463] In some embodiments, lipid nanoparticle formulations include
35-65% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 3-12% of the
neutral lipid, 15-45% of the sterol, and 0.5-10% of the PEG or
PEG-modified lipid on a molar basis.
[0464] In some embodiments, lipid nanoparticle formulations include
45-65% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 5-10% of the
neutral lipid, 25-40% of the sterol, and 0.5-10% of the PEG or
PEG-modified lipid on a molar basis.
[0465] In some embodiments, lipid nanoparticle formulations include
60% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 7.5% of the
neutral lipid, 31% of the sterol, and 1.5% of the PEG or
PEG-modified lipid on a molar basis.
[0466] In some embodiments, lipid nanoparticle formulations include
50% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 10% of the
neutral lipid, 38.5% of the sterol, and 1.5% of the PEG or
PEG-modified lipid on a molar basis.
[0467] In some embodiments, lipid nanoparticle formulations include
50% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 10% of the
neutral lipid, 35% of the sterol, 4.5% or 5% of the PEG or
PEG-modified lipid, and 0.5% of the targeting lipid on a molar
basis.
[0468] In some embodiments, lipid nanoparticle formulations include
40% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 15% of the
neutral lipid, 40% of the sterol, and 5% of the PEG or PEG-modified
lipid on a molar basis.
[0469] In some embodiments, lipid nanoparticle formulations include
57.2% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 7.1% of the
neutral lipid, 34.3% of the sterol, and 1.4% of the PEG or
PEG-modified lipid on a molar basis.
[0470] In some embodiments, lipid nanoparticle formulations include
57.5% of a cationic lipid selected from the PEG lipid is PEG-cDMA
(PEG-cDMA is further discussed in Reyes et al. (J. Controlled
Release, 107, 276-287 (2005), the contents of which are herein
incorporated by reference in their entirety), 7.5% of the neutral
lipid, 31.5% of the sterol, and 3.5% of the PEG or PEG-modified
lipid on a molar basis.
[0471] In some embodiments, lipid nanoparticle formulations
consists essentially of a lipid mixture in molar ratios of 20-70%
cationic lipid: 5-45% neutral lipid: 20-55% cholesterol: 0.5-15%
PEG-modified lipid. In some embodiments, lipid nanoparticle
formulations consists essentially of a lipid mixture in a molar
ratio of 20-60% cationic lipid: 5-25% neutral lipid: 25-55%
cholesterol: 0.5-15% PEG-modified lipid.
[0472] In some embodiments, the molar lipid ratio is 50/10/38.5/1.5
(mol % cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified
lipid, e.g., PEG-DMG, PEG-DSG or PEG-DPG), 57.2/7.1134.3/1.4 (mol %
cationic lipid/neutral lipid, e.g., DPPC/Chol/PEG-modified lipid,
e.g., PEG-cDMA), 40/15/40/5 (mol % cationic lipid/neutral lipid,
e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG),
50/10/35/4.5/0.5 (mol % cationic lipid/neutral lipid, e.g.,
DSPC/Chol/PEG-modified lipid, e.g., PEG-DSG), 50/10/35/5 (cationic
lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g.,
PEG-DMG), 40/10/40/10 (mol % cationic lipid/neutral lipid, e.g.,
DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG or PEG-cDMA),
35/15/40/10 (mol % cationic lipid/neutral lipid, e.g.,
DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG or PEG-cDMA) or
52/13/30/5 (mol % cationic lipid/neutral lipid, e.g.,
DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG or PEG-cDMA).
[0473] Non-limiting examples of lipid nanoparticle compositions and
methods of making them are described, for example, in Semple et al.
(2010) Nat. Biotechnol. 28:172-176; Jayarama et al. (2012), Angew.
Chem. Int. Ed., 51: 8529-8533; and Maier et al. (2013) Molecular
Therapy 21, 1570-1578 (the contents of each of which are
incorporated herein by reference in their entirety).
[0474] In some embodiments, lipid nanoparticle formulations may
comprise a cationic lipid, a PEG lipid and a structural lipid and
optionally comprise a non-cationic lipid. As a non-limiting
example, a lipid nanoparticle may comprise 40-60% of cationic
lipid, 5-15% of a non-cationic lipid, 1-2% of a PEG lipid and
30-50% of a structural lipid. As another non-limiting example, the
lipid nanoparticle may comprise 50% cationic lipid, 10%
non-cationic lipid, 1.5% PEG lipid and 38.5% structural lipid. As
yet another non-limiting example, a lipid nanoparticle may comprise
55% cationic lipid, 10% non-cationic lipid, 2.5% PEG lipid and
32.5% structural lipid. In some embodiments, the cationic lipid may
be any cationic lipid described herein such as, but not limited to,
DLin-KC2-DMA, DLin-MC3-DMA and di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate.
[0475] In some embodiments, the lipid nanoparticle formulations
described herein may be 4 component lipid nanoparticles. The lipid
nanoparticle may comprise a cationic lipid, a non-cationic lipid, a
PEG lipid and a structural lipid. As a non-limiting example, the
lipid nanoparticle may comprise 40-60% of cationic lipid, 5-15% of
a non-cationic lipid, 1-2% of a PEG lipid and 30-50% of a
structural lipid. As another non-limiting example, the lipid
nanoparticle may comprise 50% cationic lipid, 10% non-cationic
lipid, 1.5% PEG lipid and 38.5% structural lipid. As yet another
non-limiting example, the lipid nanoparticle may comprise 55%
cationic lipid, 10% non-cationic lipid, 2.5% PEG lipid and 32.5%
structural lipid. In some embodiments, the cationic lipid may be
any cationic lipid described herein such as, but not limited to,
DLin-KC2-DMA, DLin-MC3-DMA and di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate.
[0476] In some embodiments, the lipid nanoparticle formulations
described herein may comprise a cationic lipid, a non-cationic
lipid, a PEG lipid and a structural lipid. As a non-limiting
example, the lipid nanoparticle comprise 50% of the cationic lipid
DLin-KC2-DMA, 10% of the non-cationic lipid DSPC, 1.5% of the PEG
lipid PEG-DOMG and 38.5% of the structural lipid cholesterol. As a
non-limiting example, the lipid nanoparticle comprise 50% of the
cationic lipid DLin-MC3-DMA, 10% of the non-cationic lipid DSPC,
1.5% of the PEG lipid PEG-DOMG and 38.5% of the structural lipid
cholesterol. As a non-limiting example, the lipid nanoparticle
comprise 50% of the cationic lipid DLin-MC3-DMA, 10% of the
non-cationic lipid DSPC, 1.5% of the PEG lipid PEG-DMG and 38.5% of
the structural lipid cholesterol. As yet another non-limiting
example, the lipid nanoparticle comprise 55% of the cationic lipid
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 10% of the
non-cationic lipid DSPC, 2.5% of the PEG lipid PEG-DMG and 32.5% of
the structural lipid cholesterol.
[0477] Relative amounts of the active ingredient, the
pharmaceutically acceptable excipient, and/or any additional
ingredients in a vaccine composition may vary, depending upon the
identity, size, and/or condition of the subject being treated and
further depending upon the route by which the composition is to be
administered. For example, the composition may comprise between
0.1% and 99% (w/w) of the active ingredient. By way of example, the
composition may comprise between 0.1% and 100%, e.g., between .5
and 50%, between 1-30%, between 5-80%, at least 80% (w/w) active
ingredient.
[0478] In some embodiments, the influenza RNA (e.g. mRNA) vaccine
composition may comprise the polynucleotide described herein,
formulated in a lipid nanoparticle comprising MC3, Cholesterol,
DSPC and PEG2000-DMG, the buffer trisodium citrate, sucrose and
water for injection. As a non-limiting example, the composition
comprises: 2.0 mg/mL of drug substance, 21.8 mg/mL of MC3, 10.1
mg/mL of cholesterol, 5.4 mg/mL of DSPC, 2.7 mg/mL of PEG2000-DMG,
5.16 mg/mL of trisodium citrate, 71 mg/mL of sucrose and 1.0 mL of
water for injection.
[0479] In some embodiments, a nanoparticle (e.g., a lipid
nanoparticle) has a mean diameter of 10-500 nm, 20-400 nm, 30-300
nm, 40-200 nm. In some embodiments, a nanoparticle (e.g., a lipid
nanoparticle) has a mean diameter of 50-150 nm, 50-200 nm, 80-100
nm or 80-200 nm.
Liposomes, Lipoplexes, and Lipid Nanoparticles
[0480] The RNA (e.g., mRNA) vaccines of the disclosure can be
formulated using one or more liposomes, lipoplexes, or lipid
nanoparticles. In some embodiments, pharmaceutical compositions of
RNA (e.g., mRNA) vaccines include liposomes. Liposomes are
artificially-prepared vesicles which may primarily be composed of a
lipid bilayer and may be used as a delivery vehicle for the
administration of nutrients and pharmaceutical formulations.
Liposomes can be of different sizes such as, but not limited to, a
multilamellar vesicle (MLV) which may be hundreds of nanometers in
diameter and may contain a series of concentric bilayers separated
by narrow aqueous compartments, a small unicellular vesicle (SUV)
which may be smaller than 50 nm in diameter, and a large
unilamellar vesicle (LUV) which may be between 50 and 500 nm in
diameter. Liposome design may include, but is not limited to,
opsonins or ligands in order to improve the attachment of liposomes
to unhealthy tissue or to activate events such as, but not limited
to, endocytosis. Liposomes may contain a low or a high pH in order
to improve the delivery of the pharmaceutical formulations.
[0481] The formation of liposomes may depend on the physicochemical
characteristics such as, but not limited to, the pharmaceutical
formulation entrapped and the liposomal ingredients, the nature of
the medium in which the lipid vesicles are dispersed, the effective
concentration of the entrapped substance and its potential
toxicity, any additional processes involved during the application
and/or delivery of the vesicles, the optimization size,
polydispersity and the shelf-life of the vesicles for the intended
application, and the batch-to-batch reproducibility and possibility
of large-scale production of safe and efficient liposomal
products.
[0482] In some embodiments, pharmaceutical compositions described
herein may include, without limitation, liposomes such as those
formed from 1,2-dioleyloxy-N,N-dimethylaminopropane (DODMA)
liposomes, DiLa2 liposomes from Marina Biotech (Bothell, Wash.),
1,2-dilinoleyloxy-3-dimethylaminopropane (DLin-DMA),
2,2-dilinoleyl-4-(2-dimethylaminoethyl)[1,3]-dioxolane
(DLin-KC2-DMA), and MC3 (US20100324120; herein incorporated by
reference in its entirety) and liposomes which may deliver small
molecule drugs such as, but not limited to, DOXIL.RTM. from Janssen
Biotech, Inc. (Horsham, Pa.).
[0483] In some embodiments, pharmaceutical compositions described
herein may include, without limitation, liposomes such as those
formed from the synthesis of stabilized plasmid-lipid particles
(SPLP) or stabilized nucleic acid lipid particle (SNALP) that have
been previously described and shown to be suitable for
oligonucleotide delivery in vitro and in vivo (see Wheeler et al.
Gene Therapy. 1999 6:271-281; Zhang et al. Gene Therapy. 1999
6:1438-1447; Jeffs et al. Pharm Res. 2005 22:362-372; Morrissey et
al., Nat Biotechnol. 2005 2:1002-1007; Zimmermann et al., Nature.
2006 441:111-114; Heyes et al. J Contr Rel. 2005 107:276-287;
Semple et al. Nature Biotech. 2010 28:172-176; Judge et al. J Clin
Invest. 2009 119:661-673; deFougerolles Hum Gene Ther. 2008
19:125-132; U.S. Patent Publication No US20130122104; all of which
are incorporated herein in their entireties). The original
manufacture method by Wheeler et al. was a detergent dialysis
method, which was later improved by Jeffs et al. and is referred to
as the spontaneous vesicle formation method. The liposome
formulations are composed of 3 to 4 lipid components in addition to
the polynucleotide. As an example a liposome can contain, but is
not limited to, 55% cholesterol, 20% disteroylphosphatidyl choline
(DSPC), 10% PEG-S-DSG, and 15%
1,2-dioleyloxy-N,N-dimethylaminopropane (DODMA), as described by
Jeffs et al. As another example, certain liposome formulations may
contain, but are not limited to, 48% cholesterol, 20% DSPC, 2%
PEG-c-DMA, and 30% cationic lipid, where the cationic lipid can be
1,2-distearloxy-N,N-dimethylaminopropane (DSDMA), DODMA, DLin-DMA,
or 1,2-dilinolenyloxy-3-dimethylaminopropane (DLenDMA), as
described by Heyes et al.
[0484] In some embodiments, liposome formulations may comprise from
about 25.0% cholesterol to about 40.0% cholesterol, from about
30.0% cholesterol to about 45.0% cholesterol, from about 35.0%
cholesterol to about 50.0% cholesterol and/or from about 48.5%
cholesterol to about 60% cholesterol. In some embodiments,
formulations may comprise a percentage of cholesterol selected from
the group consisting of 28.5%, 31.5%, 33.5%, 36.5%, 37.0%, 38.5%,
39.0% and 43.5%. In some embodiments, formulations may comprise
from about 5.0% to about 10.0% DSPC and/or from about 7.0% to about
15.0% DSPC.
[0485] In some embodiments, the RNA (e.g., mRNA) vaccine
pharmaceutical compositions may be formulated in liposomes such as,
but not limited to, DiLa2 liposomes (Marina Biotech, Bothell,
Wash.), SMARTICLES.RTM. (Marina Biotech, Bothell, Wash.), neutral
DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) based liposomes
(e.g., siRNA delivery for ovarian cancer (Landen et al. Cancer
Biology & Therapy 2006 5(12)1708-1713); herein incorporated by
reference in its entirety) and hyaluronan-coated liposomes (Quiet
Therapeutics, Israel).
[0486] In some embodiments, the cationic lipid may be a low
molecular weight cationic lipid such as those described in U.S.
Patent Application No. 2013/0090372, the contents of which are
herein incorporated by reference in their entirety.
[0487] In some embodiments, the RNA (e.g., mRNA) vaccines may be
formulated in a lipid vesicle, which may have crosslinks between
functionalized lipid bilayers.
[0488] In some embodiments, the RNA (e.g., mRNA) vaccines may be
formulated in a lipid-polycation complex. The formation of the
lipid-polycation complex may be accomplished by methods known in
the art and/or as described in U.S. Pub. No. 2012/0178702, herein
incorporated by reference in its entirety. As a non-limiting
example, the polycation may include a cationic peptide or a
polypeptide such as, but not limited to, polylysine, polyornithine
and/or polyarginine. In some embodiments, the RNA (e.g., mRNA)
vaccines may be formulated in a lipid-polycation complex, which may
further include a non-cationic lipid such as, but not limited to,
cholesterol or dioleoyl phosphatidylethanolamine (DOPE).
[0489] In some embodiments, the ratio of PEG in the lipid
nanoparticle (LNP) formulations may be increased or decreased
and/or the carbon chain length of the PEG lipid may be modified
from C14 to C18 to alter the pharmacokinetics and/or
biodistribution of the LNP formulations. As a non-limiting example,
LNP formulations may contain from about 0.5% to about 3.0%, from
about 1.0% to about 3.5%, from about 1.5% to about 4.0%, from about
2.0% to about 4.5%, from about 2.5% to about 5.0% and/or from about
3.0% to about 6.0% of the lipid molar ratio of PEG-c-DOMG
(R-3-[.omega.-methoxy-poly(ethyleneglycol)2000)carbamoyl)]-1,2-dimyristyl-
oxypropyl-3-amine) (also referred to herein as PEG-DOMG) as
compared to the cationic lipid, DSPC and cholesterol. In some
embodiments, the PEG-c-DOMG may be replaced with a PEG lipid such
as, but not limited to, PEG-DSG (1,2-Distearoyl-sn-glycerol,
methoxypolyethylene glycol), PEG-DMG (1,2-Dimyristoyl-sn-glycerol)
and/or PEG-DPG (1,2-Dipalmitoyl-sn-glycerol, methoxypolyethylene
glycol). The cationic lipid may be selected from any lipid known in
the art such as, but not limited to, DLin-MC3-DMA, DLin-DMA,
C12-200 and DLin-KC2-DMA.
[0490] In some embodiments, the RNA (e.g., mRNA) vaccines may be
formulated in a lipid nanoparticle.
[0491] In some embodiments, the RNA (e.g., mRNA) vaccine
formulation comprising the polynucleotide is a nanoparticle which
may comprise at least one lipid. The lipid may be selected from,
but is not limited to, DLin-DMA, DLin-K-DMA, 98N12-5, C12-200,
DLin-MC3-DMA, DLin-KC2-DMA, DODMA, PLGA, PEG, PEG-DMG, PEGylated
lipids and amino alcohol lipids. In another aspect, the lipid may
be a cationic lipid such as, but not limited to, DLin-DMA,
DLin-D-DMA, DLin-MC3-DMA, DLin-KC2-DMA, DODMA and amino alcohol
lipids. The amino alcohol cationic lipid may be the lipids
described in and/or made by the methods described in U.S. Patent
Publication No. US20130150625, herein incorporated by reference in
its entirety. As a non-limiting example, the cationic lipid may be
2-amino-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-2-{[(9Z,2Z)-octadeca-9,12-
-dien-1-yloxy]methyl}propan-1-ol (Compound 1 in US2013/0150625);
2-amino-3-[(9Z)-octadec-9-en-1-yloxy]-2-{[(9Z)-octadec-9-en-1-yloxy]methy-
l}propan-1-ol (Compound 2 in US2013/0150625);
2-amino-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-2-[(octyloxy)methyl]propa-
n-1-ol (Compound 3 in US2013/0150625); and
2-(dimethylamino)-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-2-{[(9Z,12Z)-oc-
tadeca-9,12-dien-1-yloxy]methyl}propan-1-ol (Compound 4 in
US2013/0150625); or any pharmaceutically acceptable salt or
stereoisomer thereof.
[0492] Lipid nanoparticle formulations typically comprise a lipid,
in particular, an ionizable cationic lipid, for example,
2,2-dilinoleyl-4-dimethylaminoethyl[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), or
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, and further
comprise a neutral lipid, a sterol and a molecule capable of
reducing particle aggregation, for example a PEG or PEG-modified
lipid.
[0493] In some embodiments, the lipid nanoparticle formulation
consists essentially of (i) at least one lipid selected from the
group consisting of
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate; (ii) a neutral
lipid selected from DSPC, DPPC, POPC, DOPE and SM; (iii) a sterol,
e.g., cholesterol; and (iv) a PEG-lipid, e.g., PEG-DMG or PEG-cDMA,
in a molar ratio of about 20-60% cationic lipid: 5-25% neutral
lipid: 25-55% sterol; 0.5-15% PEG-lipid.
[0494] In some embodiments, the formulation includes from about 25%
to about 75% on a molar basis of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, e.g., from
about 35 to about 65%, from about 45 to about 65%, about 60%, about
57.5%, about 50% or about 40% on a molar basis.
[0495] In some embodiments, the formulation includes from about
0.5% to about 15% on a molar basis of the neutral lipid e.g., from
about 3 to about 12%, from about 5 to about 10% or about 15%, about
10%, or about 7.5% on a molar basis. Examples of neutral lipids
include, but are not limited to, DSPC, POPC, DPPC, DOPE and SM. In
some embodiments, the formulation includes from about 5% to about
50% on a molar basis of the sterol (e.g., about 15 to about 45%,
about 20 to about 40%, about 40%, about 38.5%, about 35%, or about
31% on a molar basis. An exemplary sterol is cholesterol. In some
embodiments, the formulation includes from about 0.5% to about 20%
on a molar basis of the PEG or PEG-modified lipid (e.g., about 0.5
to about 10%, about 0.5 to about 5%, about 1.5%, about 0.5%, about
1.5%, about 3.5%, or about 5% on a molar basis. In some
embodiments, the PEG or PEG modified lipid comprises a PEG molecule
of an average molecular weight of 2,000 Da. In other embodiments,
the PEG or PEG modified lipid comprises a PEG molecule of an
average molecular weight of less than 2,000, for example around
1,500 Da, around 1,000 Da, or around 500 Da. Examples of
PEG-modified lipids include, but are not limited to, PEG-distearoyl
glycerol (PEG-DMG) (also referred herein as PEG-C14 or C14-PEG),
PEG-cDMA (further discussed in Reyes et al. J. Controlled Release,
107, 276-287 (2005) the contents of which are herein incorporated
by reference in their entirety).
[0496] In some embodiments, the formulations of the present
disclosure include 25-75% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 0.5-15% of the
neutral lipid, 5-50% of the sterol, and 0.5-20% of the PEG or
PEG-modified lipid on a molar basis.
[0497] In some embodiments, the formulations of the present
disclosure include 35-65% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 3-12% of the
neutral lipid, 15-45% of the sterol, and 0.5-10% of the PEG or
PEG-modified lipid on a molar basis.
[0498] In some embodiments, the formulations of the present
disclosure include 45-65% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, 5-10% of the
neutral lipid, 25-40% of the sterol, and 0.5-10% of the PEG or
PEG-modified lipid on a molar basis.
[0499] In some embodiments, the formulations of the present
disclosure include about 60% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, about 7.5% of
the neutral lipid, about 31% of the sterol, and about 1.5% of the
PEG or PEG-modified lipid on a molar basis.
[0500] In some embodiments, the formulations of the present
disclosure include about 50% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, about 10% of
the neutral lipid, about 38.5% of the sterol, and about 1.5% of the
PEG or PEG-modified lipid on a molar basis.
[0501] In some embodiments, the formulations of the present
disclosure include about 50% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, about 10% of
the neutral lipid, about 35% of the sterol, about 4.5% or about 5%
of the PEG or PEG-modified lipid, and about 0.5% of the targeting
lipid on a molar basis.
[0502] In some embodiments, the formulations of the present
disclosure include about 40% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, about 15% of
the neutral lipid, about 40% of the sterol, and about 5% of the PEG
or PEG-modified lipid on a molar basis.
[0503] In some embodiments, the formulations of the present
disclosure include about 57.2% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, about 7.1% of
the neutral lipid, about 34.3% of the sterol, and about 1.4% of the
PEG or PEG-modified lipid on a molar basis.
[0504] In some embodiments, the formulations of the present
disclosure include about 57.5% of a cationic lipid selected from
the PEG lipid is PEG-cDMA (PEG-cDMA is further discussed in Reyes
et al. (J. Controlled Release, 107, 276-287 (2005), the contents of
which are herein incorporated by reference in their entirety),
about 7.5% of the neutral lipid, about 31.5% of the sterol, and
about 3.5% of the PEG or PEG-modified lipid on a molar basis.
[0505] In some embodiments, lipid nanoparticle formulation consists
essentially of a lipid mixture in molar ratios of about 20-70%
cationic lipid: 5-45% neutral lipid: 20-55% cholesterol: 0.5-15%
PEG-modified lipid; more preferably in a molar ratio of about
20-60% cationic lipid: 5-25% neutral lipid: 25-55% cholesterol:
0.5-15% PEG-modified lipid.
[0506] In some embodiments, the molar lipid ratio is approximately
50/10/38.5/1.5 (mol % cationic lipid/neutral lipid, e.g.,
DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG, PEG-DSG or PEG-DPG),
57.2/7.1134.3/1.4 (mol % cationic lipid/neutral lipid, e.g.,
DPPC/Chol/PEG-modified lipid, e.g., PEG-cDMA), 40/15/40/5 (mol %
cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid,
e.g., PEG-DMG), 50/10/35/4.5/0.5 (mol % cationic lipid/neutral
lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DSG),
50/10/35/5 (cationic lipid/neutral lipid, e.g.,
DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG), 40/10/40/10 (mol %
cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid,
e.g., PEG-DMG or PEG-cDMA), 35/15/40/10 (mol % cationic
lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g.,
PEG-DMG or PEG-cDMA) or 52/13/30/5 (mol % cationic lipid/neutral
lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG or
PEG-cDMA).
[0507] Examples of lipid nanoparticle compositions and methods of
making same are described, for example, in Semple et al. (2010)
Nat. Biotechnol. 28:172-176; Jayarama et al. (2012), Angew. Chem.
Int. Ed., 51: 8529-8533; and Maier et al. (2013) Molecular Therapy
21, 1570-1578 (the contents of each of which are incorporated
herein by reference in their entirety).
[0508] In some embodiments, the lipid nanoparticle formulations
described herein may comprise a cationic lipid, a PEG lipid and a
structural lipid and optionally comprise a non-cationic lipid. As a
non-limiting example, the lipid nanoparticle may comprise about
40-60% of cationic lipid, about 5-15% of a non-cationic lipid,
about 1-2% of a PEG lipid and about 30-50% of a structural lipid.
As another non-limiting example, the lipid nanoparticle may
comprise about 50% cationic lipid, about 10% non-cationic lipid,
about 1.5% PEG lipid and about 38.5% structural lipid. As yet
another non-limiting example, the lipid nanoparticle may comprise
about 55% cationic lipid, about 10% non-cationic lipid, about 2.5%
PEG lipid and about 32.5% structural lipid. In some embodiments,
the cationic lipid may be any cationic lipid described herein such
as, but not limited to, DLin-KC2-DMA, DLin-MC3-DMA and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate.
[0509] In some embodiments, the lipid nanoparticle formulations
described herein may be 4 component lipid nanoparticles. The lipid
nanoparticle may comprise a cationic lipid, a non-cationic lipid, a
PEG lipid and a structural lipid. As a non-limiting example, the
lipid nanoparticle may comprise about 40-60% of cationic lipid,
about 5-15% of a non-cationic lipid, about 1-2% of a PEG lipid and
about 30-50% of a structural lipid. As another non-limiting
example, the lipid nanoparticle may comprise about 50% cationic
lipid, about 10% non-cationic lipid, about 1.5% PEG lipid and about
38.5% structural lipid. As yet another non-limiting example, the
lipid nanoparticle may comprise about 55% cationic lipid, about 10%
non-cationic lipid, about 2.5% PEG lipid and about 32.5% structural
lipid. In some embodiments, the cationic lipid may be any cationic
lipid described herein such as, but not limited to, DLin-KC2-DMA,
DLin-MC3-DMA and di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate.
[0510] In some embodiments, the lipid nanoparticle formulations
described herein may comprise a cationic lipid, a non-cationic
lipid, a PEG lipid and a structural lipid. As a non-limiting
example, the lipid nanoparticle comprise about 50% of the cationic
lipid DLin-KC2-DMA, about 10% of the non-cationic lipid DSPC, about
1.5% of the PEG lipid PEG-DOMG and about 38.5% of the structural
lipid cholesterol. As a non-limiting example, the lipid
nanoparticle comprise about 50% of the cationic lipid DLin-MC3-DMA,
about 10% of the non-cationic lipid DSPC, about 1.5% of the PEG
lipid PEG-DOMG and about 38.5% of the structural lipid cholesterol.
As a non-limiting example, the lipid nanoparticle comprise about
50% of the cationic lipid DLin-MC3-DMA, about 10% of the
non-cationic lipid DSPC, about 1.5% of the PEG lipid PEG-DMG and
about 38.5% of the structural lipid cholesterol. As yet another
non-limiting example, the lipid nanoparticle comprise about 55% of
the cationic lipid di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate, about 10% of
the non-cationic lipid DSPC, about 2.5% of the PEG lipid PEG-DMG
and about 32.5% of the structural lipid cholesterol.
[0511] As a non-limiting example, the cationic lipid may be
selected from (20Z,23Z)-N,N-dimethylnonacosa-20,23-dien-10-amine,
(17Z,20Z)-N,N-dimemylhexacosa-17,20-dien-9-amine,
(1Z,19Z)-N5N-dimethylpentacosa-1 6, 19-dien-8-amine,
(13Z,16Z)-N,N-dimethyldocosa-13,16-dien-5-amine,
(12Z,15Z)-N,N-dimethylhenicosa-12,15-dien-4-amine,
(14Z,17Z)-N,N-dimethyltricosa-14,17-dien-6-amine,
(15Z,18Z)-N,N-dimethyltetracosa-15,18-dien-7-amine,
(18Z,21Z)-N,N-dimethylheptacosa-18,21-dien-10-amine,
(15Z,18Z)-N,N-dimethyltetracosa-15,18-dien-5-amine,
(14Z,17Z)-N,N-dimethyltricosa-14,17-dien-4-amine,
(19Z,22Z)-N,N-dimeihyloctacosa-19,22-dien-9-amine, (18Z,21
Z)-N,N-dimethylheptacosa-18,21-dien-8-amine,
(17Z,20Z)-N,N-dimethylhexacosa-17,20-dien-7-amine,
(16Z,19Z)-N,N-dimethylpentacosa-16,19-dien-6-amine,
(22Z,25Z)-N,N-dimethylhentriaconta-22,25-dien-10-amine, (21
Z,24Z)-N,N-dimethyltriaconta-21,24-dien-9-amine,
(18Z)-N,N-dimetylheptacos-18-en-10-amine,
(17Z)-N,N-dimethylhexacos-17-en-9-amine,
(19Z,22Z)-N,N-dimethyloctacosa-19,22-dien-7-amine,
N,N-dimethylheptacosan-10-amine,
(20Z,23Z)-N-ethyl-N-methylnonacosa-20,23-dien-10-amine,
1-[(11Z,14Z)-1-nonylicosa-11,14-dien-1-yl]pyrrolidine,
(20Z)-N,N-dimethylheptacos-20-en-10-amine, (15Z)-N,N-dimethyl
eptacos-15-en-10-amine, (14Z)-N,N-dimethylnonacos-14-en-10-amine,
(17Z)-N,N-dimethylnonacos-17-en-10-amine,
(24Z)-N,N-dimethyltritriacont-24-en-10-amine,
(20Z)-N,N-dimethylnonacos-20-en-10-amine,
(22Z)-N,N-dimethylhentriacont-22-en-10-amine,
(16Z)-N,N-dimethylpentacos-16-en-8-amine,
(12Z,15Z)-N,N-dimethyl-2-nonylhenicosa-12,15-dien-1-amine,
(13Z,16Z)-N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine,
N,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]eptadecan-8-amine,
1-[(1S,2R)-2-hexylcyclopropyl]-N,N-dimethylnonadecan-10-amine,
N,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]nonadecan-10-amine,
N,N-dimethyl-21-[(1S,2R)-2-octylcyclopropyl]henicosan-10-amine,N,N-dimeth-
yl-1-[(1S,2S)-2-{[(1R,2R)-2-pentylcycIopropyl]methyl}cyclopropyl]nonadecan-
-10-amine,N,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]hexadecan-8-amine,
N,N-dimethyl-[(1R,2S)-2-undecyIcyclopropyl]tetradecan-5-amine,
N,N-dimethyl-3-{7-[(1S,2R)-2-octylcyclopropyl]heptyl}
dodecan-1-amine, 1-[(1R,2S)-2-hepty
lcyclopropyl]-N,N-dimethyloctadecan-9-amine,
1-[(1S,2R)-2-decylcyclopropyl]-N,N-dimethylpentadecan-6-amine,
N,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]pentadecan-8-amine,
R-N,N-dimethyl-1-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-3-(octyloxy)propan-
-2-amine,
S-N,N-dimethyl-1-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-3-(octylo-
xy)propan-2-amine,
1-{2-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-1-[(octyloxy)methyl]ethyl}pyrr-
olidine, (2
S)-N,N-dimethyl-1-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-3-[(5Z)-oct-5-en--
1-yloxy]propan-2-amine,
1-{2-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-1-[(octyloxy)methyl]ethyl}azet-
idine, (2
S)-1-(hexyloxy)-N,N-dimethyl-3-[(9Z,12Z)-octadeca-9,12-dien-1-yl-
oxy]propan-2-amine,
(2S)-1-(heptyloxy)-N,N-dimethyl-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]pr-
opan-2-amine,
N,N-dimethyl-1-(nonyloxy)-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]propan-2-
-amine,
N,N-dimethyl-1-[(9Z)-octadec-9-en-1-yloxy]-3-(octyloxy)propan-2-am-
ine;
(2S)-N,N-dimethyl-1-[(6Z,9Z,12Z)-octadeca-6,9,12-trien-1-yloxy]-3-(oc-
tyloxy)propan-2-amine,
(2S)-1-[(11Z,14Z)-icosa-11,14-dien-1-yloxy]-N,N-dimethyl-3-(pentyloxy)pro-
pan-2-amine,
(2S)-1-(hexyloxy)-3-[(11Z,14Z)-icosa-11,14-dien-1-yloxy]-N,N-dimethylprop-
an-2-amine,
1-[(11Z,14Z)-icosa-11,14-dien-1-yloxy]-N,N-dimethyl-3-(octyloxy)propan-2--
amine,
1-[(13Z,16Z)-docosa-13,16-dien-1-yloxy]-N,N-dimethyl-3-(octyloxy)pr-
opan-2-amine,
(2S)-1-[(13Z,16Z)-docosa-13,16-dien-1-yloxy]-3-(hexyloxy)-N,N-dimethylpro-
pan-2-amine,
(2S)-1-[(13Z)-docos-13-en-1-yloxy]-3-(hexyloxy)-N,N-dimethylpropan-2-amin-
e,
1-[(13Z)-docos-13-en-1-yloxy]-N,N-dimethyl-3-(octyloxy)propan-2-amine,
1-[(9Z)-hexadec-9-en-1-yloxy]-N,N-dimethyl-3-(octyloxy)propan-2-amine,
(2R)-N,N-dimethyl-H(1-metoylo
ctyl)oxy]-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]propan-2-amine,
(2R)-1-[(3
,7-dimethyloctyl)oxy]-N,N-dimethyl-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy-
]propan-2-amine,
N,N-dimethyl-1-(octyloxy)-3-({8-[(1S,2S)-2-{[(1R,2R)-2-pentylcyclopropyl]-
methyl}cyclopropyl]octyl}oxy)propan-2-amine, N,N-dimethyl
-1-{[8-(2-oclylcyclopropyl)octyl]oxy}-3-(octyloxy)propan-2-amine
and (11E,20Z,23Z)-N,N-dimethylnonacosa-11,20,2-trien-10-amine or a
pharmaceutically acceptable salt or stereoisomer thereof.
[0512] In some embodiments, the LNP formulations of the RNA (e.g.,
mRNA) vaccines may contain PEG-c-DOMG at 3% lipid molar ratio. In
some embodiments, the LNP formulations of the RNA (e.g., mRNA)
vaccines may contain PEG-c-DOMG at 1.5% lipid molar ratio.
[0513] In some embodiments, the pharmaceutical compositions of the
RNA (e.g., mRNA) vaccines may include at least one of the PEGylated
lipids described in International Publication No. WO2012/099755,
the contents of which are herein incorporated by reference in their
entirety. In some embodiments, the LNP formulation may contain
PEG-DMG 2000
(1,2-dimyristoyl-sn-glycero-3-phophoethanolamine-N-[methoxy(polyethylene
glycol)-2000). In some embodiments, the LNP formulation may contain
PEG-DMG 2000, a cationic lipid known in the art and at least one
other component. In some embodiments, the LNP formulation may
contain PEG-DMG 2000, a cationic lipid known in the art, DSPC and
cholesterol. As a non-limiting example, the LNP formulation may
contain PEG-DMG 2000, DLin-DMA, DSPC and cholesterol. As another
non-limiting example the LNP formulation may contain PEG-DMG 2000,
DLin-DMA, DSPC and cholesterol in a molar ratio of 2:40:10:48 (see
e.g., Geall et al., Nonviral delivery of self-amplifying RNA (e.g.,
mRNA) vaccines, PNAS 2012; PMID: 22908294, the contents of each of
which are herein incorporated by reference in their entirety).
[0514] The lipid nanoparticles described herein may be made in a
sterile environment.
[0515] In some embodiments, the LNP formulation may be formulated
in a nanoparticle such as a nucleic acid-lipid particle. As a
non-limiting example, the lipid particle may comprise one or more
active agents or therapeutic agents; one or more cationic lipids
comprising from about 50 mol % to about 85 mol % of the total lipid
present in the particle; one or more non-cationic lipids comprising
from about 13 mol % to about 49.5 mol % of the total lipid present
in the particle; and one or more conjugated lipids that inhibit
aggregation of particles comprising from about 0.5 mol % to about 2
mol % of the total lipid present in the particle.
[0516] The nanoparticle formulations may comprise a phosphate
conjugate. The phosphate conjugate may increase in vivo circulation
times and/or increase the targeted delivery of the nanoparticle. As
a non-limiting example, the phosphate conjugates may include a
compound of any one of the formulas described in International
Application No. WO2013/033438, the contents of which are herein
incorporated by reference in its entirety.
[0517] The nanoparticle formulation may comprise a polymer
conjugate. The polymer conjugate may be a water soluble conjugate.
The polymer conjugate may have a structure as described in U.S.
Patent Application No. 2013/0059360, the contents of which are
herein incorporated by reference in its entirety. In some
embodiments, polymer conjugates with the polynucleotides of the
present disclosure may be made using the methods and/or segmented
polymeric reagents described in U.S. Patent Application No.
2013/0072709, the contents of which are herein incorporated by
reference in its entirety. In some embodiments, the polymer
conjugate may have pendant side groups comprising ring moieties
such as, but not limited to, the polymer conjugates described in
U.S. Patent Publication No. US2013/0196948, the contents which are
herein incorporated by reference in its entirety.
[0518] The nanoparticle formulations may comprise a conjugate to
enhance the delivery of nanoparticles of the present disclosure in
a subject. Further, the conjugate may inhibit phagocytic clearance
of the nanoparticles in a subject. In one aspect, the conjugate may
be a "self" peptide designed from the human membrane protein CD47
(e.g., the "self" particles described by Rodriguez et al. (Science
2013 339, 971-975), herein incorporated by reference in its
entirety). As shown by Rodriguez et al., the self peptides delayed
macrophage-mediated clearance of nanoparticles which enhanced
delivery of the nanoparticles. In another aspect, the conjugate may
be the membrane protein CD47 (e.g., see Rodriguez et al. Science
2013 339, 971-975, herein incorporated by reference in its
entirety). Rodriguez et al. showed that, similarly to "self"
peptides, CD47 can increase the circulating particle ratio in a
subject as compared to scrambled peptides and PEG coated
nanoparticles.
[0519] In some embodiments, the RNA (e.g., mRNA) vaccines of the
present disclosure are formulated in nanoparticles which comprise a
conjugate to enhance the delivery of the nanoparticles of the
present disclosure in a subject. The conjugate may be the CD47
membrane or the conjugate may be derived from the CD47 membrane
protein, such as the "self" peptide described previously. In some
embodiments, the nanoparticle may comprise PEG and a conjugate of
CD47 or a derivative thereof. In some embodiments, the nanoparticle
may comprise both the "self" peptide described above and the
membrane protein CD47.
[0520] In some embodiments, a "self" peptide and/or CD47 protein
may be conjugated to a virus-like particle or pseudovirion, as
described herein for delivery of the RNA (e.g., mRNA) vaccines of
the present disclosure.
[0521] In some embodiments, RNA (e.g., mRNA) vaccine pharmaceutical
compositions comprising the polynucleotides of the present
disclosure and a conjugate that may have a degradable linkage.
Non-limiting examples of conjugates include an aromatic moiety
comprising an ionizable hydrogen atom, a spacer moiety, and a
water-soluble polymer. As a non-limiting example, pharmaceutical
compositions comprising a conjugate with a degradable linkage and
methods for delivering such pharmaceutical compositions are
described in U.S. Patent Publication No. US2013/0184443, the
contents of which are herein incorporated by reference in their
entirety.
[0522] The nanoparticle formulations may be a carbohydrate
nanoparticle comprising a carbohydrate carrier and a RNA (e.g.,
mRNA) vaccine. As a non-limiting example, the carbohydrate carrier
may include, but is not limited to, an anhydride-modified
phytoglycogen or glycogen-type material, phytoglycogen octenyl
succinate, phytoglycogen beta-dextrin, anhydride-modified
phytoglycogen beta-dextrin. (See e.g., International Publication
No. WO2012/109121; the contents of which are herein incorporated by
reference in their entirety).
[0523] Nanoparticle formulations of the present disclosure may be
coated with a surfactant or polymer in order to improve the
delivery of the particle. In some embodiments, the nanoparticle may
be coated with a hydrophilic coating such as, but not limited to,
PEG coatings and/or coatings that have a neutral surface charge.
The hydrophilic coatings may help to deliver nanoparticles with
larger payloads such as, but not limited to, RNA (e.g., mRNA)
vaccines within the central nervous system. As a non-limiting
example nanoparticles comprising a hydrophilic coating and methods
of making such nanoparticles are described in U.S. Patent
Publication No. US2013/0183244, the contents of which are herein
incorporated by reference in their entirety.
[0524] In some embodiments, the lipid nanoparticles of the present
disclosure may be hydrophilic polymer particles. Non-limiting
examples of hydrophilic polymer particles and methods of making
hydrophilic polymer particles are described in U.S. Patent
Publication No. US2013/0210991, the contents of which are herein
incorporated by reference in their entirety.
[0525] In some embodiments, the lipid nanoparticles of the present
disclosure may be hydrophobic polymer particles.
[0526] Lipid nanoparticle formulations may be improved by replacing
the cationic lipid with a biodegradable cationic lipid which is
known as a rapidly eliminated lipid nanoparticle (reLNP). Ionizable
cationic lipids, such as, but not limited to, DLinDMA,
DLin-KC2-DMA, and DLin-MC3-DMA, have been shown to accumulate in
plasma and tissues over time and may be a potential source of
toxicity. The rapid metabolism of the rapidly eliminated lipids can
improve the tolerability and therapeutic index of the lipid
nanoparticles by an order of magnitude from a 1 mg/kg dose to a 10
mg/kg dose in rat. Inclusion of an enzymatically degraded ester
linkage can improve the degradation and metabolism profile of the
cationic component, while still maintaining the activity of the
reLNP formulation. The ester linkage can be internally located
within the lipid chain or it may be terminally located at the
terminal end of the lipid chain. The internal ester linkage may
replace any carbon in the lipid chain.
[0527] In some embodiments, the internal ester linkage may be
located on either side of the saturated carbon.
[0528] In some embodiments, an immune response may be elicited by
delivering a lipid nanoparticle which may include a nanospecies, a
polymer and an immunogen. (U.S. Publication No. 2012/0189700 and
International Publication No. WO2012/099805; each of which is
herein incorporated by reference in their entirety). The polymer
may encapsulate the nanospecies or partially encapsulate the
nanospecies. The immunogen may be a recombinant protein, a modified
RNA and/or a polynucleotide described herein. In some embodiments,
the lipid nanoparticle may be formulated for use in a vaccine such
as, but not limited to, against a pathogen.
[0529] Lipid nanoparticles may be engineered to alter the surface
properties of particles so the lipid nanoparticles may penetrate
the mucosal barrier. Mucus is located on mucosal tissue such as,
but not limited to, oral (e.g., the buccal and esophageal membranes
and tonsil tissue), ophthalmic, gastrointestinal (e.g., stomach,
small intestine, large intestine, colon, rectum), nasal,
respiratory (e.g., nasal, pharyngeal, tracheal and bronchial
membranes), genital (e.g., vaginal, cervical and urethral
membranes). Nanoparticles larger than 10-200 nm which are preferred
for higher drug encapsulation efficiency and the ability to provide
the sustained delivery of a wide array of drugs have been thought
to be too large to rapidly diffuse through mucosal barriers. Mucus
is continuously secreted, shed, discarded or digested and recycled
so most of the trapped particles may be removed from the mucosa
tissue within seconds or within a few hours. Large polymeric
nanoparticles (200 nm -500 nm in diameter) which have been coated
densely with a low molecular weight polyethylene glycol (PEG)
diffused through mucus only 4 to 6-fold lower than the same
particles diffusing in water (Lai et al. PNAS 2007 104:1482-487;
Lai et al. Adv Drug Deliv Rev. 2009 61: 158-171; each of which is
herein incorporated by reference in their entirety). The transport
of nanoparticles may be determined using rates of permeation and/or
fluorescent microscopy techniques including, but not limited to,
fluorescence recovery after photobleaching (FRAP) and high
resolution multiple particle tracking (MPT). As a non-limiting
example, compositions which can penetrate a mucosal barrier may be
made as described in U.S. Pat. No. 8,241,670 or International
Patent Publication No. WO2013/110028, the contents of each of which
are herein incorporated by reference in its entirety.
[0530] The lipid nanoparticle engineered to penetrate mucus may
comprise a polymeric material (i.e. a polymeric core) and/or a
polymer-vitamin conjugate and/or a tri-block co-polymer. The
polymeric material may include, but is not limited to, polyamines,
polyethers, polyamides, polyesters, polycarbamates, polyureas,
polycarbonates, poly(styrenes), polyimides, polysulfones,
polyurethanes, polyacetylenes, polyethylenes, polyethyeneimines,
polyisocyanates, polyacrylates, polymethacrylates,
polyacrylonitriles, and polyarylates. The polymeric material may be
biodegradable and/or biocompatible. Non-limiting examples of
biocompatible polymers are described in International Patent
Publication No. WO2013/116804, the contents of which are herein
incorporated by reference in their entirety. The polymeric material
may additionally be irradiated. As a non-limiting example, the
polymeric material may be gamma irradiated (see e.g., International
App. No. WO2012/082165, herein incorporated by reference in its
entirety). Non-limiting examples of specific polymers include
poly(caprolactone) (PCL), ethylene vinyl acetate polymer (EVA),
poly(lactic acid) (PLA), poly(L-lactic acid) (PLLA), poly(glycolic
acid) (PGA), poly(lactic acid-co-glycolic acid) (PLGA),
poly(L-lactic acid-co-glycolic acid) (PLLGA), poly(D,L-lactide)
(PDLA), poly(L-lactide) (PLLA), poly(D,L-lactide-co-caprolactone),
poly(D,L-lactide-co-caprolactone-co-glycolide),
poly(D,L-lactide-co-PEO-co-D,L-lactide),
poly(D,L-lactide-co-PPO-co-D,L-lactide), polyalkyl cyanoacralate,
polyurethane, poly-L-lysine (PLL), hydroxypropyl methacrylate
(HPMA), polyethyleneglycol, poly-L-glutamic acid, poly(hydroxy
acids), polyanhydrides, polyorthoesters, poly(ester amides),
polyamides, poly(ester ethers), polycarbonates, polyalkylenes such
as polyethylene and polypropylene, polyalkylene glycols such as
poly(ethylene glycol) (PEG), polyalkylene oxides (PEO),
polyalkylene terephthalates such as poly(ethylene terephthalate),
polyvinyl alcohols (PVA), polyvinyl ethers, polyvinyl esters such
as poly(vinyl acetate), polyvinyl halides such as poly(vinyl
chloride) (PVC), polyvinylpyrrolidone, polysiloxanes, polystyrene
(PS), polyurethanes, derivatized celluloses such as alkyl
celluloses, hydroxyalkyl celluloses, cellulose ethers, cellulose
esters, nitro celluloses, hydroxypropylcellulose,
carboxymethylcellulose, polymers of acrylic acids, such as
poly(methyl(meth)acrylate) (PMMA), poly(ethyl(meth)acrylate),
poly(butyl(meth)acrylate), poly(isobutyl(meth)acrylate),
poly(hexyl(meth)acrylate), poly(isodecyl(meth)acrylate),
poly(lauryl(meth)acrylate), poly(phenyl(meth)acrylate), poly(methyl
acrylate), poly(isopropyl acrylate), poly(isobutyl acrylate),
poly(octadecyl acrylate) and copolymers and mixtures thereof,
polydioxanone and its copolymers, polyhydroxyalkanoates,
polypropylene fumarate, polyoxymethylene, poloxamers,
poly(ortho)esters, poly(butyric acid), poly(valeric acid),
poly(lactide-co-caprolactone), PEG-PLGA-PEG and trimethylene
carbonate, polyvinylpyrrolidone. The lipid nanoparticle may be
coated or associated with a co-polymer such as, but not limited to,
a block co-polymer (such as a branched polyether-polyamide block
copolymer described in International Publication No. WO2013/012476,
herein incorporated by reference in its entirety), and
(poly(ethylene glycol))-(poly(propylene oxide))-(poly(ethylene
glycol)) triblock copolymer (see e.g., U.S. Publication
2012/0121718 and U.S. Publication 2010/0003337 and U.S. Pat. No.
8,263,665, the contents of each of which is herein incorporated by
reference in their entirety). The co-polymer may be a polymer that
is generally regarded as safe (GRAS) and the formation of the lipid
nanoparticle may be in such a way that no new chemical entities are
created. For example, the lipid nanoparticle may comprise
poloxamers coating PLGA nanoparticles without forming new chemical
entities which are still able to rapidly penetrate human mucus
(Yang et al. Angew. Chem. Int. Ed. 2011 50:2597-2600; the contents
of which are herein incorporated by reference in their entirety). A
non-limiting scalable method to produce nanoparticles which can
penetrate human mucus is described by Xu et al. (see, e.g., J
Control Release 2013, 170:279-86; the contents of which are herein
incorporated by reference in their entirety).
[0531] The vitamin of the polymer-vitamin conjugate may be vitamin
E. The vitamin portion of the conjugate may be substituted with
other suitable components such as, but not limited to, vitamin A,
vitamin E, other vitamins, cholesterol, a hydrophobic moiety, or a
hydrophobic component of other surfactants (e.g., sterol chains,
fatty acids, hydrocarbon chains and alkylene oxide chains).
[0532] The lipid nanoparticle engineered to penetrate mucus may
include surface altering agents such as, but not limited to,
polynucleotides, anionic proteins (e.g., bovine serum albumin),
surfactants (e.g., cationic surfactants such as for example
dimethyldioctadecyl-ammonium bromide), sugars or sugar derivatives
(e.g., cyclodextrin), nucleic acids, polymers (e.g., heparin,
polyethylene glycol and poloxamer), mucolytic agents (e.g.,
N-acetylcysteine, mugwort, bromelain, papain, clerodendrum,
acetylcysteine, bromhexine, carbocisteine, eprazinone, mesna,
ambroxol, sobrerol, domiodol, letosteine, stepronin, tiopronin, gel
solin, thymosin .beta.4 dornase alfa, neltenexine, erdosteine) and
various DNases including rhDNase. The surface altering agent may be
embedded or enmeshed in the particle's surface or disposed (e.g.,
by coating, adsorption, covalent linkage, or other process) on the
surface of the lipid nanoparticle. (see e.g., U.S. Publication
2010/0215580 and U.S. Publication 2008/0166414 and US2013/0164343;
the contents of each of which are herein incorporated by reference
in their entirety).
[0533] In some embodiments, the mucus penetrating lipid
nanoparticles may comprise at least one polynucleotide described
herein. The polynucleotide may be encapsulated in the lipid
nanoparticle and/or disposed on the surface of the particle. The
polynucleotide may be covalently coupled to the lipid nanoparticle.
Formulations of mucus penetrating lipid nanoparticles may comprise
a plurality of nanoparticles. Further, the formulations may contain
particles which may interact with the mucus and alter the
structural and/or adhesive properties of the surrounding mucus to
decrease mucoadhesion, which may increase the delivery of the mucus
penetrating lipid nanoparticles to the mucosal tissue.
[0534] In some embodiments, the mucus penetrating lipid
nanoparticles may be a hypotonic formulation comprising a mucosal
penetration enhancing coating. The formulation may be hypotonic for
the epithelium to which it is being delivered. Non-limiting
examples of hypotonic formulations may be found in International
Patent Publication No. WO2013/110028, the contents of which are
herein incorporated by reference in their entirety.
[0535] In some embodiments, in order to enhance the delivery
through the mucosal barrier the RNA (e.g., mRNA) vaccine
formulation may comprise or be a hypotonic solution. Hypotonic
solutions were found to increase the rate at which mucoinert
particles such as, but not limited to, mucus-penetrating particles,
were able to reach the vaginal epithelial surface (see e.g., Ensign
et al. Biomaterials 2013 34(28):6922-9, the contents of which are
herein incorporated by reference in their entirety).
[0536] In some embodiments, the RNA (e.g., mRNA) vaccine is
formulated as a lipoplex, such as, without limitation, the
ATUPLEX.TM. system, the DACC system, the DBTC system and other
siRNA-lipoplex technology from Silence Therapeutics (London, United
Kingdom), STEMFECT.TM. from STEMGENT.RTM. (Cambridge, Mass.), and
polyethylenimine (PEI) or protamine-based targeted and non-targeted
delivery of nucleic acids (Aleku et al. Cancer Res. 2008
68:9788-9798; Strumberg et al. Int J Clin Pharmacol Ther 2012
50:76-78; Santel et al., Gene Ther 2006 13:1222-1234; Santel et
al., Gene Ther 2006 13:1360-1370; Gutbier et al., Pulm Pharmacol.
Ther. 2010 23:334-344; Kaufmann et al. Microvasc Res 2010
80:286-293Weide et al. J Immunother. 2009 32:498-507; Weide et al.
J Immunother. 2008 31:180-188; Pascolo Expert Opin. Biol. Ther.
4:1285-1294; Fotin-Mleczek et al., 2011 J. Immunother. 34:1-15;
Song et al., Nature Biotechnol. 2005, 23:709-717; Peer et al., Proc
Natl Acad Sci U S A. 2007 6; 104:4095-4100; deFougerolles Hum Gene
Ther. 2008 19:125-132, the contents of each of which are
incorporated herein by reference in their entirety).
[0537] In some embodiments, such formulations may also be
constructed or compositions altered such that they passively or
actively are directed to different cell types in vivo, including
but not limited to hepatocytes, immune cells, tumor cells,
endothelial cells, antigen presenting cells, and leukocytes (Akinc
et al. Mol Ther. 2010 18:1357-1364; Song et al., Nat Biotechnol.
2005 23:709-717; Judge et al., J Clin Invest. 2009 119:661-673;
Kaufmann et al., Microvasc Res 2010 80:286-293; Santel et al., Gene
Ther 2006 13:1222-1234; Santel et al., Gene Ther 2006 13:1360-1370;
Gutbier et al., Pulm Pharmacol. Ther. 2010 23:334-344; Basha et
al., Mol. Ther. 2011 19:2186-2200; Fenske and Cullis, Expert Opin
Drug Deliv. 2008 5:25-44; Peer et al., Science. 2008 319:627-630;
Peer and Lieberman, Gene Ther. 2011 18:1127-1133, the contents of
each of which are incorporated herein by reference in their
entirety). One example of passive targeting of formulations to
liver cells includes the DLin-DMA, DLin-KC2-DMA and
DLin-MC3-DMA-based lipid nanoparticle formulations, which have been
shown to bind to apolipoprotein E and promote binding and uptake of
these formulations into hepatocytes in vivo (Akinc et al. Mol Ther.
2010 18:1357-1364, the contents of which are incorporated herein by
reference in their entirety). Formulations can also be selectively
targeted through expression of different ligands on their surface
as exemplified by, but not limited by, folate, transferrin,
N-acetylgalactosamine (GalNAc), and antibody targeted approaches
(Kolhatkar et al., Curr Drug Discov Technol. 2011 8:197-206;
Musacchio and Torchilin, Front Biosci. 2011 16:1388-1412; Yu et
al., Mol Membr Biol. 2010 27:286-298; Patil et al., Crit Rev Ther
Drug Carrier Syst. 2008 25:1-61; Benoit et al., Biomacromolecules.
2011 12:2708-2714; Zhao et al., Expert Opin Drug Deliv. 2008
5:309-319; Akinc etal., Mol Ther. 2010 18:1357-1364; Srinivasan
etal., Methods Mol Biol. 2012 820:105-116; Ben-Arie et al., Methods
Mol Biol. 2012 757:497-507; Peer 2010 J Control Release. 20:63-68;
Peer et al., Proc Natl Acad Sci U S A. 2007 104:4095-4100; Kim et
al., Methods Mol Biol. 2011 721:339-353; Subramanya et al., Mol
Ther. 2010 18:2028-2037; Song et al., Nat Biotechnol. 2005
23:709-717; Peer et al., Science. 2008 319:627-630; Peer and
Lieberman, Gene Ther. 2011 18:1127-1133, the contents of each of
which are incorporated herein by reference in their entirety).
[0538] In some embodiments, the RNA (e.g., mRNA) vaccine is
formulated as a solid lipid nanoparticle. A solid lipid
nanoparticle (SLN) may be spherical with an average diameter
between 10 to 1000 nm. SLN possess a solid lipid core matrix that
can solubilize lipophilic molecules and may be stabilized with
surfactants and/or emulsifiers. In some embodiments, the lipid
nanoparticle may be a self-assembly lipid-polymer nanoparticle (see
Zhang et al., ACS Nano, 2008, 2 , pp 1696-1702; the contents of
which are herein incorporated by reference in their entirety). As a
non-limiting example, the SLN may be the SLN described in
International Patent Publication No. WO2013/105101, the contents of
which are herein incorporated by reference in their entirety. As
another non-limiting example, the SLN may be made by the methods or
processes described in International Patent Publication No.
WO2013/105101, the contents of which are herein incorporated by
reference in their entirety.
[0539] Liposomes, lipoplexes, or lipid nanoparticles may be used to
improve the efficacy of polynucleotides directed protein production
as these formulations may be able to increase cell transfection by
the RNA (e.g., mRNA) vaccine; and/or increase the translation of
encoded protein. One such example involves the use of lipid
encapsulation to enable the effective systemic delivery of polyplex
plasmid DNA (Heyes et al., Mol Ther. 2007 15:713-720; the contents
of which are incorporated herein by reference in their entirety).
The liposomes, lipoplexes, or lipid nanoparticles may also be used
to increase the stability of the polynucleotide.
[0540] In some embodiments, the RNA (e.g., mRNA) vaccines of the
present disclosure can be formulated for controlled release and/or
targeted delivery. As used herein, "controlled release" refers to a
pharmaceutical composition or compound release profile that
conforms to a particular pattern of release to effect a therapeutic
outcome. In some embodiments, the RNA (e.g., mRNA) vaccines may be
encapsulated into a delivery agent described herein and/or known in
the art for controlled release and/or targeted delivery. As used
herein, the term "encapsulate" means to enclose, surround or
encase. As it relates to the formulation of the compounds of the
disclosure, encapsulation may be substantial, complete or partial.
The term "substantially encapsulated" means that at least greater
than 50, 60, 70, 80, 85, 90, 95, 96, 97, 98, 99, 99.9, 99.9 or
greater than 99.999% of the pharmaceutical composition or compound
of the disclosure may be enclosed, surrounded or encased within the
delivery agent. "Partially encapsulation" means that less than 10,
10, 20, 30, 40 50 or less of the pharmaceutical composition or
compound of the disclosure may be enclosed, surrounded or encased
within the delivery agent. Advantageously, encapsulation may be
determined by measuring the escape or the activity of the
pharmaceutical composition or compound of the disclosure using
fluorescence and/or electron micrograph. For example, at least 1,
5, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 95, 96, 97, 98, 99,
99.9, 99.99 or greater than 99.99% of the pharmaceutical
composition or compound of the disclosure are encapsulated in the
delivery agent.
[0541] In some embodiments, the controlled release formulation may
include, but is not limited to, tri-block co-polymers. As a
non-limiting example, the formulation may include two different
types of tri-block co-polymers (International Pub. No.
WO2012/131104 and WO2012/131106, the contents of each of which are
incorporated herein by reference in their entirety).
[0542] In some embodiments, the RNA (e.g., mRNA) vaccines may be
encapsulated into a lipid nanoparticle or a rapidly eliminated
lipid nanoparticle and the lipid nanoparticles or a rapidly
eliminated lipid nanoparticle may then be encapsulated into a
polymer, hydrogel and/or surgical sealant described herein and/or
known in the art. As a non-limiting example, the polymer, hydrogel
or surgical sealant may be PLGA, ethylene vinyl acetate (EVAc),
poloxamer, GELSITE.RTM. (Nanotherapeutics, Inc. Alachua, Fla.),
HYLENEX.RTM. (Halozyme Therapeutics, San Diego Calif.), surgical
sealants such as fibrinogen polymers (Ethicon Inc. Cornelia, Ga.),
TISSELL.RTM. (Baxter International, Inc. Deerfield, Ill.),
PEG-based sealants, and COSEAL.RTM. (Baxter International, Inc
Deerfield, Ill.).
[0543] In some embodiments, the lipid nanoparticle may be
encapsulated into any polymer known in the art which may form a gel
when injected into a subject. As another non-limiting example, the
lipid nanoparticle may be encapsulated into a polymer matrix which
may be biodegradable.
[0544] In some embodiments, the RNA (e.g., mRNA) vaccine
formulation for controlled release and/or targeted delivery may
also include at least one controlled release coating. Controlled
release coatings include, but are not limited to, OPADRY.RTM.,
polyvinylpyrrolidone/vinyl acetate copolymer, polyvinylpyrrolidone,
hydroxypropyl methylcellulose, hydroxypropyl cellulose,
hydroxyethyl cellulose, EUDRAGIT RL.RTM., EUDRAGIT RS.RTM. and
cellulose derivatives such as ethylcellulose aqueous dispersions
(AQUACOAT.RTM. and SURELEASE.RTM.).
[0545] In some embodiments, the RNA (e.g., mRNA) vaccine controlled
release and/or targeted delivery formulation may comprise at least
one degradable polyester which may contain polycationic side
chains. Degradeable polyesters include, but are not limited to,
poly(serine ester), poly(L-lactide-co-L-lysine),
poly(4-hydroxy-L-proline ester), and combinations thereof. In some
embodiments, the degradable polyesters may include a PEG
conjugation to form a PEGylated polymer.
[0546] In some embodiments, the RNA (e.g., mRNA) vaccine controlled
release and/or targeted delivery formulation comprising at least
one polynucleotide may comprise at least one PEG and/or PEG related
polymer derivatives as described in U.S. Pat. No. 8,404,222, the
contents of which are incorporated herein by reference in their
entirety.
[0547] In some embodiments, the RNA (e.g., mRNA) vaccine controlled
release delivery formulation comprising at least one polynucleotide
may be the controlled release polymer system described in
US2013/0130348, the contents of which are incorporated herein by
reference in their entirety.
[0548] In some embodiments, the RNA (e.g., mRNA) vaccines of the
present disclosure may be encapsulated in a therapeutic
nanoparticle, referred to herein as "therapeutic nanoparticle RNA
(e.g., mRNA) vaccines." Therapeutic nanoparticles may be formulated
by methods described herein and known in the art such as, but not
limited to, International Pub Nos. WO2010/005740, WO2010/030763,
WO2010/005721, WO2010/005723, WO2012/054923,
[0549] U.S. Publication Nos. US2011/0262491, US2010/0104645,
US2010/0087337, US2010/0068285, US2011/0274759, US2010/0068286,
US2012/0288541, US2013/0123351 and US2013/0230567 and U.S. Pat.
Nos. 8,206,747, 8,293,276, 8,318,208 and 8,318,211; the contents of
each of which are herein incorporated by reference in their
entirety. In some embodiments, therapeutic polymer nanoparticles
may be identified by the methods described in US Pub No.
US2012/0140790, the contents of which are herein incorporated by
reference in their entirety.
[0550] In some embodiments, the therapeutic nanoparticle RNA (e.g.,
mRNA) vaccine may be formulated for sustained release. As used
herein, "sustained release" refers to a pharmaceutical composition
or compound that conforms to a release rate over a specific period
of time. The period of time may include, but is not limited to,
hours, days, weeks, months and years. As a non-limiting example,
the sustained release nanoparticle may comprise a polymer and a
therapeutic agent such as, but not limited to, the polynucleotides
of the present disclosure (see International Pub No. WO2010/075072
and US Pub No. US2010/0216804, US2011/0217377 and US2012/0201859,
the contents of each of which are incorporated herein by reference
in their entirety). In another non-limiting example, the sustained
release formulation may comprise agents which permit persistent
bioavailability such as, but not limited to, crystals,
macromolecular gels and/or particulate suspensions (see U.S. Patent
Publication No US2013/0150295, the contents of each of which are
incorporated herein by reference in their entirety).
[0551] In some embodiments, the therapeutic nanoparticle RNA (e.g.,
mRNA) vaccines may be formulated to be target specific. As a
non-limiting example, the therapeutic nanoparticles may include a
corticosteroid (see International Pub. No. WO2011/084518, the
contents of which are incorporated herein by reference in their
entirety). As a non-limiting example, the therapeutic nanoparticles
may be formulated in nanoparticles described in International Pub
No. WO2008/121949, WO2010/005726, WO2010/005725, WO2011/084521 and
US Pub No. US2010/0069426, US2012/0004293 and US2010/0104655, the
contents of each of which are incorporated herein by reference in
their entirety.
[0552] In some embodiments, the nanoparticles of the present
disclosure may comprise a polymeric matrix. As a non-limiting
example, the nanoparticle may comprise two or more polymers such
as, but not limited to, polyethylenes, polycarbonates,
polyanhydrides, polyhydroxyacids, polypropylfumerates,
polycaprolactones, polyamides, polyacetals, polyethers, polyesters,
poly(orthoesters), polycyanoacrylates, polyvinyl alcohols,
polyurethanes, polyphosphazenes, polyacrylates, polymethacrylates,
polycyanoacrylates, polyureas, polystyrenes, polyamines,
polylysine, poly(ethylene imine), poly(serine ester),
poly(L-lactide-co-L-lysine), poly(4-hydroxy-L-proline ester) or
combinations thereof.
[0553] In some embodiments, the therapeutic nanoparticle comprises
a diblock copolymer. In some embodiments, the diblock copolymer may
include PEG in combination with a polymer such as, but not limited
to, polyethylenes, polycarbonates, polyanhydrides,
polyhydroxyacids, polypropylfumerates, polycaprolactones,
polyamides, polyacetals, polyethers, polyesters, poly(orthoesters),
polycyanoacrylates, polyvinyl alcohols, polyurethanes,
polyphosphazenes, polyacrylates, polymethacrylates,
polycyanoacrylates, polyureas, polystyrenes, polyamines,
polylysine, poly(ethylene imine), poly(serine ester),
poly(L-lactide-co-L-lysine), poly(4-hydroxy-L-proline ester) or
combinations thereof. In yet another embodiment, the diblock
copolymer may be a high-X diblock copolymer such as those described
in International Patent Publication No. WO2013/120052, the contents
of which are incorporated herein by reference in their
entirety.
[0554] As a non-limiting example the therapeutic nanoparticle
comprises a PLGA-PEG block copolymer (see U.S. Publication No.
US2012/0004293 and U.S. Pat. No. 8,236,330, each of which is herein
incorporated by reference in their entirety). In another
non-limiting example, the therapeutic nanoparticle is a stealth
nanoparticle comprising a diblock copolymer of PEG and PLA or PEG
and PLGA (see U.S. Pat. No 8,246,968 and International Publication
No. WO2012/166923, the contents of each of which are herein
incorporated by reference in their entirety). In yet another
non-limiting example, the therapeutic nanoparticle is a stealth
nanoparticle or a target-specific stealth nanoparticle as described
in U.S. Patent Publication No. US2013/0172406, the contents of
which are herein incorporated by reference in their entirety.
[0555] In some embodiments, the therapeutic nanoparticle may
comprise a multiblock copolymer (see e.g., U.S. Pat. Nos. 8,263,665
and 8,287,910 and U.S. Patent Pub. No. US2013/0195987, the contents
of each of which are herein incorporated by reference in their
entirety).
[0556] In yet another non-limiting example, the lipid nanoparticle
comprises the block copolymer PEG-PLGA-PEG (see e.g., the
thermosensitive hydrogel (PEG-PLGA-PEG) was used as a TGF-betal
gene delivery vehicle in Lee et al. Thermosensitive Hydrogel as a
TGF-.beta.1 Gene Delivery Vehicle Enhances Diabetic Wound Healing.
Pharmaceutical Research, 2003 20(12): 1995-2000; as a controlled
gene delivery system in Li et al. Controlled Gene Delivery System
Based on Thermosensitive Biodegradable Hydrogel. Pharmaceutical
Research 2003 20:884-888; and Chang et al., Non-ionic amphiphilic
biodegradable PEG-PLGA-PEG copolymer enhances gene delivery
efficiency in rat skeletal muscle. J Controlled Release. 2007
118:245-253, the contents of each of which are herein incorporated
by reference in their entirety). The RNA (e.g., mRNA) vaccines of
the present disclosure may be formulated in lipid nanoparticles
comprising the PEG-PLGA-PEG block copolymer.
[0557] In some embodiments, the therapeutic nanoparticle may
comprise a multiblock copolymer (see e.g., U.S. Pat. Nos. 8,263,665
and 8,287,910 and U.S. Patent Pub. No. US2013/0195987, the contents
of each of which are herein incorporated by reference in their
entirety).
[0558] In some embodiments, the block copolymers described herein
may be included in a polyion complex comprising a non-polymeric
micelle and the block copolymer. (see e.g., U.S. Publication No.
2012/0076836, the contents of which are herein incorporated by
reference in their entirety).
[0559] In some embodiments, the therapeutic nanoparticle may
comprise at least one acrylic polymer. Acrylic polymers include but
are not limited to, acrylic acid, methacrylic acid, acrylic acid
and methacrylic acid copolymers, methyl methacrylate copolymers,
ethoxyethyl methacrylates, cyanoethyl methacrylate, amino alkyl
methacrylate copolymer, poly(acrylic acid), poly(methacrylic acid),
polycyanoacrylates and combinations thereof.
[0560] In some embodiments, the therapeutic nanoparticles may
comprise at least one poly(vinyl ester) polymer. The poly(vinyl
ester) polymer may be a copolymer such as a random copolymer. As a
non-limiting example, the random copolymer may have a structure
such as those described in International Application No.
WO2013/032829 or U.S. Patent Publication No US2013/0121954, the
contents of each of which are herein incorporated by reference in
their entirety. In some embodiments, the poly(vinyl ester) polymers
may be conjugated to the polynucleotides described herein.
[0561] In some embodiments, the therapeutic nanoparticle may
comprise at least one diblock copolymer. The diblock copolymer may
be, but it not limited to, a poly(lactic) acid-poly(ethylene)glycol
copolymer (see, e.g., International Patent Publication No.
WO2013/044219, the contents of which are herein incorporated by
reference in their entirety). As a non-limiting example, the
therapeutic nanoparticle may be used to treat cancer (see
International publication No. WO2013/044219, the contents of which
are herein incorporated by reference in their entirety).
[0562] In some embodiments, the therapeutic nanoparticles may
comprise at least one cationic polymer described herein and/or
known in the art.
[0563] In some embodiments, the therapeutic nanoparticles may
comprise at least one amine-containing polymer such as, but not
limited to polylysine, polyethylene imine, poly(amidoamine)
dendrimers, poly(beta-amino esters) (see, e.g., U.S. Pat. No.
8,287,849, the contents of which are herein incorporated by
reference in their entirety) and combinations thereof.
[0564] In some embodiments, the nanoparticles described herein may
comprise an amine cationic lipid such as those described in
International Patent Application No. WO2013/059496, the contents of
which are herein incorporated by reference in their entirety. In
some embodiments, the cationic lipids may have an amino-amine or an
amino-amide moiety.
[0565] In some embodiments, the therapeutic nanoparticles may
comprise at least one degradable polyester which may contain
polycationic side chains. Degradeable polyesters include, but are
not limited to, poly(serine ester), poly(L-lactide-co-L-lysine),
poly(4-hydroxy-L-proline ester), and combinations thereof. In some
embodiments, the degradable polyesters may include a PEG
conjugation to form a PEGylated polymer.
[0566] In some embodiments, the synthetic nanocarriers may contain
an immunostimulatory agent to enhance the immune response from
delivery of the synthetic nanocarrier. As a non-limiting example,
the synthetic nanocarrier may comprise a Th1 immunostimulatory
agent, which may enhance a Th1-based response of the immune system
(see International Pub No. WO2010/123569 and U.S. Publication No.
US2011/0223201, the contents of each of which are herein
incorporated by reference in their entirety).
[0567] In some embodiments, the synthetic nanocarriers may be
formulated for targeted release. In some embodiments, the synthetic
nanocarrier is formulated to release the polynucleotides at a
specified pH and/or after a desired time interval. As a
non-limiting example, the synthetic nanoparticle may be formulated
to release the RNA (e.g., mRNA) vaccines after 24 hours and/or at a
pH of 4.5 (see International Publication Nos. WO2010/138193 and
WO2010/138194 and US Pub Nos. US2011/0020388 and US2011/0027217,
each of which is herein incorporated by reference in their
entireties).
[0568] In some embodiments, the synthetic nanocarriers may be
formulated for controlled and/or sustained release of the
polynucleotides described herein. As a non-limiting example, the
synthetic nanocarriers for sustained release may be formulated by
methods known in the art, described herein and/or as described in
International Pub No. WO2010/138192 and US Pub No. 2010/0303850,
each of which is herein incorporated by reference in their
entirety.
[0569] In some embodiments, the RNA (e.g., mRNA) vaccine may be
formulated for controlled and/or sustained release wherein the
formulation comprises at least one polymer that is a crystalline
side chain (CYSC) polymer. CYSC polymers are described in U.S. Pat.
No. 8,399,007, herein incorporated by reference in its
entirety.
[0570] In some embodiments, the synthetic nanocarrier may be
formulated for use as a vaccine. In some embodiments, the synthetic
nanocarrier may encapsulate at least one polynucleotide which
encode at least one antigen. As a non-limiting example, the
synthetic nanocarrier may include at least one antigen and an
excipient for a vaccine dosage form (see International Publication
No. WO2011/150264 and U.S. Publication No. US2011/0293723, the
contents of each of which are herein incorporated by reference in
their entirety). As another non-limiting example, a vaccine dosage
form may include at least two synthetic nanocarriers with the same
or different antigens and an excipient (see International
Publication No. WO2011/150249 and U.S. Publication No.
US2011/0293701, the contents of each of which are herein
incorporated by reference in their entirety). The vaccine dosage
form may be selected by methods described herein, known in the art
and/or described in International Publication No. WO2011/150258 and
U.S. Publication No. US2012/0027806, the contents of each of which
are herein incorporated by reference in their entirety).
[0571] In some embodiments, the synthetic nanocarrier may comprise
at least one polynucleotide which encodes at least one adjuvant. As
non-limiting example, the adjuvant may comprise
dimethyldioctadecylammonium-bromide,
dimethyldioctadecylammonium-chloride,
dimethyldioctadecylammonium-phosphate or
dimethyldioctadecylammonium-acetate (DDA) and an apolar fraction or
part of said apolar fraction of a total lipid extract of a
mycobacterium (see, e.g., U.S. Pat. No. 8,241,610, the content of
which is herein incorporated by reference in its entirety). In some
embodiments, the synthetic nanocarrier may comprise at least one
polynucleotide and an adjuvant. As a non-limiting example, the
synthetic nanocarrier comprising and adjuvant may be formulated by
the methods described in International Publication No.
WO2011/150240 and U.S. Publication No. US2011/0293700, the contents
of each of which are herein incorporated by reference in their
entirety.
[0572] In some embodiments, the synthetic nanocarrier may
encapsulate at least one polynucleotide that encodes a peptide,
fragment or region from a virus. As a non-limiting example, the
synthetic nanocarrier may include, but is not limited to, any of
the nanocarriers described in International Publication No.
WO2012/024621, WO2012/02629, WO2012/024632 and U.S. Publication No.
US2012/0064110, US2012/0058153 and US2012/0058154, the contents of
each of which are herein incorporated by reference in their
entirety.
[0573] In some embodiments, the synthetic nanocarrier may be
coupled to a polynucleotide which may be able to trigger a humoral
and/or cytotoxic T lymphocyte (CTL) response (see, e.g.,
International Publication No. WO2013/019669, the contents of which
are herein incorporated by reference in their entirety).
[0574] In some embodiments, the RNA (e.g., mRNA) vaccine may be
encapsulated in, linked to and/or associated with zwitterionic
lipids. Non-limiting examples of zwitterionic lipids and methods of
using zwitterionic lipids are described in U.S. Patent Publication
No. US2013/0216607, the contents of which are herein incorporated
by reference in their entirety. In some aspects, the zwitterionic
lipids may be used in the liposomes and lipid nanoparticles
described herein.
[0575] In some embodiments, the RNA (e.g., mRNA) vaccine may be
formulated in colloid nanocarriers as described in U.S. Patent
Publication No. US2013/0197100, the contents of which are herein
incorporated by reference in their entirety.
[0576] In some embodiments, the nanoparticle may be optimized for
oral administration. The nanoparticle may comprise at least one
cationic biopolymer such as, but not limited to, chitosan or a
derivative thereof. As a non-limiting example, the nanoparticle may
be formulated by the methods described in U.S. Publication No.
US2012/0282343, the contents of which are herein incorporated by
reference in their entirety.
[0577] In some embodiments, LNPs comprise the lipid KL52 (an
amino-lipid disclosed in U.S. Application Publication No.
2012/0295832, the contents of which are herein incorporated by
reference in their entirety. Activity and/or safety (as measured by
examining one or more of ALT/AST, white blood cell count and
cytokine induction, for example) of LNP administration may be
improved by incorporation of such lipids. LNPs comprising KL52 may
be administered intravenously and/or in one or more doses. In some
embodiments, administration of LNPs comprising KL52 results in
equal or improved mRNA and/or protein expression as compared to
LNPs comprising MC3.
[0578] In some embodiments, RNA (e.g., mRNA) vaccine may be
delivered using smaller LNPs. Such particles may comprise a
diameter from below 0.1 um up to 100 nm such as, but not limited
to, less than 0.1 um, less than 1.0 um, less than 5 um, less than
10 um, less than 15 um, less than 20 um, less than 25 um, less than
30 um, less than 35 um, less than 40 um, less than 50 um, less than
55 um, less than 60 um, less than 65 um, less than 70 um, less than
75 um, less than 80 um, less than 85 um, less than 90 um, less than
95 um, less than 100 um, less than 125 um, less than 150 um, less
than 175 um, less than 200 um, less than 225 um, less than 250 um,
less than 275 um, less than 300 um, less than 325 um, less than 350
um, less than 375 um, less than 400 um, less than 425 um, less than
450 um, less than 475 um, less than 500 um, less than 525 um, less
than 550 um, less than 575 um, less than 600 um, less than 625 um,
less than 650 um, less than 675 um, less than 700 um, less than 725
um, less than 750 um, less than 775 um, less than 800 um, less than
825 um, less than 850 um, less than 875 um, less than 900 um, less
than 925 um, less than 950 um, less than 975 um, or less than 1000
um.
[0579] In some embodiments, RNA (e.g., mRNA) vaccines may be
delivered using smaller LNPs, which may comprise a diameter from
about 1 nm to about 100 nm, from about 1 nm to about 10 nm, about 1
nm to about 20 nm, from about 1 nm to about 30 nm, from about 1 nm
to about 40 nm, from about 1 nm to about 50 nm, from about 1 nm to
about 60 nm, from about 1 nm to about 70 nm, from about 1 nm to
about 80 nm, from about 1 nm to about 90 nm, from about 5 nm to
about from 100 nm, from about 5 nm to about 10 nm, about 5 nm to
about 20 nm, from about 5 nm to about 30 nm, from about 5 nm to
about 40 nm, from about 5 nm to about 50 nm, from about 5 nm to
about 60 nm, from about 5 nm to about 70 nm, from about 5 nm to
about 80 nm, from about 5 nm to about 90 nm, about 10 to about 50
nm, from about 20 to about 50 nm, from about 30 to about 50 nm,
from about 40 to about 50 nm, from about 20 to about 60 nm, from
about 30 to about 60 nm, from about 40 to about 60 nm, from about
20 to about 70 nm, from about 30 to about 70 nm, from about 40 to
about 70 nm, from about 50 to about 70 nm, from about 60 to about
70 nm, from about 20 to about 80 nm, from about 30 to about 80 nm,
from about 40 to about 80 nm, from about 50 to about 80 nm, from
about 60 to about 80 nm, from about 20 to about 90 nm, from about
30 to about 90 nm, from about 40 to about 90 nm, from about 50 to
about 90 nm, from about 60 to about 90 nm and/or from about 70 to
about 90 nm.
[0580] In some embodiments, such LNPs are synthesized using methods
comprising microfluidic mixers. Examples of microfluidic mixers may
include, but are not limited to, a slit interdigital micromixer
including, but not limited to those manufactured by Microinnova
(Allerheiligen bei Wildon, Austria) and/or a staggered herringbone
micromixer (SHM) (Zhigaltsev, I.V. et al., Bottom-up design and
synthesis of limit size lipid nanoparticle systems with aqueous and
triglyceride cores using millisecond microfluidic mixing have been
published (Langmuir. 2012. 28:3633-40; Belliveau, N.M. et al.,
Microfluidic synthesis of highly potent limit-size lipid
nanoparticles for in vivo delivery of siRNA. Molecular
Therapy-Nucleic Acids. 2012. 1:e37; Chen, D. et al., Rapid
discovery of potent siRNA-containing lipid nanoparticles enabled by
controlled microfluidic formulation. J Am Chem Soc. 2012.
134(16):6948-51, the contents of each of which are herein
incorporated by reference in their entirety). In some embodiments,
methods of LNP generation comprising SHM, further comprise the
mixing of at least two input streams wherein mixing occurs by
microstructure-induced chaotic advection (MICA). According to this
method, fluid streams flow through channels present in a
herringbone pattern causing rotational flow and folding the fluids
around each other. This method may also comprise a surface for
fluid mixing wherein the surface changes orientations during fluid
cycling. Methods of generating LNPs using SHM include those
disclosed in U.S. Application Publication Nos. 2004/0262223 and
2012/0276209, the contents of each of which are herein incorporated
by reference in their entirety.
[0581] In some embodiments, the RNA (e.g., mRNA) vaccine of the
present disclosure may be formulated in lipid nanoparticles created
using a micromixer such as, but not limited to, a Slit Interdigital
Microstructured Mixer (SIMM-V2) or a Standard Slit Interdigital
Micro Mixer (SSIMM) or Caterpillar (CPMM) or Impinging-jet
(IJMM)from the Institut fur Mikrotechnik Mainz GmbH, Mainz
Germany).
[0582] In some embodiments, the RNA (e.g., mRNA) vaccines of the
present disclosure may be formulated in lipid nanoparticles created
using microfluidic technology (see, e.g., Whitesides, George M. The
Origins and the Future of Microfluidics. Nature, 2006 442: 368-373;
and Abraham et al. Chaotic Mixer for Microchannels. Science, 2002
295: 647-651; each of which is herein incorporated by reference in
its entirety). As a non-limiting example, controlled microfluidic
formulation includes a passive method for mixing streams of steady
pressure-driven flows in micro channels at a low Reynolds number
(see, e.g., Abraham et al. Chaotic Mixer for Microchannels.
Science, 2002 295: 647-651, the contents of which are herein
incorporated by reference in their entirety).
[0583] In some embodiments, the RNA (e.g., mRNA) vaccines of the
present disclosure may be formulated in lipid nanoparticles created
using a micromixer chip such as, but not limited to, those from
Harvard Apparatus (Holliston, Mass.) or Dolomite Microfluidics
(Royston, UK). A micromixer chip can be used for rapid mixing of
two or more fluid streams with a split and recombine mechanism.
[0584] In some embodiments, the RNA (e.g., mRNA) vaccines of the
disclosure may be formulated for delivery using the drug
encapsulating microspheres described in International Patent
Publication No. WO2013063468 or U.S. Pat. No. 8,440,614, the
contents of each of which are herein incorporated by reference in
their entirety. The microspheres may comprise a compound of the
formula (I), (II), (III), (IV), (V) or (VI) as described in
International Patent Publication No. WO2013/063468, the contents of
which are herein incorporated by reference in their entirety. In
some embodiments, the amino acid, peptide, polypeptide, lipids
(APPL) are useful in delivering the RNA (e.g., mRNA) vaccines of
the disclosure to cells (see International Patent Publication No.
WO2013/063468, the contents of which are herein incorporated by
reference in their entirety).
[0585] In some embodiments, the RNA (e.g., mRNA) vaccines of the
disclosure may be formulated in lipid nanoparticles having a
diameter from about 10 to about 100 nm such as, but not limited to,
about 10 to about 20 nm, about 10 to about 30 nm, about 10 to about
40 nm, about 10 to about 50 nm, about 10 to about 60 nm, about 10
to about 70 nm, about 10 to about 80 nm, about 10 to about 90 nm,
about 20 to about 30 nm, about 20 to about 40 nm, about 20 to about
50 nm, about 20 to about 60 nm, about 20 to about 70 nm, about 20
to about 80 nm, about 20 to about 90 nm, about 20 to about 100 nm,
about 30 to about 40 nm, about 30 to about 50 nm, about 30 to about
60 nm, about 30 to about 70 nm, about 30 to about 80 nm, about 30
to about 90 nm, about 30 to about 100 nm, about 40 to about 50 nm,
about 40 to about 60 nm, about 40 to about 70 nm, about 40 to about
80 nm, about 40 to about 90 nm, about 40 to about 100 nm, about 50
to about 60 nm, about 50 to about 70 nm about 50 to about 80 nm,
about 50 to about 90 nm, about 50 to about 100 nm, about 60 to
about 70 nm, about 60 to about 80 nm, about 60 to about 90 nm,
about 60 to about 100 nm, about 70 to about 80 nm, about 70 to
about 90 nm, about 70 to about 100 nm, about 80 to about 90 nm,
about 80 to about 100 nm and/or about 90 to about 100 nm.
[0586] In some embodiments, the lipid nanoparticles may have a
diameter from about 10 to 500 nm.
[0587] In some embodiments, the lipid nanoparticle may have a
diameter greater than 100 nm, greater than 150 nm, greater than 200
nm, greater than 250 nm, greater than 300 nm, greater than 350 nm,
greater than 400 nm, greater than 450 nm, greater than 500 nm,
greater than 550 nm, greater than 600 nm, greater than 650 nm,
greater than 700 nm, greater than 750 nm, greater than 800 nm,
greater than 850 nm, greater than 900 nm, greater than 950 nm or
greater than 1000 nm.
[0588] In some embodiments, the lipid nanoparticle may be a limit
size lipid nanoparticle described in International Patent
Publication No. WO2013/059922, the contents of which are herein
incorporated by reference in their entirety. The limit size lipid
nanoparticle may comprise a lipid bilayer surrounding an aqueous
core or a hydrophobic core; where the lipid bilayer may comprise a
phospholipid such as, but not limited to,
diacylphosphatidylcholine, a diacylphosphatidylethanolamine, a
ceramide, a sphingomyelin, a dihydrosphingomyelin, a cephalin, a
cerebroside, a C8-C20 fatty acid diacylphophatidylcholine, and
1-palmitoyl-2-oleoyl phosphatidylcholine (POPC). In some
embodiments, the limit size lipid nanoparticle may comprise a
polyethylene glycol-lipid such as, but not limited to, DLPE-PEG,
DMPE-PEG, DPPC-PEG and DSPE-PEG.
[0589] In some embodiments, the RNA (e.g., mRNA) vaccines may be
delivered, localized and/or concentrated in a specific location
using the delivery methods described in International Patent
Publication No. WO2013/063530, the contents of which are herein
incorporated by reference in their entirety. As a non-limiting
example, a subject may be administered an empty polymeric particle
prior to, simultaneously with or after delivering the RNA (e.g.,
mRNA) vaccines to the subject. The empty polymeric particle
undergoes a change in volume once in contact with the subject and
becomes lodged, embedded, immobilized or entrapped at a specific
location in the subject.
[0590] In some embodiments, the RNA (e.g., mRNA) vaccines may be
formulated in an active substance release system (see, e.g., U.S.
Patent Publication No. US2013/0102545, the contents of which are
herein incorporated by reference in their entirety). The active
substance release system may comprise 1) at least one nanoparticle
bonded to an oligonucleotide inhibitor strand which is hybridized
with a catalytically active nucleic acid and 2) a compound bonded
to at least one substrate molecule bonded to a therapeutically
active substance (e.g., polynucleotides described herein), where
the therapeutically active substance is released by the cleavage of
the substrate molecule by the catalytically active nucleic
acid.
[0591] In some embodiments, the RNA (e.g., mRNA) vaccines may be
formulated in a nanoparticle comprising an inner core comprising a
non-cellular material and an outer surface comprising a cellular
membrane. The cellular membrane may be derived from a cell or a
membrane derived from a virus. As a non-limiting example, the
nanoparticle may be made by the methods described in International
Patent Publication No. WO2013/052167, the contents of which are
herein incorporated by reference in their entirety. As another
non-limiting example, the nanoparticle described in International
Patent Publication No. WO2013/052167, the contents of which are
herein incorporated by reference in their entirety, may be used to
deliver the RNA (e.g., mRNA) vaccines described herein.
[0592] In some embodiments, the RNA (e.g., mRNA) vaccines may be
formulated in porous nanoparticle-supported lipid bilayers
(protocells). Protocells are described in International Patent
Publication No. WO2013/056132, the contents of which are herein
incorporated by reference in their entirety.
[0593] In some embodiments, the RNA (e.g., mRNA) vaccines described
herein may be formulated in polymeric nanoparticles as described in
or made by the methods described in U.S. Pat. Nos. 8,420,123 and
8,518,963 and European Patent No. EP2073848B1, the contents of each
of which are herein incorporated by reference in their entirety. As
a non-limiting example, the polymeric nanoparticle may have a high
glass transition temperature such as the nanoparticles described in
or nanoparticles made by the methods described in U.S. Pat. No.
8,518,963, the contents of which are herein incorporated by
reference in their entirety. As another non-limiting example, the
polymer nanoparticle for oral and parenteral formulations may be
made by the methods described in European Patent No. EP2073848B1,
the contents of which are herein incorporated by reference in their
entirety.
[0594] In some embodiments, the RNA (e.g., mRNA) vaccines described
herein may be formulated in nanoparticles used in imaging. The
nanoparticles may be liposome nanoparticles such as those described
in U.S. Patent Publication No US2013/0129636, herein incorporated
by reference in its entirety. As a non-limiting example, the
liposome may comprise
gadolinium(III)2-{4,7-bis-carboxymethyl-10-[(N,N-distearylamidomethyl-N'--
amido-methyl]-1,4,7,10-tetra-azacyclododec-1-yl}-acetic acid and a
neutral, fully saturated phospholipid component (see, e.g., U.S.
Patent Publication No US2013/0129636, the contents of which are
herein incorporated by reference in their entirety).
[0595] In some embodiments, the nanoparticles which may be used in
the present disclosure are formed by the methods described in U.S.
Patent Application No. US2013/0130348, the contents of which are
herein incorporated by reference in their entirety.
[0596] The nanoparticles of the present disclosure may further
include nutrients such as, but not limited to, those which
deficiencies can lead to health hazards from anemia to neural tube
defects (see, e.g., the nanoparticles described in International
Patent Publication No WO2013/072929, the contents of which are
herein incorporated by reference in their entirety). As a
non-limiting example, the nutrient may be iron in the form of
ferrous, ferric salts or elemental iron, iodine, folic acid,
vitamins or micronutrients.
[0597] In some embodiments, the RNA (e.g., mRNA) vaccines of the
present disclosure may be formulated in a swellable nanoparticle.
The swellable nanoparticle may be, but is not limited to, those
described in U.S. Pat. No. 8,440,231, the contents of which are
herein incorporated by reference in their entirety. As a
non-limiting embodiment, the swellable nanoparticle may be used for
delivery of the RNA (e.g., mRNA) vaccines of the present disclosure
to the pulmonary system (see, e.g., U.S. Pat. No. 8,440,231, the
contents of which are herein incorporated by reference in their
entirety).
[0598] The RNA (e.g., mRNA) vaccines of the present disclosure may
be formulated in polyanhydride nanoparticles such as, but not
limited to, those described in U.S. Pat. No. 8,449,916, the
contents of which are herein incorporated by reference in their
entirety.
[0599] The nanoparticles and microparticles of the present
disclosure may be geometrically engineered to modulate macrophage
and/or the immune response. In some embodiments, the geometrically
engineered particles may have varied shapes, sizes and/or surface
charges in order to incorporated the polynucleotides of the present
disclosure for targeted delivery such as, but not limited to,
pulmonary delivery (see, e.g., International Publication No
WO2013/082111, the contents of which are herein incorporated by
reference in their entirety). Other physical features the
geometrically engineering particles may have include, but are not
limited to, fenestrations, angled arms, asymmetry and surface
roughness, charge which can alter the interactions with cells and
tissues. As a non-limiting example, nanoparticles of the present
disclosure may be made by the methods described in International
Publication No WO2013/082111, the contents of which are herein
incorporated by reference in their entirety.
[0600] In some embodiments, the nanoparticles of the present
disclosure may be water soluble nanoparticles such as, but not
limited to, those described in International Publication No.
WO2013/090601, the contents of which are herein incorporated by
reference in their entirety. The nanoparticles may be inorganic
nanoparticles which have a compact and zwitterionic ligand in order
to exhibit good water solubility. The nanoparticles may also have
small hydrodynamic diameters (HD), stability with respect to time,
pH, and salinity and a low level of non-specific protein
binding.
[0601] In some embodiments the nanoparticles of the present
disclosure may be developed by the methods described in U.S. Patent
Publication No. US2013/0172406, the contents of which are herein
incorporated by reference in their entirety.
[0602] In some embodiments, the nanoparticles of the present
disclosure are stealth nanoparticles or target-specific stealth
nanoparticles such as, but not limited to, those described in U.S.
Patent Publication No. US2013/0172406, the contents of which are
herein incorporated by reference in their entirety. The
nanoparticles of the present disclosure may be made by the methods
described in U.S. Patent Publication No. US2013/0172406, the
contents of which are herein incorporated by reference in their
entirety.
[0603] In some embodiments, the stealth or target-specific stealth
nanoparticles may comprise a polymeric matrix. The polymeric matrix
may comprise two or more polymers such as, but not limited to,
polyethylenes, polycarbonates, polyanhydrides, polyhydroxyacids,
polypropylfumerates, polycaprolactones, polyamides, polyacetals,
polyethers, polyesters, poly(orthoesters), polycyanoacrylates,
polyvinyl alcohols, polyurethanes, polyphosphazenes, polyacrylates,
polymethacrylates, polycyanoacrylates, polyureas, polystyrenes,
polyamines, polyesters, polyanhydrides, polyethers, polyurethanes,
polymethacrylates, polyacrylates, polycyanoacrylates or
combinations thereof.
[0604] In some embodiments, the nanoparticle may be a
nanoparticle-nucleic acid hybrid structure having a high density
nucleic acid layer. As a non-limiting example, the
nanoparticle-nucleic acid hybrid structure may made by the methods
described in U.S. Patent Publication No. US2013/0171646, the
contents of which are herein incorporated by reference in their
entirety. The nanoparticle may comprise a nucleic acid such as, but
not limited to, polynucleotides described herein and/or known in
the art.
[0605] At least one of the nanoparticles of the present disclosure
may be embedded in in the core a nanostructure or coated with a low
density porous 3-D structure or coating which is capable of
carrying or associating with at least one payload within or on the
surface of the nanostructure. Non-limiting examples of the
nanostructures comprising at least one nanoparticle are described
in International Patent Publication No. WO2013/123523, the contents
of which are herein incorporated by reference in their
entirety.
[0606] In some embodiments the RNA (e.g., mRNA) vaccine may be
associated with a cationic or polycationic compounds, including
protamine, nucleoline, spermine or spermidine, or other cationic
peptides or proteins, such as poly-L-lysine (PLL), polyarginine,
basic polypeptides, cell penetrating peptides (CPPs), including
HIV-binding peptides, HIV-1 Tat (HIV), Tat-derived peptides,
Penetratin, VP.sup.22 derived or analog peptides, Pestivirus Ems,
HSV, VP.sup.22 (Herpes simplex), MAP, KALA or protein transduction
domains (PTDs), PpT620, prolin-rich peptides, arginine-rich
peptides, lysine-rich peptides, MPG-peptide(s), Pep-1, L-oligomers,
Calcitonin peptide(s), Antennapedia-derived peptides (particularly
from Drosophila antennapedia), pAntp, pIsl, FGF, Lactoferrin,
Transportan, Buforin-2, Bac715-24, SynB, SynB, pVEC, hCT-derived
peptides, SAP, histones, cationic polysaccharides, for example
chitosan, polybrene, cationic polymers, e.g. polyethyleneimine
(PEI), cationic lipids, e.g. DOTMA:
[1-(2,3-sioleyloxy)propyl)]-N,N,N-trimethylammonium chloride,
DMRIE, di-C14-amidine, DOTIM, SAINT, DC-Chol, BGTC, CTAP, DOPC,
DODAP, DOPE: Dioleyl phosphatidylethanol-amine, DOSPA, DODAB, DOIC,
DMEPC, DOGS: Dioctadecylamidoglicylspermin, DIMRI:
Dimyristooxypropyl dimethyl hydroxyethyl ammonium bromide, DOTAP:
dioleoyloxy-3-(trimethylammonio)propane, DC-6-14:
O,O-ditetradecanoyl-N-.alpha.-trimethylammonioacetyl)diethanolamine
chloride, CLIP 1:
rac-[(2,3-dioctadecyloxypropyl)(2-hydroxyethyl)]-dimethylammonium
chloride, CLIP6:
rac-[2(2,3-dihexadecyloxypropyloxymethyloxy)ethyl]-trimethylammonium,
CLIPS:
rac-[2(2,3-dihexadecyloxypropyloxysuccinyloxy)ethyl]-trimethylammo-
-nium, oligofectamine, or cationic or polycationic polymers, e.g.
modified polyaminoacids, such as beta-aminoacid-polymers or
reversed polyamides, etc., modified polyethylenes, such as PVP
(poly(N-ethyl-4-vinylpyridinium bromide)), etc., modified
acrylates, such as pDMAEMA (poly(dimethylaminoethyl
methylacrylate)), etc., modified amidoamines such as pAMAM
(poly(amidoamine)), etc., modified polybetaminoester (PBAE), such
as diamine end modified 1,4 butanediol
diacrylate-co-5-amino-1-pentanol polymers, etc., dendrimers, such
as polypropylamine dendrimers or pAMAM based dendrimers, etc.,
polyimine(s), such as PEI: poly(ethyleneimine),
poly(propyleneimine), etc., polyallylamine, sugar backbone based
polymers, such as cyclodextrin based polymers, dextran based
polymers, chitosan, etc., silan backbone based polymers, such as
PMOXA-PDMS copolymers, etc., blockpolymers consisting of a
combination of one or more cationic blocks (e.g. selected from a
cationic polymer as mentioned above) and of one or more hydrophilic
or hydrophobic blocks (e.g. polyethyleneglycole), etc.
[0607] In other embodiments the RNA (e.g., mRNA) vaccine is not
associated with a cationic or polycationic compounds.
[0608] In some embodiments, a nanoparticle comprises compounds of
Formula (I):
##STR00005##
[0609] or a salt or isomer thereof, wherein:
[0610] R.sub.1 is selected from the group consisting of C.sub.5-30
alkyl, C.sub.5-20 alkenyl, --R*YR'', --YR'', and --R''M'R';
[0611] R.sub.2 and R.sub.3 are independently selected from the
group consisting of H, C.sub.1-14 alkyl, C.sub.2-14 alkenyl,
--R*YR'', --YR'', and --R*OR'', or R.sub.2 and R.sub.3, together
with the atom to which they are attached, form a heterocycle or
carbocycle;
[0612] R.sub.4 is selected from the group consisting of a C.sub.3-6
carbocycle, --(CH.sub.2).sub.nQ, --(CH.sub.2).sub.nCHQR, --CHQR,
--CQ(R).sub.2, and unsubstituted C.sub.1-6 alkyl, where Q is
selected from a carbocycle, heterocycle, --OR,
--O(CH.sub.2).sub.nN(R).sub.2, --C(O)OR, --OC(O)R, --CX.sub.3,
--CX.sub.2H, --CXH.sub.2, --CN, --N(R).sub.2, --C(O)N(R).sub.2,
--N(R)C(O)R, --N(R)S(O).sub.2R, --N(R)C(O)N(R).sub.2,
--N(R)C(S)N(R).sub.2, --N(R)R.sub.8, --O(CH.sub.2).sub.nOR,
--N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)N(R).sub.2,
--C(.dbd.NR.sub.9)R, --C(O)N(R)OR, and --C(R)N(R).sub.2C(O)OR, and
each n is independently selected from 1, 2, 3, 4, and 5;
[0613] each R.sub.5 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0614] each R.sub.6 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0615] M and M' are independently selected from --C(O)O--,
--OC(O)--, --C(O)N(R')--, --N(R')C(O)--, --C(O)--, --C(S)--,
--C(S)S--, --SC(S)--, --CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--,
--S--S--, an aryl group, and a heteroaryl group;
[0616] R.sub.7 is selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H;
[0617] R.sub.8 is selected from the group consisting of C.sub.3-6
carbocycle and heterocycle;
[0618] R.sub.9 is selected from the group consisting of H, CN,
NO.sub.2, C.sub.1-6 alkyl, --OR, --S(O).sub.2R,
--S(O).sub.2N(R).sub.2, C.sub.2-6 alkenyl, C.sub.3-6 carbocycle and
heterocycle;
[0619] each R is independently selected from the group consisting
of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0620] each R' is independently selected from the group consisting
of C.sub.1-18 alkyl, C.sub.2-18 alkenyl, --R*YR'', --YR'', and
H;
[0621] each R'' is independently selected from the group consisting
of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
[0622] each R* is independently selected from the group consisting
of C.sub.1-12 alkyl and C.sub.2-12 alkenyl;
[0623] each Y is independently a C.sub.3-6 carbocycle;
[0624] each X is independently selected from the group consisting
of F, Cl, Br, and I; and
[0625] m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.
[0626] In some embodiments, a subset of compounds of Formula (I)
includes those in which when R.sub.4 is --(CH.sub.2).sub.nQ,
--(CH.sub.2).sub.nCHQR, --CHQR, or --CQ(R).sub.2, then (i) Q is not
--N(R).sub.2 when n is 1, 2, 3, 4 or 5, or (ii) Q is not 5, 6, or
7-membered heterocycloalkyl when n is 1 or 2.
[0627] In some embodiments, another subset of compounds of Formula
(I) includes those in which
[0628] R.sub.1 is selected from the group consisting of C.sub.5-30
alkyl, C.sub.5-20 alkenyl, --R*YR'', --YR'', and --R''M'R';
[0629] R.sub.2 and R.sub.3 are independently selected from the
group consisting of H, C.sub.1-14 alkyl, C.sub.2-14 alkenyl,
--R*YR'', --YR'', and --R*OR'', or R.sub.2 and R.sub.3, together
with the atom to which they are attached, form a heterocycle or
carbocycle;
[0630] R.sub.4 is selected from the group consisting of a C.sub.3-6
carbocycle, --(CH.sub.2).sub.nQ, --(CH.sub.2).sub.nCHQR, --CHQR,
--CQ(R).sub.2, and unsubstituted C.sub.1-6 alkyl, where Q is
selected from a C.sub.3-6 carbocycle, a 5- to 14-membered
heteroaryl having one or more heteroatoms selected from N, O, and
S, --OR, --O(CH.sub.2).sub.nN(R).sub.2, --C(O)OR, --OC(O)R,
--CX.sub.3, --CX.sub.2H, --CXH.sub.2, --CN, --C(O)N(R).sub.2,
--N(R)C(O)R, --N(R)S(O).sub.2R, --N(R)C(O)N(R).sub.2,
--N(R)C(S)N(R).sub.2, --CRN(R).sub.2C(O)OR, --N(R)R.sub.8,
--O(CH.sub.2).sub.nOR, --N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)N(R).sub.2,
--C(.dbd.NR.sub.9)R, --C(O)N(R)OR, and a 5- to 14-membered
heterocycloalkyl having one or more heteroatoms selected from N, O,
and S which is substituted with one or more substituents selected
from oxo (.dbd.O), OH, amino, mono- or di-alkylamino, and C.sub.1-3
alkyl, and each n is independently selected from 1, 2, 3, 4, and
5;
[0631] each R.sub.5 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0632] each R.sub.6 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0633] M and M' are independently selected from --C(O)O--,
--OC(O)--, --C(O)N(R')--, --N(R')C(O)--, --C(O)--, --C(S)--,
--C(S)S--, --SC(S)--, --CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--,
--S--S--, an aryl group, and a heteroaryl group;
[0634] R.sub.7 is selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H;
[0635] R.sub.8 is selected from the group consisting of C.sub.3-6
carbocycle and heterocycle;
[0636] R.sub.9 is selected from the group consisting of H, CN,
NO.sub.2, C.sub.1-6 alkyl, --OR, --S(O).sub.2R,
--S(O).sub.2N(R).sub.2, C.sub.2-6 alkenyl, C.sub.3-6 carbocycle and
heterocycle;
[0637] each R is independently selected from the group consisting
of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0638] each R' is independently selected from the group consisting
of C.sub.1-18 alkyl, C.sub.2-18 alkenyl, --R*YR'', --YR'', and
H;
[0639] each R'' is independently selected from the group consisting
of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
[0640] each R* is independently selected from the group consisting
of C.sub.1-12 alkyl and C.sub.2-12 alkenyl; each Y is independently
a C.sub.3-6 carbocycle;
[0641] each X is independently selected from the group consisting
of F, Cl, Br, and I; and
[0642] m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13, or
salts or isomers thereof.
[0643] In some embodiments, another subset of compounds of Formula
(I) includes those in which
[0644] R.sub.1 is selected from the group consisting of C.sub.5-30
alkyl, C.sub.5-20 alkenyl, --R*YR'', --YR'', and --R''M'R';
[0645] R.sub.2 and R.sub.3 are independently selected from the
group consisting of H, C.sub.1-14 alkyl, C.sub.2-14 alkenyl,
--R*YR'', --YR'', and --R*OR'', or R.sub.2 and R.sub.3, together
with the atom to which they are attached, form a heterocycle or
carbocycle;
[0646] R.sub.4 is selected from the group consisting of a C.sub.3-6
carbocycle, --(CH.sub.2).sub.nQ, --(CH.sub.2).sub.nCHQR, --CHQR,
--CQ(R).sub.2, and unsubstituted C.sub.1-6 alkyl, where Q is
selected from a C.sub.3-6 carbocycle, a 5- to 14-membered
heterocycle having one or more heteroatoms selected from N, O, and
S, --OR, --O(CH.sub.2).sub.nN(R).sub.2, --C(O)OR, --OC(O)R,
--CX.sub.3, --CX.sub.2H, --CXH.sub.2, --CN,
--C(O)N(R).sub.2,--N(R)C(O)R, --N(R)S(O).sub.2R,
--N(R)C(O)N(R).sub.2, --N(R)C(S)N(R).sub.2, --CRN(R).sub.2C(O)OR,
--N(R)R.sub.8, --O(CH.sub.2).sub.nOR,
--N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)R,
--C(O)N(R)OR, and --C(.dbd.NR.sub.9)N(R).sub.2, and each n is
independently selected from 1, 2, 3, 4, and 5; and when Q is a 5-
to 14-membered heterocycle and (i) R.sub.4 is --(CH.sub.2).sub.nQ
in which n is 1 or 2, or (ii) R.sub.4 is --(CH.sub.2).sub.nCHQR in
which n is 1, or (iii) R.sub.4 is --CHQR, and --CQ(R).sub.2, then Q
is either a 5- to 14-membered heteroaryl or 8- to 14-membered
heterocycloalkyl;
[0647] each R.sub.5 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0648] each R.sub.6 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0649] M and M' are independently selected from --C(O)O--,
--OC(O)--, --C(O)N(R')--, --N(R')C(O)--, --C(O)--, --C(S)--,
--C(S)S--, --SC(S)--, --CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--,
--S--S--, an aryl group, and a heteroaryl group;
[0650] R.sub.7 is selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H;
[0651] R.sub.8 is selected from the group consisting of C.sub.3-6
carbocycle and heterocycle;
[0652] R.sub.9 is selected from the group consisting of H, CN,
NO.sub.2, C.sub.1-6 alkyl, --OR, --S(O).sub.2R,
--S(O).sub.2N(R).sub.2, C.sub.2-6 alkenyl, C.sub.3-6 carbocycle and
heterocycle; each R is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0653] each R' is independently selected from the group consisting
of C.sub.1-18 alkyl, C.sub.2-18 alkenyl, --R*YR'', --YR'', and
H;
[0654] each R'' is independently selected from the group consisting
of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
[0655] each R* is independently selected from the group consisting
of C.sub.1-12 alkyl and C.sub.2-12 alkenyl;
[0656] each Y is independently a C.sub.3-6 carbocycle;
[0657] each X is independently selected from the group consisting
of F, Cl, Br, and I; and
[0658] m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,
[0659] or salts or isomers thereof.
[0660] In some embodiments, another subset of compounds of Formula
(I) includes those in which
[0661] R.sub.1 is selected from the group consisting of C.sub.5-30
alkyl, C.sub.5-20 alkenyl, --R*YR'', --YR'', and --R''M'R';
[0662] R.sub.2 and R.sub.3 are independently selected from the
group consisting of H, C.sub.1-14 alkyl, C.sub.2-14 alkenyl,
--R*YR'', --YR'', and --R*OR'', or R.sub.2 and R.sub.3, together
with the atom to which they are attached, form a heterocycle or
carbocycle;
[0663] R.sub.4 is selected from the group consisting of a C.sub.3-6
carbocycle, --(CH.sub.2).sub.nQ, --(CH.sub.2).sub.nCHQR, --CHQR,
--CQ(R).sub.2, and unsubstituted C.sub.1-6 alkyl, where Q is
selected from a
[0664] C.sub.3-6 carbocycle, a 5- to 14-membered heteroaryl having
one or more heteroatoms selected from N, O, and S, --OR,
--O(CH.sub.2).sub.nN(R).sub.2, --C(O)OR, --OC(O)R, --CX.sub.3,
--CX.sub.2H, --CXH.sub.2, --CN, --C(O)N(R).sub.2, --N(R)C(O)R,
--N(R)S(O).sub.2R, --N(R)C(O)N(R).sub.2, --N(R)C(S)N(R).sub.2,
--CRN(R).sub.2C(O)OR, --N(R)R.sub.8, --O(CH.sub.2).sub.nOR,
--N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)R,
--C(O)N(R)OR, and --C(.dbd.NR.sub.9)N(R).sub.2, and each n is
independently selected from 1, 2, 3, 4, and 5;
[0665] each R.sub.5 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0666] each R.sub.6 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0667] M and M' are independently selected from --C(O)O--,
--OC(O)--, --C(O)N(R')--, --N(R')C(O)--, --C(O)--, --C(S)--,
--C(S)S--, --SC(S)--, --CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--,
--S--S--, an aryl group, and a heteroaryl group;
[0668] R.sub.7 is selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H;
[0669] R.sub.8 is selected from the group consisting of C.sub.3-6
carbocycle and heterocycle;
[0670] R.sub.9 is selected from the group consisting of H, CN,
NO.sub.2, C.sub.1-6 alkyl, --OR, --S(O).sub.2R,
--S(O).sub.2N(R).sub.2, C.sub.2-6 alkenyl, C.sub.3-6 carbocycle and
heterocycle;
[0671] each R is independently selected from the group consisting
of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0672] each R' is independently selected from the group consisting
of C.sub.1-18 alkyl, C.sub.2-18 alkenyl, --R*YR'', --YR'', and
H;
[0673] each R'' is independently selected from the group consisting
of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
[0674] each R* is independently selected from the group consisting
of C.sub.1-12 alkyl and C.sub.2-12 alkenyl;
[0675] each Y is independently a C.sub.3-6 carbocycle;
[0676] each X is independently selected from the group consisting
of F, Cl, Br, and I; and
[0677] m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,
[0678] or salts or isomers thereof.
[0679] In some embodiments, another subset of compounds of Formula
(I) includes those in which
[0680] R.sub.1 is selected from the group consisting of C.sub.5-30
alkyl, C.sub.5-20 alkenyl, --R*YR'', --YR'', and --R''M'R';
[0681] R.sub.2 and R.sub.3 are independently selected from the
group consisting of H, C.sub.2-14 alkyl, C.sub.2-14 alkenyl,
--R*YR'', --YR'', and --R*OR'', or R.sub.2 and R.sub.3, together
with the atom to which they are attached, form a heterocycle or
carbocycle;
[0682] R.sub.4 is --(CH.sub.2).sub.nQ or --(CH.sub.2).sub.nCHQR,
where Q is --N(R).sub.2, and n is selected from 3, 4, and 5;
[0683] each R.sub.5 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0684] each R.sub.6 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0685] M and M' are independently selected from --C(O)O--,
--OC(O)--, --C(O)N(R')--, --N(R')C(O)--, --C(O)--, --C(S)--,
--C(S)S--, --SC(S)--, --CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--,
--S--S--, an aryl group, and a heteroaryl group;
[0686] R.sub.7 is selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; each R is independently selected
from the group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl,
and H;
[0687] each R' is independently selected from the group consisting
of C.sub.1-18 alkyl, C.sub.2-18 alkenyl, --R*YR'', --YR'', and
H;
[0688] each R'' is independently selected from the group consisting
of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
[0689] each R* is independently selected from the group consisting
of C.sub.1-12 alkyl and C.sub.1-12 alkenyl;
[0690] each Y is independently a C.sub.3-6 carbocycle;
[0691] each X is independently selected from the group consisting
of F, Cl, Br, and I; and
[0692] m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,
[0693] or salts or isomers thereof.
[0694] In some embodiments, another subset of compounds of Formula
(I) includes those in which
[0695] R.sub.1 is selected from the group consisting of C.sub.5-30
alkyl, C.sub.5-20 alkenyl, --R*YR'', --YR'', and --R''M'R';
[0696] R.sub.2 and R.sub.3 are independently selected from the
group consisting of C.sub.1-14 alkyl, C.sub.2-14 alkenyl, --R*YR'',
--YR'', and --R*OR'', or R.sub.2 and R.sub.3, together with the
atom to which they are attached, form a heterocycle or
carbocycle;
[0697] R.sub.4 is selected from the group consisting of
--(CH.sub.2).sub.nQ, --(CH.sub.2).sub.nCHQR, --CHQR, and
--CQ(R).sub.2, where Q is --N(R).sub.2, and n is selected from 1,
2, 3, 4, and 5;
[0698] each R.sub.5 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0699] each R.sub.6 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0700] M and M' are independently selected from --C(O)O--,
--OC(O)--, --C(O)N(R')--, --N(R')C(O)--, --C(O)--, --C(S)--,
--C(S)S--, --SC(S)--, --CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--,
--S--S--, an aryl group, and a heteroaryl group;
[0701] R.sub.7 is selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; each R is independently selected
from the group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl,
and H;
[0702] each R' is independently selected from the group consisting
of C.sub.1-18 alkyl, C.sub.2-18 alkenyl, --R*YR'', --YR'', and
H;
[0703] each R'' is independently selected from the group consisting
of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
[0704] each R* is independently selected from the group consisting
of C.sub.1-12 alkyl and C.sub.1-12 alkenyl;
[0705] each Y is independently a C.sub.3-6 carbocycle;
[0706] each X is independently selected from the group consisting
of F, Cl, Br, and I; and
[0707] m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,
[0708] or salts or isomers thereof.
[0709] In some embodiments, a subset of compounds of Formula (I)
includes those of Formula (IA):
##STR00006##
[0710] or a salt or isomer thereof, wherein 1 is selected from 1,
2, 3, 4, and 5; m is selected from 5, 6, 7, 8, and 9; M.sub.1 is a
bond or M'; R.sub.4 is unsubstituted C.sub.1-3 alkyl, or
--(CH.sub.2).sub.nQ, in which Q is OH, --NHC(S)N(R).sub.2,
--NHC(O)N(R).sub.2, --N(R)C(O)R, --N(R)S(O).sub.2R, --N(R)R.sub.8,
--NHC(.dbd.NR.sub.9)N(R).sub.2, --NHC(.dbd.CHR.sub.9)N(R).sub.2,
--OC(O)N(R).sub.2, --N(R)C(O)OR, heteroaryl or heterocycloalkyl; M
and M' are independently selected from --C(O)O--, --OC(O)--,
--C(O)N(R')--, --P(O)(OR')O--, --S--S--, an aryl group, and a
heteroaryl group; and R.sub.2 and R.sub.3 are independently
selected from the group consisting of H, C.sub.1-14 alkyl, and
C.sub.2-14 alkenyl.
[0711] In some embodiments, a subset of compounds of Formula (I)
includes those of Formula (II):
##STR00007##
or a salt or isomer thereof, wherein l is selected from 1, 2, 3, 4,
and 5; M.sub.1 is a bond or M'; R.sub.4 is unsubstituted C.sub.1-3
alkyl, or --(CH.sub.2).sub.nQ, in which n is 2, 3, or 4, and Q is
OH, --NHC(S)N(R).sub.2, --NHC(O)N(R).sub.2, --N(R)C(O)R,
--N(R)S(O).sub.2R, --N(R)R.sub.8, --NHC(.dbd.NR.sub.9)N(R).sub.2,
--NHC(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
heteroaryl or heterocycloalkyl; M and M' are independently selected
from --C(O)O--, --OC(O)--, --C(O)N(R')--, --P(O)(OR')O--, --S--S--,
an aryl group, and a heteroaryl group; and R.sub.2 and R.sub.3 are
independently selected from the group consisting of H, C.sub.1-14
alkyl, and C.sub.2-14 alkenyl.
[0712] In some embodiments, a subset of compounds of Formula (I)
includes those of Formula (IIa), (IIb), (IIc), or (IIe):
##STR00008##
[0713] or a salt or isomer thereof, wherein R.sub.4 is as described
herein.
[0714] In some embodiments, a subset of compounds of Formula (I)
includes those of Formula (IId):
##STR00009##
[0715] or a salt or isomer thereof, wherein n is 2, 3, or 4; and m,
R', R'', and R.sub.2 through R.sub.6 are as described herein. For
example, each of R.sub.2 and R.sub.3 may be independently selected
from the group consisting of C.sub.5-14 alkyl and C.sub.5-14
alkenyl.
[0716] In some embodiments, the compound of Formula (I) is selected
from the group consisting of:
##STR00010## ##STR00011## ##STR00012## ##STR00013## ##STR00014##
##STR00015## ##STR00016## ##STR00017##
[0717] In further embodiments, the compound of Formula (I) is
selected from the group consisting of:
##STR00018##
[0718] In some embodiments, the compound of Formula (I) is selected
from the group consisting of:
##STR00019## ##STR00020## ##STR00021## ##STR00022## ##STR00023##
##STR00024## ##STR00025## ##STR00026## ##STR00027## ##STR00028##
##STR00029## ##STR00030## ##STR00031## ##STR00032## ##STR00033##
##STR00034## ##STR00035## ##STR00036## ##STR00037## ##STR00038##
##STR00039## ##STR00040## ##STR00041## ##STR00042## ##STR00043##
##STR00044##
and salts and isomers thereof.
[0719] In some embodiments, a nanoparticle comprises the following
compound:
##STR00045##
or salts and isomers thereof.
[0720] In some embodiments, the disclosure features a nanoparticle
composition including a lipid component comprising a compound as
described herein (e.g., a compound according to Formula (I), (IA),
(II), (IIa), (IIb), (IIc), (IId) or (IIe)).
[0721] In some embodiments, the disclosure features a
pharmaceutical composition comprising a nanoparticle composition
according to the preceding embodiments and a pharmaceutically
acceptable carrier. For example, the pharmaceutical composition is
refrigerated or frozen for storage and/or shipment (e.g., being
stored at a temperature of 4.degree. C. or lower, such as a
temperature between about -150.degree. C. and about 0.degree. C. or
between about -80.degree. C. and about -20.degree. C. (e.g., about
-5.degree. C., -10.degree. C., -15.degree. C., -20.degree. C.,
-25.degree. C., -30.degree. C., -40.degree. C., -50.degree. C.,
-60.degree. C., -70.degree. C., -80.degree. C., -90.degree. C.,
-130.degree. C. or -150.degree. C.). For example, the
pharmaceutical composition is a solution that is refrigerated for
storage and/or shipment at, for example, about -20.degree. C.,
-30.degree. C., -40.degree. C., -50.degree. C., -60.degree. C.,
-70.degree. C., or -80.degree. C.
[0722] In some embodiments, the disclosure provides a method of
delivering a therapeutic and/or prophylactic (e.g., RNA, such as
mRNA) to a cell (e.g., a mammalian cell). This method includes the
step of administering to a subject (e.g., a mammal, such as a
human) a nanoparticle composition including (i) a lipid component
including a phospholipid (such as a polyunsaturated lipid), a PEG
lipid, a structural lipid, and a compound of Formula (I), (IA),
(II), (IIa), (IIb), (IIc), (IId) or (IIe) and (ii) a therapeutic
and/or prophylactic, in which administering involves contacting the
cell with the nanoparticle composition, whereby the therapeutic
and/or prophylactic is delivered to the cell.
[0723] In some embodiments, the disclosure provides a method of
producing a polypeptide of interest in a cell (e.g., a mammalian
cell). The method includes the step of contacting the cell with a
nanoparticle composition including (i) a lipid component including
a phospholipid (such as a polyunsaturated lipid), a PEG lipid, a
structural lipid, and a compound of Formula (I), (IA), (II), (IIa),
(IIb), (IIc), (IId) or (IIe) and (ii) an mRNA encoding the
polypeptide of interest, whereby the mRNA is capable of being
translated in the cell to produce the polypeptide.
[0724] In some embodiments, the disclosure provides a method of
treating a disease or disorder in a mammal (e.g., a human) in need
thereof. The method includes the step of administering to the
mammal a therapeutically effective amount of a nanoparticle
composition including (i) a lipid component including a
phospholipid (such as a polyunsaturated lipid), a PEG lipid, a
structural lipid, and a compound of Formula (I), (IA), (II), (IIa),
(IIb), (IIc), (IId) or (IIe) and (ii) a therapeutic and/or
prophylactic (e.g., an mRNA). In some embodiments, the disease or
disorder is characterized by dysfunctional or aberrant protein or
polypeptide activity. For example, the disease or disorder is
selected from the group consisting of rare diseases, infectious
diseases, cancer and proliferative diseases, genetic diseases
(e.g., cystic fibrosis), autoimmune diseases, diabetes,
neurodegenerative diseases, cardio- and reno-vascular diseases, and
metabolic diseases.
[0725] In some embodiments, the disclosure provides a method of
delivering (e.g., specifically delivering) a therapeutic and/or
prophylactic to a mammalian organ (e.g., a liver, spleen, lung, or
femur). This method includes the step of administering to a subject
(e.g., a mammal) a nanoparticle composition including (i) a lipid
component including a phospholipid, a PEG lipid, a structural
lipid, and a compound of Formula (I), (IA), (II), (IIa), (IIb),
(IIc), (IId) or (IIe) and (ii) a therapeutic and/or prophylactic
(e.g., an mRNA), in which administering involves contacting the
cell with the nanoparticle composition, whereby the therapeutic
and/or prophylactic is delivered to the target organ (e.g., a
liver, spleen, lung, or femur).
[0726] In some embodiments, the disclosure features a method for
the enhanced delivery of a therapeutic and/or prophylactic (e.g.,
an mRNA) to a target tissue (e.g., a liver, spleen, lung, or
femur). This method includes administering to a subject (e.g., a
mammal) a nanoparticle composition, the composition including (i) a
lipid component including a compound of Formula (I), (IA), (II),
(IIa), (IIb), (IIc), (IId) or (IIe) , a phospholipid, a structural
lipid, and a PEG lipid; and (ii) a therapeutic and/or prophylactic,
the administering including contacting the target tissue with the
nanoparticle composition, whereby the therapeutic and/or
prophylactic is delivered to the target tissue.
[0727] In some embodiments, the disclosure features a method of
lowering immunogenicity comprising introducing the nanoparticle
composition of the disclosure into cells, wherein the nanoparticle
composition reduces the induction of the cellular immune response
of the cells to the nanoparticle composition, as compared to the
induction of the cellular immune response in cells induced by a
reference composition which comprises a reference lipid instead of
a compound of Formula (I), (IA), (II), (IIa), (IIb), (IIc), (IId)
or (IIe). For example, the cellular immune response is an innate
immune response, an adaptive immune response, or both.
[0728] The disclosure also includes methods of synthesizing a
compound of Formula (I), (IA), (II), (IIa), (IIb), (IIc), (IId) or
(IIe) and methods of making a nanoparticle composition including a
lipid component comprising the compound of Formula (I), (IA), (II),
(IIa), (IIb), (IIc), (IId) or (IIe).
Modes of Vaccine Administration
[0729] Influenza RNA (e.g. mRNA) vaccines may be administered by
any route which results in a therapeutically effective outcome.
These include, but are not limited, to intradermal, intramuscular,
intranasal and/or subcutaneous administration. The present
disclosure provides methods comprising administering RNA (e.g.,
mRNA) vaccines to a subject in need thereof. The exact amount
required will vary from subject to subject, depending on the
species, age, and general condition of the subject, the severity of
the disease, the particular composition, its mode of
administration, its mode of activity, and the like. Influenza RNA
(e.g., mRNA) vaccines compositions are typically formulated in
dosage unit form for ease of administration and uniformity of
dosage. It will be understood, however, that the total daily usage
of RNA (e.g., mRNA) vaccine compositions may be decided by the
attending physician within the scope of sound medical judgment. The
specific therapeutically effective, prophylactically effective, or
appropriate imaging dose level for any particular patient will
depend upon a variety of factors including the disorder being
treated and the severity of the disorder; the activity of the
specific compound employed; the specific composition employed; the
age, body weight, general health, sex and diet of the patient; the
time of administration, route of administration, and rate of
excretion of the specific compound employed; the duration of the
treatment; drugs used in combination or coincidental with the
specific compound employed; and like factors well known in the
medical arts.
[0730] In some embodiments, influenza disease RNA (e.g. mRNA)
vaccines compositions may be administered at dosage levels
sufficient to deliver 0.0001 mg/kg to 100 mg/kg, 0.001 mg/kg to
0.05 mg/kg, 0.005 mg/kg to 0.05 mg/kg, 0.001 mg/kg to 0.005 mg/kg,
0.05 mg/kg to 0.5 mg/kg, 0.01 mg/kg to 50 mg/kg, 0.1 mg/kg to 40
mg/kg, 0.5 mg/kg to 30 mg/kg, 0.01 mg/kg to 10 mg/kg, 0.1 mg/kg to
10 mg/kg, or 1 mg/kg to 25 mg/kg, of subject body weight per day,
one or more times a day, per week, per month, etc. to obtain the
desired therapeutic, diagnostic, prophylactic, or imaging effect
(see, e.g., the range of unit doses described in International
Publication No WO2013/078199, the contents of which are herein
incorporated by reference in their entirety). The desired dosage
may be delivered three times a day, two times a day, once a day,
every other day, every third day, every week, every two weeks,
every three weeks, every four weeks, every 2 months, every three
months, every 6 months, etc. In some embodiments, the desired
dosage may be delivered using multiple administrations (e.g., two,
three, four, five, six, seven, eight, nine, ten, eleven, twelve,
thirteen, fourteen, or more administrations). When multiple
administrations are employed, split dosing regimens such as those
described herein may be used. In exemplary embodiments, influenza
RNA (e.g., mRNA) vaccines compositions may be administered at
dosage levels sufficient to deliver 0.0005 mg/kg to 0.01 mg/kg,
e.g., about 0.0005 mg/kg to about 0.0075 mg/kg, e.g., about 0.0005
mg/kg, about 0.001 mg/kg, about 0.002 mg/kg, about 0.003 mg/kg,
about 0.004 mg/kg or about 0.005 mg/kg.
[0731] In some embodiments, influenza disease RNA (e.g., mRNA)
vaccine compositions may be administered once or twice (or more) at
dosage levels sufficient to deliver 0.025 mg/kg to 0.250 mg/kg,
0.025 mg/kg to 0.500 mg/kg, 0.025 mg/kg to 0.750 mg/kg, or 0.025
mg/kg to 1.0 mg/kg.
[0732] In some embodiments, influenza disease RNA (e.g., mRNA)
vaccine compositions may be administered twice (e.g., Day 0 and Day
7, Day 0 and Day 14, Day 0 and Day 21, Day 0 and Day 28, Day 0 and
Day 60, Day 0 and Day 90, Day 0 and Day 120, Day 0 and Day 150, Day
0 and Day 180, Day 0 and 3 months later, Day 0 and 6 months later,
Day 0 and 9 months later, Day 0 and 12 months later, Day 0 and 18
months later, Day 0 and 2 years later, Day 0 and 5 years later, or
Day 0 and 10 years later) at a total dose of or at dosage levels
sufficient to deliver a total dose of 0.0100 mg, 0.025 mg, 0.050
mg, 0.075 mg, 0.100 mg, 0.125 mg, 0.150 mg, 0.175 mg, 0.200 mg,
0.225 mg, 0.250 mg, 0.275 mg, 0.300 mg, 0.325 mg, 0.350 mg, 0.375
mg, 0.400 mg, 0.425 mg, 0.450 mg, 0.475 mg, 0.500 mg, 0.525 mg,
0.550 mg, 0.575 mg, 0.600 mg, 0.625 mg, 0.650 mg, 0.675 mg, 0.700
mg, 0.725 mg, 0.750 mg, 0.775 mg, 0.800 mg, 0.825 mg, 0.850 mg,
0.875 mg, 0.900 mg, 0.925 mg, 0.950 mg, 0.975 mg, or 1.0 mg. Higher
and lower dosages and frequency of administration are encompassed
by the present disclosure. For example, an influenza RNA (e.g.,
mRNA) vaccine composition may be administered three or four
times.
[0733] In some embodiments, influenza RNA (e.g., mRNA) vaccine
compositions may be administered twice (e.g., Day 0 and Day 7, Day
0 and Day 14, Day 0 and Day 21, Day 0 and Day 28, Day 0 and Day 60,
Day 0 and Day 90, Day 0 and Day 120, Day 0 and Day 150, Day 0 and
Day 180, Day 0 and 3 months later, Day 0 and 6 months later, Day 0
and 9 months later, Day 0 and 12 months later, Day 0 and 18 months
later, Day 0 and 2 years later, Day 0 and 5 years later, or Day 0
and 10 years later) at a total dose of or at dosage levels
sufficient to deliver a total dose of 0.010 mg, 0.025 mg, 0.100 mg
or 0.400 mg.
[0734] In some embodiments, the influenza RNA (e.g., mRNA) vaccine
for use in a method of vaccinating a subject is administered to the
subject as a single dosage of between 10 .mu.g/kg and 400 .mu.g/kg
of the nucleic acid vaccine (in an effective amount to vaccinate
the subject).
[0735] In some embodiments the RNA (e.g., mRNA) vaccine for use in
a method of vaccinating a subject is administered to the subject as
a single dosage of between 10 .mu.g and 400 .mu.g of the nucleic
acid vaccine (in an effective amount to vaccinate the subject). In
some embodiments, an influenza RNA (e.g., mRNA) vaccine for use in
a method of vaccinating a subject is administered to the subject as
a single dosage of 25-1000 .mu.g. In some embodiments, an influenza
RNA (e.g., mRNA) vaccine is administered to the subject as a single
dosage of 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550,
600, 650, 700, 750, 800, 850, 900, 950 or 1000 .mu.g. For example,
an influenza RNA (e.g., mRNA) vaccine may be administered to a
subject as a single dose of 25-100, 25-500, 50-100, 50-500,
50-1000, 100-500, 100-1000, 250-500, 250-1000, or 500-1000 .mu.g.
In some embodiments, an influenza RNA (e.g., mRNA) vaccine for use
in a method of vaccinating a subject is administered to the subject
as two dosages, the combination of which equals 25-1000 .mu.g of
the influenza RNA (e.g., mRNA) vaccine.
[0736] An influenza RNA (e.g. mRNA) vaccine pharmaceutical
composition described herein can be formulated into a dosage form
described herein, such as an intranasal, intratracheal, or
injectable (e.g., intravenous, intraocular, intravitreal,
intramuscular, intradermal, intracardiac, intraperitoneal,
intranasal and subcutaneous).
Influenza Virus RNA (e.g., mRNA) vaccine formulations and methods
of use
[0737] Some aspects of the present disclosure provide formulations
of the influenza RNA (e.g., mRNA) vaccine, wherein the RNA (e.g.,
mRNA) vaccine is formulated in an effective amount to produce an
antigen specific immune response in a subject (e.g., production of
antibodies specific to an influenza antigenic polypeptide). "An
effective amount" is a dose of an RNA (e.g., mRNA) vaccine
effective to produce an antigen-specific immune response. Also
provided herein are methods of inducing an antigen-specific immune
response in a subject.
[0738] In some embodiments, the antigen-specific immune response is
characterized by measuring an anti-influenza antigenic polypeptide
antibody titer produced in a subject administered an influenza RNA
(e.g., mRNA) vaccine as provided herein. An antibody titer is a
measurement of the amount of antibodies within a subject, for
example, antibodies that are specific to a particular antigen
(e.g., an influenza antigenic polypeptide) or epitope of an
antigen. Antibody titer is typically expressed as the inverse of
the greatest dilution that provides a positive result.
Enzyme-linked immunosorbent assay (ELISA) is a common assay for
determining antibody titers, for example.
[0739] In some embodiments, an antibody titer is used to assess
whether a subject has had an infection or to determine whether
immunizations are required. In some embodiments, an antibody titer
is used to determine the strength of an autoimmune response, to
determine whether a booster immunization is needed, to determine
whether a previous vaccine was effective, and to identify any
recent or prior infections. In accordance with the present
disclosure, an antibody titer may be used to determine the strength
of an immune response induced in a subject by the influenza RNA
(e.g., mRNA) vaccine.
[0740] In some embodiments, an anti-influenza antigenic polypeptide
antibody titer produced in a subject is increased by at least 1 log
relative to a control. For example, anti-antigenic polypeptide
antibody titer produced in a subject may be increased by at least
1.5, at least 2, at least 2.5, or at least 3 log relative to a
control. In some embodiments, the anti-antigenic polypeptide
antibody titer produced in the subject is increased by 1, 1.5, 2,
2.5 or 3 log relative to a control. In some embodiments, the
anti-antigenic polypeptide antibody titer produced in the subject
is increased by 1-3 log relative to a control. For example, the
anti-antigenic polypeptide antibody titer produced in a subject may
be increased by 1-1.5, 1-2, 1-2.5, 1-3, 1.5-2, 1.5-2.5, 1.5-3,
2-2.5, 2-3, or 2.5-3 log relative to a control.
[0741] In some embodiments, the anti-influenza antigenic
polypeptide antibody titer produced in a subject is increased at
least 2 times relative to a control. For example, the
anti-antigenic polypeptide antibody titer produced in a subject may
be increased at least 3 times, at least 4 times, at least 5 times,
at least 6 times, at least 7 times, at least 8 times, at least 9
times, or at least 10 times relative to a control. In some
embodiments, the anti-antigenic polypeptide antibody titer produced
in the subject is increased 2, 3, 4, 5 ,6, 7, 8, 9, or 10 times
relative to a control. In some embodiments, the anti-antigenic
polypeptide antibody titer produced in a subject is increased 2-10
times relative to a control. For example, the anti-antigenic
polypeptide antibody titer produced in a subject may be increased
2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6,
3-5, 3-4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-10, 5-9, 5-8, 5-7, 5-6,
6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8, 8-10, 8-9, or 9-10 times
relative to a control.
[0742] A control, in some embodiments, is the anti-influenza
antigenic polypeptide antibody titer produced in a subject who has
not been administered an influenza RNA (e.g., mRNA) vaccine of the
present disclosure. In some embodiments, a control is an
anti-influenza antigenic polypeptide antibody titer produced in a
subject who has been administered a live attenuated influenza
vaccine. An attenuated vaccine is a vaccine produced by reducing
the virulence of a viable (live). An attenuated virus is altered in
a manner that renders it harmless or less virulent relative to
live, unmodified virus. In some embodiments, a control is an
anti-influenza antigenic polypeptide antibody titer produced in a
subject administered inactivated influenza vaccine. In some
embodiments, a control is an anti-influenza antigenic polypeptide
antibody titer produced in a subject administered a recombinant or
purified influenza protein vaccine. Recombinant protein vaccines
typically include protein antigens that either have been produced
in a heterologous expression system (e.g., bacteria or yeast) or
purified from large amounts of the pathogenic organism. In some
embodiments, a control is an anti-influenza antigenic polypeptide
antibody titer produced in a subject who has been administered an
influenza virus-like particle (VLP) vaccine.
[0743] In some embodiments, an effective amount of an influenza RNA
(e.g., mRNA) vaccine is a dose that is reduced compared to the
standard of care dose of a recombinant influenza protein vaccine. A
"standard of care," as provided herein, refers to a medical or
psychological treatment guideline and can be general or specific.
"Standard of care" specifies appropriate treatment based on
scientific evidence and collaboration between medical professionals
involved in the treatment of a given condition. It is the
diagnostic and treatment process that a physician/clinician should
follow for a certain type of patient, illness or clinical
circumstance. A "standard of care dose," as provided herein, refers
to the dose of a recombinant or purified influenza protein vaccine,
or a live attenuated or inactivated influenza vaccine, that a
physician/clinician or other medical professional would administer
to a subject to treat or prevent influenza, or a related condition,
while following the standard of care guideline for treating or
preventing influenza, or a related condition.
[0744] In some embodiments, the anti-influenza antigenic
polypeptide antibody titer produced in a subject administered an
effective amount of an influenza RNA (e.g., mRNA) vaccine is
equivalent to an anti-influenza antigenic polypeptide antibody
titer produced in a control subject administered a standard of care
dose of a recombinant or purified influenza protein vaccine or a
live attenuated or inactivated influenza vaccine.
[0745] In some embodiments, an effective amount of an influenza RNA
(e.g., mRNA) vaccine is a dose equivalent to an at least 2-fold
reduction in a standard of care dose of a recombinant or purified
influenza protein vaccine. For example, an effective amount of an
influenza RNA (e.g., mRNA) vaccine may be a dose equivalent to an
at least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold,
at least 7-fold, at least 8-fold, at least 9-fold, or at least
10-fold reduction in a standard of care dose of a recombinant or
purified influenza protein vaccine. In some embodiments, an
effective amount of an influenza RNA (e.g., mRNA) vaccine is a dose
equivalent to an at least at least 100-fold, at least 500-fold, or
at least 1000-fold reduction in a standard of care dose of a
recombinant or purified influenza protein vaccine. In some
embodiments, an effective amount of an influenza RNA (e.g., mRNA)
vaccine is a dose equivalent to a 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-,
10-, 20-, 50-, 100-, 250-, 500-, or 1000-fold reduction in a
standard of care dose of a recombinant or purified influenza
protein vaccine. In some embodiments, the anti-influenza antigenic
polypeptide antibody titer produced in a subject administered an
effective amount of an influenza RNA (e.g., mRNA) vaccine is
equivalent to an anti-influenza antigenic polypeptide antibody
titer produced in a control subject administered the standard of
care dose of a recombinant or protein influenza protein vaccine or
a live attenuated or inactivated influenza vaccine. In some
embodiments, an effective amount of an influenza RNA (e.g., mRNA)
vaccine is a dose equivalent to a 2-fold to 1000-fold (e.g., 2-fold
to 100-fold, 10-fold to 1000-fold) reduction in the standard of
care dose of a recombinant or purified influenza protein vaccine,
wherein the anti-influenza antigenic polypeptide antibody titer
produced in the subject is equivalent to an anti-influenza
antigenic polypeptide antibody titer produced in a control subject
administered the standard of care dose of a recombinant or purified
influenza protein vaccine or a live attenuated or inactivated
influenza vaccine.
[0746] In some embodiments, the effective amount of an influenza
RNA (e.g., mRNA) vaccine is a dose equivalent to a 2 to 1000-, 2 to
900-, 2 to 800-, 2 to 700-, 2 to 600-, 2 to 500-, 2 to 400-, 2 to
300-, 2 to 200-, 2 to 100-, 2 to 90-, 2 to 80-, 2 to 70-, 2 to 60-,
2 to 50-, 2 to 40-, 2 to 30-, 2 to 20-, 2 to 10-, 2 to 9-, 2 to 8-,
2 to 7-, 2 to 6-, 2 to 5-, 2 to 4-, 2 to 3-, 3 to 1000-, 3 to 900-,
3 to 800-, 3 to 700-, 3 to 600-, 3 to 500-, 3 to 400-, 3 to 3 to
00-, 3 to 200-, 3 to 100-, 3 to 90-, 3 to 80-, 3 to 70-, 3 to 60-,
3 to 50-, 3 to 40-, 3 to 30-, 3 to 20-, 3 to 10-, 3 to 9-, 3 to 8-,
3 to 7-, 3 to 6-, 3 to 5-, 3 to 4-, 4 to 1000-, 4 to 900-, 4 to
800-, 4 to 700-, 4 to 600- , 4 to 500-, 4 to 400-, 4 to 300-, 4 to
200-, 4 to 100-, 4 to 90-, 4 to 80-, 4 to 70-, 4 to 60-, 4 to 50-,
4 to 40-, 4 to 30-, 4 to 20-, 4 to 10-, 4 to 9-, 4 to 8-, 4 to 7-,
4 to 6-, 4 to 5-, 4 to 4-, 5 to 1000-, 5 to 900-, 5 to 800-, 5 to
700-, 5 to 600-, 5 to 500-, 5 to 400-, 5 to 300-, 5 to 200-, 5 to
100-, 5 to 90-, 5 to 80-, 5 to 70-, 5 to 60-, 5 to 50-, 5 to 40-, 5
to 30-, 5 to 20-, 5 to 10-, 5 to 9- , 5 to 8-, 5 to 7-, 5 to 6-, 6
to 1000-, 6 to 900-, 6 to 800-, 6 to 700-, 6 to 600-, 6 to 500-, 6
to 400-, 6 to 300-, 6 to 200-, 6 to 100-, 6 to 90-, 6 to 80-, 6 to
70-, 6 to 60-, 6 to 50-, 6 to 40-, 6 to 30-, 6 to 20-, 6 to 10-, 6
to 9-, 6 to 8-, 6 to 7-, 7 to 1000-, 7 to 900-, 7 to 800-, 7 to
700-, 7 to 600-, 7 to 500-, 7 to 400-, 7 to 300-, 7 to 200-, 7 to
100-, 7 to 90-, 7 to 80-, 7 to 70-, 7 to 60-, 7 to 50-, 7 to 40-, 7
to 30-, 7 to 20-, 7 to 10-, 7 to 9-, 7 to 8-, 8 to 1000-, 8 to
900-, 8 to 800-, 8 to 700-, 8 to 600-, 8 to 500-, 8 to 400-, 8 to
300-, 8 to 200-, 8 to 100-, 8 to 90-, 8 to 80-, 8 to 70-, 8 to 60-,
8 to 50-, 8 to 40-, 8 to 30-, 8 to 20-, 8 to 10-, 8 to 9-, 9 to
1000-, 9 to 900-, 9 to 800-, 9 to 700-, 9 to 600-, 9 to 500-, 9 to
400-, 9 to 300-, 9 to 200-, 9 to 100-, 9 to 90-, 9 to 80-, 9 to
70-, 9 to 60-, 9 to 50-, 9 to 40-, 9 to 30-, 9 to 20-, 9 to 10-, 10
to 1000-, 10 to 900-, 10 to 800-, 10 to 700-, 10 to 600-, 10 to
500-, 10 to 400-, 10 to 300-, 10 to 200-, 10 to 100-, 10 to 90-, 10
to 80-, 10 to 70-, 10 to 60-, 10 to 50-, 10 to 40-, 10 to 30-, 10
to 20-, 20 to 1000-, 20 to 900-, 20 to 800-, 20 to 700-, 20 to
600-, 20 to 500-, 20 to 400-, 20 to 300-, 20 to 200-, 20 to 100-,
20 to 90-, 20 to 80-, 20 to 70-, 20 to 60-, 20 to 50-, 20 to 40-,
20 to 30-, 30 to 1000-, 30 to 900-, 30 to 800-, 30 to 700-, 30 to
600-, 30 to 500-, 30 to 400-, 30 to 300-, 30 to 200-, 30 to 100-,
30 to 90-, 30 to 80-, 30 to 70-, 30 to 60-, 30 to 50-, 30 to 40-,
40 to 1000-, 40 to 900-, 40 to 800-, 40 to 700-, 40 to 600-, 40 to
500-, 40 to 400-, 40 to 300-, 40 to 200-, 40 to 100-, 40 to 90-, 40
to 80-, 40 to 70-, 40 to 60-, 40 to 50-, 50 to 1000-, 50 to 900-,
50 to 800-, 50 to 700-, 50 to 600-, 50 to 500-, 50 to 400-, 50 to
300-, 50 to 200-, 50 to 100-, 50 to 90-, 50 to 80-, 50 to 70-, 50
to 60-, 60 to 1000-, 60 to 900-, 60 to 800-, 60 to 700-, 60 to
600-, 60 to 500-, 60 to 400-, 60 to 300-, 60 to 200-, 60 to 100-,
60 to 90-, 60 to 80-, 60 to 70-, 70 to 1000-, 70 to 900-, 70 to
800-, 70 to 700-, 70 to 600-, 70 to 500-, 70 to 400-, 70 to 300-,
70 to 200-, 70 to 100-, 70 to 90-, 70 to 80-, 80 to 1000-, 80 to
900-, 80 to 800-, 80 to 700-, 80 to 600-, 80 to 500-, 80 to 400-,
80 to 300-, 80 to 200-, 80 to 100-, 80 to 90-, 90 to 1000-, 90 to
900-, 90 to 800-, 90 to 700-, 90 to 600-, 90 to 500-, 90 to 400-,
90 to 300-, 90 to 200-, 90 to 100-, 100 to 1000-, 100 to 900-, 100
to 800-, 100 to 700-, 100 to 600-, 100 to 500-, 100 to 400-, 100 to
300-, 100 to 200-, 200 to 1000-, 200 to 900-, 200 to 800-, 200 to
700-, 200 to 600-, 200 to 500-, 200 to 400-, 200 to 300-, 300 to
1000-, 300 to 900-, 300 to 800-, 300 to 700-, 300 to 600-, 300 to
500-, 300 to 400-, 400 to 1000-, 400 to 900-, 400 to 800-, 400 to
700-, 400 to 600-, 400 to 500-, 500 to 1000-, 500 to 900-, 500 to
800-, 500 to 700-, 500 to 600-, 600 to 1000-, 600 to 900-, 600 to
800-, 600 to 700-, 700 to 1000-, 700 to 900-, 700 to 800-, 800 to
1000-, 800 to 900-, or 900 to 1000-fold reduction in the standard
of care dose of a recombinant influenza protein vaccine. In some
embodiments, the anti-antigenic polypeptide antibody titer produced
in the subj ect is equivalent to an anti-antigenic polypeptide
antibody titer produced in a control subj ect administered the
standard of care dose of a recombinant or purified influenza
protein vaccine or a live attenuated or inactivated influenza
vaccine. In some embodiments, the effective amount is a dose
equivalent to (or equivalent to an at least) 2-, 3-,4-,5-,6-, 7-,
8-, 9-, 10-, 20-, 30-, 40-, 50-, 60-, 70-, 80-, 90-, 100-, 110-,
120-, 130-, 140-, 150-, 160-, 170-, 1280-, 190-, 200-, 210-, 220-,
230-, 240-, 250-, 260-, 270-, 280-, 290-, 300-, 310-, 320-, 330-,
340-, 350-, 360-, 370-, 380-, 390-, 400-, 410-, 420-, 430-, 440-,
450-, 4360-, 470-, 480-, 490-, 500-, 510-, 520-, 530-, 540-, 550-,
560-, 5760-, 580-, 590-, 600-, 610-, 620-, 630-, 640-, 650-, 660-,
670-, 680-, 690-, 700-, 710-, 720-, 730-, 740-, 750-, 760-, 770-,
780-, 790-, 800-, 810-, 820--, 830-, 840-, 850-, 860-, 870-, 880-,
890-, 900-, 910-, 920-, 930-, 940-, 950-, 960-, 970-, 980-, 990-,
or 1000-fold reduction in the standard of care dose of a
recombinant influenza protein vaccine. In some embodiments, an
anti-antigenic polypeptide antibody titer produced in the subject
is equivalent to an anti-antigenic polypeptide antibody titer
produced in a control subject administered the standard of care
dose of a recombinant or purified influenza protein vaccine or a
live attenuated or inactivated an influenza vaccine.
[0747] In some embodiments, the effective amount of an influenza
RNA (e.g., mRNA) vaccine is a total dose of 50-1000 In some
embodiments, the effective amount of an influenza RNA (e.g., mRNA)
vaccine is a total dose of 50-1000, 50-900, 50-800, 50-700, 50-600,
50-500, 50-400, 50-300, 50-200, 50-100, 50-90, 50-80, 50-70, 50-60,
60-1000, 60-900, 60-800, 60-700, 60-600, 60-500, 60-400, 60-300,
60-200, 60-100, 60-90, 60-80, 60-70, 70-1000, 70-900, 70-800,
70-700, 70-600, 70-500, 70-400, 70-300, 70-200, 70-100, 70-90,
70-80, 80-1000, 80-900, 80-800, 80-700, 80-600, 80-500, 80-400,
80-300, 80-200, 80-100, 80-90, 90-1000, 90-900, 90-800, 90-700,
90-600, 90-500, 90-400, 90-300, 90-200, 90-100, 100-1000, 100-900,
100-800, 100-700, 100-600, 100-500, 100-400, 100-300, 100-200,
200-1000, 200-900, 200-800, 200-700, 200-600, 200-500, 200-400,
200-300, 300-1000, 300-900, 300-800, 300-700, 300-600, 300-500,
300-400, 400-1000, 400-900, 400-800, 400-700, 400-600, 400-500,
500-1000, 500-900, 500-800, 500-700, 500-600, 600-1000, 600-900,
600-900, 600-700, 700-1000, 700-900, 700-800, 800-1000, 800-900, or
900-1000 pg. In some embodiments, the effective amount of an
influenza RNA (e.g., mRNA) vaccine is a total dose of 50, 100, 150,
200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800,
850, 900, 950 or 1000 In some embodiments, the effective amount is
a dose of 25-500 administered to the subject a total of two times.
In some embodiments, the effective amount of an influenza RNA
(e.g., mRNA) vaccine is a dose of 25-500, 25-400, 25-300, 25-200,
25-100, 25-50, 50-500, 50-400, 50-300, 50-200, 50-100, 100-500,
100-400, 100-300, 100-200, 150-500, 150-400, 150-300, 150-200,
200-500, 200-400, 200-300, 250-500, 250-400, 250-300, 300-500,
300-400, 350-500, 350-400, 400-500 or 450-500 .mu.g administered to
the subject a total of two times. In some embodiments, the
effective amount of an influenza RNA (e.g., mRNA) vaccine is a
total dose of 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or
500 .mu.g administered to the subject a total of two times.
Additional Embodiments
[0748] 1. An influenza virus vaccine or composition or immunogenic
composition, comprising:
[0749] at least one messenger ribonucleic acid (mRNA)
polynucleotide having a 5' terminal cap, an open reading frame
encoding at least one influenza antigenic polypeptide, and a 3'
polyA tail. [0750] 2. The vaccine of paragraph 1, wherein the at
least one mRNA polynucleotide is encoded by a sequence identified
by SEQ ID NO: 447-457, 459, 461, 505-523, or 570-573. [0751] 3. The
vaccine of paragraph 1, wherein the at least one mRNA
polynucleotide comprises a sequence identified by SEQ ID NO:
491-503, 524-542, or 566-569. [0752] 4. The vaccine of paragraph 1,
wherein the at least one antigenic polypeptide comprises a sequence
identified by SEQ ID NO: 1-444, 458, 460, 462-479, or 543-565.
[0753] 5. The vaccine of paragraph 1, wherein the at least one mRNA
polynucleotide is encoded by a sequence identified by SEQ ID NO:
457. [0754] 6. The vaccine of paragraph 1, wherein the at least one
mRNA polynucleotide comprises a sequence identified by SEQ ID NO:
501. [0755] 7. The vaccine of paragraph 1, wherein the at least one
antigenic polypeptide comprises a sequence identified by SEQ ID NO:
458. [0756] 8. The vaccine of paragraph 1, wherein the at least one
mRNA polynucleotide is encoded by a sequence identified by SEQ ID
NO: 459. [0757] 9. The vaccine of paragraph 1, wherein the at least
one mRNA polynucleotide comprises a sequence identified by SEQ ID
NO: 502. [0758] 10. The vaccine of paragraph 1, wherein the at
least one antigenic polypeptide comprises a sequence identified by
SEQ ID NO: 460. [0759] 11. The vaccine of paragraph 1, wherein the
at least one mRNA polynucleotide is encoded by a sequence
identified by SEQ ID NO: 461. [0760] 12. The vaccine of paragraph
1, wherein the at least one mRNA polynucleotide comprises a
sequence identified by SEQ ID NO: 503. [0761] 13. The vaccine of
paragraph 1, wherein the at least one antigenic polypeptide
comprises a sequence identified by SEQ ID NO: 462. [0762] 14. The
vaccine of any one of paragraphs 1-13, wherein the 5' terminal cap
is or comprises 7mG(5')ppp(5')NlmpNp. [0763] 15. The vaccine of any
one of paragraphs 1-14, wherein 100% of the uracil in the open
reading frame is modified to include N1-methyl pseudouridine at the
5-position of the uracil. [0764] 16. The vaccine of any one of
paragraphs 1-15, wherein the vaccine is formulated in a lipid
nanoparticle comprising: DLin-MC3-DMA; cholesterol;
1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC); and polyethylene
glycol (PEG)2000-DMG. [0765] 17. The vaccine of paragraph 16,
wherein the lipid nanoparticle further comprises trisodium citrate
buffer, sucrose and water. [0766] 18. A influenza virus vaccine or
composition or immunogenic composition, comprising:
[0767] at least one messenger ribonucleic acid (mRNA)
polynucleotide having a 5' terminal cap 7mG(5')ppp(5')NlmpNp, a
sequence identified by SEQ ID NO: 501 and a 3' polyA tail, wherein
the uracil nucleotides of the sequence identified by SEQ ID NO: 501
are modified to include N1-methyl pseudouridine at the 5-position
of the uracil nucleotide. [0768] 19. A influenza virus vaccine,
comprising:
[0769] at least one messenger ribonucleic acid (mRNA)
polynucleotide having a 5' terminal cap 7mG(5')ppp(5')NlmpNp, a
sequence identified by SEQ ID NO: 502 and a 3' polyA tail, wherein
the uracil nucleotides of the sequence identified by SEQ ID NO: 502
are modified to include N1-methyl pseudouridine at the 5-position
of the uracil nucleotide. [0770] 20. A influenza virus vaccine or
composition or immunogenic composition, comprising:
[0771] at least one messenger ribonucleic acid (mRNA)
polynucleotide having a 5' terminal cap 7mG(5')ppp(5')NlmpNp, a
sequence identified by SEQ ID NO: 503 and a 3' polyA tail, wherein
the uracil nucleotides of the sequence identified by SEQ ID NO: 503
are modified to include N1-methyl pseudouridine at the 5-position
of the uracil nucleotide. [0772] 21. The vaccine of any one of
paragraphs 18-20 formulated in a lipid nanoparticle comprising
DLin-MC3-DMA, cholesterol, 1,2-Di stearoyl
-sn-glycero-3-phosphocholine (DSPC), and polyethylene glycol
(PEG)2000-DMG. [0773] 22. The vaccine of any one of paragraphs 1-21
formulated in a lipid nanoparticle comprising at least one cationic
lipid selected from compounds of Formula (I):
[0773] ##STR00046## [0774] or a salt or isomer thereof, wherein:
[0775] R1 is selected from the group consisting of C5-30 alkyl,
C5-20 alkenyl, R*YR'', YR'', and R''M'R'; [0776] R2 and R3 are
independently selected from the group consisting of H, C1-14 alkyl,
C2-14 alkenyl, R*YR'', YR'', and R*OR'', or R2 and R3, together
with the atom to which they are attached, form a heterocycle or
carbocycle; [0777] R4 is selected from the group consisting of a
C3-6 carbocycle, (CH2)nQ, (CH2)nCHQR, CHQR, CQ(R)2, and
unsubstituted C1-6 alkyl, where Q is selected from a carbocycle,
heterocycle, --OR, --O(CH2)nN(R)2, C(O)OR, --OC(O)R, CX3, CX2H,
CXH2, CN, N(R)2, C(O)N(R)2, N(R)C(O)R, N(R)S(O)2R, N(R)C(O)N(R)2,
N(R)C(S)N(R)2, N(R)R8, O(CH2)nOR, N(R)C(.dbd.NR9)N(R)2,
N(R)C(.dbd.CHR9)N(R)2, OC(O)N(R)2, N(R)C(O)OR, N(OR)C(O)R,
N(OR)S(O)2R, N(OR)C(O)OR, N(OR)C(O)N(R)2, N(OR)C(S)N(R)2,
N(OR)C(.dbd.NR9)N(R)2, N(OR)C(.dbd.CHR9)N(R)2, C(.dbd.NR9)N(R)2,
C(.dbd.NR9)R, C(O)N(R)OR, and --C(R)N(R)2C(O)OR, and each n is
independently selected from 1, 2, 3, 4, and 5; [0778] each R5 is
independently selected from the group consisting of C1-3 alkyl,
C2-3 alkenyl, and H; [0779] each R6 is independently selected from
the group consisting of C1-3 alkyl, C2-3 alkenyl, and H; [0780] M
and M' are independently selected from C(O)O, OC(O), C(O)N(R'),
N(R')C(O), C(O), C(S), C(S)S, SC(S), CH(OH), P(O)(OR')O, S(O)2, S,
an aryl group, and a heteroaryl group; [0781] R7 is selected from
the group consisting of C1-3 alkyl, C2-3 alkenyl, and H; [0782] R8
is selected from the group consisting of C3-6 carbocycle and
heterocycle; [0783] R9 is selected from the group consisting of H,
CN, NO2, C1-6 alkyl, --OR, --S(O)2R, --S(O)2N(R)2, C2-6 alkenyl,
C3-6 carbocycle and heterocycle; each R is independently selected
from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
[0784] each R' is independently selected from the group consisting
of C1-18 alkyl, C2-18 alkenyl, R*YR'', YR'', and H; [0785] each R''
is independently selected from the group consisting of C3-14 alkyl
and C3-14 alkenyl; [0786] each R* is independently selected from
the group consisting of C1-12 alkyl and C2-12 alkenyl; [0787] each
Y is independently a C3-6 carbocycle; [0788] each X is
independently selected from the group consisting of F, Cl, Br, and
I; and [0789] m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.
[0790] 23. The vaccine of paragraph 22, wherein a subset of
compounds of Formula (I) includes those in which when R4 is
(CH2)nQ, (CH2)nCHQR, --CHQR, or CQ(R)2, then (i) Q is not N(R)2
when n is 1, 2, 3, 4 or 5, or (ii) Q is not 5, 6, or 7-membered
heterocycloalkyl when n is 1 or2. [0791] 24. The vaccine of
paragraph 22, wherein a subset of compounds of Formula (I) includes
those in which [0792] R1 is selected from the group consisting of
C5-30 alkyl, C5-20 alkenyl, R*YR'', YR'', and R''M'R'; [0793] R2
and R3 are independently selected from the group consisting of H,
C1-14 alkyl, C2-14 alkenyl, R*YR'', YR'', and R*OR'', or R2 and R3,
together with the atom to which they are attached, form a
heterocycle or carbocycle; [0794] R4 is selected from the group
consisting of a C3-6 carbocycle, (CH2)nQ, (CH2)nCHQR, CHQR, CQ(R)2,
and unsubstituted C1-6 alkyl, where Q is selected from a C3-6
carbocycle, a 5- to 14-membered heteroaryl having one or more
heteroatoms selected from N, O, and S, --OR, --O(CH2)nN(R)2,
C(O)OR, --OC(O)R, CX3, CX2H, CXH2, CN, C(O)N(R)2, N(R)C(O)R,
N(R)S(O)2R, N(R)C(O)N(R)2, N(R)C(S)N(R)2, CRN(R)2C(O)OR, N(R)R8,
O(CH2)nOR, N(R)C(.dbd.NR9)N(R)2, N(R)C(.dbd.CHR9)N(R)2, OC(O)N(R)2,
N(R)C(O)OR, N(OR)C(O)R, N(OR)S(O)2R, N(OR)C(O)OR, N(OR)C(O)N(R)2,
N(OR)C(S)N(R)2, N(OR)C(.dbd.NR9)N(R)2, N(OR)C(.dbd.CHR9)N(R)2,
C(.dbd.NR9)N(R)2, C(.dbd.NR9)R, C(O)N(R)OR, and a 5- to 14-membered
heterocycloalkyl having one or more heteroatoms selected from N, O,
and S which is substituted with one or more substituents selected
from oxo (.dbd.O), OH, amino, mono- or di-alkylamino, and C1-3
alkyl, and each n is independently selected from 1, 2, 3, 4, and 5;
[0795] each R5 is independently selected from the group consisting
of C1-3 alkyl, C2-3 alkenyl, and H; [0796] each R6 is independently
selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and
H; [0797] M and M' are independently selected from C(O)O, OC(O),
C(O)N(R'), N(R')C(O), C(O), C(S), C(S)S, SC(S), CH(OH), P(O)(OR')O,
S(O)2, S, an aryl group, and a heteroaryl group; R7 is selected
from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
[0798] R8 is selected from the group consisting of C3-6 carbocycle
and heterocycle; [0799] R9 is selected from the group consisting of
H, CN, NO2, C1-6 alkyl, --OR, --S(O)2R, --S(O)2N(R)2, C2-6 alkenyl,
C3-6 carbocycle and heterocycle; [0800] each R is independently
selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and
H; [0801] each R' is independently selected from the group
consisting of C1-18 alkyl, C2-18 alkenyl, R*YR'', YR'', and H;
[0802] each R'' is independently selected from the group consisting
of C3-14 alkyl and C3-14 alkenyl; [0803] each R* is independently
selected from the group consisting of C1-12 alkyl and C2-12
alkenyl; [0804] each Y is independently a C3-6 carbocycle; [0805]
each X is independently selected from the group consisting of F,
Cl, Br, and I; and [0806] m is selected from 5, 6, 7, 8, 9, 10, 11,
12, and 13, [0807] or salts or isomers thereof. [0808] 25. The
vaccine of paragraph 22, wherein a subset of compounds of Formula
(I) includes those in which [0809] R1 is selected from the group
consisting of C5-30 alkyl, C5-20 alkenyl, R*YR'', YR'', and
R''M'R'; [0810] R2 and R3 are independently selected from the group
consisting of H, C1-14 alkyl, C2-14 alkenyl, R*YR'', YR'', and
R*OR'', or R2 and R3, together with the atom to which they are
attached, form a heterocycle or carbocycle; [0811] R4 is selected
from the group consisting of a C3-6 carbocycle, (CH2)nQ,
(CH2)nCHQR, CHQR, CQ(R)2, and unsubstituted C1-6 alkyl, where Q is
selected from a C3-6 carbocycle, a 5- to 14-membered heterocycle
having one or more heteroatoms selected from N, O, and S, --OR,
--O(CH2)nN(R)2, C(O)OR, --OC(O)R, CX3, CX2H, CXH2, CN, C(O)N(R)2,
N(R)C(O)R, N(R)S(O)2R, N(R)C(O)N(R)2, N(R)C(S)N(R)2, CRN(R)2C(O)OR,
N(R)R8, O(CH2)nOR, N(R)C(.dbd.NR9)N(R)2, N(R)C(.dbd.CHR9)N(R)2,
OC(O)N(R)2, N(R)C(O)OR, N(OR)C(O)R, N(OR)S(O)2R, N(OR)C(O)OR,
N(OR)C(O)N(R)2, N(OR)C(S)N(R)2, N(OR)C(.dbd.NR9)N(R)2,
N(OR)C(.dbd.CHR9)N(R)2, C(.dbd.NR9)R, C(O)N(R)OR, and
C(.dbd.NR9)N(R)2, and each n is independently selected from 1, 2,
3, 4, and 5; and when Q is a 5- to 14-membered heterocycle and (i)
R4 is (CH2)nQ in which n is 1 or 2, or (ii) R4 is (CH2)nCHQR in
which n is 1, or (iii) R4 is CHQR, and CQ(R)2, then Q is either a
5- to 14-membered heteroaryl or 8- to 14-membered heterocycloalkyl;
[0812] each R5 is independently selected from the group consisting
of C1-3 alkyl, C2-3 alkenyl, and H; [0813] each R6 is independently
selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and
H; [0814] M and M' are independently selected from C(O)O, OC(O),
C(O)N(R'), N(R')C(O), C(O), C(S), C(S)S, SC(S), CH(OH), P(O)(OR')O,
S(O)2, S, an aryl group, and a heteroaryl group; [0815] R7 is
selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and
H; [0816] R8 is selected from the group consisting of C3-6
carbocycle and heterocycle; [0817] R9 is selected from the group
consisting of H, CN, NO2, C1-6 alkyl, --OR, --S(O)2R, --S(O)2N(R)2,
C2-6 alkenyl, C3-6 carbocycle and heterocycle; each R is
independently selected from the group consisting of C1-3 alkyl,
C2-3 alkenyl, and H; [0818] each R' is independently selected from
the group consisting of C1-18 alkyl, C2-18 alkenyl, R*YR'', YR'',
and H; [0819] each R'' is independently selected from the group
consisting of C3-14 alkyl and C3-14 alkenyl; [0820] each R* is
independently selected from the group consisting of C1-12 alkyl and
C2-12 alkenyl; [0821] each Y is independently a C3-6 carbocycle;
[0822] each X is independently selected from the group consisting
of F, Cl, Br, and I; and [0823] m is selected from 5, 6, 7, 8, 9,
10, 11, 12, and 13, [0824] or salts or isomers thereof. [0825] 26.
The vaccine of paragraph 22, wherein a subset of compounds of
Formula (I) includes those in which [0826] R1 is selected from the
group consisting of C5-30 alkyl, C5-20 alkenyl, R*YR'', YR'', and
R''M'R'; [0827] R2 and R3 are independently selected from the group
consisting of H, C1-14 alkyl, C2-14 alkenyl, R*YR'', YR'', and
R*OR'', or R2 and R3, together with the atom to which they are
attached, form a heterocycle or carbocycle; [0828] R4 is selected
from the group consisting of a C3-6 carbocycle, (CH2)nQ,
(CH2)nCHQR, CHQR, CQ(R)2, and unsubstituted C1-6 alkyl, where Q is
selected from a C3-6 carbocycle, a 5- to 14-membered heteroaryl
having one or more heteroatoms selected from N, O, and S, --OR,
--O(CH2)nN(R)2, C(O)OR, --OC(O)R, CX3, CX2H, CXH2, CN, C(O)N(R)2,
N(R)C(O)R, N(R)S(O)2R, N(R)C(O)N(R)2, N(R)C(S)N(R)2, CRN(R)2C(O)OR,
N(R)R8, O(CH2)nOR, N(R)C(.dbd.NR9)N(R)2, N(R)C(.dbd.CHR9)N(R)2,
OC(O)N(R)2, N(R)C(O)OR, N(OR)C(O)R, N(OR)S(O)2R, N(OR)C(O)OR,
N(OR)C(O)N(R)2, N(OR)C(S)N(R)2, N(OR)C(.dbd.NR9)N(R)2,
N(OR)C(.dbd.CHR9)N(R)2, C(.dbd.NR9)R, C(O)N(R)OR, and
C(.dbd.NR9)N(R)2, and each n is independently selected from 1, 2,
3, 4, and 5; [0829] each R5 is independently selected from the
group consisting of C1-3 alkyl, C2-3 alkenyl, and H; [0830] each R6
is independently selected from the group consisting of C1-3 alkyl,
C2-3 alkenyl, and H; [0831] M and M' are independently selected
from C(O)O, OC(O), C(O)N(R'), N(R')C(O), C(O), C(S), C(S)S, SC(S),
CH(OH), P(O)(OR')O, S(O)2, SS, an aryl group, and a heteroaryl
group; [0832] R7 is selected from the group consisting of C1-3
alkyl, C2-3 alkenyl, and H; [0833] R8 is selected from the group
consisting of C3-6 carbocycle and heterocycle; [0834] R9 is
selected from the group consisting of H, CN, NO2, C1-6 alkyl, --OR,
--S(O)2R, --S(O)2N(R)2, C2-6 alkenyl, C3-6 carbocycle and
heterocycle; [0835] each R is independently selected from the group
consisting of C1-3 alkyl, C2-3 alkenyl, and H; [0836] each R' is
independently selected from the group consisting of C1-18 alkyl,
C2-18 alkenyl, R*YR'', YR'', and H; [0837] each R'' is
independently selected from the group consisting of C3-14 alkyl and
C3-14 alkenyl; [0838] each R* is independently selected from the
group consisting of C1-12 alkyl and C2-12 alkenyl; [0839] each Y is
independently a C3-6 carbocycle; [0840] each X is independently
selected from the group consisting of F, Cl, Br, and I; and [0841]
m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13, [0842] or
salts or isomers thereof. [0843] 27. The vaccine of paragraph 22,
wherein a subset of compounds of Formula (I) includes those in
which [0844] R1 is selected from the group consisting of C5-30
alkyl, C5-20 alkenyl, R*YR'', YR'', and R''M'R'; [0845] R2 and R3
are independently selected from the group consisting of H, C2-14
alkyl, C2-14 alkenyl, R*YR'', YR'', and R*OR'', or R2 and R3,
together with the atom to which they are attached, form a
heterocycle or carbocycle; [0846] R4 is (CH2)nQ or (CH2)nCHQR,
where Q is N(R)2, and n is selected from 3, 4, and 5; [0847] each
R5 is independently selected from the group consisting of C1-3
alkyl, C2-3 alkenyl, and H; [0848] each R6 is independently
selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and
H; [0849] M and M' are independently selected from C(O)O, OC(O),
C(O)N(R'), N(R')C(O), C(O), C(S), C(S)S, SC(S), CH(OH), P(O)(OR')O,
S(O)2, SS, an aryl group, and a heteroaryl group; R7 is selected
from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H; each
R is independently selected from the group consisting of C1-3
alkyl, C2-3 alkenyl, and H; [0850] each R' is independently
selected from the group consisting of C1-18 alkyl, C2-18 alkenyl,
R*YR'', YR'', and H; [0851] each R'' is independently selected from
the group consisting of C3-14 alkyl and C3-14 alkenyl; [0852] each
R* is independently selected from the group consisting of C1-12
alkyl and C1-12 alkenyl; [0853] each Y is independently a C3-6
carbocycle; [0854] each X is independently selected from the group
consisting of F, Cl, Br, and I; and [0855] m is selected from 5, 6,
7, 8, 9, 10, 11, 12, and 13, [0856] or salts or isomers thereof.
[0857] 28. The vaccine of paragraph 22, wherein a subset of
compounds of Formula (I) includes those in which [0858] R1 is
selected from the group consisting of C5-30 alkyl, C5-20 alkenyl,
R*YR'', YR'', and R''M'R'; [0859] R2 and R3 are independently
selected from the group consisting of C1-14 alkyl, C2-14 alkenyl,
R*YR'', YR'', and R*OR'', or R2 and R3, together with the atom to
which they are attached, form a heterocycle or carbocycle; [0860]
R4 is selected from the group consisting of (CH2)nQ, (CH2)nCHQR,
CHQR, and CQ(R)2, where Q is N(R)2, and n is selected from 1, 2, 3,
4, and 5; [0861] each R5 is independently selected from the group
consisting of C1-3 alkyl, C2-3 alkenyl, and H; [0862] each R6 is
independently selected from the group consisting of C1-3 alkyl,
C2-3 alkenyl, and H; [0863] M and M' are independently selected
from C(O)O, OC(O), C(O)N(R'), N(R')C(O), C(O), C(S), C(S)S, SC(S),
CH(OH), P(O)(OR')O, S(O)2, SS, an aryl group, and a heteroaryl
group; [0864] R7 is selected from the group consisting of C1-3
alkyl, C2-3 alkenyl, and H; [0865] each R is independently selected
from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
[0866] each R' is independently selected from the group consisting
of C1-18 alkyl, C2-18 alkenyl, R*YR'', YR'', and H; [0867] each R''
is independently selected from the group consisting of C3-14 alkyl
and C3-14 alkenyl; [0868] each R* is independently selected from
the group consisting of C1-12 alkyl and C1-12 alkenyl; [0869] each
Y is independently a C3-6 carbocycle; [0870] each X is
independently selected from the group consisting of F, Cl, Br, and
I; and [0871] m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,
[0872] or salts or isomers thereof. [0873] 29. The vaccine of
paragraph 22, wherein a subset of compounds of Formula (I) includes
those of Formula (IA):
##STR00047##
[0873] or a salt or isomer thereof, wherein 1 is selected from 1,
2, 3, 4, and 5; m is selected from 5, 6, 7, 8, and 9; M1 is a bond
or M'; R4 is unsubstituted C1-3 alkyl, or (CH2)nQ, in which Q is
OH, NHC(S)N(R)2, NHC(O)N(R)2, N(R)C(O)R, N(R)S(O)2R, N(R)R8,
NHC(.dbd.NR9)N(R)2, NHC(.dbd.CHR9)N(R)2, --OC(O)N(R)2, N(R)C(O)OR,
heteroaryl or heterocycloalkyl; M and M' are independently selected
from C(O)O, OC(O), C(O)N(R'), P(O)(OR')O, SS, an aryl group, and a
heteroaryl group; and R2 and R3 are independently selected from the
group consisting of H, C1-14 alkyl, and C2-14 alkenyl.
[0874] This invention is not limited in its application to the
details of construction and the arrangement of components set forth
in the following description or illustrated in the drawings. The
invention is capable of other embodiments and of being practiced or
of being carried out in various ways. Also, the phraseology and
terminology used herein is for the purpose of description and
should not be regarded as limiting. The use of "including,"
"comprising," or "having," "containing," "involving," and
variations thereof herein, is meant to encompass the items listed
thereafter and equivalents thereof as well as additional items.
EXAMPLES
Example 1: Manufacture of Polynucleotides
[0875] According to the present disclosure, the manufacture of
polynucleotides and/or parts or regions thereof may be accomplished
utilizing the methods taught in International Publication
WO2014/152027, entitled "Manufacturing Methods for Production of
RNA Transcripts," the contents of which is incorporated herein by
reference in its entirety.
[0876] Purification methods may include those taught in
International Publication WO2014/152030 and International
Publication WO2014/152031, each of which is incorporated herein by
reference in its entirety.
[0877] Detection and characterization methods of the
polynucleotides may be performed as taught in International
Publication WO2014/144039, which is incorporated herein by
reference in its entirety.
[0878] Characterization of the polynucleotides of the disclosure
may be accomplished using polynucleotide mapping, reverse
transcriptase sequencing, charge distribution analysis, detection
of RNA impurities, or any combination of two or more of the
foregoing. "Characterizing" comprises determining the RNA
transcript sequence, determining the purity of the RNA transcript,
or determining the charge heterogeneity of the RNA transcript, for
example. Such methods are taught in, for example, International
Publication WO2014/144711 and International Publication
WO2014/144767, the content of each of which is incorporated herein
by reference in its entirety.
Example 2: Chimeric Polynucleotide Synthesis
[0879] According to the present disclosure, two regions or parts of
a chimeric polynucleotide may be joined or ligated using
triphosphate chemistry. A first region or part of 100 nucleotides
or less is chemically synthesized with a 5' monophosphate and
terminal 3'desOH or blocked OH, for example. If the region is
longer than 80 nucleotides, it may be synthesized as two strands
for ligation.
[0880] If the first region or part is synthesized as a
non-positionally modified region or part using in vitro
transcription (IVT), conversion the 5'monophosphate with subsequent
capping of the 3' terminus may follow.
[0881] Monophosphate protecting groups may be selected from any of
those known in the art.
[0882] The second region or part of the chimeric polynucleotide may
be synthesized using either chemical synthesis or IVT methods. IVT
methods may include an RNA polymerase that can utilize a primer
with a modified cap. Alternatively, a cap of up to 130 nucleotides
may be chemically synthesized and coupled to the IVT region or
part.
[0883] For ligation methods, ligation with DNA T4 ligase, followed
by treatment with DNase should readily avoid concatenation.
[0884] The entire chimeric polynucleotide need not be manufactured
with a phosphate-sugar backbone. If one of the regions or parts
encodes a polypeptide, then such region or part may comprise a
phosphate-sugar backbone.
[0885] Ligation is then performed using any known click chemistry,
orthoclick chemistry, solulink, or other bioconjugate chemistries
known to those in the art.
[0886] Synthetic route
[0887] The chimeric polynucleotide may be made using a series of
starting segments. Such segments include:
[0888] (a) a capped and protected 5' segment comprising a normal
3'OH (SEG. 1)
[0889] (b) a 5' triphosphate segment, which may include the coding
region of a polypeptide and a normal 3'OH (SEG. 2)
[0890] (c) a 5' monophosphate segment for the 3' end of the
chimeric polynucleotide (e.g., the tail) comprising cordycepin or
no 3'OH (SEG. 3)
[0891] After synthesis (chemical or IVT), segment 3 (SEG. 3) may be
treated with cordycepin and then with pyrophosphatase to create the
5' monophosphate.
[0892] Segment 2 (SEG. 2) may then be ligated to SEG. 3 using RNA
ligase. The ligated polynucleotide is then purified and treated
with pyrophosphatase to cleave the diphosphate. The treated
SEG.2-SEG. 3 construct may then be purified and SEG. 1 is ligated
to the 5' terminus. A further purification step of the chimeric
polynucleotide may be performed.
[0893] Where the chimeric polynucleotide encodes a polypeptide, the
ligated or joined segments may be represented as: 5'UTR (SEG. 1),
open reading frame or ORF (SEG. 2) and 3'UTR+PolyA (SEG. 3).
[0894] The yields of each step may be as much as 90-95%.
Example 3: PCR for cDNA Production
[0895] PCR procedures for the preparation of cDNA may be performed
using 2.times. KAPA HIFI.TM. HotStart ReadyMix by Kapa Biosystems
(Woburn, Mass). This system includes 2.times. KAPA ReadyMix 12.5
.mu.l; Forward Primer (10 .mu.M) 0.75 .mu.l; Reverse Primer (10
.mu.M) 0.75 .mu.l; Template cDNA 100 ng; and dH.sub.20 diluted to
25.0 .mu.l. The reaction conditions may be at 95.degree. C. for 5
min. The reaction may be performed for 25 cycles of 98.degree. C.
for 20 sec, then 58.degree. C. for 15 sec, then 72.degree. C. for
45 sec, then 72.degree. C. for 5 min, then 4.degree. C. to
termination.
[0896] The reaction may be cleaned up using Invitrogen's
PURELINK.TM. PCR Micro Kit (Carlsbad, Calif.) per manufacturer's
instructions (up to 5 .mu.g). Larger reactions may require a
cleanup using a product with a larger capacity. Following the
cleanup, the cDNA may be quantified using the NANODROP.TM. and
analyzed by agarose gel electrophoresis to confirm that the cDNA is
the expected size. The cDNA may then be submitted for sequencing
analysis before proceeding to the in vitro transcription
reaction.
Example 4: In vitro Transcription (IVT)
[0897] The in vitro transcription reaction generates RNA
polynucleotides. Such polynucleotides may comprise a region or part
of the polynucleotides of the disclosure, including chemically
modified RNA (e.g., mRNA) polynucleotides. The chemically modified
RNA polynucleotides can be uniformly modified polynucleotides. The
in vitro transcription reaction utilizes a custom mix of nucleotide
triphosphates (NTPs). The NTPs may comprise chemically modified
NTPs, or a mix of natural and chemically modified NTPs, or natural
NTPs.
[0898] A typical in vitro transcription reaction includes the
following:
TABLE-US-00001 1) Template cDNA 1.0 .mu.g 2) 10x transcription
buffer 2.0 .mu.l (400 mM Tris-HCl pH 8.0, 190 mM MgCl.sub.2, 50 mM
DTT, 10 mM Spermidine) 3) Custom NTPs (25 mM each) 0.2 .mu.l 4)
RNase Inhibitor 20 U 5) T7 RNA polymerase 3000 U 6) dH.sub.20 up to
20.0 .mu.l. and 7) Incubation at 37.degree. C. for 3 hr-5 hrs.
[0899] The crude IVT mix may be stored at 4.degree. C. overnight
for cleanup the next day. 1 U of RNase-free DNase may then be used
to digest the original template. After 15 minutes of incubation at
37.degree. C., the mRNA may be purified using Ambion's
MEGACLEAR.TM. Kit (Austin, Tex.) following the manufacturer's
instructions. This kit can purify up to 500 .mu.g of RNA. Following
the cleanup, the RNA polynucleotide may be quantified using the
NANODROP.sup.TM and analyzed by agarose gel electrophoresis to
confirm the RNA polynucleotide is the proper size and that no
degradation of the RNA has occurred.
Example 5: Enzymatic Capping
[0900] Capping of a RNA polynucleotide is performed as follows
where the mixture includes: IVT RNA 60 .mu.g-180 .mu.g and
dH.sub.20 up to 72 .mu.l. The mixture is incubated at 65.degree. C.
for 5 minutes to denature RNA, and then is transferred immediately
to ice.
[0901] The protocol then involves the mixing of 10.times. Capping
Buffer (0.5 M Tris-HCl (pH 8.0), 60 mM KCl, 12.5 mM MgCl.sub.2)
(10.0 .mu.l); 20 mM GTP (5.0 .mu.l); 20 mM S-Adenosyl Methionine
(2.5 .mu.l); RNase Inhibitor (100 U); 2'-O-Methyltransferase (400
U); Vaccinia capping enzyme (Guanylyl transferase) (40 U);
dH.sub.20 (Up to 28 .mu.l); and incubation at 37.degree. C. for 30
minutes for 60 .mu.g RNA or up to 2 hours for 180 .mu.s of RNA.
[0902] The RNA polynucleotide may then be purified using Ambion's
MEGACLEAR.TM. Kit (Austin, Tex.) following the manufacturer's
instructions. Following the cleanup, the RNA may be quantified
using the NANODROP.TM. (ThermoFisher, Waltham, Mass.) and analyzed
by agarose gel electrophoresis to confirm the RNA polynucleotide is
the proper size and that no degradation of the RNA has occurred.
The RNA polynucleotide product may also be sequenced by running a
reverse-transcription-PCR to generate the cDNA for sequencing.
Example 6: PolyA Tailing Reaction
[0903] Without a poly-T in the cDNA, a poly-A tailing reaction must
be performed before cleaning the final product. This is done by
mixing capped IVT RNA (100 .mu.l); RNase Inhibitor (20 U);
10.times. Tailing Buffer (0.5 M Tris-HCl (pH 8.0), 2.5 M NaCl, 100
mM MgCl.sub.2) (12.0 .mu.l); 20 mM ATP (6.0 .mu.l); Poly-A
Polymerase (20 U); dH.sub.2O up to 123.5 .mu.l and incubation at
37.degree. C. for 30 min. If the poly-A tail is already in the
transcript, then the tailing reaction may be skipped and proceed
directly to cleanup with Ambion's MEGACLEAR.TM. kit (Austin, Tex.)
(up to 500 .mu.g). Poly-A Polymerase may be a recombinant enzyme
expressed in yeast.
[0904] It should be understood that the processivity or integrity
of the polyA tailing reaction may not always result in an exact
size polyA tail. Hence, polyA tails of approximately between 40-200
nucleotides, e.g., about 40, 50, 60, 70, 80, 90, 91, 92, 93, 94,
95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108,
109, 110, 150-165, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164
or 165 are within the scope of the present disclosure.
Example 7: Natural 5' Caps and 5' Cap Analogues
[0905] 5'-capping of polynucleotides may be completed concomitantly
during the in vitro-transcription reaction using the following
chemical RNA cap analogs to generate the 5'-guanosine cap structure
according to manufacturer protocols: 3'-O-Me-m7G(5')ppp(5') G [the
ARCA cap]; G(5)ppp(5')A; G(5')ppp(5')G; m7G(5')ppp(5')A;
m7G(5')ppp(5')G (New England BioLabs, Ipswich, Mass.). 5'-capping
of modified RNA may be completed post-transcriptionally using a
Vaccinia Virus Capping Enzyme to generate the "Cap 0"
structure:
[0906] m7G(5')ppp(5')G (New England BioLabs, Ipswich, Mass.). Cap 1
structure may be generated using both Vaccinia Virus Capping Enzyme
and a 2'-O methyl-transferase to generate:
m7G(5')ppp(5')G-2'-O-methyl. Cap 2 structure may be generated from
the Cap 1 structure followed by the 2'-O-methylation of the
5'-antepenultimate nucleotide using a 2'-O methyl-transferase. Cap
3 structure may be generated from the Cap 2 structure followed by
the 2'-O-methylation of the 5'-preantepenultimate nucleotide using
a 2'-O methyl-transferase. Enzymes are preferably derived from a
recombinant source.
[0907] When transfected into mammalian cells, the modified mRNAs
have a stability of between 12-18 hours or more than 18 hours,
e.g., 24, 36, 48, 60, 72 or greater than 72 hours.
Example 8: Capping Assays
Protein Expression Assay
[0908] Polynucleotides (e.g., mRNA) encoding a polypeptide,
containing any of the caps taught herein, can be transfected into
cells at equal concentrations. The amount of protein secreted into
the culture medium can be assayed by ELISA at 6, 12, 24 and/or 36
hours post-transfection. Synthetic polynucleotides that secrete
higher levels of protein into the medium correspond to a synthetic
polynucleotide with a higher translationally-competent cap
structure.
Purity Analysis Synthesis
[0909] RNA (e.g., mRNA) polynucleotides encoding a polypeptide,
containing any of the caps taught herein can be compared for purity
using denaturing Agarose-Urea gel electrophoresis or HPLC analysis.
RNA polynucleotides with a single, consolidated band by
electrophoresis correspond to the higher purity product compared to
polynucleotides with multiple bands or streaking bands. Chemically
modified RNA polynucleotides with a single HPLC peak also
correspond to a higher purity product. The capping reaction with a
higher efficiency provides a more pure polynucleotide
population.
Cytokine Analysis
[0910] RNA (e.g., mRNA) polynucleotides encoding a polypeptide,
containing any of the caps taught herein can be transfected into
cells at multiple concentrations. The amount of pro-inflammatory
cytokines, such as TNF-alpha and IFN-beta, secreted into the
culture medium can be assayed by ELISA at 6, 12, 24 and/or 36 hours
post-transfection. RNA polynucleotides resulting in the secretion
of higher levels of pro-inflammatory cytokines into the medium
correspond to a polynucleotides containing an immune-activating cap
structure.
Capping Reaction Efficiency
[0911] RNA (e.g., mRNA) polynucleotides encoding a polypeptide,
containing any of the caps taught herein can be analyzed for
capping reaction efficiency by LC-MS after nuclease treatment.
Nuclease treatment of capped polynucleotides yield a mixture of
free nucleotides and the capped 5'-5-triphosphate cap structure
detectable by LC-MS. The amount of capped product on the LC-MS
spectra can be expressed as a percent of total polynucleotide from
the reaction and correspond to capping reaction efficiency. The cap
structure with a higher capping reaction efficiency has a higher
amount of capped product by LC-MS.
Example 9: Agarose Gel Electrophoresis of Modified RNA or RT PCR
Products
[0912] Individual RNA polynucleotides (200-400 ng in a 20 .mu.l
volume) or reverse transcribed PCR products (200-400 ng) may be
loaded into a well on a non-denaturing 1.2% Agarose E-Gel
(Invitrogen, Carlsbad, CA) and run for 12-15 minutes, according to
the manufacturer protocol.
Example 10: NANODROP.TM. Modified RNA Quantification and UV
Spectral Data
[0913] Chemically modified RNA polynucleotides in TE buffer (1
.mu.l) are used for NANODROP.TM. UV absorbance readings to
quantitate the yield of each polynucleotide from an chemical
synthesis or in vitro transcription reaction.
Example 11: Formulation of Modified mRNA Using Lipidoids
[0914] RNA (e.g., mRNA) polynucleotides may be formulated for in
vitro experiments by mixing the polynucleotides with the lipidoid
at a set ratio prior to addition to cells. In vivo formulation may
require the addition of extra ingredients to facilitate circulation
throughout the body. To test the ability of these lipidoids to form
particles suitable for in vivo work, a standard formulation process
used for siRNA-lipidoid formulations may be used as a starting
point. After formation of the particle, polynucleotide is added and
allowed to integrate with the complex. The encapsulation efficiency
is determined using a standard dye exclusion assays.
Example 12: Mouse Immunogenicity Studies
Comparison of HA Stem Antigens
[0915] In this example, assays were carried out to evaluate the
immune response to influenza virus vaccine antigens delivered using
an mRNA/LNP platform in comparison to protein antigens. The instant
study was designed to test the immunogenicity in mice of candidate
influenza virus vaccines comprising an mRNA polynucleotide encoding
HA stem protein obtained from different strains of influenza virus.
Animals tested were 6-8 week old female BALB/c mice obtained from
Charles River Laboratories. Test vaccines included the following
mRNAs formulated in MC3 LNP: stem of H1/Puerto Rico/8/1934 (based
on Mallajosyula V et al. PNAS 2014 Jun. 24; 111(25):E2514-23), stem
of H1/New Caledonia/20/1999 (based on Mallajosyula V et al. PNAS
2014 Jun. 24; 111(25):E2514-23), stem of H1/California/04/2009
(based on Mallajosyula Vet al. PNAS 2014 Jun. 24;
111(25):E2514-23), stem of H5/Vietnam/1194/2004 (based on
Mallajosyula V et al. PNAS 2014 Jun. 24; 111(25):E2514-23), stem of
H10/Jiangxi-Donghu/346/2013, and full-length
H10/Jiangxi-Donghu/346/2013 .
[0916] Protein vaccines tested in this study included the
pH1HA10-Foldon protein, as described in Mallajosyula et al. Proc
Natl Acad Sci USA. 2014; 111(25):E2514-23. Additional controls
included MC3 (control for effects of LNP) and PR8 influenza
virus.
[0917] Mice were immunized intramuscularly with a total volume of
100 .mu.L of each test vaccine, which was administered in a 50
.mu.L immunization to each quadricep, except for administration of
the PR8 influenza virus control which was delivered intranasally in
a volume of 20 .mu.L while the animals were sedated with a mixture
of Ketamine and Xylazine. The group numbers for each test vaccine
along with the vaccine dose are outlined in the table below:
TABLE-US-00002 TABLE 1 RNA Test Vaccines Group # Antigen dose
formulation 1 H10/Jiangxi- 10 .mu.g MC3 Donghu/346/2013 full-length
RNA 2 H10N8 A/JX346/2013 stem 10 .mu.g MC3 RNA 3 H1N1 A/Puerto
Rico/8/1934 10 .mu.g MC3 stem RNA 4 H1N1 A/New 10 .mu.g MC3
Caledonia/20/99 stem RNA 5 H1N1 A/Califomia/04/2009 10 .mu.g MC3
stem RNA 6 H5N1 A/Vietnam/1203/2004 10 .mu.g MC3 stem RNA 7
pH1HA10-Foldon protein 20 .mu.g CpG 7909 8 MC3 0 .mu.g MC3 9 0.1
LD90 PR8 virus 0.1 LD90 None
Mice were immunized with two doses of the various influenza virus
RNA vaccine formulations at weeks 0 and 3, and serum was collected
two weeks after immunization with the second dose.
[0918] To test the sera for the presence of antibodies capable of
binding to hemagglutinin (HA) from a wide variety of influenza
strains, ELISA plates were coated with 100 ng of the following
recombinant HAs obtained from Sino Biological Inc.: Influenza A
H1N1 (A/New Caledonia/20/99), cat #11683-V08H; Influenza A H3N2
(A/Aichi/2/1968), cat #11707-V08H; Influenza A H1N1
(A/California/04/2009) cat #11055-V08H; Influenza A H1N1 (A/Puerto
Rico/8/34) cat #11684-V08H; Influenza A H3N2 (A/Brisbane/10/2007),
cat #11056-V08H; Influenza A H2N2 (A/Japan/305/1957) cat
#11088-V08H; Influenza A H7N9 (A/Anhui/1/2013) cat #40103-V08H;
Influenza H5N1 (A/Vietnam/1194/2004) cat #11062-V08H1; Influenza
H9N2 (A/Hong Kong/1073/99) cat #11229-V08H and Influenza A H10N8
(A/Jiangxi-Donghu/346/2013) cat #40359-V08B. After coating, the
plates were washed, blocked with Phosphate Buffered Saline with
0.05% Tween-20 (PBST)+3% milk, and 100 .mu.L of control antibodies
or sera from immunized mice (diluted in PBST+3% milk) were added to
the top well of each plate and serially diluted. Plates were sealed
and incubated at room temperature for 2 hours. Plates were washed,
and goat anti-mouse IgG (H+L)-HRP conjugate (Novex, diluted 1:2000
in PBST/3% milk) was added to each well containing mouse sera.
Plates were incubated at room temperature for 1 hr, washed, and
incubated with TMB substrate (Thermo Scientific). The color was
allowed to develop for 10 minutes and then quenched with 100 .mu.L
of 2N sulfuric acid. The plates were read at 450 nM on a microplate
reader. Endpoint titers (2.5-fold above background) were
calculated.
[0919] In FIG. 1, the vaccines tested are shown on the y-axis and
the endpoint titer to HA from each of the different strains of
influenza are plotted. HAs from group 1 (H1, H2, H5, H9) strains of
influenza are indicated by filled circles while HAs from group 2
(H3, H7, H10) strains of influenza are indicated by open circles.
FIG. 1 illustrates that mRNA based vaccines encoding HA-based
antigens that are encapsulated in the MC3 lipid nanoparticle
induced high antibody binding titers to HA. FIG. 1 also illustrates
that mRNA vaccines designed to express a portion of the stem domain
from different H1N1 or H5N1 strains of influenza elicited high
antibody titers that were capable of binding all strains of group 1
HA tested as well as several group 2 strains. FIG. 1 also
illustrates that mRNA vaccines designed to express a portion of the
H1N1 A/California/04/2009 stem domain induced higher titers than a
protein vaccine of the same stem domain.
[0920] In another mouse immunogenicity study, the immune response
to additional influenza virus vaccine antigens delivered using an
mRNA/LNP platform was evaluated. The purpose of this study was to
evaluate the ability of a second set of mRNA vaccine antigens to
elicit cross-protective immune responses in the mouse and to assess
the potential for mRNA vaccines encoding influenza HA antigens to
be co-dosed. Animals tested were 6-8 week old female BALB/c mice
obtained from Charles River Laboratories. Test vaccines included
the following mRNAs formulated in MC3 LNP: H1HA6 (based on
Bommakanti G et al. J Virol. 2012 Dec; 86(24):13434-44); H3HA6
(based on Bommakanti G et al. PNAS 2010 Aug. 3; 107(31):13701-6);
H1HA10-Foldon delta Ngly; eH1HA (ectodomain of HA from H1N1
A/Puerto Rico/8/34); eH1HA_native signal seq (eH1HA with its native
signal sequence); H3N2 A/Wisconsin/67/2005 stem; H3N2 A/Hong
Kong/1/1968 stem (based on Mallajosyula V et al. Front Immunol.
2015 Jun. 26; 6:329); H7N9 A/Anhui/1/2013 stem; H1N1
A/California/04/2009 stem RNA (based on Mallajosyula Vet al. PNAS
2014 Jun. 24; 111(25):E2514-23); and H1N1 A/Puerto Rico/8/1934 stem
RNA (based on Mallajosyula V et al. PNAS 2014 Jun 24;
111(25):E2514-23).
[0921] Controls included: MC3 (control for effects of LNP); Naive
(unvaccinated animals); and vaccination with H1N1 A/PR/8/34 and
H3N2 A/HK/1/68 influenza viruses (positive controls).
[0922] Mice were immunized intramuscularly with a total volume of
100 .mu.L of each test vaccine, which was administered in a 50
.mu.L immunization to each quadricep, except for administration of
the H1N1 A/PR/8/34 and H3N2 A/HK/1/68 virus influenza virus
controls which were delivered intranasally in a volume of 20 .mu.L
while the animals were sedated with a mixture of Ketamine and
Xylazine. The group numbers for each test vaccine along with the
vaccine dose are outlined in the table below:
TABLE-US-00003 TABLE 2 Test Vaccines For- Antigen mula- Volume,
Group # Antigen dose tion Route 1 H1HA6 RNA 10 .mu.g MC3 100 .mu.l,
i.m. 2 H3HA6 RNA 10 .mu.g MC3 100 .mu.l, i.m. 3 H1HA10-Foldon_delta
Ngly 10 .mu.g MC3 100 .mu.l, i.m. 4 eH1HA 10 .mu.g MC3 100 .mu.l,
i.m. 5 eH1HA_native signal seq 10 .mu.g MC3 100 .mu.l, i.m. 6 H3N2
A/Wisconsin/67/2005 10 .mu.g MC3 100 .mu.l, i.m. stem RNA 7 H3N2
A/Hong Kong/1/1968 10 .mu.g MC3 100 .mu.l, i.m. stem RNA 8 H7N9
A/Anhui/1/2013 stem 10 .mu.g MC3 100 .mu.l, i.m. RNA 9 H1N1
A/Puerto Rico/8/1934 10 .mu.g MC3 100 .mu.l, i.m. stem RNA AND H3N2
A/Wisconsin/67/2005 stem RNA (RNAs mixed prior to formulation) 10
H1N1 A/Puerto Rico/8/1934 10 .mu.g MC3 100 .mu.l, i.m. stem RNA AND
H3N2 A/Wisconsin/67/2005 stem RNA (RNAs formulated and then mixed
11 H1N1 A/California/04/2009 10 .mu.g MC3 100 .mu.l, i.m. stem RNA
12 H1N1 A/Puerto Rico/8/1934 10 .mu.g MC3 100 .mu.l, i.m. stem RNA
13 MC3 0 .mu.g MC3 100 .mu.l, i.m. 14 Naive 0 .mu.g None None 15
H3N2 A/HK/1/68 virus 0.1 LD90 None 20 .mu.l, i.n. 16 H1N1 A/PR/8/34
virus 0.1 LD90 None 20 .mu.l, i.n.
[0923] Animals were immunized on the study start day and then again
three weeks after the initial immunization. Sera were collected
from the animals two weeks after the second dose. To test the sera
for the presence of antibodies capable of binding to hemagglutinin
(HA) from a wide variety of influenza strains, ELISA plates were
coated with 100 ng of the following recombinant HAs obtained from
Sino Biological Inc.: Influenza A H1N1 (A/New Caledonia/20/99), cat
#11683-V08H; Influenza A H3N2 (A/Aichi/2/1968), cat #11707-V08H;
Influenza A H1N1 (A/California/04/2009) cat #11055-V08H; Influenza
A H1N1 (A/Puerto Rico/8/34) cat #11684-V08H; Influenza A H3N2
(A/Brisbane/10/2007), cat #11056-V08H; Influenza A H2N2
(A/Japan/305/1957) cat #11088-V08H; Influenza A H7N9
(A/Anhui/1/2013) cat #40103-V08H and Influenza A H3N2
(A/Moscow/10/99) cat #40154-V08. The ELISA assay was performed and
endpoint titers were calculated as described above. FIGS. 2 and 3
show the endpoint anti-HA antibody titers following the second
immunization with the test vaccines. The vaccines tested are shown
on the x-axis and the binding to HA from each of the different
strains of influenza is plotted. All mRNA vaccines encoding HA stem
were immunogenic and elicited a robust antibody response
recognizing HA from a diverse set of influenza A virus strains. The
H1HA6, eH1HA, and eH1HA_native-signal-sequence mRNAs elicited the
highest overall binding titers across the panel of group 1 HAs,
while the H3HA6 RNA elicited the highest overall binding titers
across group 2 Has (FIG. 2). Immunogenicity of combinations of stem
mRNA vaccines was also tested. In this study, individual mRNAs were
mixed prior to formulation with LNP (Group 9, co-form) or
individual mRNAs were formulated with LNP prior to mixing (Group
10, mix-form). As shown in FIG. 3, combining H1 and H3 stem-based
mRNAs did not result in interference in the immune response to
either antigen, regardless of the method of formulation.
Example 13: Mouse Efficacy Studies
[0924] Influenza A challenge #1
[0925] This study was designed to test the immunogenicity and
efficacy in mice of candidate influenza virus vaccines. Animals
tested were 6-8 week old female BALB/c mice obtained from Charles
River Laboratories. Test vaccines included the following mRNAs
formulated in MC3 LNP: NIHGen6HASS-foldon mRNA (based on Yassine et
al. Nat. Med. 2015 September; 21(9):1065-70), an mRNA encoding the
nucleoprotein NP from an H3N2 strain, or one of several
combinations of NIHGen6HASS-foldon and NP mRNAs. Several methods of
vaccine antigen co-delivery were tested including: mixing
individual mRNAs prior to formulation with LNP (co-form),
formulation of individual mRNAs prior to mixing (mix ind LNPs), and
formulating mRNAs individually and injecting distal sites (opposite
legs) (ind LNPs remote). Control animals were vaccinated with an
RNA encoding the ectodomain of the HA from H1N1 A/Puerto
Rico/8/1934 (eH1HA, positive control) or empty MC3 LNP (to control
for effects of the LNP) or were not vaccinated (naive).
[0926] At week 0 and week 3, animals were immunized intramuscularly
(IM) with a total volume of 100 .mu.L of each test vaccine, which
was administered in a 50 .mu.L immunization to each quadricep.
Candidate influenza virus vaccines evaluated in this study were
described above and are outlined in the table below. Sera were
collected from all animals two weeks after the second dose. At week
6, spleens were harvested from a subset of the animals (n=4). The
remaining animals (n=6) were challenged intranasally while sedated
with a mixture of Ketamine and Xylazine with a lethal dose of
mouse-adapted influenza virus strain H1N1 A/Puerto Rico/8/1934.
Mortality was recorded and individual mouse weight was assessed
daily for 20 days post-infection.
TABLE-US-00004 TABLE 3 Test Vaccines Group Antigen Formu- Volume, #
Antigen dose lation Route 1 NIHGen6HASS-foldon 10 .mu.g MC3 100
.mu.l, i.m. RNA 2 NIHGen6HASS-foldon 5 .mu.g MC3 100 .mu.l, i.m.
RNA 3 NIHGen6HASS-foldon 2 .mu.g MC3 100 .mu.l, i.m. RNA 4 NP RNA 5
.mu.g MC3 100 .mu.l, i.m. 5 NIHGen6HASS-foldon 5 .mu.g of each MC3
100 .mu.l, i.m. RNA + NP RNA RNA mixed, then formulated 6
NIHGen6HASS-foldon 5 .mu.g of each MC3 100 .mu.l, i.m. RNA + NP RNA
RNA formulated, then mixed 7 NIHGen6HASS-foldon 5 .mu.g of each MC3
100 .mu.l, i.m. RNA + NP RNA RNA formulated and injected into
separate legs 8 NIHGen6HASS-foldon 5 .mu.g of NP + MC3 100 .mu.l,
i.m. RNA + NP RNA 2 .mu.g of NIHGen6HASS-foldon RNA mixed, then
formulated 9 eH1HA RNA 10 .mu.g MC3 100 .mu.l, i.m. 10 MC3 0 .mu.g
MC3 100 .mu.l, i.m. 11 Naive 0 .mu.g None None
[0927] To test the sera for the presence of antibodies capable of
binding to hemagglutinin (HA) from a wide variety of influenza
strains or nucleoprotein (NP), ELISA plates were coated with 100 ng
of the following recombinant proteins obtained from Sino Biological
Inc.: Influenza A H1N1 (A/New Caledonia/20/99) HA, cat #11683-V08H;
Influenza A H3N2 (A/Aichi/2/1968) HA, cat #11707-V08H; Influenza A
H1N1 (A/California/04/2009) HA, cat # 11055-V08H; Influenza A H1N1
(A/Puerto Rico/8/34) HA, cat #11684-V08H; Influenza A H1N1
(A/Brisbane/59/2007) HA, cat #11052-V08H; Influenza A H2N2
(A/Japan/305/1957) HA, cat #11088-V08H; Influenza A H7N9
(A/Anhui/1/2013) HA, cat #40103-V08H, Influenza A H3N2
(A/Moscow/10/99) HA, cat #40154-V08 and Influenza A H3N2
(A/Aichi/2/1968) Nucleoprotein cat #40207-V08B. The ELISA assay was
performed and endpoint titers were calculated as described above.
FIG. 4 depicts the endpoint titers of the pooled serum from animals
vaccinated with the test vaccines. The vaccines tested are shown on
the x-axis of FIG. 4A and the binding to HA from each of the
different strains of influenza is plotted. The NIHGen6HASS-foldon
mRNA vaccine elicited high titers of antibodies that bound all H1,
H2 and H7 HAs tested. Combining the NIHGen6HASS-foldon mRNA with
one that encodes NP did not negatively affect the observed anti-HA
response, regardless of the method of mRNA co-formulation or
co-delivery. In serum collected from identical groups from a
separate study, a robust antibody response to NP protein was also
detected in serum from animals vaccinated with NP mRNA containing
vaccines, either NP alone or co-formulated with NIHGen6HASS-foldon
mRNA(FIG. 4B).
[0928] To probe the functional antibody response, the ability of
serum to neutralize a panel of HA-pseudotyped viruses was assessed
(FIG. 5). Briefly, 293 cells were co-transfected with a
replication-defective retroviral vector containing a firefly
luciferase gene, an expression vector encoding a human airway
serine protease, and expression vectors encoding influenza
hemagglutinin (HA) and neuraminidase (NA) proteins. The resultant
pseudoviruses were harvested from the culture supernatant,
filtered, and titered. Serial dilutions of serum were incubated in
96 well plates at 37.degree. C. for one hour with pseudovirus
stocks (30,000-300,000 relative light units per well) before 293
cells were added to each well. The cultures were incubated at
37.degree. C. for 72 hours, luciferase substrate and cell lysing
reagents were added, and relative light units (RLU) were measured
on a luminometer. Neutralization titers are expressed as the
reciprocal of the serum dilution that inhibited 50% of pseudovirus
infection (IC50).
[0929] For each sample tested (listed along the x-axis), each bar
represents the IC50 for neutralization of a different virus
pseudotype. While the serum from naive or NP RNA vaccinated mice
was unable to inhibit pseudovirus infection, the serum from mice
vaccinated with 10 .mu.g or 5.mu.g of NIHGen6HASS-foldon mRNA or
with a combination of NIHGen6HASS-foldon and NP mRNAs neutralized,
to a similar extent, all H1 and H5 virus pseudotypes tested.
[0930] The ability of NIHGen6HASS-foldon antisera to mediate
antibody-dependent cell cytotoxicity (ADCC) surrogate activity in
vitro was also assessed. Briefly, serially titrated mouse serum
samples were incubated with A549 cells stably expressing HA from
H1N1 A/Puerto Rico/8/1934 on the cell surface. Subsequently, ADCC
Bioassay Effector cells (Promega, mouse FcgRIV NFAT-Luc effector
cells) were added to the serum/target cell mixture. Approximately 6
hours later, Bio-glo reagent (Promega) was added to sample wells
and luminescence was measured. Data was plotted as fold induction
(sample luminescence/background luminescence) versus serum
concentration (FIG. 6). When incubated with the appropriate target
cells, serum from NIHGen6HASS-foldon mRNA vaccinated mice was able
to stimulate the surrogate ADCC effector cell line, suggesting that
the vaccine may induce antibodies capable of mediating in vivo ADCC
activity.
[0931] Three weeks after the administration of the second vaccine
dose, spleens were harvested from a subset of animals in each group
and splenocytes from animals in the same group were pooled. Splenic
lymphocytes were stimulated with a pool of HA or NP peptides, and
IFN-.gamma., IL-2 or TNF-.alpha. production was measured by
intracellular staining and flow cytometry. FIG. 7 is a
representation of responses following stimulation with a pool of NP
peptides, and FIG. 8 is a representation of responses following
stimulation with a pool of H1 HA peptides. Following vaccination
with NP mRNA, either in the presence or absence of
NIHGen6HASS-foldon mRNA, antigen-specific CD4 and CD8 T cells were
found in the spleen. Following vaccination with NIHGen6HASS-foldon
RNA or delivery of NIHGen6HASS-foldon and NP RNAs to distal
injections sites (dist. site), only HA-specific CD4 cells were
observed. However, when NIHGen6HASS-foldon and NP RNAs were
co-administered to the same injection site (co-form, mix), an
HA-specific CD8 T cell response was detected.
[0932] Following lethal challenge with mouse-adapted H1N1 A/Puerto
Rico/8/1934, all naive animals succumbed to infection by day 12
post-infection (FIG. 9). In contrast, all animals vaccinated with
NIHGen6HASS-foldon mRNA, NP mRNA, any combination of
NIHGen6HASS-foldon and NP mRNAs, or eH1HA mRNA survived the
challenge. As seen in FIG. 9, although there was no mortality, mice
that were vaccinated with an H3N2 NP mRNA and challenged with H1N1
virus lost a significant amount (.about.15%) of weight prior to
recovery. Those vaccinated with NIHGen6HASS-foldon RNA also lost
.about.5% body weight. In contrast, mice vaccinated with a
combination of NIHGen6HASS-foldon and NP mRNAs appeared to be
completely protected from lethal influenza virus challenge, similar
to those vaccinated with mRNA expressing an HA antigen homologous
to that of the challenge virus (eH1HA). Vaccine efficacy was
similar at all vaccine doses, as well as with all co-formulation
and co-delivery methods assessed (FIG. 10).
Influenza A challenge #2
[0933] This study was designed to test the immunogenicity and
efficacy in mice of candidate influenza virus vaccines. Animals
tested were 6-8 week old female BALB/c mice obtained from Charles
River Laboratories. Test vaccines included the following mRNAs
formulated in MC3 LNP: NIHGen6HASS-foldon mRNA (based on Yassine et
al. Nat. Med. 2015 September; 21(9):1065-70) and NIHGen6HASS-TM2
mRNA. Control animals were vaccinated with an mRNA encoding the
ectodomain of the HA from H1N1 A/Puerto Rico/8/1934 (eH1HA,
positive control) or were not vaccinated (naive).
[0934] At week 0 and week 3, animals were immunized intramuscularly
(IM) with a total volume of 100 .mu.L of each test vaccine, which
was administered in a 50 .mu.L immunization to each quadricep.
Candidate influenza virus vaccines evaluated in this study were
described above and outlined in the table below. Sera were
collected from all animals two weeks after the second dose. At week
6, all animals were challenged intranasally while sedated with a
mixture of Ketamine and Xylazine with a lethal dose of
mouse-adapted influenza virus strain H1N1 A/Puerto Rico/8/1934.
Mortality was recorded and group mouse weight was assessed daily
for 20 days post-infection.
TABLE-US-00005 TABLE 4 Test Vaccines Group Antigen Formu- Volume, #
Antigen dose lation Route 1 NIHGen6HASS-foldon 5 .mu.g MC3 100
.mu.l, i.m. RNA 2 NIHGen6HASS-foldon- 5 .mu.g MC3 100 .mu.l, i.m.
TM2 RNA 3 eH1HA RNA 10 .mu.g MC3 100 .mu.l, i.m. 4 Naive 0 .mu.g
None None
[0935] To test the sera for the presence of antibody capable of
binding to hemagglutinin (HA) from a wide variety of influenza
strains, ELISA plates were coated with 100 ng of the following
recombinant HAs obtained from Sino Biological Inc.: Influenza A
H1N1 (A/New Caledonia/20/99), cat #11683-V08H; Influenza A H3N2
(A/Aichi/2/1968), cat #11707-V08H; Influenza A H1N1
(A/California/04/2009) cat #11055-V08H; Influenza A H1N1 (A/Puerto
Rico/8/34) cat #11684-V08H; Influenza A H1N1 (A/Brisbane/59/2007),
cat #11052-V08H; Influenza A H2N2 (A/Japan/305/1957) cat
#11088-V08H; Influenza A H7N9 (A/Anhui/1/2013) cat #40103-V08H and
Influenza A H3N2 (A/Moscow/10/99) cat #40154-V08. The ELISA assay
was performed and endpoint titers were calculated as described
above. FIG. 11A depicts the endpoint titers of the pooled serum
from animals vaccinated with the test vaccines. The vaccines tested
are shown on the x-axis and the binding to HA from each of the
different strains of influenza is plotted. The NIHGen6HASS-foldon
mRNA vaccine elicited high titers of antibodies that bound all H1,
H2 and H7 HAs tested. The binding titers from NIHGen6HASS-TM2 mRNA
vaccinated mice were reduced as compared to those from
NIHGen6HASS-foldon mRNA vaccinated mice.
[0936] Following lethal challenge with mouse-adapted H1N1 A/Puerto
Rico/8/1934, all naive animals succumbed to infection by day 16
post-infection (FIG. 11B). In contrast, all animals vaccinated with
NIHGen6HASS-foldon mRNA, NIHGen6HASS-TM2 mRNA, or eH1HA RNA
survived the challenge. As shown in FIG. 11B, the efficacy of the
NIHGen6HASS-TM2 vaccine was equivalent to that of the
NIHGen6HASS-foldon vaccine.
Influenza A challenge #3
[0937] In this example, two animal studies and assays were carried
out to evaluate the immune response to influenza virus consensus
hemagglutinin (HA) vaccine antigens delivered using an mRNA/LNP
platform. The purpose of these studies was to evaluate the ability
of consensus HA mRNA vaccine antigens to elicit cross-protective
immune responses in the mouse.
[0938] To generate consensus HA sequences, 2415 influenza A
serotype H1 HA sequences were obtained from the NIAID Influenza
Research Database (IRD) (Squires et al., Influenza Other Respir
Viruses. 2012 November; 6(6): 404-416.) through the web site at
http://www.fludb.org. After removal of duplicate sequences and lab
strains, 2385 entries remained, including 1735 H1 sequences from
pandemic H1N1 strains (pH1N1) and 650 from seasonal H1N1 strains
(sH1N1). Pandemic and seasonal H1 sequences were separately aligned
and a consensus sequence was generated for each group using the
Matlab 9.0 Bioinformatics toolbox (MathWorks, Natick, Mass.).
Sequence profiles were generated for both groups separately using a
modified Seq2Logo program (Thomsen et al., Nucleic Acids Res. 2012
Jul; 40 (Web Server issue):W281-7).
[0939] Animals tested were 6-8 week old female BALB/c mice obtained
from Charles River Laboratories. Test vaccines included the
following mRNAs formulated in MC3 LNP: ConH1 and ConH3 (based on
Webby et al., PLoS One. 2015 Oct 15; 10(10):e0140702.); Cobra_P1
and Cobra_X3 (based on Carter et al., J Virol. 2016 Apr 14;
90(9):4720-34); MRK_pH1_Con and MRK_sH1_Con (pandemic and seasonal
consensus sequences described above); and each of the above
mentioned six antigens with a ferritin fusion sequence for
potential particle formation.
[0940] Controls included: MC3 (control for effects of LNP); Naive
(unvaccinated animals); and vaccination with eH1HA RNA, which
encode the ectodomain of HA from strain H1N1 A/PR/8/34 (positive
control for the virus challenge).
[0941] At week 0 and week 3, animals were immunized intramuscularly
(IM) with a total volume of 100 .mu.L of each test vaccine, which
was administered in a 50 .mu.L immunization to each quadricep.
Candidate influenza virus vaccines evaluated in this study were
described above and are outlined in the table below. Sera were
collected from all animals two weeks after the second dose (week
5). At week 6, the animals were challenged intranasally while
sedated with a mixture of Ketamine and Xylazine with a lethal dose
of mouse-adapted influenza virus strain H1N1 A/Puerto Rico/8/1934
(PR8). Mortality was recorded and group weight was assessed daily
for 20 days post-infection.
TABLE-US-00006 TABLE 5 Test Vaccines Group Antigen Formu- Volume, #
Antigen dose lation Route 1 Con_H1 RNA 10 .mu.g MC3 100 .mu.l, i.m.
2 Con_H3 RNA 10 .mu.g MC3 100 .mu.l, i.m. 3 Merck_pH1_Con RNA 10
.mu.g MC3 100 .mu.l, i.m. 4 Merck_sH1_Con RNA 10 .mu.g MC3 100
.mu.l, i.m. 5 Cobra_P1 RNA 10 .mu.g MC3 100 .mu.l, i.m. 6 Cobra_X3
RNA 10 .mu.g MC3 100 .mu.l, i.m. 7 ConH1_ferritin RNA 10 .mu.g MC3
100 .mu.l, i.m. 8 ConH3_ferritin RNA 10 .mu.g MC3 100 .mu.l, i.m. 9
Merck_pH1_Con_ferritin 10 .mu.g MC3 100 .mu.l, i.m. RNA 10
Merck_sH1_Con_ferritin 10 .mu.g MC3 100 .mu.l, i.m. RNA 11
Cobra_P1_ferritin RNA 10 .mu.g MC3 100 .mu.l, i.m. 12
Cobra_X3_ferritin RNA 10 .mu.g MC3 100 .mu.l, i.m. 13 eH1HA 10
.mu.g MC3 100 .mu.l, i.m. 14 MC3 0 .mu.g MC3 100 .mu.l, i.m. 15
Naive 0 .mu.g None None
[0942] To test the ability of the serum antibodies to neutralize
the challenge virus strain, a microneutralization assay using a
modified PR8 virus with a Gaussia luciferase reporter gene (Pan et
al., Nat Commun. 2013; 4:2369) was performed. Briefly, PR8
luciferase virus was diluted in virus diluent with TPCK-treated
trypsin. Serum samples were diluted 1:10 and then serially diluted
3-fold in 96-well cell culture plates. 50 .mu.L of each diluted
serum sample and an equal volume of diluted virus were mixed in the
well and incubated at 37.degree. C. with 5% CO.sub.2 for 1 hr
before 100 .mu.L of MDCK cells at 1.5.times.10{circumflex over (
)}5 cells/mL were added. Plates were then incubated at 37.degree.
C. with 5% CO.sub.2 for 72 hrs. Luminescence signal was read with a
Gaussia Luciferase Glow Assay Kit (Pierce) on an EnVision reader
(Perkin Elmer). As shown in FIG. 12A, serum from mice immunized
with mRNA encoding consensus HA antigens from the H1 subtype was
able to detectably neutralize the PR8 luciferase virus, even though
the HA sequences of these antigens were 8-19% different from that
of the PR8 strain. The HA sequence-matched antigen (eH1HA) elicited
a much higher serum neutralizing antibody response against this
virus. Serum from mice vaccinated with RNA encoding the consensus
H3 antigen (ConH3), in contrast, was not able to neutralize the PR8
luciferase virus, suggesting that the consensus sequences from
different subtypes (H1 and H3, for example) may not cross-react.
Similarly, serum from mice immunized with mRNA encoding H1 subtype
consensus HA antigens with a ferritin fusion sequence was able to
detectably neutralize the PR8 luciferase virus, except for the
MerckpH1 Conferritin mRNA, while serum from mice vaccinated with an
mRNA encoding the consensus H3 antigen with a ferritin fusion
sequence was not able to neutralize the PR8 luciferase virus (FIG.
12B). Consistent with the serum neutralization data, mice immunized
with the consensus H1 HA antigens (with or without ferritin fusion)
survived the lethal PR8 virus challenge and showed no weight loss,
except for the Merck_pH1_Con_ferritin mRNA group, while mice in the
ConH3, naive and LNP only control groups rapidly lost weight upon
challenge (FIG. 13). Mice immunized with Merck_pH1_Con_ferritin
mRNA survived the lethal PR8 virus challenge and showed 5-10%
weight loss, suggesting that partial protection may be mediated by
mechanism(s) other than virus neutralization.
[0943] To assess the breadth of the serum neutralizing activity
elicited by the consensus HA antigens, neutralization assays were
performed on a panel of pseudoviruses as described above (FIG. 14).
As expected, serum from mice immunized with influenza virus H1N1
A/Puerto Rico/8/1934 (from studies described in Example 12) was
only able to neutralize a matched pseudovirus strain (PR8). In
contrast, serum from mice immunized with the consensus H1 HA
antigens, as well as the eH1HA antigen, were able to neutralize a
panel of diverse group 1 pseudoviruses, including strains from
subtypes H1 and H5, but not a strain from group 2 (subtype H3).
Consistently, serum from mice immunized with the consensus H3 HA
antigen was able to neutralize a strain from group 2 (subtype H3)
but not any of the group 1 pseudoviruses.
Influenza B challenge
[0944] This study was designed to test the immunogenicity and
efficacy in mice of candidate influenza virus vaccines. Animals
tested were 6-8 week old female BALB/c mice obtained from Charles
River Laboratories. Test vaccines included the following mRNAs
formulated in MC3 LNP: B/Phuket/3073/2013 sHA (soluble HA),
B/Phuket/3073/2013 mHA (full-length HA with membrane anchor),
B/Brisbane/60/2008 sHA, B/Victoria/02/1987 sHA, B/Victoria/02/1987
mHA, B/Yamagata/16/1988 mHA, or BHA10 (HA stem design). Control
animals were vaccinated with a nonlethal dose of mouse-adapted
B/Ann Arbor/1954 (positive control) or empty MC3 LNP (to control
for effects of the LNP) or were not vaccinated (naive).
[0945] At week 0 and week 3, animals were immunized intramuscularly
(IM) with a total volume of 100 .mu.L of each test vaccine, which
was administered in a 50 .mu.L immunization to each quadricep.
Candidate influenza virus vaccines evaluated in this study were
described above and are outlined in the table below. Sera were
collected from all animals two weeks after the second dose. At week
6, all animals (n=10 per group) were challenged intranasally while
sedated with a mixture of Ketamine and Xylazine with a lethal dose
of mouse-adapted influenza virus strain B/Ann Arbor/1954. Mortality
was recorded and group mouse weight was assessed daily for 20 days
post-infection.
[0946] Each of the sequences described herein encompasses a
chemically modified sequence or an unmodified sequence which
includes no nucleotide modifications.
TABLE-US-00007 TABLE 6 Test Vaccines Group Antigen Formu- Volume, #
Antigen dose lation Route 1 B/Phuket/3073/2013 10 .mu.g MC3 100
.mu.l, i.m. sHA RNA 2 B/Phuket/3073/2013 10 .mu.g MC3 100 .mu.l,
i.m. mHA RNA 3 B/Brisbane/60/2008 10 .mu.g MC3 100 .mu.l, i.m. sHA
RNA 4 B/Victoria/02/1987 10 .mu.g MC3 100 .mu.l, i.m. sHA RNA 5
B/Victoria/02/1987 10 .mu.g MC3 100 .mu.l, i.m. mHA RNA 6
B/Yamagata/16/1988 10 .mu.g MC3 100 .mu.l, i.m. mHA RNA 7 BHA10 RNA
10 .mu.g MC3 100 .mu.l, i.m. 8 MC3 0 .mu.g MC3 100 .mu.l, i.m. 9
Naive 0 .mu.g None 100 .mu.l, i.m. 10 B/Ann Arbor/1954 0.1 LD90
None 20 .mu.l, i.n.
[0947] FIG. 15A depicts the ELISA endpoint anti-HA antibody titers
of the pooled serum from animals vaccinated with the test vaccines.
The vaccines tested are shown on the x-axis and the binding to HA
from each of the different strains of influenza is plotted. All
vaccines tested, except for those derived from B/Phuket/3073/2013
were immunogenic, and serum antibody bound to HA from both
B/Yamagata/16/1988 (Yamagata lineage) and B/Florida/4/2006
(Victoria lineage).
[0948] Following lethal challenge with mouse-adapted B/Ann
Arbor/1954, 90% of MC3-vaccinated and naive animals succumbed to
infection by day 16 post-infection (FIG. 15B). The
B/Phuket/3073/2013 sHA and mHA mRNA vaccines showed no efficacy
against lethal challenge, and the BHA10 stem mRNA vaccine protected
only half of the animals. All other vaccines tested protected mice
completely from mortality (FIG. 15B), but only the
B/Yamagata/16/1988 mHA RNA vaccine was able to prevent lethality
and weight loss in animals challenged with a heterologous virus
strain (FIG. 15B).
Example 14: Non-Human Primate Immunogenicity
[0949] This study was designed to test the immunogenicity in rhesus
macaques of candidate influenza virus vaccines. Test vaccines
included the following mRNAs formulated in MC3 LNP:
NIHGen6HASS-foldon mRNA (based on Yassine et al. Nat. Med. 2015
September; 21(9):1065-70) and NP mRNA encoding NP protein from an
H3N2 influenza strain.
[0950] Animals in Group 1 had been previously vaccinated with
seasonal inactivated influenza vaccine (FLUZONE.RTM.) and were
boosted intramuscularly (IM) at day 0 with 300 .mu.g of
NIHGen6HASS-foldon mRNA. Animals in Groups 2 and 3 were influenza
naive at the study start and were vaccinated at days 0, 28 and 56
with 300 .mu.g of NIHGen6HASS-foldon mRNA or 300 .mu.g of NP mRNA,
respectively. Serum was collected from all animals prior to the
study start (day -8) as well as at days 14, 28, 42, 56, 70, 84,
112, 140 and 168.
[0951] The NIHGen6HASS-foldon vaccine elicited a robust antibody
response as measured by ELISA assay (plates coated with
recombinantly-expressed NIHGen6HASS-foldon [HA stem] or NP
proteins), and the data is depicted in FIG. 16. FIG. 16A shows
titers to HA stem, over time, for four rhesus macaques previously
vaccinated with FLUZONE.RTM. and boosted a single time with
NIHGen6HASS-foldon mRNA vaccine. FIG. 16B depicts titers to HA
stem, over time, from four rhesus macaques vaccinated at days 0, 28
and 56 with the same NIHGen6HASS-foldon RNA vaccine. The
NIHGen6HASS-foldon RNA vaccine was able to boost anti-HA stem
antibody binding titers in animal previously vaccinated with
inactivated influenza vaccine as well as elicited a robust response
in naive animals. In both groups, HA stem titers remained elevated
over baseline to at least study day 168. FIG. 16C illustrates
antibody titers to NP, over time, for four rhesus macaques
vaccinated at days 0, 28 and 56 with the NP mRNA vaccine and shows
that the vaccine elicited a robust antibody response to NP.
[0952] To test the Group 1 and 2 sera for the presence of antibody
capable of binding to hemagglutinin (HA) from a wide variety of
influenza strains, ELISA plates were coated with recombinant HAs
from a diverse set of influenza strains as described above. EC10
titers were calculated as the reciprocal of the serum dilution that
reached 10% of the maximal signal. For animals in Group 1 (FIG.
17A), a single dose of NIHGen6HASS-foldon vaccine boosted titers to
H1 HAs .about.40-60 fold, and titers peaked approximately 28 days
post-vaccination. Titers decreased from days 28-70, but day 70
titers were still .about.10-30-fold above the titers measured prior
to vaccination. The NIHGen6HASS-foldon mRNA vaccine did not boost
titers to HAs from H3 or H7 influenza strains. For animals in Group
2 (FIG. 17B), antibody titers to H1 and H2 HAs rose after each dose
of NIHGen6HASS-foldon mRNA vaccine, and titers appeared to rise
most dramatically after dose 2.
[0953] In addition to robust antibody responses, the NP mRNA
vaccine also elicited cell-mediated immunity in rhesus. On study
day 0, 42, 70 and 140, PBMCs were collected from Group 3 NP mRNA
vaccinated rhesus macaques. Lymphocytes were stimulated with a pool
of NP peptides, and IFN-.gamma., IL-2 or TNF-.alpha. production
were measured by intracellular staining and flow cytometry. FIG. 18
is a representation of responses following NP peptide pool
stimulation. Following vaccination with NP mRNA, antigen-specific
CD4 and CD8 T cells were found in the peripheral blood, and these
cells were maintained above baseline to at least study day 140.
Example 15: H7N9 Immunogenicity Studies
[0954] The instant study was designed to test H7N9 immunogenicity.
Intramuscular immunizations of 25 .mu.M were administered on days 1
and 22 to 40 animals, and blood was collected on days 1, 8, 22, and
43. Hemagglutination inhibition (HAI) and microneutralization tests
were conducted using the blood samples.
[0955] The HAI test showed a geometric mean titer (GMT) of 45 for
all of the animals, including the placebo group. The GMT of the
responders only was 116 (FIG. 19). The HAI kinetics for each
individual subject are given in FIG. 20.
[0956] The microneutralization (MN) test showed a geometric mean
titer (GMT) of 36 for all of the animals, including the placebo
group. The GMT of the responders only was 84 (FIG. 21). The MN test
kinetics for each subject are given in FIG. 22.
[0957] HAI and MN showed a very strong correlation (FIG. 23). Only
one subject had a protective titer in one assay , but not in the
other. Also, 10 subjects had no detectable HAI or MN titer at Day
43.
Example 16: Mouse Immunogenicity Studies
[0958] This study was designed to test the immunogenicity and
efficacy in mice of candidate influenza virus vaccines. Animals
tested were 6-8 week old female BALB/c mice obtained from Charles
River Laboratories. Test vaccines included the following mRNAs
formulated in a cationic LNP: MRK_H1 cot_all, MRK_H3 cot_all,
MRK_H3 con_all, MRK_H3_Consensus A and MRK_H3_Consensus B. Control
animals were vaccinated with an mRNA encoding the HA from H1N1
A/Puerto Rico/8/1934 (FLHA_PR8, positive control for PR8
infection), vaccinated with empty LNP, infected with a nonlethal
dose of mouse-adapted H3 A/Hong Kong/1/1968, or were not vaccinated
(naive).
[0959] At week 0 and week 3, animals were immunized intramuscularly
(IM) with a total volume of 100 mL of each test vaccine, which was
administered in a 50 mL immunization to each quadricep. Candidate
influenza virus vaccines evaluated in this study were described
above and outlined in the table below. Sera were collected from all
animals two weeks after the second dose. At week 6, all animals
were challenged intranasally while sedated with a mixture of
Ketamine and Xylazine with a lethal dose of mouse-adapted influenza
virus strain H1N1 A/Puerto Rico/8/1934 (PR8) or H3 A/Hong
Kong/1/1968 (HK68). Mortality was recorded and group mouse weight
was assessed daily for 20 days post-infection.
TABLE-US-00008 TABLE A Group Antigen Formu- Volume, # Antigen dose
lation Route 1 FLHA_PR8 RNA 5 ug LNP 100 ul, i.m. (SEQ ID NO: 541)
2 MRK_H1_cot_all RNA 10 ug LNP 100 ul, i.m. (SEQ ID NO: 530) 3
MRK_H3_cot_all RNA 10 ug LNP 100 ul, i.m. (SEQ ID NO: 534) 4
MRK_H3_con_all RNA 10 ug LNP 100 ul, i.m. (SEQ ID NO: 533) 5
MRK_H3_Consensus A 10 ug LNP 100 ul, i.m. RNA (SEQ ID NO: 531) 6
MRK_H3 _Consensus B 10 ug LNP 100 ul, i.m. RNA (SEQ ID NO: 532) 7
Empty LNP 0 ug LNP 100 ul, i.m. 8 Mouse-adapted H3 0.1 LD90 None 20
ul, i.n. A/Hong Kong/1/1968 virus 9 Naive 0 ug None None
[0960] To assess the breadth of the serum activity elicited by the
antigens, hemagglutination inhibition assays (HAI) were performed
using a panel of H1N1 and H3N2 influenza viruses (Tables B and C.
Briefly, serum samples were treated with receptor destroying enzyme
(RDE) for 18-20 hrs at 37.degree. C. before inactivation at
56.degree. C. for 35-45 min. RDE-treated sera was then serially
diluted in a 96 well plate and mixed with 4 hemagglutinating units
of virus. An equal volume of 0.5% turkey red blood cells was added
to each well, and plates were incubated at room temperature for 30
min. The highest dilution with no visible agglutination was
assigned as the serum titer. While the MRK_H1 cot_all mRNA vaccine
elicited titers to only two viruses in the H1 HAI panel (Table B),
the MRK_H3 cot_all, MRKH3con_all, MRK_H3_Consensus A and
MRK_H3_Consensus B mRNAs induced high HAI titers to multiple H3
strains isolated between 1997 and 2014 (Table C).
[0961] Although mice immunized with MRKH1cot all mRNA did not have
detectable HAI titers to the PR8 virus, they were partially
protected from lethal challenge with PR8 virus. In contrast to
naive or LNP vaccinated mice, all MRK_H1 cot_all mRNA immunized
mice survived challenge (FIG. 24A), though they lost, on average,
approximately 10% of their body weight post-infection (FIG. 24B).
Similarly, mice vaccinated with any of the H3 COT or consensus
mRNAs tested survived challenge with a lethal dose of HK68 virus
(FIG. 24C) but lost between 10 and 15% or their body weight
post-infection (FIG. 24D).
TABLE-US-00009 TABLE B A/Puerto A/Fort/Monmouth/ A/New A/Brazil/
A/Singapore/ A/Texas/ Vaccine Rico/8/1934 1/1947 Jersey/10/1976
11/1978 6/1986 36/1991 MRK H1 cot all <10 <10 2,560 <10
<10 <10 Naive <10 <10 <10 <10 <10 <10
A/Beijing/ A/New A/Solomon A/Brisbane/ A/California/ Vaccine
262/1995 Caledonia/20/1999 Islands/3/2006 59/2007 07/2009 -- MRK H1
cot all <10 <10 <10 <10 10,240 -- Naive <10 <10
<10 <10 <10 --
TABLE-US-00010 TABLE C A/HongKong/ A/Philippines/ A/Sydney/
A/Texas/ A/Switzerland/ A/HongKong/ Vaccine 1/1968 1982 5/1997
50/2012 9715293/2013 4801/2014 H3_cot_all <10 <10 <10
40,960 20,480 10,240 MRK_H3_con_all <10 <10 <10 40,960
10,240 10,240 MRK_H3_ConA <10 <10 10,240 640 320 20
MRK_H3_ConB <10 <10 <10 40,960 10,240 10,240 Naive <10
<10 <10 <10 <10 <10
TABLE-US-00011 TABLE 7 Influenza H1N1 Antigens GenBank/GI
Strain/Protein Length Accession No. Influenza A virus
(A/Bayern/7/95(H1N1)) NA 1,459 bp AJ518104.1 gene for
neuraminidase, genomic RNA linear mRNA GI: 31096418 Influenza A
virus (A/Brazil/11/1978(X- 1,072 bp X86654.1 71)(H1N1)) mRNA for
hemagglutinin HA1, escape linear mRNA GI: 995549 variant 1
Influenza A virus (A/Brazil/11/1978(X- 1,072 bp X86655.1 71)(H1N1))
mRNA for hemagglutinin HA1, escape linear mRNA GI: 995550 variant 2
Influenza A virus (A/Brazil/11/1978(X- 1,072 bp X86656.1 71)(H1N1))
mRNA for hemagglutinin HA1, escape linear mRNA GI: 995551 variant 3
Influenza A virus (A/Brazil/11/1978(X- 1,072 bp X86657.1 71)(H1N1))
mRNA for hemagglutinin HA1, escape linear mRNA GI: 995552 variant 4
Influenza A virus 1,220 bp AF116575.1 (A/Brevig_Mission/1/18(H1N1))
hemagglutinin linear mRNA GI: 4325017 (HA) mRNA, partial cds
Influenza A virus 1,410 bp AF250356.2 (A/Brevig_Mission/1/18(H1N1))
neuraminidase linear mRNA GI: 13260556 (NA) gene, complete cds
Influenza A virus (A/Brevig 1,497 bp AY744935.1
Mission/1/1918(H1N1)) nucleoprotein (np) linear mRNA GI: 55273940
mRNA, complete cds Influenza A virus (A/Brevig 2,280 bp DQ208309.1
Mission/1/1918(H1N1)) polymerase PB2 (PB2) linear mRNA GI: 76786704
mRNA, complete cds Influenza A virus (A/Brevig 2,274 bp DQ208310.1
Mission/1/1918(H1N1)) polymerase PB1 (PB1) linear mRNA GI: 76786706
mRNA, complete cds Influenza A virus (A/Brevig 2,151 bp DQ208311.1
Mission/1/1918(H1N1)) polymerase PA (PA) linear mRNA GI: 76786708
mRNA, complete cds Influenza A virus 366 bp M73975.1
(A/camel/Mongolia/1982(H1N1)) hemagglutinin linear mRNA GI: 324242
mRNA, partial cds Influenza A virus 460 bp M73978.1
(A/camel/Mongolia/1982(H1N1)) matrix protein linear mRNA GI: 324402
mRNA, partial cds Influenza A virus 310 bp M73976.1
(A/camel/Mongolia/1982(H1N1)) neuraminidase linear mRNA GI: 324579
(NA) mRNA, partial cds Influenza A Virus A/camel/Mongolia/82 NS1
273 bp M73977.1 protein mRNA, partial cds linear mRNA GI: 324768
Influenza A virus 227 bp M73974.1 (A/camel/Mongolia/1982(H1N1)) PA
polymerase linear mRNA GI: 324931 mRNA, partial cds Influenza A
virus 531 bp M73973.1 (A/camel/Mongolia/1982(H1N1)) PB1 protein
linear mRNA GI: 324971 mRNA, partial cds Influenza A Virus
(A/camel/Mongolia/82(H1N1)) 379 bp M73972.1 polymerase 2 (P2) mRNA,
partial cds linear mRNA GI: 324993 Influenza A virus
(A/chicken/Hong 1,169 bp U46782.1 Kong/14/1976(H1N1)) hemagglutinin
precursor linear mRNA GI: 1912328 (HA) mRNA, partial cds Influenza
A virus (A/Chonnam/07/2002(H1N1)) 1,452 bp AY297141.1 neuraminidase
(NA) mRNA, complete cds linear mRNA GI: 31871990 Influenza A virus
(A/Chonnam/07/2002(H1N1)) 1,137 bp AY297154.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 32140347 Influenza A virus
(A/Chonnam/18/2002(H1N1)) 1,458 bp AY297143.1 neuraminidase (NA)
mRNA, complete cds linear mRNA GI: 31871994 Influenza A virus
(A/Chonnam/18/2002(H1N1)) 1,176 bp AY297156.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 32140355 Influenza A virus
(A/Chonnam/19/2002(H1N1)) 1,458 bp AY310410.1 neuraminidase (NA)
mRNA, complete cds linear mRNA GI: 31872389 Influenza A virus
(A/Chonnam/19/2002(H1N1)) 1,167 bp AY299502.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 32140392 Influenza A virus
(A/Chonnam/51/2002(H1N1)) 1,443 bp AY310412.1 neuraminidase (NA)
mRNA, complete cds linear mRNA GI: 31873090 Influenza A virus
(A/Chonnam/51/2002(H1N1)) 1,161 bp AY299498.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 32140384 Influenza A virus
(A/Chungbuk/50/2002(H1N1)) 1,425 bp AY297150.1 neuraminidase (NA)
mRNA, partial cds linear mRNA GI: 31872010 Influenza A virus
(A/Chungbuk/50/2002(H1N1)) 1,161 bp AY299506.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 32140400 Influenza A virus
(A/Denmark/40/2000(H1N1)) 1,458 bp AJ518095.1 NA gene for
neuraminidase, genomic RNA linear mRNA GI: 31096400 Influenza A
virus (A/Denver/1/57(H1N1)) 379 bp AF305216.1 neuraminidase mRNA,
partial cds linear mRNA GI: 10732818 Influenza A virus
(A/Denver/1/57(H1N1)) 442 bp AF305217.1 matrix protein gene,
partial cds linear mRNA GI: 10732820 Influenza A virus
(A/Denver/1/57(H1N1)) 215 bp AF305218.1 hemagglutinin gene, partial
cds linear mRNA GI: 10732822 Influenza A virus 981 bp U47309.1
(A/duck/Australia/749/80(H1N1)) hemagglutinin linear mRNA GI:
1912348 precursor (HA) mRNA, partial cds Influenza A virus 1,777 bp
AF091312.1 (A/duck/Australia/749/80(H1N1)) segment 4 linear mRNA
GI: 4585166 hemagglutinin precursor (HA) mRNA, complete cds
Influenza A virus (A/duck/Bavaria/1/77 1,777 bp AF091313.1 (H1N1))
segment 4 hemagglutinin precursor linear mRNA GI: 4585168 (HA)
mRNA, complete cds Influenza A virus (A/duck/Bavaria/2/77(H1N1))
981 bp U47308.1 hemagglutinin precursor (HA) mRNA, partial linear
mRNA GI: 1912346 cds Influenza A virus (A/duck/Eastern 1,458 bp
EU429749.1 China/103/2003(H1N1)) segment 6 neuraminidase linear
mRNA GI: 167859463 (NA) mRNA, complete cds Influenza A virus
(A/duck/Eastern 1,461 bp EU429751.1 China/152/2003(H1N1)) segment 6
neuraminidase linear mRNA GI: 167859467 (NA) mRNA, complete cds
Influenza A virus (A/Duck/Ohio/118C/93 1,410 bp AF250361.2 (H1N1))
neuraminidase (NA) gene, complete cds linear mRNA GI: 13260576
Influenza A virus (A/Duck/Ohio/175/86 (H1N1)) 1,410 bp AF250358.2
neuraminidase (NA) gene, complete cds linear mRNA GI: 13260565
Influenza A virus (A/Duck/Ohio/194/86 (H1N1)) 1,410 bp AF250360.2
neuraminidase (NA) gene, complete cds linear mRNA GI: 13260573
Influenza A virus (A/Duck/Ohio/30/86 (H1N1)) 1,410 bp AF250359.2
neuraminidase (NA) gene, complete cds linear mRNA GI: 13260570
Influenza A virus strain 1,460 bp AJ006954.1 A/Fiji/15899/83(H1N1)
mRNA for neuraminidase linear mRNA GI: 4210707 Influenza A Virus
(A/Fiji/15899/83(H1N1)) 2,341 bp AJ564805.1 mRNA for PB2 protein
linear mRNA GI: 31442134 Influenza A Virus (A/Fiji/15899/83(H1N1))
2,113 bp AJ564807.1 partial mRNA for PB1 protein linear mRNA GI:
31442138 Influenza A virus (A/FM/1/47 (H1N1)) 1,395 bp AF250357.2
neuraminidase (NA) gene, complete cds linear mRNA GI: 13260561
Influenza A virus (A/goose/Hong 1,091 bp U46021.1
Kong/8/1976(H1N1)) hemagglutinin precursor linear mRNA GI: 1912326
(HA) mRNA, partial cds Influenza A virus (A/goose/Hong 261 bp
U48284.1 Kong/8/1976(H1N1)) polymerase (PB1) mRNA, linear mRNA GI:
1912372 partial cds Influenza A virus (A/goose/Hong 1,395 bp
U49093.1 Kong/8/1976(H1N1)) nucleoprotein (NP) mRNA, linear mRNA
GI: 1912384 partial cds Influenza A virus 1,775 bp EU382986.1
(A/Guangzhou/1561/2006(H1N1)) segment 4 linear mRNA GI: 170762603
hemagglutinin (HA) mRNA, complete cds Influenza A virus 1,462 bp
EU382993.1 (A/Guangzhou/1561/2006(H1N1)) segment 6 linear mRNA GI:
170762617 neuraminidase (NA) mRNA, complete cds Influenza A virus
1,775 bp EU382987.1 (A/Guangzhou/1684/2006(H1N1)) segment 4 linear
mRNA GI: 170762605 hemagglutinin (HA) mRNA, complete cds Influenza
A virus 1,462 bp EU382994.1 (A/Guangzhou/1684/2006(H1N1)) segment 6
linear mRNA GI: 170762619 neuraminidase (NA) mRNA, complete cds
Influenza A virus 1,775 bp EU382981.1 (A/Guangzhou/483/2006(H1N1))
segment 4 linear mRNA GI: 170762593 hemagglutinin (HA) mRNA,
complete cds Influenza A virus 1,462 bp EU382988.1
(A/Guangzhou/483/2006(H1N1)) segment 6 linear mRNA GI: 170762607
neuraminidase (NA) mRNA, complete cds Influenza A virus 1,775 bp
EU382982.1 (A/Guangzhou/506/2006(H1N1)) segment 4 linear mRNA GI:
170762595 hemagglutinin (HA) mRNA, complete cds Influenza A virus
1,461 bp EU382989.1 (A/Guangzhou/506/2006(H1N1)) segment 6 linear
mRNA GI: 170762609 neuraminidase (NA) mRNA, complete cds Influenza
A virus 1,775 bp EU382983.1 (A/Guangzhou/555/2006(H1N1)) segment 4
linear mRNA GI: 170762597 hemagglutinin (HA) mRNA, complete cds
Influenza A virus 1,462 bp EU382990.1 (A/Guangzhou/555/2006(H1N1))
segment 6 linear mRNA GI: 170762611 neuraminidase (NA) mRNA,
complete cds Influenza A virus 1,775 bp EU382984.1
(A/Guangzhou/657/2006(H1N1)) segment 4 linear mRNA GI: 170762599
hemagglutinin (HA) mRNA, complete cds Influenza A virus 1,462 bp
EU382991.1 (A/Guangzhou/657/2006(H1N1)) segment 6 linear mRNA GI:
170762613 neuraminidase (NA) mRNA, complete cds Influenza A virus
1,775 bp EU382985.1 (A/Guangzhou/665/2006(H1N1)) segment 4 linear
mRNA GI: 170762601 hemagglutinin (HA) mRNA, complete cds Influenza
A virus 1,462 bp EU382992.1 (A/Guangzhou/665/2006(H1N1)) segment 6
linear mRNA GI: 170762615 neuraminidase (NA) mRNA, complete cds
Influenza A virus (A/Gwangju/55/2002(H1N1)) 1,431 bp AY297151.1
neuraminidase (NA) mRNA, complete cds linear mRNA GI: 31872012
Influenza A virus (A/Gwangju/55/2002(H1N1)) 1,179 bp AY299507.1
hemagglutinin (HA) mRNA, partial cds linear mRNA GI: 32140402
Influenza A virus (A/Gwangju/57/2002(H1N1)) 1,446 bp AY297152.1
neuraminidase (NA) mRNA, complete cds linear mRNA GI: 31872014
Influenza A virus (A/Gwangju/57/2002(H1N1)) 1,167 bp AY299508.1
hemagglutinin (HA) mRNA, partial cds linear mRNA GI: 32140404
Influenza A virus (A/Gwangju/58/2002(H1N1)) 1,434 bp AY297153.1
neuraminidase (NA) mRNA, complete cds linear mRNA GI: 31872016
Influenza A virus (A/Gwangju/58/2002(H1N1)) 1,176 bp AY299509.1
hemagglutinin (HA) mRNA, partial cds linear mRNA GI: 32140406
Influenza A virus (A/Gwangju/90/2002(H1N1)) 1,446 bp AY297147.1
neuraminidase (NA) mRNA, complete cds linear mRNA GI: 31872002
Influenza A virus (A/Gwangju/90/2002(H1N1)) 1,164 bp AY299499.1
hemagglutinin (HA) mRNA, partial cds linear mRNA GI: 32140386
Influenza A virus (A/Hong 1,403 bp AJ518101.1 Kong/437/2002(H1N1))
partial NA gene for linear mRNA GI: 31096412 neuraminidase, genomic
RNA Influenza A virus (A/Hong 1,352 bp AJ518102.1
Kong/747/2001(H1N1)) partial NA gene for linear mRNA GI: 31096414
neuraminidase, genomic RNA Influenza A virus
(A/London/1/1918(H1N1)) 563 bp AY184805.1 hemagglutinin (HA) mRNA,
partial cds linear mRNA GI: 32395285 Influenza A virus
(A/London/1/1919(H1N1)) 563 bp AY184806.1 hemagglutinin (HA) mRNA,
partial cds linear mRNA GI: 32395287 Influenza A virus
(A/Loygang/4/1957(H1N1)) 1,565 bp M76604.1 nucleoprotein mRNA,
complete cds linear mRNA GI: 324255 Influenza A virus
(A/Lyon/651/2001(H1N1)) 1,318 bp AJ518103.1 partial NA gene for
neuraminidase, genomic linear mRNA GI: 31096416 RNA Influenza A
virus (A/mallard/Alberta/119/98 947 bp AY664487.1 (H1N1))
nonfunctional matrix protein mRNA, linear mRNA GI: 51011891 partial
sequence Influenza A virus 981 bp U47310.1
(A/duck/Alberta/35/76(H1N1)) hemagglutinin linear mRNA GI: 1912350
precursor (HA) mRNA, partial cds Influenza A virus 1,777 bp
AF091309.1 (A/duck/Alberta/35/76(H1N1)) segment 4 linear mRNA GI:
4585160 hemagglutinin precursor (HA) mRNA, complete cds Influenza A
virus 1,410 bp AF250362.2 (A/duck/Alberta/35/76(H1N1))
neuraminidase linear mRNA GI: 13260579 (NA) gene, complete cds
Influenza A virus 981 bp U47307.1 (A/mallard/Tennessee/11464/85
(H1N1)) linear mRNA GI: 1912344 hemagglutinin precursor (HA) mRNA,
partial cds Influenza A virus 1,777 bp AF091311.1
(A/mallard/Tennessee/11464/85 (H1N1)) segment linear mRNA GI:
4585164 4 hemagglutinin precursor (HA) mRNA, complete cds Influenza
A virus (A/New 294 bp HQ008884.1 Caledonia/20/1999(H1N1)) segment 7
matrix linear mRNA GI: 302566794 protein 2 (M2) mRNA, complete cds
Influenza A virus (A/New Jersey/4/1976(H1N1)) 1,565 bp M76605.1
nucleoprotein mRNA, complete cds linear mRNA GI: 324581 Influenza A
virus (A/New Jersey/8/1976(H1N1)) 1,565 bp M76606.1 nucleoprotein
mRNA, complete cds linear mRNA GI: 324583 Influenza A virus
(A/New_York/1/18(H1N1)) 1,220 bp AF116576.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 4325019 Influenza A virus
(A/Ohio/3523/1988(H1N1)) 1,565 bp M76602.1 nucleoprotein mRNA,
complete cds linear mRNA GI: 324889 Influenza A virus
(A/Pusan/22/2002(H1N1)) 1,455 bp AY310411.1 neuraminidase (NA)
mRNA, complete cds linear mRNA GI: 31872391 Influenza A virus
(A/Pusan/22/2002(H1N1)) 1,149 bp AY299503.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 32140394 Influenza A virus
(A/Pusan/23/2002(H1N1)) 1,440 bp AY297144.1 neuraminidase (NA)
mRNA, complete cds linear mRNA GI: 31871996 Influenza A virus
(A/Pusan/23/2002(H1N1)) 1,158 bp AY297157.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 32140357 Influenza A virus
(A/Pusan/24/2002(H1N1)) 1,449 bp AY297145.1 neuraminidase (NA)
mRNA, complete cds linear mRNA GI: 31871998 Influenza A virus
(A/Pusan/24/2002(H1N1)) 1,128 bp AY299494.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 32140376 Influenza A virus
(A/Pusan/44/2002(H1N1)) 1,431 bp AY297148.1
neuraminidase (NA) mRNA, complete cds linear mRNA GI: 31872004
Influenza A virus (A/Pusan/44/2002(H1N1)) 1,167 bp AY299504.1
hemagglutinin (HA) mRNA, partial cds linear mRNA GI: 32140396
Influenza A virus (A/Pusan/45/2002(H1N1)) 1,434 bp AY297146.1
neuraminidase (NA) mRNA, complete cds linear mRNA GI: 31872000
Influenza A virus (A/Pusan/45/2002(H1N1)) 1,167 bp AY299496.1
hemagglutinin (HA) mRNA, partial cds linear mRNA GI: 32140380
Influenza A virus (A/Pusan/46/2002(H1N1)) 1,422 bp AY310408.1
neuraminidase (NA) mRNA, complete cds linear mRNA GI: 31872385
Influenza A virus (A/Pusan/46/2002(H1N1)) 1,176 bp AY299497.1
hemagglutinin (HA) mRNA, partial cds linear mRNA GI: 32140382
Influenza A virus (A/Pusan/47/2002(H1N1)) 1,437 bp AY297149.1
neuraminidase (NA) mRNA, complete cds linear mRNA GI: 31872008
Influenza A virus (A/Pusan/47/2002(H1N1)) 1,170 bp AY299505.1
hemagglutinin (HA) mRNA, partial cds linear mRNA GI: 32140398
Influenza A virus (A/Saudi 789 bp AJ519463.1
Arabia/7971/2000(H1N1)) partial NS1 gene for linear mRNA GI:
31096450 non structural protein 1 and partial NS2 gene for non
structural protein 2, genomic RNA Influenza A virus
(A/Seoul/11/2002(H1N1)) 1,452 bp AY297142.1 neuraminidase (NA)
mRNA, complete cds linear mRNA GI: 31871992 Influenza A virus
(A/Seoul/11/2002(H1N1)) 1,176 bp AY297155.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 32140349 Influenza A virus
(A/Seoul/13/2002(H1N1)) 1,452 bp AY310409.1 neuraminidase (NA)
mRNA, complete cds linear mRNA GI: 31872387 Influenza A virus
(A/Seoul/13/2002(H1N1)) 1,167 bp AY299500.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 32140388 Influenza A virus
(A/Seoul/15/2002(H1N1)) 1,449 bp AY297140.1 neuraminidase (NA)
mRNA, complete cds linear mRNA GI: 31871988 Influenza A virus
(A/Seoul/15/2002(H1N1)) 1,149 bp AY299501.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 32140390 Influenza A virus
(A/Seoul/33/2002(H1N1)) 1,437 bp AY310407.1 neuraminidase (NA)
mRNA, complete cds linear mRNA GI: 31872383 Influenza A virus
(A/Seoul/33/2002(H1N1)) 1,167 bp AY299495.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 32140378 Influenza A virus 1,050
bp Z46437.1 (A/swine/Arnsberg/6554/1979(H1N1)) mRNA for linear mRNA
GI: 565609 hemagglutinin HA1 Influenza A virus 1,595 bp U46783.1
(A/swine/Beijing/47/1991(H1N1)) hemagglutinin linear mRNA GI:
1912330 precursor (HA) mRNA, partial cds Influenza A virus 1,565 bp
U49091.1 (A/swine/Beijing/94/1991(H1N1)) nucleoprotein linear mRNA
GI: 1912380 (NP) mRNA, complete cds Influenza A virus 1,778 bp
AF091316.1 (A/swine/Belgium/1/83(H1N1)) segment 4 linear mRNA GI:
4585174 hemagglutinin precursor (HA) mRNA, complete cds Influenza A
virus (A/swine/Cotes 1,116 bp AM490219.1 d'Armor/0118/2006(H1N1))
partial mRNA for linear mRNA GI: 222062898 haemagglutinin precursor
(HA1 gene) Influenza A virus (A/swine/Cotes 1,043 bp AM490223.1
d'Armor/013618/2006(H1N1)) partial mRNA for linear mRNA GI:
222062906 haemagglutinin precursor (HA1 gene) Influenza A virus
(A/swine/Cotes 1,089 bp AM490220.1 d'Armor/0184/2006(H1N1)) partial
mRNA for linear mRNA GI: 222062900 haemagglutinin precursor (HA1
gene) Influenza A virus (A/swine/Cotes 1,068 bp AM490221.1
d'Armor/0227/2005(H1N1)) partial mRNA for linear mRNA GI: 222062902
haemagglutinin precursor (HA1 gene) Influenza A virus
(A/swine/Cotes 1,024 bp AM490222.1 d'Armor/0250/2006(H1N1)) partial
mRNA for linear mRNA GI: 222062904 haemagglutinin precursor (HA1
gene) Influenza A virus (A/swine/Cotes 1,011 bp AJ517820.1
d'Armor/736/2001(H1N1)) partial HA gene for linear mRNA GI:
38422533 Haemagglutinin, genomic RNA Influenza A virus
(A/Swine/England/195852/92 1,410 bp AF250366.2 (H1N1))
neuraminidase (NA) gene, complete cds linear mRNA GI: 13260593
Influenza A virus PB2 gene for Polymerase 2 2,268 bp AJ311457.1
protein, genomic RNA, strain linear mRNA GI: 13661037
A/Swine/Finistere/2899/82 Influenza A virus PB1 gene for Polymerase
1 2,341 bp AJ311462.1 protein, genomic RNA, strain linear mRNA GI:
13661047 A/Swine/Finistere/2899/82 Influenza A virus PA gene for
Polymerase A 2,233 bp AJ311463.1 protein, genomic RNA, strain
linear mRNA GI: 13661049 A/Swine/Finistere/2899/82 Influenza A
virus 1,002 bp AJ316059.1 (A/swine/Finistere/2899/82(H1N1) M1 gene
for linear mRNA GI: 20068128 matrix protein 1 and M2 gene for
matrix protein 2, genomic RNA Influenza A virus 864 bp AJ344037.1
(A/swine/Finistere/2899/82(H1N1)) NS1 gene linear mRNA GI: 20068185
for non structural protein 1 and NS2 gene for non structural
protein 2, genomic RNA Influenza A virus 838 bp X75786.1
(A/swine/Germany/2/1981(H1N1)) mRNA for PA linear mRNA GI: 438106
polymerase Influenza A virus 305 bp Z30277.1
(A/swine/Germany/2/1981(H1N1)) mRNA for linear mRNA GI: 530399
neuraminidase (partial) Influenza A virus 1,730 bp Z30276.1
(A/swine/Germany/2/1981(H1N1)) mRNA for linear mRNA GI: 563490
hemagglutinin 165. Influenza A virus 1,730 bp Z46434.1
(A/swine/Germany/8533/1991(H1N1)) mRNA for linear mRNA GI: 565611
hemagglutinin precursor Influenza A virus 1,690 bp AY852271.1
(A/swine/Guangdong/711/2001(H1N1)) linear mRNA GI: 60327789
nonfunctional hemagglutinin (HA) mRNA, partial sequence Influenza A
virus 1,809 bp EU163946.1 (A/swine/Haseluenne/IDT2617/03(H1N1))
linear mRNA GI: 157679548 hemagglutinin mRNA, complete cds
Influenza A virus (A/swine/Hokkaido/2/81 981 bp U47306.1 (H1N1))
hemagglutinin precursor (HA) mRNA, linear mRNA GI: 1912342 partial
cds Influenza A virus (A/swine/Hokkaido/2/81 1,778 bp AF091306.1
(H1N1)) segment 4 hemagglutinin precursor linear mRNA GI: 4585154
(HA) mRNA, complete cds Influenza A virus (A/swine/Hong 1,113 bp
U44482.1 Kong/168/1993(H1N1)) hemagglutinin precursor linear mRNA
GI: 1912318 (HA) mRNA, partial cds Influenza A virus (A/swine/Hong
416 bp U47817.1 Kong/168/1993(H1N1)) neuraminidase (NA) mRNA,
linear mRNA GI: 1912354 partial cds Influenza A virus (A/swine/Hong
286 bp U48286.1 Kong/168/1993(H1N1)) polymerase (PB2) mRNA, linear
mRNA GI: 1912358 partial cds Influenza A virus (A/swine/Hong 379 bp
U48283.1 Kong/168/1993(H1N1)) polymerase (PB1) mRNA, linear mRNA
GI: 1912370 partial cds Influenza A virus (A/swine/Hong 308 bp
U48850.1 Kong/168/1993(H1N1)) polymerase (PA) mRNA, linear mRNA GI:
1912376 partial cds Influenza A virus (A/swine/Hong 1,397 bp
U49096.1 Kong/168/1993(H1N1)) nucleoprotein (NP) mRNA, linear mRNA
GI: 1912390 partial cds Influenza A virus (A/swine/Hong 1,315 bp
U46020.1 Kong/172/1993(H1N1)) hemagglutinin precursor linear mRNA
GI: 1912324 (HA) mRNA, partial cds Influenza A virus (A/swine/Hong
1,113 bp U45451.1 Kong/176/1993(H1N1)) hemagglutinin precursor
linear mRNA GI: 1912320 (HA) mRNA, partial cds Influenza A virus
(A/swine/Hong 1,330 bp U45452.1 Kong/273/1994(H1N1)) hemagglutinin
precursor linear mRNA GI: 1912322 (HA) mRNA, partial cds Influenza
A virus (A/swine/Hong 241 bp U47818.1 Kong/273/1994(H1N1))
neuraminidase (NA) mRNA, linear mRNA GI: 1912356 partial cds
Influenza A virus (A/swine/Hong 328 bp U48287.1
Kong/273/1994(H1N1)) polymerase (PB2) mRNA, linear mRNA GI: 1912360
partial cds Influenza A virus (A/swine/Hong 240 bp U48282.1
Kong/273/1994(H1N1)) polymerase (PB1) mRNA, linear mRNA GI: 1912368
partial cds Influenza A virus (A/swine/Hong 336 bp U48851.1
Kong/273/1994(H1N1)) polymerase (PA) mRNA, linear mRNA GI: 1912378
partial cds Influenza A virus (A/swine/Hong 1,422 bp U49092.1
Kong/273/1994(H1N1)) nucleoprotein (NP) mRNA, linear mRNA GI:
1912382 partial cds Influenza A virus 1,761 bp EU163947.1
(A/swine/IDT/Re230/92hp(H1N1)) hemagglutinin linear mRNA GI:
157679550 mRNA, complete cds Influenza A virus 1,550 bp L46849.1
(A/swine/IN/1726/1988(H1N1)) nucleoprotein linear mRNA GI: 954755
(segment 5) mRNA, complete cds Influenza A virus
(A/swine/Iowa/15/30(H1N1)) 981 bp U47305.1 hemagglutinin precursor
(HA) mRNA, partial linear mRNA GI: 1912340 cds Influenza A virus
(A/swine/Iowa/15/30 (H1N1)) 1,778 bp AF091308.1 segment 4
hemagglutinin precursor (HA) mRNA, linear mRNA GI: 4585158 complete
cds Influenza A virus (A/Swine/Iowa/30 (H1N1)) 1,410 bp AF250364.2
neuraminidase (NA) gene, complete cds linear mRNA GI: 13260586
Influenza A virus (A/swine/Iowa/17672/88 981 bp U47304.1 (H1N1))
hemagglutinin precursor (HA) mRNA, linear mRNA GI: 1912338 partial
cds Influenza A virus 864 bp AJ519462.1
(A/swine/Italy/3364/00(H1N1)) partial NS1 linear mRNA GI: 31096447
gene for non structural protein 1 and partial NS2 gene for non
structural protein 2, genomic RNA Influenza A virus (A/swine/Italy-
1,777 bp AF091315.1 Virus/671/87(H1N1)) segment 4 hemagglutinin
linear mRNA GI: 4585172 precursor (HA) mRNA, complete cds Influenza
A Virus 1,028 bp Z46436.1 (A/swine/Italy/v.147/1981(H1N1)) mRNA for
linear mRNA GI: 854214 hemagglutinin HA1 Influenza A virus 1,118 bp
AM490218.1 (A/swine/Morbihan/0070/2005(H1N1)) partial linear mRNA
GI: 222062896 mRNA for haemagglutinin precursor (HA1 gene)
Influenza A virus 1,770 bp L09063.1 (A/swine/Nebraska/1/92(H1N1))
HA protein linear mRNA GI: 290722 mRNA, complete cds Influenza A
virus 1,550 bp L11164.1 (A/swine/Nebraska/1/1992(H1N1)) segment 5
linear mRNA GI: 290724 nucleoprotein (NP) mRNA, complete cds
Influenza A virus 981 bp U46943.1
(A/swine/Netherlands/12/1985(H1N1)) linear mRNA GI: 1912336
hemagglutinin (HA) mRNA, partial cds Influenza A virus 1,776 bp
AF091317.1 (A/swine/Netherlands/12/85(H1N1)) segment 4 linear mRNA
GI: 4585176 hemagglutinin precursor (HA) mRNA, complete cds
Influenza A virus 539 bp X75791.1
(A/swine/Netherlands/25/1980(H1N1)) mRNA for linear mRNA GI: 438105
nucleoprotein Influenza A virus 981 bp U46942.1
(A/swine/Netherlands/3/1980(H1N1)) linear mRNA GI: 1912334
hemagglutinin (HA) mRNA, partial cds Influenza A virus 1,778 bp
AF091314.1 (A/swine/Netherlands/3/80(H1N1)) segment 4 linear mRNA
GI: 4585170 hemagglutinin precursor (HA) mRNA, complete cds
Influenza A virus (A/NJ/11/76 (H1N1)) 1,410 bp AF250363.2
neuraminidase (NA) gene, complete cds linear mRNA GI: 13260583
Influenza A virus (A/Swine/Quebec/192/81 1,438 bp U86144.1
(SwQc81)) neuraminidase mRNA, complete cds linear mRNA GI: 4099318
Influenza A virus (A/Swine/Quebec/5393/91 1,438 bp U86145.1
(SwQc91)) neuraminidase mRNA, complete cds linear mRNA GI: 4099320
Influenza A virus (A/swine/Schleswig- 1,730 bp Z46435.1
Holstein/1/1992(H1N1)) mRNA for hemagglutinin linear mRNA GI:
854216 precursor Influenza A Virus (A/swine/Schleswig- 1,554 bp
Z46438.1 Holstein/1/1993(H1N1)) mRNA for nucleoprotein linear mRNA
GI: 854222 Influenza A virus 1,778 bp AF091307.1
(A/swine/Wisconsin/1/61(H1N1)) segment 4 linear mRNA GI: 4585156
hemagglutinin precursor (HA) mRNA, complete cds 212. Influenza A
virus 1,565 bp M76607.1 (A/swine/Wisconsin/1/1967(H1N1)) linear
mRNA GI: 325086 nucleoprotein mRNA, complete cds Influenza A virus
1,565 bp M76608.1 (A/swine/Wisconsin/1915/1988(H1N1)) linear mRNA
GI: 325088 nucleoprotein mRNA, complete cds Influenza A virus 1,550
bp L46850.1 (A/swine/WI/1915/1988(H1N1)) nucleoprotein linear mRNA
GI: 954757 (segment 5) mRNA, complete cds Influenza A virus 729 bp
AJ532568.1 (A/Switzerland/8808/2002(H1N1)) partial m1 linear mRNA
GI: 31096461 gene for matrix protein 1 and partial m2 gene for
matrix protein 2, genomic RNA Influenza A virus 561 bp AF362803.1
(A/human/Taiwan/0012/00(H1N1)) hemagglutinin linear mRNA GI:
14571975 (HA) mRNA, partial cds Influenza A virus 561 bp AF362779.1
(A/human/Taiwan/0016/00(H1N1)) hemagglutinin linear mRNA GI:
14571927 (HA) mRNA, partial cds Influenza A virus
(A/Taiwan/0016/2000 (H1N1)) 303 bp AY303752.1 polymerase basic
protein 1 (PB1) mRNA, linear mRNA GI: 32330993 partial cds
Influenza A virus 561 bp AF362780.1 (A/human/Taiwan/0030/00(H1N1))
hemagglutinin linear mRNA GI: 14571929 (HA) mRNA, partial cds
Influenza A virus (A/Taiwan/0030/2000 (H1N1)) 303 bp AY303704.1
polymerase basic protein 1 (PB1) mRNA, linear mRNA GI: 32330897
partial cds Influenza A virus (A/Taiwan/0032/2002(H1N1)) 494 bp
AY604804.1 hemagglutinin mRNA, partial cds linear mRNA GI:
50727488
Influenza A virus (A/Taiwan/0061/2002(H1N1)) 494 bp AY604795.1
hemagglutinin mRNA, partial cds linear mRNA GI: 50727470 Influenza
A virus (A/Taiwan/0069/2002(H1N1)) 494 bp AY604803.1 hemagglutinin
mRNA, partial cds linear mRNA GI: 50727486 Influenza A virus
(A/Taiwan/0078/2002(H1N1)) 494 bp AY604805.1 hemagglutinin mRNA,
partial cds linear mRNA GI: 50727490 Influenza A virus
(A/Taiwan/0094/2002(H1N1)) 494 bp AY604797.1 hemagglutinin mRNA,
partial cds linear mRNA GI: 50727474 Influenza A virus
(A/Taiwan/0116/2002(H1N1)) 494 bp AY604796.1 hemagglutinin mRNA,
partial cds linear mRNA GI: 50727472 Influenza A virus 564 bp
AF362781.1 (A/human/Taiwan/0130/96(H1N1)) hemagglutinin linear mRNA
GI: 14571931 (HA) mRNA, partial cds Influenza A virus
(A/Taiwan/0130/96 (H1N1)) 303 bp AY303707.1 polymerase basic
protein 1 (PB1) mRNA, linear mRNA GI: 32330903 partial cds
Influenza A virus 564 bp AF362782.1 (A/human/Taiwan/0132/96(H1N1))
hemagglutinin linear mRNA GI: 14571933 (HA) mRNA, partial cds
Influenza A virus (A/Taiwan/0132/96 (H1N1)) 303 bp AY303708.1
polymerase basic protein 1 (PB1) mRNA, linear mRNA GI: 32330905
partial cds Influenza A virus 564 bp AF362783.1
(A/human/Taiwan/0211/96(H1N1)) hemagglutinin linear mRNA GI:
14571935 (HA) mRNA, partial cds Influenza A virus (A/Taiwan/0211/96
(H1N1)) 303 bp AY303709.1 polymerase basic protein 1 (PB1) mRNA,
linear mRNA GI: 32330907 partial cds Influenza A virus 564 bp
AF362784.1 (A/human/Taiwan/0235/96(H1N1)) hemagglutinin linear mRNA
GI: 14571937 (HA) mRNA, partial cds Influenza A virus
(A/Taiwan/0235/96 (H1N1)) 303 bp AY303710.1 polymerase basic
protein 1 (PB1) mRNA, linear mRNA GI: 32330909 partial cds
Influenza A virus 564 bp AF362785.1 (A/human/Taiwan/0255/96(H1N1))
hemagglutinin linear mRNA GI: 14571939 (HA) mRNA, partial cds
Influenza A virus (A/Taiwan/0255/96 (H1N1)) 303 bp AY303711.1
polymerase basic protein 1 (PB1) mRNA, linear mRNA GI: 32330911
partial cds Influenza A virus 564 bp AF362786.1
(A/human/Taiwan/0337/96(H1N1)) hemagglutinin linear mRNA GI:
14571941 (HA) mRNA, partial cds Influenza A virus 564 bp AF362787.1
(A/human/Taiwan/0342/96(H1N1)) hemagglutinin linear mRNA GI:
14571943 (HA) mRNA, partial cds Influenza A virus (A/Taiwan/0342/96
(H1N1)) 303 bp AY303714.1 polymerase basic protein 1 (PB1) mRNA,
linear mRNA GI: 32330917 partial cds Influenza A virus 561 bp
AF362788.1 (A/human/Taiwan/0464/99(H1N1)) hemagglutinin linear mRNA
GI: 14571945 (HA) mRNA, partial cds Influenza A virus 564 bp
AF362789.1 (A/human/Taiwan/0562/95(H1N1)) hemagglutinin linear mRNA
GI: 14571947 (HA) mRNA, partial cds Influenza A virus
(A/Taiwan/0562/95 (H1N1)) 303 bp AY303720.1 polymerase basic
protein 1 (PB1) mRNA, linear mRNA GI: 32330929 partial cds
Influenza A virus 564 bp AF362790.1 (A/human/Taiwan/0563/95(H1N1))
hemagglutinin linear mRNA GI: 14571949 (HA) mRNA, partial cds
Influenza A virus (A/Taiwan/0563/95 (H1N1)) 303 bp AY303721.1
polymerase basic protein 1 (PB1) mRNA, linear mRNA GI: 32330931
partial cds Influenza A virus 564 bp AF362791.1
(A/human/Taiwan/0657/95(H1N1)) hemagglutinin linear mRNA GI:
14571951 (HA) mRNA, partial cds Influenza A virus (A/Taiwan/0657/95
(H1N1)) 303 bp AY303724.1 polymerase basic protein 1 (PB1) mRNA,
linear mRNA GI: 32330937 partial cds Influenza A virus
(A/Taiwan/0859/2002(H1N1)) 494 bp AY604801.1 hemagglutinin mRNA,
partial cds linear mRNA GI: 50727482 Influenza A virus 561 bp
AF362792.1 (A/human/Taiwan/0892/99(H1N1)) hemagglutinin linear mRNA
GI: 14571953 (HA) mRNA, partial cds Influenza A virus
(A/Taiwan/0983/2002(H1N1)) 494 bp AY604800.1 hemagglutinin mRNA,
partial cds linear mRNA GI: 50727480 Influenza A virus
(A/Taiwan/1007/2006(H1N1)) 507 bp EU068163.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 158452199 Influenza A virus
(A/Taiwan/1015/2006(H1N1)) 507 bp EU068171.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 158452215 Influenza A virus
(A/Taiwan/112/1996-1(H1N1)) 1,176 bp AF026153.1 haemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 2554950 Influenza A virus
(A/Taiwan/112/1996-2(H1N1)) 1,176 bp AF026154.1 haemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 2554952 Influenza A virus
(A/Taiwan/117/1996-1(H1N1)) 1,176 bp AF026155.1 haemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 2554954 Influenza A virus
(A/Taiwan/117/1996-2(H1N1)) 1,176 bp AF026156.1 haemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 2554956 Influenza A virus
(A/Taiwan/117/1996-3(H1N1)) 1,176 bp AF026157.1 haemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 2554958 Influenza A virus
(A/Taiwan/118/1996-1(H1N1)) 1,176 bp AF026158.1 haemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 2554960 Influenza A virus
(A/Taiwan/118/1996-2(H1N1)) 1,176 bp AF026159.1 haemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 2554962 Influenza A virus
(A/Taiwan/118/1996-3(H1N1)) 1,176 bp AF026160.1 haemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 2554964 Influenza A virus 561 bp
AF362793.1 (A/human/Taiwan/1184/99(HIN1)) hemagglutinin linear mRNA
GI: 14571955 (HA) mRNA, partial cds Influenza A virus
(A/Taiwan/1184/99 (H1N1)) 303 bp AY303726.1 polymerase basic
protein 1 (PB1) mRNA, linear mRNA GI: 32330941 partial cds
Influenza A virus 564 bp AF362794.1 (A/human/Taiwan/1190/95(H1N1))
hemagglutinin linear mRNA GI: 14571957 (HA) mRNA, partial cds
Influenza A virus (A/Taiwan/1190/95 (H1N1)) 303 bp AY303727.1
polymerase basic protein 1 (PB1) mRNA, linear mRNA GI: 32330943
partial cds Influenza A virus (A/Taiwan/1523/2003(H1N1)) 494 bp
AY604808.1 hemagglutinin mRNA, partial cds linear mRNA GI: 50727496
Influenza A virus (A/Taiwan/1566/2003(H1N1)) 494 bp AY604806.1
hemagglutinin mRNA, partial cds linear mRNA GI: 50727492 Influenza
A virus (A/Taiwan/1769/96(H1N1)) 875 bp AF138710.2 matrix protein
M1 (M) mRNA, partial cds linear mRNA GI: 4996871 Influenza A virus
(A/Taiwan/1906/2002(H1N1)) 494 bp AY604799.1 hemagglutinin mRNA,
partial cds linear mRNA GI: 50727478 Influenza A virus
(A/Taiwan/1922/2002(H1N1)) 494 bp AY604802.1 hemagglutinin mRNA,
partial cds linear mRNA GI: 50727484 Influenza A virus
(A/Taiwan/2069/2006(H1N1)) 507 bp EU068168.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 158452209 Influenza A virus
(A/Taiwan/2157/2001 (H1N1)) 303 bp AY303733.1 polymerase basic
protein 1 (PB1) mRNA, linear mRNA GI: 32330955 partial cds
Influenza A virus (A/Taiwan/2175/2001 (H1N1)) 561 bp AY303734.1
hemagglutinin (HA) mRNA, partial cds linear mRNA GI: 32330957
Influenza A virus 564 bp AF362795.1 (A/human/Taiwan/2200/95(H1N1))
hemagglutinin linear mRNA GI: 14571959 (HA) mRNA, partial cds
Influenza A virus (A/Taiwan/2200/95 (H1N1)) 303 bp AY303737.1
polymerase basic protein 1 (PB1) mRNA, linear mRNA GI: 32330963
partial cds Influenza A virus (A/Taiwan/2966/2006(H1N1)) 507 bp
EU068170.1 hemagglutinin (HA) mRNA, partial cds linear mRNA GI:
158452213 Influenza A virus (A/Taiwan/3168/2005(H1N1)) 507 bp
EU068174.1 hemagglutinin (HA) mRNA, partial cds linear mRNA GI:
158452221 Influenza A virus 561 bp AF362796.1
(A/human/Taiwan/3355/97(H1N1)) hemagglutinin linear mRNA GI:
14571961 (HA) mRNA, partial cds Influenza A virus (A/Taiwan/3355/97
(H1N1)) 303 bp AY303739.1 polymerase basic protein 1 (PB1) mRNA,
linear mRNA GI: 32330967 partial cds Influenza A virus
(A/Taiwan/3361/2001 (H1N1)) 303 bp AY303740.1 polymerase basic
protein 1 (PB1) mRNA, linear mRNA GI: 32330969 partial cds
Influenza A virus (A/Taiwan/3361/2001 (H1N1)) 561 bp AY303741.1
hemagglutinin (HA) mRNA, partial cds linear mRNA GI: 32330971
Influenza A virus (A/Taiwan/3518/2006(H1N1)) 507 bp EU068169.1
hemagglutinin (HA) mRNA, partial cds linear mRNA GI: 158452211
Influenza A virus 581 bp AF362797.1 (A/human/Taiwan/3825/00(H1N1))
hemagglutinin linear mRNA GI: 14571963 (HA) mRNA, partial cds
Influenza A virus (A/Taiwan/3896/2001 (H1N1)) 303 bp AY303746.1
polymerase basic protein 1 (PB1) mRNA, linear mRNA GI: 32330981
partial cds Influenza A virus (A/Taiwan/3896/2001 (H1N1)) 561 bp
AY303747.1 hemagglutinin (HA) mRNA, partial cds linear mRNA GI:
32330983 Influenza A virus (A/Taiwan/4050/2003(H1N1)) 494 bp
AY604807.1 hemagglutinin mRNA, partial cds linear mRNA GI: 50727494
Influenza A virus (A/Taiwan/4054/2006(H1N1)) 507 bp EU068160.1
hemagglutinin (HA) mRNA, partial cds linear mRNA GI: 158452193
Influenza A virus 561 bp AF362798.1 (A/human/Taiwan/4360/99(H1N1))
hemagglutinin linear mRNA GI: 14571965 (HA) mRNA, partial cds
Influenza A virus (A/Taiwan/4360/99 (H1N1)) 303 bp AY303748.1
polymerase basic protein 1 (PB1) mRNA, linear mRNA GI: 32330985
partial cds Influenza A virus 561 bp AF362799.1
(A/human/Taiwan/4415/99(H1N1)) hemagglutinin linear mRNA GI:
14571967 (HA) mRNA, partial cds Influenza A virus (A/Taiwan/4415/99
(H1N1)) 303 bp AY303749.1 polymerase basic protein 1 (PB1) mRNA,
linear mRNA GI: 32330987 partial cds Influenza A virus
(A/Taiwan/4509/2006(H1N1)) 507 bp EU068165.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 158452203 Influenza A virus 561
bp AF362800.1 (A/human/Taiwan/4845/99(H1N1)) hemagglutinin linear
mRNA GI: 14571969 (HA) mRNA, partial cds Influenza A virus
(A/Taiwan/4845/99 (H1N1)) 303 bp AY303750.1 polymerase basic
protein 1 (PB1) mRNA, linear mRNA GI: 32330989 partial cds
Influenza A virus 561 bp AF362801.1 (A/human/Taiwan/4943/99(H1N1))
hemagglutinin linear mRNA GI: 14571971 (HA) mRNA, partial cds
Influenza A virus (A/Taiwan/5010/2006(H1N1)) 507 bp EU068167.1
hemagglutinin (HA) mRNA, partial cds linear mRNA GI: 158452207
Influenza A virus 561 bp AF362802.1 (A/human/Taiwan/5063/99(H1N1))
hemagglutinin linear mRNA GI: 14571973 (HA) mRNA, partial cds
Influenza A virus (A/Taiwan/5063/99 (H1N1)) 303 bp AY303751.1
polymerase basic protein 1 (PB1) mRNA, linear mRNA GI: 32330991
partial cds Influenza A virus (A/Taiwan/5084/2006(H1N1)) 507 bp
EU068166.1 hemagglutinin (HA) mRNA, partial cds linear mRNA GI:
158452205 Influenza A virus (A/Taiwan/511/96(H1N1)) 875 bp
AF138708.2 matrix protein M1 (M) mRNA, partial cds linear mRNA GI:
4996867 Influenza A virus (A/Taiwan/557/2006(H1N1)) 507 bp
EU068156.1 hemagglutinin (HA) mRNA, partial cds linear mRNA GI:
158452185 Influenza A virus (A/Taiwan/562/2006(H1N1)) 507 bp
EU068159.1 hemagglutinin (HA) mRNA, partial cds linear mRNA GI:
158452191 Influenza A virus 561 bp AF362778.1
(A/human/Taiwan/5779/98(H1N1)) hemagglutinin linear mRNA GI:
14571925 (HA) mRNA, partial cds Influenza A virus (A/Taiwan/5779/98
(H1N1)) 303 bp AY303702.1 polymerase basic protein 1 (PB1) mRNA,
linear mRNA GI: 32330893 partial cds Influenza A virus
(A/Taiwan/6025/2005(H1N1)) 507 bp EU068172.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 158452217 Influenza A virus
(A/Taiwan/607/2006(H1N1)) 507 bp EU068157.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 158452187 Influenza A virus
(A/Taiwan/615/2006(H1N1)) 507 bp EU068162.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 158452197 Influenza A virus
(A/Taiwan/645/2006(H1N1)) 507 bp EU068164.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 158452201 Influenza A virus
(A/Taiwan/680/2005(H1N1)) 507 bp EU068173.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 158452219 Influenza A virus
(A/Taiwan/719/2006(H1N1)) 507 bp EU068158.1 hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 158452189 Influenza A virus 1,410
bp EU021285.1 (A/Thailand/CU124/2006(H3N2)) neuraminidase linear
mRNA GI: 154224724 (NA) mRNA, complete cds Influenza A virus 1,413
bp EU021265.1 (A/Thailand/CU32/2006(H1N1)) neuraminidase linear
mRNA GI: 154224704 (NA) mRNA, complete cds Influenza A virus 1,698
bp EU021264.1 (A/Thailand/CU32/2006(H1N1)) hemagglutinin linear
mRNA GI: 154224775 (HA) mRNA, complete cds Influenza A virus 1,413
bp EU021247.1 (A/Thailand/CU41/2006(H1N1)) neuraminidase linear
mRNA GI: 154224686 (NA) mRNA, complete cds Influenza A virus 1,698
bp EU021246.1 (A/Thailand/CU41/2006(H1N1)) hemagglutinin linear
mRNA GI: 154224757 (HA) mRNA, complete cds Influenza A virus 1,413
bp EU021259.1 (A/Thailand/CU44/2006(H1N1)) neuraminidase linear
mRNA GI: 154224698 (NA) mRNA, complete cds Influenza A virus 1,698
bp EU021258.1 (A/Thailand/CU44/2006(H1N1)) hemagglutinin linear
mRNA GI: 154224769 (HA) mRNA, complete cds Influenza A virus 1,413
bp EU021255.1 (A/Thailand/CU51/2006(H1N1)) neuraminidase linear
mRNA GI: 154224694 (NA) mRNA, complete cds Influenza A virus 1,698
bp EU021254.1 (A/Thailand/CU51/2006(H1N1)) hemagglutinin linear
mRNA GI: 154224765 (HA) mRNA, complete cds Influenza A virus 1,413
bp EU021249.1 (A/Thailand/CU53/2006(H1N1)) neuraminidase linear
mRNA GI: 154224688 (NA) mRNA, complete cds Influenza A virus 1,698
bp EU021248.1 (A/Thailand/CU53/2006(H1N1)) hemagglutinin linear
mRNA GI: 154224759 (HA) mRNA, complete cds
Influenza A virus 1,413 bp EU021257.1 (A/Thailand/CU57/2006(H1N1))
neuraminidase linear mRNA GI: 154224696 (NA) mRNA, complete cds
Influenza A virus 1,698 bp EU021256.1 (A/Thailand/CU57/2006(H1N1))
hemagglutinin linear mRNA GI: 154224767 (HA) mRNA, complete cds
Influenza A virus 1,413 bp EU021251.1 (A/Thailand/CU67/2006(H1N1))
neuraminidase linear mRNA GI: 154224690 (NA) mRNA, complete cds
Influenza A virus 1,698 bp EU021250.1 (A/Thailand/CU67/2006(H1N1))
hemagglutinin linear mRNA GI: 154224761 (HA) mRNA, complete cds
Influenza A virus 1,413 bp EU021261.1 (A/Thailand/CU68/2006(H1N1))
neuraminidase linear mRNA GI: 154224700 (NA) mRNA, complete cds
Influenza A virus 1,698 bp EU021260.1 (A/Thailand/CU68/2006(H1N1))
hemagglutinin linear mRNA GI: 154224771 (HA) mRNA, complete cds
Influenza A virus 1,413 bp EU021263.1 (A/Thailand/CU75/2006(H1N1))
neuraminidase linear mRNA GI: 154224702 (NA) mRNA, complete cds
Influenza A virus 1,698 bp EU021262.1 (A/Thailand/CU75/2006(H1N1))
hemagglutinin linear mRNA GI: 154224773 (HA) mRNA, complete cds
Influenza A virus 1,413 bp EU021253.1 (A/Thailand/CU88/2006(H1N1))
neuraminidase linear mRNA GI: 154224692 (NA) mRNA, complete cds
Influenza A virus 1,698 bp EU021252.1 (A/Thailand/CU88/2006(H1N1))
hemagglutinin linear mRNA GI: 154224763 (HA) mRNA, complete cds
Influenza A virus 1,565 bp M76603.1
(A/turkey/England/647/1977(H1N1)) linear mRNA GI: 325094
nucleoprotein mRNA, complete cds Influenza A virus 1,445 bp
AJ416626.1 (A/turkey/France/87075/87(H1N1)) N1 gene for linear mRNA
GI: 39840719 neuraminidase, genomic RNA Influenza A virus 394 bp
Z30272.1 (A/turkey/Germany/3/91(H1N1)) mRNA for PB2 linear mRNA GI:
456652 polymerase (partial) Influenza A virus 97 bp Z30275.1
(A/turkey/Germany/3/91(H1N1)) mRNA for linear mRNA GI: 530398
neuraminidase (UTR) Influenza A virus 264 bp Z30274.1
(A/turkey/Germany/3/91(H1N1)) mRNA for PA linear mRNA GI: 530401
polymerase Influenza A virus 247 bp Z30273.1
(A/turkey/Germany/3/91(H1N1)) mRNA for PBI linear mRNA GI: 530403
polymerase (partial) Influenza A virus 1,038 bp Z46441.1
(A/turkey/Germany/3/91(H1N1)) mRNA for linear mRNA GI: 854218
hemagglutinin HA1 Influenza A virus 981 bp U46941.1
(A/turkey/Minnesota/1661/1981(H1N1)) linear mRNA GI: 1912332
hemagglutinin (HA) mRNA, partial cds Influenza A virus 1,777 bp
AF091310.1 (A/turkey/Minnesota/1661/81(H1N1)) segment 4 linear mRNA
GI: 4585162 hemagglutinin precursor (HA) mRNA, complete cds
Influenza A virus (A/turkey/North 1,565 bp M7 6609.1
Carolina/1790/1988(H1N1)) nucleoprotein mRNA, linear mRNA GI:
325096 complete cds Influenza A virus (A/Weiss/43 (H1N1)) 1,410 bp
AF250365.2 neuraminidase (NA) gene, complete cds linear mRNA GI:
13260589 Influenza A virus (A/Wilson-Smith/1933(H1N1)) 1,497 bp
EU330203.1 nucleocapsid protein (NP) mRNA, complete cds linear mRNA
GI: 167989512 Influenza A virus 241 bp U47816.1
(A/Wisconsin/3523/1988(H1N1)) neuraminidase linear mRNA GI: 1912352
(NA) mRNA, partial cds Influenza A virus 1,565 bp M7 6610.1
(A/Wisconsin/3623/1988(H1N1)) nucleoprotein linear mRNA GI: 325103
mRNA, complete cds Influenza A virus (A/WI/4754/1994(H1N1)) PB1 235
bp U53156.1 (PB1) mRNA, partial cds linear mRNA GI: 1399590
Influenza A virus (A/WI/4754/1994(H1N1)) PB2 168 bp U53158.1 (PB2)
mRNA, partial cds linear mRNA GI: 1399594 Influenza A virus
(A/WI/4754/1994(H1N1)) PA 621 bp U53160.1 (PA) mRNA, partial cds
linear mRNA GI: 1399598 Influenza A virus (A/WI/4754/1994(H1N1))
1,778 bp U53162.1 hemagglutinin (HA) mRNA, complete cds linear mRNA
GI: 1399602 Influenza A virus (A/WI/4754/1994(H1N1)) NP 200 bp
U53164.1 (NP) mRNA, partial cds linear mRNA GI: 1399606 Influenza A
virus (A/WI/4754/1994(H1N1)) 1,458 bp U53166.1 neuraminidase (NA)
mRNA, complete cds linear mRNA GI: 1399610 Influenza A virus
(A/WI/4754/1994(H1N1)) M 1,027 bp U53168.1 (M) mRNA, complete cds
linear mRNA GI: 1399614 Influenza A virus (A/WI/4754/1994(H1N1)) NS
890 bp U53170.1 (NS) mRNA, complete cds linear mRNA GI: 1399618
Influenza A virus (A/WI/4755/1994(H1N1)) PB1 203 bp U53157.1 (PB1)
mRNA, partial cds linear mRNA GI: 1399592 Influenza A virus
(A/WI/4755/1994(H1N1)) PB2 173 bp U53159.1 (PB2) mRNA, partial cds
linear mRNA GI: 1399596 Influenza A virus (A/WI/4755/1994(H1N1)) PA
621 bp U53161.1 (PA) mRNA, partial cds linear mRNA GI: 1399600
Influenza A virus (A/WI/4755/1994(H1N1)) 1,778 bp U53163.1
hemagglutinin (HA) mRNA, complete cds linear mRNA GI: 1399604
Influenza A virus (A/WI/4755/1994(H1N1)) NP 215 bp U53165.1 (NP)
mRNA, partial cds linear mRNA GI: 1399608 Influenza A virus
(A/WI/4755/1994(H1N1)) 209 bp U53167.1 neuraminidase (NA) mRNA,
partial cds linear mRNA GI: 1399612 Influenza A virus
(A/WI/4755/1994(H1N1)) M 1,027 bp U53169.1 (M) mRNA, complete cds
linear mRNA GI: 1399616 Influenza A virus (A/WI/4755/1994(H1N1)) NS
890 bp U53171.1 (NS) mRNA, complete cds linear mRNA GI: 1399620
Influenza A virus (A/WSN/33) segment 5 543 bp AF306656.1
nucleocapsid protein (NP) mRNA, partial cds linear mRNA GI:
11935089
TABLE-US-00012 TABLE 8 Influenza H3N2 Antigens GenBank/GI
Strain/Protein Length Accession No. 1. Influenza A virus
(A/Aichi/2/1968(H3N2)) 1,704 bp EF614248.1 hemagglutinin (HA) mRNA,
complete cds linear mRNA GI: 148910819 2. Influenza A virus
(A/Aichi/2/1968(H3N2)) 1,698 bp EF614249.1 hemagglutinin (HA) mRNA,
partial cds linear mRNA GI: 148910821 3. Influenza A virus
(A/Aichi/2/1968(H3N2)) 1,698 bp EF614250.1 hemagglutinin (HA) mRNA,
partial cds linear mRNA GI: 148910823 4. Influenza A virus
(A/Aichi/2/1968(H3N2)) 1,698 bp EF614251.1 hemagglutinin (HA) mRNA,
partial cds linear mRNA GI: 148910825 5. Influenza A virus
(A/Akita/1/1995(H3N2)) 1,032 bp U48444.1 haemagglutinin mRNA,
partial cds linear mRNA GI: 1574989 6. Influenza A virus 1,041 bp
Z46392.1 (A/Beijing/32/1992(H3N2)) mRNA for linear mRNA GI: 609020
haemagglutinin 7. Influenza A virus 987 bp AF501516.1
(A/Canada/33312/99(H3N2)) hemagglutinin (HA) linear mRNA GI:
21314288 mRNA, partial cds 8. Influenza A virus 987 bp AF297094.1
(A/Charlottesville/10/99 (H3N2)) linear mRNA GI: 11228917
hemagglutinin mRNA, partial cds 9. Influenza A virus 987 bp
AF297096.1 (A/Charlottesville/49/99 (H3N2)) linear mRNA GI:
11228921 hemagglutinin mRNA, partial cds 10. Influenza A virus 987
bp AF297097.1 (A/Charlottesville/69/99 (H3N2)) linear mRNA GI:
11228923 hemagglutinin mRNA, partial cds 11. Influenza A virus 987
bp AF297095.1 (A/Charlottesville/73/99 (H3N2)) linear mRNA GI:
11228919 hemagglutinin mRNA, partial cds 12. Influenza A virus
1,041 bp Z46393.1 (A/England/1/1993(H3N2)) mRNA for linear mRNA GI:
609024 haemagglutinin 13. Influenza A virus 1,041 bp Z46394.1
(A/England/247/1993(H3N2)) mRNA for linear mRNA GI: 609025
haemagglutinin 14. Influenza A virus 1,041 bp Z46395.1
(A/England/269/93(H3N2)) mRNA for linear mRNA GI: 609027
haemagglutinin 15. Influenza A virus 1,041 bp Z46396.1
(A/England/284/1993(H3N2)) mRNA for linear mRNA GI: 609029
haemagglutinin 16. Influenza A virus 1,041 bp Z46397.1
(A/England/286/1993(H3N2)) mRNA for linear mRNA GI: 609031
haemagglutinin 17. Influenza A virus 1,041 bp Z46398.1
(A/England/289/1993(H3N2)) mRNA for linear mRNA GI: 609033
haemagglutinin 18. Influenza A virus 1,041 bp Z46399.1
(A/England/328/1993(H3N2)) mRNA for linear mRNA GI: 609035
haemagglutinin 19. Influenza A virus 1,041 bp Z46400.1
(A/England/346/1993(H3N2)) mRNA for linear mRNA GI: 609037
haemagglutinin 20. Influenza A virus 1,041 bp Z46401.1
(A/England/347/1993(H3N2)) mRNA for linear mRNA GI: 609039
haemagglutinin 21. Influenza A virus 1,091 bp AF201875.1
(A/England/42/72(H3N2)) hemagglutinin mRNA, linear mRNA GI: 6470274
partial cds 22. Influenza A virus 1,041 bp Z46402.1
(A/England/471/1993(H3N2)) mRNA for linear mRNA GI: 609041
haemagglutinin 23. Influenza A virus 1,041 bp Z46403.1
(A/England/67/1994(H3N2)) mRNA for linear mRNA GI: 609043
haemagglutinin 24. Influenza A virus 1,041 bp Z46404.1
(A/England/68/1994(H3N2)) mRNA for linear mRNA GI: 609045
haemagglutinin 25. Influenza A virus 1,041 bp Z46405.1
(A/England/7/1994(H3N2)) mRNA for linear mRNA GI: 609047
haemagglutinin 28. Influenza A virus 1,041 bp Z46406.1
(A/Guangdong/25/1993(H3N2)) mRNA for linear mRNA GI: 609049
haemagglutinin 29. Influenza A virus (A/Hong 1,091 bp AF201874.1
Kong/1/68(H3N2)) hemagglutinin mRNA, partial linear mRNA GI:
6470272 cds 30. Influenza A virus (A/Hong 1,041 bp Z46407.1
Kong/1/1994(H3N2)) mRNA for haemagglutinin linear mRNA GI: 609051
31. Influenza A virus (A/Hong 1,762 bp AF382319.1
Kong/1143/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14487957
complete cds 32. Influenza A virus (A/Hong 1,762 bp AF382320.1
Kong/1143/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14487959
complete cds 33. Influenza A virus (A/Hong 1,466 bp AF382329.1
Kong/1143/99(H3N2)) neuraminidase mRNA, linear mRNA GI: 14487977
complete cds 34. Influenza A virus (A/Hong 1,466 bp AF382330.1
Kong/1143/99(H3N2)) neuraminidase mRNA, linear mRNA GI: 14487979
complete cds 35. Influenza A virus (A/Hong 1,762 bp AY035589.1
Kong/1144/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14486403
complete cds 36. Influenza A virus (A/Hong 1,762 bp AF382321.1
Kong/1144/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14487961
complete cds 37. Influenza A virus (A/Hong 1,762 bp AF382322.1
Kong/1144/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14487963
complete cds 38. Influenza A virus (A/Hong 1,466 bp AF382331.1
Kong/1144/99(H3N2)) neuraminidase mRNA, linear mRNA GI: 14487981
complete cds 39. Influenza A virus (A/Hong 1,466 bp AF382332.1
Kong/1144/99(H3N2)) neuraminidase mRNA, linear mRNA GI: 14487983
complete cds 40. Influenza A virus (A/Hong 1,762 bp AY035590.1
Kong/1179/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14486405
complete cds 41. Influenza A virus (A/Hong 1,762 bp AF382323.1
Kong/1179/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14487965
complete cds 42. Influenza A virus (A/Hong 1,762 bp AF382324.1
Kong/1179/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14487967
complete cds 43. Influenza A virus (A/Hong 1,762 bp AY035591.1
Kong/1180/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14486407
complete cds 44. Influenza A virus (A/Hong 1,762 bp AF382325.1
Kong/1180/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14487969
complete cds 45. Influenza A virus (A/Hong 1,762 bp AF382326.1
Kong/1180/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14487971
complete cds 46. Influenza A virus (A/Hong 1,762 bp AF382327.1
Kong/1182/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14487973
complete cds 47. Influenza A virus (A/Hong 1,762 bp AF382328.1
Kong/1182/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14487975
complete cds 48. Influenza A virus (A/Hong 1,041 bp Z46408.1
Kong/2/1994(H3N2)) mRNA for haemagglutinin linear mRNA GI: 609055
49. Influenza A virus (A/Hong 1,041 bp Z46410.1 Kong/23/1992(H3N2))
mRNA for haemagglutinin linear mRNA GI: 609053 50. Influenza A
virus (A/Hong 1,041 bp Z46409.1 Kong/34/1990(H3N2)) mRNA for
haemagglutinin linear mRNA GI: 609057 51. Influenza A virus 1,041
bp Z46397.1 (A/England/286/1993(H3N2)) mRNA for linear mRNA GI:
609031 haemagglutinin 52. Influenza A virus 1,041 bp Z46398.1
(A/England/289/1993(H3N2)) mRNA for linear mRNA GI: 609033
haemagglutinin 53. Influenza A virus 1,041 bp Z46399.1
(A/England/328/1993(H3N2)) mRNA for linear mRNA GI: 609035
haemagglutinin 54. Influenza A virus 1,041 bp Z46400.1
(A/England/346/1993(H3N2)) mRNA for linear mRNA GI: 609037
haemagglutinin 55. Influenza A virus 1,041 bp Z46401.1
(A/England/347/1993(H3N2)) mRNA for linear mRNA GI: 609039
haemagglutinin 56. Influenza A virus 1,091 bp AF201875.1
(A/England/42/72(H3N2)) hemagglutinin mRNA, linear mRNA GI: 6470274
partial cds 57. Influenza A virus 1,041 bp Z46402.1
(A/England/471/1993(H3N2)) mRNA for linear mRNA GI: 609041
haemagglutinin 58. Influenza A virus 1,041 bp Z46403.1
(A/England/67/1994(H3N2)) mRNA for linear mRNA GI: 609043
haemagglutinin 59. Influenza A virus 1,041 bp Z46404.1
(A/England/68/1994(H3N2)) mRNA for linear mRNA GI: 609045
haemagglutinin 60. Influenza A virus 1,041 bp Z46405.1
(A/England/7/1994(H3N2)) mRNA for linear mRNA GI: 609047
haemagglutinin 63. Influenza A virus 1,032 bp U48442.1
(A/Guandong/28/1994(H3N2)) haemagglutinin linear mRNA GI: 1574985
mRNA, partial cds 64. Influenza A virus 1,041 bp Z46406.1
(A/Guangdong/25/1993(H3N2)) mRNA for linear mRNA GI: 609049
haemagglutinin 65. Influenza A virus 1,032 bp U48447.1
(A/Hebei/19/1995(H3N2)) haemagglutinin mRNA, linear mRNA GI:
1574995 partial cds 66. Influenza A virus 1,032 bp U48441.1
(A/Hebei/41/1994(H3N2)) haemagglutinin mRNA, linear mRNA GI:
1574983 partial cds 67. Influenza A virus (A/Hong 1,091 bp
AF201874.1 Kong/1/68(H3N2)) hemagglutinin mRNA, partial linear mRNA
GI: 6470272 cds 68. Influenza A virus (A/Hong 1,041 bp Z46407.1
Kong/1/1994(H3N2)) mRNA for haemagglutinin linear mRNA GI: 609051
69. Influenza A virus (A/Hong 1,762 bp AY035588.1
Kong/1143/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14486401
complete cds 70. Influenza A virus (A/Hong 1,762 bp AF382319.1
Kong/1143/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14487957
complete cds 71. Influenza A virus (A/Hong 1,762 bp AF382320.1
Kong/1143/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14487959
complete cds 72. Influenza A virus (A/Hong 1,466 bp AF382329.1
Kong/1143/99(H3N2)) neuraminidase mRNA, linear mRNA GI: 14487977
complete cds 73. Influenza A virus (A/Hong 1,466 bp AF382330.1
Kong/1143/99(H3N2)) neuraminidase mRNA, linear mRNA GI: 14487979
complete cds 74. Influenza A virus (A/Hong 1,762 bp AY035589.1
Kong/1144/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14486403
complete cds 75. Influenza A virus (A/Hong 1,762 bp AF382321.1
Kong/1144/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14487961
complete cds 76. Influenza A virus (A/Hong 1,762 bp AF382322.1
Kong/1144/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14487963
complete cds 77. Influenza A virus (A/Hong 1,466 bp AF382331.1
Kong/1144/99(H3N2)) neuraminidase mRNA, linear mRNA GI: 14487981
complete cds 78. Influenza A virus (A/Hong 1,466 bp AF382332.1
Kong/1144/99(H3N2)) neuraminidase mRNA, linear mRNA GI: 14487983
complete cds 79. Influenza A virus (A/Hong 1,762 bp AY035590.1
Kong/1179/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14486405
complete cds 80. Influenza A virus (A/Hong 1,762 bp AF382323.1
Kong/1179/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14487965
complete cds 81. Influenza A virus (A/Hong 1,762 bp AF382324.1
Kong/1179/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14487967
complete cds 82. Influenza A virus (A/Hong 1,762 bp AY035591.1
Kong/1180/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14486407
complete cds 83. Influenza A virus (A/Hong 1,762 bp AF382325.1
Kong/1180/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14487969
complete cds 84. Influenza A virus (A/Hong 1,762 bp AF382326.1
Kong/1180/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14487971
complete cds 85. Influenza A virus (A/Hong 1,762 bp AY035592.1
Kong/1182/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14486409
complete cds 86. Influenza A virus (A/Hong 1,762 bp AF382327.1
Kong/1182/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14487973
complete cds 87. Influenza A virus (A/Hong 1,762 bp AF382328.1
Kong/1182/99(H3N2)) hemagglutinin mRNA, linear mRNA GI: 14487975
complete cds 88. Influenza A virus (A/Hong 1,041 bp Z46408.1
Kong/2/1994(H3N2)) mRNA for haemagglutinin linear mRNA GI: 609055
89. Influenza A virus (A/Hong 1,041 bp Z46410.1 Kong/23/1992(H3N2))
mRNA for haemagglutinin linear mRNA GI: 609053 90. Influenza A
virus (A/Hong 1,041 bp Z46409.1
Kong/34/1990(H3N2)) mRNA for haemagglutinin linear mRNA GI: 609057
91. Influenza A virus 987 bp AF501534.1 (A/Indiana/28170/99(H3N2))
hemagglutinin linear mRNA GI: 21314324 (HA) mRNA, partial cds 92.
Influenza A virus 529 bp AY961997.1 (A/Kinmen/618/03(H3N2))
hemagglutinin (HA) linear mRNA GI: 68138151 mRNA, partial cds 93.
Influenza A virus 383 bp AY973325.1 (A/Kinmen/618/03(H3N2))
neuraminidase (NA) linear mRNA GI: 70673206 mRNA, partial cds 94.
Influenza A virus 882 bp AY986986.1 (A/Kinmen/618/03(H3N2))
nucleoprotein (NP) linear mRNA GI: 70728099 mRNA, partial cds 95.
Influenza A virus 545 bp AY962017.1 (A/Kinmen/621/03(H3N2))
hemagglutinin (HA) linear mRNA GI: 68138191 mRNA, partial cds 96.
Influenza A virus 386 bp AY973326.1 (A/Kinmen/621/03(H3N2))
neuraminidase (NA) linear mRNA GI: 70673208 mRNA, partial cds 97.
Influenza A virus 882 bp AY986987.1 (A/Kinmen/621/03(H3N2))
nucleoprotein (NP) linear mRNA GI: 70728101 mRNA, partial cds 98.
Influenza A virus 786 bp AY962008.1 (A/Kinmen/639/04(H3N2))
hemagglutinin (HA) linear mRNA GI: 68138173 mRNA, partial cds 99.
Influenza A virus 381 bp AY973327.1 (A/Kinmen/639/04(H3N2))
neuraminidase (NA) linear mRNA GI: 70673210 mRNA, partial cds 100.
Influenza A virus 882 bp AY986988.1 (A/Kinmen/639/04(H3N2))
nucleoprotein (NP) linear mRNA GI: 70728103 mRNA, partial cds 101.
Influenza A virus 596 bp AY962004.1 (A/Kinmen/641/04(H3N2))
hemagglutinin (HA) linear mRNA GI: 68138165 mRNA, partial cds 102.
Influenza A virus 785 bp AY973328.1 (A/Kinmen/641/04(H3N2))
neuraminidase (NA) linear mRNA GI: 70673212 mRNA, partial cds 103.
Influenza A virus 576 bp AY962001.1 (A/Kinmen/642/04(H3N2))
hemagglutinin (HA) linear mRNA GI: 68138159 mRNA, partial cds 104.
Influenza A virus 580 bp AY973329.1 (A/Kinmen/642/04(H3N2))
neuraminidase (NA) linear mRNA GI: 70673214 mRNA, partial cds 105.
Influenza A virus 882 bp AY986989.1 (A/Kinmen/642/04(H3N2))
nucleoprotein (NP) linear mRNA GI: 70728105 mRNA, partial cds 106.
Influenza A virus 789 bp AY962009.1 (A/Kinmen/645/04(H3N2))
hemagglutinin (HA) linear mRNA GI: 68138175 mRNA, partial cds 107.
Influenza A virus 581 bp AY973330.1 (A/Kinmen/645/04(H3N2))
neuraminidase (NA) linear mRNA GI: 70673216 mRNA, partial cds 108.
Influenza A virus 981 bp AY986990.1 (A/Kinmen/645/04(H3N2))
nucleoprotein (NP) linear mRNA GI: 70728107 mRNA, partial cds 109.
Influenza A virus 2,341 bp U62543.1 (A/LosAngeles/2/1987(H3N2))
polymerase linear mRNA GI: 1480737 protein basic 2 (PB2) mRNA,
complete cds 110. Influenza A virus 1,041 bp Z46411.1
(A/Madrid/252/1993(H3N2)) mRNA for linear mRNA GI: 609067
haemagglutinin 111. Influenza A virus 987 bp AF501531.1
(A/Michigan/22568/99(H3N2)) hemagglutinin linear mRNA GI: 21314318
(HA) mRNA, partial cds 112. Influenza A virus 987 bp AF501518.1
(A/Michigan/22692/99(H3N2)) hemagglutinin linear mRNA GI: 21314292
(HA) mRNA, partial cds 113. Influenza A virus 754 bp AJ519454.1
(A/Moscow/10/99(H3N2)) partial NS1 gene for linear mRNA GI:
31096423 non structural protein 1 and partial NS2 gene for non
structural protein 2, genomic RNA 114. Influenza A virus 987 bp
AY138518.1 (A/ningbo/17/2002(H3N2)) hemagglutinin (HA) linear mRNA
GI: 24895178 mRNA, partial cds 115. Influenza A virus 987 bp
AY138517.1 (A/ningbo/25/2002(H3N2)) hemagglutinin (HA) linear mRNA
GI: 24895169 mRNA, partial cds 116. Influenza A virus 1,765 bp
V01103.1 (A/NT/60/68/29C(H3N2)) mRNA for linear mRNA GI: 60800
haemagglutinin (HA1 and HA2 genes) 117. Influenza A virus 1,701 bp
DQ059385.1 (A/Oklahoma/323/03(H3N2)) hemagglutinin linear mRNA GI:
66933143 mRNA, complete cds 118. Influenza A virus 1,410 bp
DQ059384.2 (A/Oklahoma/323/03(H3N2)) neuraminidase linear mRNA GI:
75859981 mRNA, complete cds 119. Influenza A virus 766 bp
AJ519458.1 (A/Panama/2007/99(H3N2)) partial NS1 gene linear mRNA
GI: 31096435 for non structural protein 1 and partial NS2 gene for
non structural protein 2, genomic RNA 120. Influenza A virus 987 bp
AF501526.1 (A/Pennsylvania/20109/99(H3N2)) linear mRNA GI: 21314308
hemagglutinin (HA) mRNA, partial cds 121. Influenza A virus 1,091
bp AF233691.1 (A/Philippines/2/82(H3N2)) hemagglutinin linear mRNA
GI: 7331124 mRNA, partial cds 122. Influenza A virus 767 bp
AY962000.1 (A/Pingtung/303/04(H3N2)) hemagglutinin (HA) linear mRNA
GI: 68138157 mRNA, partial cds 123. Influenza A virus 783 bp
AY973331.1 (A/Pingtung/303/04(H3N2)) neuraminidase (NA) linear mRNA
GI: 70673218 mRNA, partial cds 124. Influenza A virus 928 bp
AY986991.1 (A/Pingtung/303/04(H3N2)) nucleoprotein (NP) linear mRNA
GI: 70728109 mRNA, partial cds 125. Influenza A virus 788 bp
AY961999.1 (A/Pingtung/313/04(H3N2)) hemagglutinin (HA) linear mRNA
GI: 68138155 mRNA, partial cds 126. Influenza A virus 787 bp
AY973332.1 (A/Pingtung/313/04(H3N2)) neuraminidase (NA) linear mRNA
GI: 70673220 mRNA, partial cds 127. Influenza A virus 882 bp
AY986992.1 (A/Pingtung/313/04(H3N2)) nucleoprotein (NP) linear mRNA
GI: 70728111 mRNA, partial cds 128. Influenza A virus (A/ruddy 927
bp AY664458.1 turnstone/Delaware/142/99 (H3N2)) linear mRNA GI:
51011862 nonfunctional matrix protein mRNA, partial sequence 129.
Influenza A virus 1,041 bp Z46413.1 (A/Scotland/142/1993(H3N2))
mRNA for linear mRNA GI: 609059 haemagglutinin 130. Influenza A
virus 1,041 bp Z46414.1 (A/Scotland/160/1993(H3N2)) mRNA for linear
mRNA GI: 609061 haemagglutinin 131. Influenza A virus 1,041 bp
Z46416.1 (A/Scotland/173/1993(H3N2)) mRNA for linear mRNA GI:
609063 haemagglutinin 132. Influenza A virus 1,041 bp Z46415.1
(A/Scotland/174/1993(H3N2)) mRNA for linear mRNA GI: 609065
haemagglutinin 133. Influenza A virus 1,041 bp Z46412.1
(A/Scotland/2/1993(H3N2)) mRNA for linear mRNA GI: 609069
haemagglutinin 134. Influenza A virus 1,032 bp U48439.1
(A/Sendai/C182/1994(H3N2)) haemagglutinin linear mRNA GI: 1574979
mRNA, partial cds 135. Influenza A virus 1,032 bp U48445.1
(A/Sendai/c373/1995(H3N2)) haemagglutinin linear mRNA GI: 1574991
mRNA, partial cds 136. Influenza A virus 1,032 bp U48440.1
(A/Sendai/c384/1994(H3N2)) haemagglutinin linear mRNA GI: 1574981
mRNA, partial cds 137. Influenza A virus 1,041 bp Z46417.1
(A/Shangdong/9/1993(H3N2)) mRNA for linear mRNA GI: 609071
haemagglutinin 138. Influenza A virus 987 bp L19416.1
(A/Shanghai/11/1987/X99aE high yield linear mRNA GI: 348117
reassortant(H3N2)) hemagglutinin (HA) mRNA, partial cds 139.
Influenza A virus 2,280 bp AF225514.1 (A/sw/Shizuoka/110/97(H3N2))
polymerase linear mRNA GI: 27462098 basic 2 (PB2) mRNA, complete
cds 140. Influenza A virus 2,274 bp AF225518.1
(A/sw/Shizuoka/110/97(H3N2)) polymerase linear mRNA GI: 27462106
basic 1 (PB1) mRNA, complete cds 141. Influenza A virus 2,151 bp
AF225522.1 (A/sw/Shizuoka/110/97(H3N2)) polymerase linear mRNA GI:
27462114 acidic (PA) mRNA, complete cds 142. Influenza A virus
1,497 bp AF225534.1 (A/sw/Shizuoka/110/97(H3N2)) nucleoprotein
linear mRNA GI: 27462146 (NP) mRNA, complete cds 143. Influenza A
virus 1,410 bp AF225538.1 (A/sw/Shizuoka/110/97(H3N2))
neuraminidase linear mRNA GI: 27462154 (NA) mRNA, complete cds 144.
Influenza A virus 984 bp AF225542.1 (A/sw/Shizuoka/110/97(H3N2))
hemagglutinin linear mRNA GI: 27462162 (HA1) mRNA, partial cds 145.
Influenza A virus 2,280 bp AF225515.1 (A/sw/Shizuoka/115/97(H3N2))
polymerase linear mRNA GI: 27462100 basic 2 (PB2) mRNA, complete
cds 146. Influenza A virus 2,274 bp AF225519.1
(A/sw/Shizuoka/115/97(H3N2)) polymerase linear mRNA GI: 27462108
basic 1 (PB1) mRNA, complete cds 147. Influenza A virus 2,151 bp
AF225523.1 (A/sw/Shizuoka/115/97(H3N2)) polymerase linear mRNA GI:
27462116 acidic (PA) mRNA, complete cds 148. Influenza A virus
1,497 bp AF225535.1 (A/sw/Shizuoka/115/97(H3N2)) nucleoprotein
linear mRNA GI: 27462148 (NP) mRNA, complete cds 149. Influenza A
virus 1,410 bp AF225539.1 (A/sw/Shizuoka/115/97(H3N2))
neuraminidase linear mRNA GI: 27462156 (NA) mRNA, complete cds 150.
Influenza A virus 984 bp AF225543.1 (A/sw/Shizuoka/115/97(H3N2))
hemagglutinin linear mRNA GI: 27462164 (HA1) mRNA, partial cds 151.
Influenza A virus 2,280 bp AF225516.1 (A/sw/Shizuoka/119/97(H3N2))
polymerase linear mRNA GI: 27462102 basic 2 (PB2) mRNA, complete
cds 152. Influenza A virus 2,274 bp AF225520.1
(A/sw/Shizuoka/119/97(H3N2)) polymerase linear mRNA GI: 27462110
basic 1 (PB1) mRNA, complete cds 153. Influenza A virus 2,151 bp
AF225524.1 (A/sw/Shizuoka/119/97(H3N2)) polymerase linear mRNA GI:
27462118 acidic (PA) mRNA, complete cds 154. Influenza A virus
1,497 bp AF225536.1 (A/sw/Shizuoka/119/97(H3N2)) nucleoprotein
linear mRNA GI: 27462150 (NP) mRNA, complete cds 155. Influenza A
virus 1,410 bp AF225540.1 (A/sw/Shizuoka/119/97(H3N2))
neuraminidase linear mRNA GI: 27462158 (NA) mRNA, complete cds 156.
Influenza A virus 984 bp AF225544.1 (A/sw/Shizuoka/119/97(H3N2))
hemagglutinin linear mRNA GI: 27462166 (HA1) mRNA, partial cds 159.
Influenza A virus 1,410 bp EU163948.1
(A/swine/Bakum/1DTI769/2003(H3N2)) linear mRNA GI: 157679552
neuraminidase mRNA, complete cds 163. Influenza A virus 1,738 bp
AY857957.1 (A/swine/Fujian/668/01(H3N2)) nonfunctional linear mRNA
GI: 58042507 hemagglutinin mRNA, complete sequence 164. Influenza A
virus PB2 gene for 2,280 bp AJ311459.1 Polymerase 2 protein,
genomic RNA, strain linear mRNA GI: 13661041 A/Swine/Italy/1523/98
165. Influenza A virus PB1 gene for 2,274 bp AJ311460.1 Polymerase
1 protein, genomic RNA, strain linear mRNA GI: 13661043
A/Swine/Italy/1523/98 166. Influenza A virus 821 bp AJ344024.1
(A/swine/Italy/1523/98(H3N2)) NS1 gene for linear mRNA GI: 20068146
non structural protein 1 and NS2 gene for non structural protein 2,
genomic RNA 167. Influenza A virus 1,465 bp EU163949.1
(A/swine/Re220/92hp(H3N2)) neuraminidase linear mRNA GI: 157679554
mRNA, complete cds 168. Influenza A virus 2,280 bp AF225517.1
(A/sw/Shizuoka/120/97(H3N2)) polymerase linear mRNA GI: 27462104
basic 2 (PB2) mRNA, complete cds 169. Influenza A virus 2,274 bp
AF225521.1 (A/sw/Shizuoka/120/97(H3N2)) polymerase linear mRNA GI:
27462112 basic 1 (PB1) mRNA, complete cds 170. Influenza A virus
2,151 bp AF225525.1 (A/sw/Shizuoka/120/97(H3N2)) polymerase linear
mRNA GI: 27462120 acidic (PA) mRNA, complete cds 171. Influenza A
virus 1,497 bp AF225537.1 (A/sw/Shizuoka/120/97(H3N2))
nucleoprotein linear mRNA GI: 27462152 (NP) mRNA, complete cds 172.
Influenza A virus 1,410 bp AF225541.1 (A/sw/Shizuoka/120/97(H3N2))
neuraminidase linear mRNA GI: 27462160 (NA) mRNA, complete cds 173.
Influenza A virus 984 bp AF225545.1 (A/sw/Shizuoka/120/97(H3N2))
hemagglutinin linear mRNA GI: 27462168 (HA1) mRNA, partial cds 174.
Influenza A virus 1,762 bp AY032978.1 (A/Switzerland/7729/98(H3N2))
hemagglutinin linear mRNA GI: 14161723 mRNA, complete cds 175.
Influenza A virus 1,762 bp AF382318.1 (A/Switzerland/7729/98(H3N2))
hemagglutinin linear mRNA GI: 14487955 mRNA, complete cds 176.
Influenza A virus 528 bp AY962011.1 (A/Tainan/704/03(H3N2))
hemagglutinin (HA) linear mRNA GI: 68138179 mRNA, partial cds
177. Influenza A virus 384 bp AY973333.1 (A/Tainan/704/03(H3N2))
neuraminidase (NA) linear mRNA GI: 70673222 mRNA, partial cds 178.
Influenza A virus 882 bp AY986993.1 (A/Tainan/704/03(H3N2))
nucleoprotein (NP) linear mRNA GI: 70728113 mRNA, partial cds 179.
Influenza A virus 519 bp AY962012.1 (A/Tainan/712/03(H3N2))
hemagglutinin (HA) linear mRNA GI: 68138181 mRNA, partial cds 180.
Influenza A virus 383 bp AY973334.1 (A/Tainan/712/03(H3N2))
neuraminidase (NA) linear mRNA GI: 70673224 mRNA, partial cds 181.
Influenza A virus 882 bp AY986994.1 (A/Tainan/712/03(H3N2))
nucleoprotein (NP) linear mRNA GI: 70728115 mRNA, partial cds 182.
Influenza A virus 784 bp AY962005.1 (A/Tainan/722/03(H3N2))
hemagglutinin (HA) linear mRNA GI: 68138167 mRNA, partial cds 183.
Influenza A virus 592 bp AY973335.1 (A/Tainan/722/03(H3N2))
neuraminidase (NA) linear mRNA GI: 70673226 mRNA, partial cds 184.
Influenza A virus 936 bp AY986995.1 (A/Tainan/722/03(H3N2))
nucleoprotein (NP) linear mRNA GI: 70728117 mRNA, partial cds 185.
Influenza A virus 788 bp AY961998.1 (A/Taipei/407/03(H3N2))
hemagglutinin (HA) linear mRNA GI: 68138153 mRNA, partial cds 186.
Influenza A virus 787 bp AY973336.1 (A/Taipei/407/03(H3N2))
neuraminidase (NA) linear mRNA GI: 70673228 mRNA, partial cds 187.
Influenza A virus 882 bp AY986996.1 (A/Taipei/407/03(H3N2))
nucleoprotein (NP) linear mRNA GI: 70728119 mRNA, partial cds 188.
Influenza A virus 787 bp AY962007.1 (A/Taipei/416/03(H3N2))
hemagglutinin (HA) linear mRNA GI: 68138171 mRNA, partial cds 189.
Influenza A virus 782 bp AY973337.1 (A/Taipei/416/03(H3N2))
neuraminidase (NA) linear mRNA GI: 70673230 mRNA, partial cds 190.
Influenza A virus 882 bp AY986997.1 (A/Taipei/416/03(H3N2))
nucleoprotein (NP) linear mRNA GI: 70728121 mRNA, partial cds 191.
Influenza A virus (A/Taiwan/0020/98 297 bp AY303703.1 (H3N2))
polymerase basic protein 1 (PB1) linear mRNA GI: 32330895 mRNA,
partial cds 192. Influenza A virus 791 bp AY604817.1
(A/Taiwan/0040/2003(H3N2)) hemagglutinin linear mRNA GI: 50727514
mRNA, partial cds 193. Influenza A virus (A/Taiwan/0045/98 297 bp
AY303705.1 (H3N2)) polymerase basic protein 1 (PB1) linear mRNA GI:
32330899 mRNA, partial cds 194. Influenza A virus 844 bp AF362820.1
(A/human/Taiwan/0095/96(H3N2)) hemagglutinin linear mRNA GI:
15055140 (HA) mRNA, partial cds 195. Influenza A virus 791 bp
AY604828.1 (A/Taiwan/0097/2003(H3N2)) hemagglutinin linear mRNA GI:
50727536 mRNA, partial cds 196. Influenza A virus
(A/Taiwan/0104/2001 297 bp AY303706.1 (H3N2)) polymerase basic
protein 1 (PB1) linear mRNA GI: 32330901 mRNA, partial cds 197.
Influenza A virus 844 bp AF362805.1 (A/human/Taiwan/0118/98(H3N2))
hemagglutinin linear mRNA GI: 15055110 (HA) mRNA, partial cds 198.
Influenza A virus 791 bp AY604823.1 (A/Taiwan/0122/2003(H3N2))
hemagglutinin linear mRNA GI: 50727526 mRNA, partial cds 199.
Influenza A virus 844 bp AF362806.1 (A/human/Taiwan/0149/00(H3N2))
hemagglutinin linear mRNA GI: 15055112 (HA) mRNA, partial cds 200.
Influenza A virus (A/Taiwan/0275/2000 297 bp AY303712.1 (H3N2))
polymerase basic protein 1 (PB1) linear mRNA GI: 32330913 mRNA,
partial cds 201. Influenza A virus (A/Taiwan/0275/2000 844 bp
AY303713.1 (H3N2)) hemagglutinin (HA) mRNA, partial cds linear mRNA
GI: 32330915 202. Influenza A virus 844 bp AF362807.1
(A/human/Taiwan/0293/98(H3N2)) hemagglutinin linear mRNA GI:
15055114 (HA) mRNA, partial cds 203. Influenza A virus
(A/Taiwan/0346/98 297 bp AY303715.1 (H3N2)) polymerase basic
protein 1 (PB1) linear mRNA GI: 32330919 mRNA, partial cds 204.
Influenza A virus (A/Taiwan/0379/2000 297 bp AY303716.1 (H3N2))
polymerase basic protein 1 (PB1) linear mRNA GI: 32330921 mRNA,
partial cds 205. Influenza A virus (A/Taiwan/0379/2000 844 bp
AY303717.1 (H3N2)) hemagglutinin (HA) mRNA, partial cds linear mRNA
GI: 32330923 206. Influenza A virus 791 bp AY625729.1
(A/Taiwan/0388/2001(H3N2)) hemagglutinin linear mRNA GI: 50604415
(HA) mRNA, partial cds 207. Influenza A virus 844 bp AF362808.1
(A/human/Taiwan/0389/99(H3N2)) hemagglutinin linear mRNA GI:
15055116 (HA) mRNA, partial cds 208. Influenza A virus 844 bp
AF362809.1 (A/human/Taiwan/0423/98(H3N2)) hemagglutinin linear mRNA
GI: 15055118 (HA) mRNA, partial cds 209. Influenza A virus
(A/Taiwan/0423/98 297 bp AY303718.1 (H3N2)) polymerase basic
protein 1 (PB1) linear mRNA GI: 32330925 mRNA, partial cds 210.
Influenza A virus 844 bp AF362810.1 (A/human/Taiwan/0464/98(H3N2))
hemagglutinin linear mRNA GI: 15055120 (HA) mRNA, partial cds 211.
Influenza A virus (A/Taiwan/0464/98 297 bp AY303719.1 (H3N2))
polymerase basic protein 1 (PB1) linear mRNA GI: 32330927 mRNA,
partial cds 212. Influenza A virus 791 bp AY625730.1
(A/Taiwan/0568/2001(H3N2)) hemagglutinin linear mRNA GI: 50604440
(HA) mRNA, partial cds 213. Influenza A virus 791 bp AY604822.1
(A/Taiwan/0570/2003(H3N2)) hemagglutinin linear mRNA GI: 50727524
mRNA, partial cds 214. Influenza A virus 791 bp AY604827.1
(A/Taiwan/0572/2003(H3N2)) hemagglutinin linear mRNA GI: 50727534
mRNA, partial cds 215. Influenza A virus 791 bp AY604821.1
(A/Taiwan/0578/2003(H3N2)) hemagglutinin linear mRNA GI: 50727522
mRNA, partial cds 216. Influenza A virus 791 bp AY604820.1
(A/Taiwan/0583/2003(H3N2)) hemagglutinin linear mRNA GI: 50727520
mRNA, partial cds 217. Influenza A virus (A/Taiwan/0646/2000 297 bp
AY303722.1 (H3N2)) polymerase basic protein 1 (PB1) linear mRNA GI:
32330933 mRNA, partial cds 218. Influenza A virus
(A/Taiwan/0646/2000 844 bp AY303723.1 (H3N2)) hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 32330935 219. Influenza A virus
844 bp AF362811.1 (A/human/Taiwan/0830/99(H3N2)) hemagglutinin
linear mRNA GI: 15055122 (HA) mRNA, partial cds 220. Influenza A
virus 791 bp AY625731.1 (A/Taiwan/0964/2001(H3N2)) hemagglutinin
linear mRNA GI: 50604469 (HA) mRNA, partial cds 221. Influenza A
virus 844 bp AF362812.1 (A/human/Taiwan/1008/99(H3N2))
hemagglutinin linear mRNA GI: 15055124 (HA) mRNA, partial cds 222.
Influenza A virus (A/Taiwan/1008/99 297 bp AY303725.1 (H3N2))
polymerase basic protein 1 (PB1) linear mRNA GI: 32330939 mRNA,
partial cds 223. Influenza A virus 750 bp EU068138.1
(A/Taiwan/1219/2004(H3N2)) hemagglutinin linear mRNA GI: 158452149
(HA) mRNA, partial cds 224. Influenza A virus 750 bp EU068125.1
(A/Taiwan/1315/2005(H3N2)) hemagglutinin linear mRNA GI: 158452123
(HA) mRNA, partial cds 225. Influenza A virus 750 bp EU068153.1
(A/Taiwan/1511/2004(H3N2)) hemagglutinin linear mRNA GI: 158452179
(HA) mRNA, partial cds 226. Influenza A virus 750 bp EU068119.1
(A/Taiwan/1533/2003(H3N2)) hemagglutinin linear mRNA GI: 158452111
(HA) mRNA, partial cds 227. Influenza A virus 844 bp AF362813.1
(A/human/Taiwan/1537/99(H3N2)) hemagglutinin linear mRNA GI:
15055126 (HA) mRNA, partial cds 228. Influenza A virus
(A/Taiwan/1537/99 297 bp AY303728.1 (H3N2)) polymerase basic
protein 1 (PB1) linear mRNA GI: 32330945 mRNA, partial cds 229.
Influenza A virus 791 bp AY604826.1 (A/Taiwan/1566/2003(H3N2))
hemagglutinin linear mRNA GI: 50727532 mRNA, partial cds 230.
Influenza A virus 791 bp AY604819.1 (A/Taiwan/1568/2003(H3N2))
hemagglutinin linear mRNA GI: 50727518 mRNA, partial cds 231.
Influenza A virus 750 bp EU068116.1 (A/Taiwan/158/2003(H3N2))
hemagglutinin (HA) linear mRNA GI: 158452105 mRNA, partial cds 232.
Influenza A virus 875 bp AF138709.2 (A/Taiwan/1600/96(H3N2)) matrix
protein M1 linear mRNA GI: 4996869 (M) mRNA, partial cds 233.
Influenza A virus 750 bp EU068117.1 (A/Taiwan/1613/2003(H3N2))
hemagglutinin linear mRNA GI: 158452107 (HA) mRNA, partial cds 234.
Influenza A virus 750 bp EU068148.1 (A/Taiwan/1651/2004(H3N2))
hemagglutinin linear mRNA GI: 158452169 (HA) mRNA, partial cds 235.
Influenza A virus 844 bp AF362814.1 (A/human/Taiwan/1748/97(H3N2))
hemagglutinin linear mRNA GI: 15055128 (HA) mRNA, partial cds 236.
Influenza A virus (A/Taiwan/1748/97 297 bp AY303729.1 (H3N2))
polymerase basic protein 1 (PB1) linear mRNA GI: 32330947 mRNA,
partial cds 237. Influenza A virus 872 bp AF138707.2
(A/Taiwan/179/96(H3N2)) matrix protein M1 linear mRNA GI: 4996865
(M) mRNA, partial cds 238. Influenza A virus 750 bp EU068139.1
(A/Taiwan/1817/2004(H3N2)) hemagglutinin linear mRNA GI: 158452151
(HA) mRNA, partial cds 239. Influenza A virus 750 bp EU068154.1
(A/Taiwan/1904/2003(H3N2)) hemagglutinin linear mRNA GI: 158452181
(HA) mRNA, partial cds 240. Influenza A virus 750 bp EU068155.1
(A/Taiwan/1921/2003(H3N2)) hemagglutinin linear mRNA GI: 158452183
(HA) mRNA, partial cds 241. Influenza A virus 844 bp AF362815.1
(A/human/Taiwan/1986/96(H3N2)) hemagglutinin linear mRNA GI:
15055130 (HA) mRNA, partial cds 242. Influenza A virus
(A/Taiwan/1990/96 297 bp AY303730.1 (H3N2)) polymerase basic
protein 1 (PB1) linear mRNA GI: 32330949 mRNA, partial cds 243.
Influenza A virus (A/Taiwan/1990/96 844 bp AY303731.1 (H3N2))
hemagglutinin (HA) mRNA, partial cds linear mRNA GI: 32330951 244.
Influenza A virus 861 bp AF139938.1 (A/Taiwan/20/98(H3N2)) H3
hemagglutinin (HA) linear mRNA GI: 4972940 mRNA, partial cds 245.
Influenza A virus 392 bp AF140627.1 (A/Taiwan/20/98(H3N2)) N2
neuraminidase (NA) linear mRNA GI: 4972988 mRNA, partial cds 246.
Influenza A virus 875 bp AF138715.2 (A/Taiwan/20/98(H3N2)) matrix
protein M1 (M) linear mRNA GI: 4996879 mRNA, partial cds 247.
Influenza A virus 844 bp AF362816.1 (A/human/Taiwan/2031/97(H3N2))
hemagglutinin linear mRNA GI: 15055132 (HA) mRNA, partial cds 248.
Influenza A virus 861 bp AF139937.1 (A/Taiwan/2034/96(H3N2)) H3
hemagglutinin linear mRNA GI: 4972938 (HA) mRNA, partial cds 249.
Influenza A virus 392 bp AF140620.1 (A/Taiwan/2034/96(H3N2)) N2
neuraminidase linear mRNA GI: 4972974 (NA) mRNA, partial cds 250.
Influenza A virus 297 bp AY303732.1 (A/Taiwan/2034/96(H3N2))
polymerase basic linear mRNA GI: 32330953 protein 1 (PB1) mRNA,
partial cds 251. Influenza A virus 791 bp AY604818.1
(A/Taiwan/2040/2003(H3N2)) hemagglutinin linear mRNA GI: 50727516
mRNA, partial cds 252. Influenza A virus 750 bp EU068131.1
(A/Taiwan/2072/2006(H3N2)) hemagglutinin linear mRNA GI: 158452135
(HA) mRNA, partial cds 253. Influenza A virus 861 bp AF139934.1
(A/Taiwan/21/98(H3N2)) H3 hemagglutinin (HA) linear mRNA GI:
4972932 mRNA, partial cds 254. Influenza A virus 392 bp AF140624.1
(A/Taiwan/21/98(H3N2)) N2 neuraminidase (NA) linear mRNA GI:
4972982 mRNA, partial cds 255. Influenza A virus 875 bp AF138716.2
(A/Taiwan/21/98(H3N2)) matrix protein M1 (M) linear mRNA GI:
4996881 mRNA, partial cds 256. Influenza A virus 861 bp AF139932.1
(A/Taiwan/2191/96(H3N2)) H3 hemagglutinin linear mRNA GI: 4972928
(HA) mRNA, partial cds 257. Influenza A virus 392 bp AF140622.1
(A/Taiwan/2191/96(H3N2)) N2 neuraminidase linear mRNA GI: 4972978
(NA) mRNA, partial cds 258. Influenza A virus 875 bp AF138711.3
(A/Taiwan/2191/96(H3N2)) matrix protein M1 linear mRNA GI:
156147502 (M) mRNA, partial cds 259. Influenza A virus 861 bp
AF139936.1 (A/Taiwan/2192/96(H3N2)) H3 hemagglutinin linear mRNA
GI: 4972936 (HA) mRNA, partial cds 260. Influenza A virus 392 bp
AF140626.1 (A/Taiwan/2192/96(H3N2)) N2 neuraminidase linear mRNA
GI: 4972986 (NA) mRNA, partial cds 261. Influenza A virus
(A/Taiwan/2195/96 297 bp AY303735.1 (H3N2)) polymerase basic
protein 1 (PB1) linear mRNA GI: 32330959 mRNA, partial cds
262. Influenza A virus (A/Taiwan/2195/96 844 bp AY303736.1 (H3N2))
hemagglutinin (HA) mRNA, partial cds linear mRNA GI: 32330961 263.
Influenza A virus 875 bp AF138718.2 (A/Taiwan/224/98(H3N2)) matrix
protein M1 linear mRNA GI: 4996885 (M) mRNA, partial cds 264.
Influenza A virus 844 bp AF362817.1 (A/human/Taiwan/2548/99(H3N2))
hemagglutinin linear mRNA GI: 15055134 (HA) mRNA, partial cds 265.
Influenza A virus 750 bp EU068120.1 (A/Taiwan/268/2005(H3N2))
hemagglutinin (HA) linear mRNA GI: 158452113 mRNA, partial cds 266.
Influenza A virus 750 bp EU068149.1 (A/Taiwan/3008/2004(H3N2))
hemagglutinin linear mRNA GI: 158452171 (HA) mRNA, partial cds 267.
Influenza A virus 750 bp EU068152.1 (A/Taiwan/3075/2003(H3N2))
hemagglutinin linear mRNA GI: 158452177 (HA) mRNA, partial cds 268.
Influenza A virus 940 bp AF362818.1 (A/human/Taiwan/3083/00(H3N2))
hemagglutinin linear mRNA GI: 15055136 (HA) mRNA, partial cds 269.
Influenza A virus 791 bp AY604811.1 (A/Taiwan/3131/2002(H3N2))
hemagglutinin linear mRNA GI: 50727502 mRNA, partial cds 270.
Influenza A virus 750 bp EU068145.1 (A/Taiwan/3154/2004(H3N2))
hemagglutinin linear mRNA GI: 158452163 (HA) mRNA, partial cds 271.
Influenza A virus 750 bp EU068141.1 (A/Taiwan/3187/2004(H3N2))
hemagglutinin linear mRNA GI: 158452155 (HA) mRNA, partial cds 272.
Influenza A virus 750 bp EU068134.1 (A/Taiwan/3245/2004(H3N2))
hemagglutinin linear mRNA GI: 158452141 (HA) mRNA, partial cds 273.
Influenza A virus 750 bp EU068133.1 (A/Taiwan/3294/2005(H3N2))
hemagglutinin linear mRNA GI: 158452139 (HA) mRNA, partial cds 274.
Influenza A virus 861 bp AF139935.1 (A/Taiwan/3351/97(H3N2)) H3
hemagglutinin linear mRNA GI: 4972934 (HA) mRNA, partial cds 275.
Influenza A virus 392 bp AF140625.1 (A/Taiwan/3351/97(H3N2)) N2
neuraminidase linear mRNA GI: 4972984 (NA) mRNA, partial cds 276.
Influenza A virus 875 bp AF138713.2 (A/Taiwan/3351/97(H3N2)) matrix
protein M1 linear mRNA GI: 4996875 (M) mRNA, partial cds 277.
Influenza A virus 297 bp AY303738.1 (A/Taiwan/3351/97(H3N2))
polymerase basic linear mRNA GI: 32330965 protein 1 (PB1) mRNA,
partial cds 278. Influenza A virus 750 bp EU068132.1
(A/Taiwan/3387/2005(H3N2)) hemagglutinin linear mRNA GI: 158452137
(HA) mRNA, partial cds 279. Influenza A virus (A/Taiwan/3396/97 297
bp AY303742.1 (H3N2)) polymerase basic protein 1 (PB1) linear mRNA
GI: 32330973 mRNA, partial cds 280. Influenza A virus
(A/Taiwan/3396/97 844 bp AY303743.1 (H3N2)) hemagglutinin (HA)
mRNA, partial cds linear mRNA GI: 32330975 281. Influenza A virus
861 bp AF139930.1 (A/Taiwan/3427/97(H3N2)) H3 hemagglutinin linear
mRNA GI: 4972924 (HA) mRNA, partial cds 282. Influenza A virus 392
bp AF140619.1 (A/Taiwan/3427/97(H3N2)) N2 neuraminidase linear mRNA
GI: 4972972 (NA) mRNA, partial cds 283. Influenza A virus 861 bp
AF139940.1 (A/Taiwan/346/98(H3N2)) H3 hemagglutinin linear mRNA GI:
4972944 (HA) mRNA, partial cds 284. Influenza A virus 392 bp
AF140787.1 (A/Taiwan/346/98(H3N2)) N2 neuraminidase linear mRNA GI:
4972992 (NA) mRNA, partial cds 285. Influenza A virus 875 bp
AF138719.2 (A/Taiwan/346/98(H3N2)) matrix protein M1 linear mRNA
GI: 4996887 (M) mRNA, partial cds 286. Influenza A virus 942 bp
AF362819.1 (A/human/Taiwan/3460/00(H3N2)) truncated linear mRNA GI:
15055138 hemagglutinin (HA) mRNA, partial cds 287. Influenza A
virus 861 bp AF139933.1 (A/Taiwan/3469/97(H3N2)) H3 hemagglutinin
linear mRNA GI: 4972930 (HA) mRNA, partial cds 288. Influenza A
virus 392 bp AF140623.1 (A/Taiwan/3469/97(H3N2)) N2 neuraminidase
linear mRNA GI: 4972980 (NA) mRNA, partial cds 289. Influenza A
virus 875 bp AF138714.2 (A/Taiwan/3469/97(H3N2)) matrix protein M1
linear mRNA GI: 4996877 (M) mRNA, partial cds 290. Influenza A
virus (A/Taiwan/3503/97 297 bp AY303744.1 (H3N2)) polymerase basic
protein 1 (PB1) linear mRNA GI: 32330977 mRNA, partial cds 291.
Influenza A virus (A/Taiwan/3503/97 844 bp AY303745.1 (H3N2))
hemagglutinin (HA) mRNA, partial cds linear mRNA GI: 32330979 292.
Influenza A virus 919 bp AF138712.1 (A/Taiwan/3513/96(H3N2)) matrix
protein M1 linear mRNA GI: 4928900 (M) mRNA, partial cds 293.
Influenza A virus 861 bp AF139931.1 (A/Taiwan/3513/97(H3N2)) H3
hemagglutinin linear mRNA GI: 4972926 (HA) mRNA, partial cds 294.
Influenza A virus 392 bp AF140621.1 (A/Taiwan/3513/97(H3N2)) N2
neuraminidase linear mRNA GI: 4972976 (NA) mRNA, partial cds 295.
Influenza A virus 791 bp AY604814.1 (A/Taiwan/3744/2002(H3N2))
hemagglutinin linear mRNA GI: 50727508 mRNA, partial cds 296.
Influenza A virus 940 bp AF362804.1 (A/human/Taiwan/3760/00(H3N2))
hemagglutinin linear mRNA GI: 15055108 (HA) mRNA, partial cds 297.
Influenza A virus (A/Taiwan/3896/2001 561 bp AY303747.1 (H1N1))
hemagglutinin (HA) mRNA, partial cds linear mRNA GI: 32330983 298.
Influenza A virus 791 bp AY604825.1 (A/Taiwan/4050/2003(H3N2))
hemagglutinin linear mRNA GI: 50727530 mRNA, partial cds 299.
Influenza A virus 791 bp AY604824.1 (A/Taiwan/4063/2003(H3N2))
hemagglutinin linear mRNA GI: 50727528 mRNA, partial cds 300.
Influenza A virus 750 bp EU068137.1 (A/Taiwan/41/2004(H3N2))
hemagglutinin (HA) linear mRNA GI: 158452147 mRNA, partial cds 301.
Influenza A virus 861 bp AF139939.1 (A/Taiwan/45/98(H3N2)) H3
hemagglutinin (HA) linear mRNA GI: 4972942 mRNA, partial cds 302.
Influenza A virus 392 bp AF140628.1 (A/Taiwan/45/98(H3N2)) N2
neuraminidase (NA) linear mRNA GI: 4972990 mRNA, partial cds 303.
Influenza A virus 875 bp AF138717.2 (A/Taiwan/45/98(H3N2)) matrix
protein M1 (M) linear mRNA GI: 4996883 mRNA, partial cds 304.
Influenza A virus 750 bp EU068114.1 (A/Taiwan/4548/2003(H3N2))
hemagglutinin linear mRNA GI: 158452101 (HA) mRNA, partial cds 305.
Influenza A virus 791 bp AY604813.1 (A/Taiwan/4673/2002(H3N2))
hemagglutinin linear mRNA GI: 50727506 mRNA, partial cds 306.
Influenza A virus 791 bp AY604812.1 (A/Taiwan/4680/2002(H3N2))
hemagglutinin linear mRNA GI: 50727504 mRNA, partial cds 307.
Influenza A virus 750 bp EU068136.1 (A/Taiwan/4735/2004(H3N2))
hemagglutinin linear mRNA GI: 158452145 (HA) mRNA, partial cds 308.
Influenza A virus 750 bp EU068142.1 (A/Taiwan/4829/2005(H3N2))
hemagglutinin linear mRNA GI: 158452157 (HA) mRNA, partial cds 309.
Influenza A virus 750 bp EU068130.1 (A/Taiwan/4836/2005(H3N2))
hemagglutinin linear mRNA GI: 158452133 (HA) mRNA, partial cds 310.
Influenza A virus 750 bp EU068143.1 (A/Taiwan/4865/2005(H3N2))
hemagglutinin linear mRNA GI: 158452159 (HA) mRNA, partial cds 311.
Influenza A virus 750 bp EU068121.1 (A/Taiwan/4883/2005(H3N2))
hemagglutinin linear mRNA GI: 158452115 (HA) mRNA, partial cds 312.
Influenza A virus 791 bp AY604809.1 (A/Taiwan/4938/2002(H3N2))
hemagglutinin linear mRNA GI: 50727498 mRNA, partial cds 313.
Influenza A virus 791 bp AY604815.1 (A/Taiwan/4954/2002(H3N2))
hemagglutinin linear mRNA GI: 50727510 mRNA, partial cds 314.
Influenza A virus 791 bp AY604810.1 (A/Taiwan/4963/2002(H3N2))
hemagglutinin linear mRNA GI: 50727500 mRNA, partial cds 315.
Influenza A virus 750 bp EU068122.1 (A/Taiwan/4987/2005(H3N2))
hemagglutinin linear mRNA GI: 158452117 (HA) mRNA, partial cds 316.
Influenza A virus 750 bp EU068127.1 (A/Taiwan/4990/2005(H3N2))
hemagglutinin linear mRNA GI: 158452127 (HA) mRNA, partial cds 317.
Influenza A virus 750 bp EU068118.1 (A/Taiwan/5/2003(H3N2))
hemagglutinin (HA) linear mRNA GI: 158452109 mRNA, partial cds 318.
Influenza A virus 791 bp AY604816.1 (A/Taiwan/5153/2002(H3N2))
hemagglutinin linear mRNA GI: 50727512 mRNA, partial cds 319.
Influenza A virus 750 bp EU068128.1 (A/Taiwan/5267/2005(H3N2))
hemagglutinin linear mRNA GI: 158452129 (HA) mRNA, partial cds 320.
Influenza A virus 750 bp EU068146.1 (A/Taiwan/556/2004(H3N2))
hemagglutinin (HA) linear mRNA GI: 158452165 mRNA, partial cds 321.
Influenza A virus 750 bp EU068126.1 (A/Taiwan/5694/2005(H3N2))
hemagglutinin linear mRNA GI: 158452125 (HA) mRNA, partial cds 322.
Influenza A virus 750 bp EU068147.1 (A/Taiwan/587/2004(H3N2))
hemagglutinin (HA) linear mRNA GI: 158452167 mRNA, partial cds 323.
Influenza A virus 750 bp EU068151.1 (A/Taiwan/592/2004(H3N2))
hemagglutinin (HA) linear mRNA GI: 158452175 mRNA, partial cds 324.
Influenza A virus 791 bp AY604829.1 (A/Taiwan/7099/2003(H3N2))
hemagglutinin linear mRNA GI: 50727538 mRNA, partial cds 325.
Influenza A virus 791 bp AY604830.1 (A/Taiwan/7100/2003(H3N2))
hemagglutinin linear mRNA GI: 50727540 mRNA, partial cds 326.
Influenza A virus 750 bp EU068150.1 (A/Taiwan/7196/2003(H3N2))
hemagglutinin linear mRNA GI: 158452173 (HA) mRNA, partial cds 327.
Influenza A virus 750 bp EU068135.1 (A/Taiwan/7568/2004(H3N2))
hemagglutinin linear mRNA GI: 158452143 (HA) mRNA, partial cds 328.
Influenza A virus 750 bp EU068144.1 (A/Taiwan/7601/2005(H3N2))
hemagglutinin linear mRNA GI: 158452161 (HA) mRNA, partial cds 329.
Influenza A virus 750 bp EU068124.1 (A/Taiwan/7681/2005(H3N2))
hemagglutinin linear mRNA GI: 158452121 (HA) mRNA, partial cds 330.
Influenza A virus 750 bp EU068123.1 (A/Taiwan/7702/2005(H3N2))
hemagglutinin linear mRNA GI: 158452119 (HA) mRNA, partial cds 331.
Influenza A virus 750 bp EU068129.1 (A/Taiwan/7873/2005(H3N2))
hemagglutinin linear mRNA GI: 158452131 (HA) mRNA, partial cds 332.
Influenza A virus 750 bp EU068115.1 (A/Taiwan/8/2003(H3N2))
hemagglutinin (HA) linear mRNA GI: 158452103 mRNA, partial cds 333.
Influenza A virus 750 bp EU068140.1 (A/Taiwan/93/2004(H3N2))
hemagglutinin (HA) linear mRNA GI: 158452153 mRNA, partial cds 334.
Influenza A virus 528 bp AY962016.1 (A/Taoyuan/108/02(H3N2))
hemagglutinin (HA) linear mRNA GI: 68138189 mRNA, partial cds 335.
Influenza A virus 754 bp AY973338.1 (A/Taoyuan/108/02(H3N2))
neuraminidase (NA) linear mRNA GI: 70673232 mRNA, partial cds 336.
Influenza A virus 882 bp AY986998.1 (A/Taoyuan/108/02(H3N2))
nucleoprotein (NP) linear mRNA GI: 70728123 mRNA, partial cds 337.
Influenza A virus 1,410 bp EU021285.1 (A/Thailand/CU124/2006(H3N2))
neuraminidase linear mRNA GI: 154224724 (NA) mRNA, complete cds
338. Influenza A virus 1,701 bp EU021284.1
(A/Thailand/CU124/2006(H3N2)) hemagglutinin linear mRNA GI:
154224795 (HA) mRNA, complete cds 339. Influenza A virus 1,410 bp
EU021275.1 (A/Thailand/CU228/2006(H3N2)) neuraminidase linear mRNA
GI: 154224714 (NA) mRNA, complete cds 340. Influenza A virus 1,701
bp EU021274.1 (A/Thailand/CU228/2006(H3N2)) hemagglutinin linear
mRNA GI: 154224785 (HA) mRNA, complete cds 341. Influenza A virus
1,347 bp EU021267.1 (A/Thailand/CU23/2006(H3N2)) neuraminidase
linear mRNA GI: 154224706 (NA) mRNA, partial cds 342. Influenza A
virus 1,701 bp EU021266.1 (A/Thailand/CU23/2006(H3N2))
hemagglutinin linear mRNA GI: 154224777 (HA) mRNA, complete cds
343. Influenza A virus 1,410 bp EU021283.1
(A/Thailand/CU231/2006(H3N2)) neuraminidase linear mRNA GI:
154224722 (NA) mRNA, complete cds 344. Influenza A virus 1,701 bp
EU021282.1 (A/Thailand/CU231/2006(H3N2)) hemagglutinin linear mRNA
GI: 154224793 (HA) mRNA, complete cds 345. Influenza A virus 1,410
bp EU021279.1 (A/Thailand/CU259/2006(H3N2)) neuraminidase linear
mRNA GI: 154224718 (NA) mRNA, complete cds 346. Influenza A virus
1,701 bp EU021278.1 (A/Thailand/CU259/2006(H3N2)) hemagglutinin
linear mRNA GI: 154224789 (HA) mRNA, complete cds
347. Influenza A virus 1,410 bp EU021281.1
(A/Thailand/CU260/2006(H3N2)) neuraminidase linear mRNA GI:
154224720 (NA) mRNA, complete cds 348. Influenza A virus 1,129 bp
EU021280.1 (A/Thailand/CU260/2006(H3N2)) hemagglutinin linear mRNA
GI: 154224791 (HA) mRNA, partial cds 349. Influenza A virus 1,410
bp EU021271.1 (A/Thailand/CU272/2007(H3N2)) neuraminidase linear
mRNA GI: 154224710 (NA) mRNA, complete cds 350. Influenza A virus
1,701 bp EU021270.1 (A/Thailand/CU272/2007(H3N2)) hemagglutinin
linear mRNA GI: 154224781 (HA) mRNA, complete cds 351. Influenza A
virus 1,410 bp EU021273.1 (A/Thailand/CU280/2007(H3N2))
neuraminidase linear mRNA GI: 154224712 (NA) mRNA, complete cds
352. Influenza A virus 1,701 bp EU021272.1
(A/Thailand/CU280/2007(H3N2)) hemagglutinin linear mRNA GI:
154224783 (HA) mRNA, complete cds 353. Influenza A virus 1,410 bp
EU021277.1 (A/Thailand/CU282/2007(H3N2)) neuraminidase linear mRNA
GI: 154224716 (NA) mRNA, complete cds 354. Influenza A virus 1,701
bp EU021276.1 (A/Thailand/CU282/2007(H3N2)) hemagglutinin linear
mRNA GI: 154224787 (HA) mRNA, complete cds 355. Influenza A virus
1,413 bp EU021265.1 (A/Thailand/CU32/2006(H1N1)) neuraminidase
linear mRNA GI: 154224704 (NA) mRNA, complete cds 361. Influenza A
virus 1,410 bp EU021269.1 (A/Thailand/CU46/2006(H3N2))
neuraminidase linear mRNA GI: 154224708 (NA) mRNA, complete cds
362. Influenza A virus 1,701 bp EU021268.1
(A/Thailand/CU46/2006(H3N2)) hemagglutinin linear mRNA GI:
154224779 (HA) mRNA, complete cds 377. Influenza A virus 987 bp
U77837.1 (A/Tottori/849AM1AL3/1994(H3N2)) linear mRNA GI: 2992515
hemagglutinin (HA) mRNA, partial cds 378. Influenza A virus 987 bp
U77833.1 (A/Tottori/849AM2/1994(H3N2)) hemagglutinin linear mRNA
GI: 2992507 (HA) mRNA, partial cds 379. Influenza A virus 987 bp
U77839.1 (A/Tottori/849AM2AL3/1994(H3N2)) linear mRNA GI: 2992519
hemagglutinin (HA) mRNA, partial cds 380. Influenza A virus 987 bp
U77835.1 (A/Tottori/849AM4/1994(H3N2)) hemagglutinin linear mRNA
GI: 2992511 (HA) mRNA, partial cds 382. Influenza A virus 987 bp
U77834.1 (A/Tottori/872AM2/1994(H3N2)) hemagglutinin linear mRNA
GI: 2992509 (HA) mRNA, partial cds 383. Influenza A virus 987 bp
U77840.1 (A/Tottori/872AM2AL3/1994(H3N2)) linear mRNA GI: 2992521
hemagglutinin (HA) mRNA, partial cds 384. Influenza A virus 987 bp
U77836.1 (A/Tottori/872AM4/1994(H3N2)) hemagglutinin linear mRNA
GI: 2992513 (HA) mRNA, partial cds 385. Influenza A virus 987 bp
U77832.1 (A/Tottori/872K4/1994(H3N2)) hemagglutinin linear mRNA GI:
2992505 (HA) mRNA, partial cds 386. Influenza A virus (A/United 987
bp AF501529.1 Kingdom/26554/99(H3N2)) hemagglutinin (HA) linear
mRNA GI: 21314314 mRNA, partial cds 387. Influenza A virus
(A/United 987 bp AF501527.1 Kingdom/34300/99(H3N2)) hemagglutinin
(HA) linear mRNA GI: 21314310 mRNA, partial cds 388. Influenza A
virus 987 bp AF501533.1 (A/Utah/20997/99(H3N2)) hemagglutinin (HA)
linear mRNA GI: 21314322 mRNA, partial cds 389. Influenza A virus
(A/Victoria/3/75) 1,565 bp AF072545.1 segment 5 nucleoprotein mRNA,
complete cds linear mRNA GI: 4218933 390. Influenza A virus 1,762
bp AF017270.2 (A/Vienna/47/96M(H3N2)) hemagglutinin (HA) linear
mRNA GI: 14286338 mRNA, complete cds 391. Influenza A virus 1,762
bp AF017272.2 (A/Vienna/47/96V(H3N2)) hemagglutinin (HA) linear
mRNA GI: 15004991 mRNA, complete cds 392. Influenza A virus 1,069
bp AF017271.1 (A/Vienna/81/96V(H3N2)) hemagglutinin (HA) linear
mRNA GI: 2407251 mRNA, partial cds 393. Influenza A virus 987 bp
AF501532.1 (A/Virginia/21712/99(H3N2)) hemagglutinin linear mRNA
GI: 21314320 (HA) mRNA, partial cds 394. Influenza A virus 987 bp
AF501515.1 (A/Virginia/21716/99(H3N2)) hemagglutinin linear mRNA
GI: 21314286 (HA) mRNA, partial cds 395. Influenza A virus 987 bp
AF501530.1 (A/Virginia/21735/99(H3N2)) hemagglutinin linear mRNA
GI: 21314316 (HA) mRNA, partial cds 396. Influenza A virus 987 bp
AF501524.1 (A/Virginia/21743/99(H3N2)) hemagglutinin linear mRNA
GI: 21314304 (HA) mRNA, partial cds 397. Influenza A virus 987 bp
AF501519.1 (A/Virginia/21754/99(H3N2)) hemagglutinin linear mRNA
GI: 21314294 (HA) mRNA, partial cds 398. Influenza A virus 987 bp
AF501523.1 (A/Virginia/21799/99(H3N2)) hemagglutinin linear mRNA
GI: 21314302 (HA) mRNA, partial cds 399. Influenza A virus 987 bp
AF501525.1 (A/Virginia/21817/99(H3N2)) hemagglutinin linear mRNA
GI: 21314306 (HA) mRNA, partial cds 400. Influenza A virus 987 bp
AF501520.1 (A/Virginia/21822/99(H3N2)) hemagglutinin linear mRNA
GI: 21314296 (HA) mRNA, partial cds 401. Influenza A virus 987 bp
AF501528.1 (A/Virginia/21828/99(H3N2)) hemagglutinin linear mRNA
GI: 21314312 (HA) mRNA, partial cds 402. Influenza A virus 987 bp
AF501517.1 (A/Virginia/21833/99(H3N2)) hemagglutinin linear mRNA
GI: 21314290 (HA) mRNA, partial cds 403. Influenza A virus 987 bp
AF501522.1 (A/Virginia/21845/99(H3N2)) hemagglutinin linear mRNA
GI: 21314300 (HA) mRNA, partial cds 404. Influenza A virus 987 bp
AF501535.1 (A/Virginia/21847/99(H3N2)) hemagglutinin linear mRNA
GI: 21314326 (HA) mRNA, partial cds 405. Influenza A virus 987 bp
AF501521.1 (A/Virginia/G1/99(H3N2)) hemagglutinin (HA) linear mRNA
GI: 21314298 mRNA, partial cds 406. Influenza A virus 755 bp
AY973339.1 (A/Yilan/508/03(H3N2)) neuraminidase (NA) linear mRNA
GI: 70673234 mRNA, partial cds 407. Influenza A virus 882 bp
AY986999.1 (A/Yilan/508/03(H3N2)) nucleoprotein (NP) linear mRNA
GI: 70728125 mRNA, partial cds 408. Influenza A virus 740 bp
AY962015.1 (A/Yilan/513/03(H3N2)) hemagglutinin (HA) linear mRNA
GI: 68138187 mRNA, partial cds 409. Influenza A virus 396 bp
AY973340.1 (A/Yilan/513/03(H3N2)) neuraminidase (NA) linear mRNA
GI: 70673236 mRNA, partial cds 410. Influenza A virus 882 bp
AY987000.1 (A/Yilan/513/03(H3N2)) nucleoprotein (NP) linear mRNA
GI: 70728127 mRNA, partial cds 411. Influenza A virus 511 bp
AY962010.1 (A/Yilan/515/03(H3N2)) hemagglutinin (HA) linear mRNA
GI: 68138177 mRNA, partial cds 412. Influenza A virus 394 bp
AY973341.1 (A/Yilan/515/03(H3N2)) neuraminidase (NA) linear mRNA
GI: 70673238 mRNA, partial cds 413. Influenza A virus 882 bp
AY987001.1 (A/Yilan/516/03(H3N2)) nucleoprotein (NP) linear mRNA
GI: 70728129 mRNA, partial cds 414. Influenza A virus 530 bp
AY962006.1 (A/Yilan/518/03(H3N2)) hemagglutinin (HA) linear mRNA
GI: 68138169 mRNA, partial cds 415. Influenza A virus 397 bp
AY973342.1 (A/Yilan/518/03(H3N2)) neuraminidase (NA) linear mRNA
GI: 70673240 mRNA, partial cds 416. Influenza A virus 882 bp
AY987002.1 (A/Yilan/518/03(H3N2)) nucleoprotein (NP) linear mRNA
GI: 70728131 mRNA, partial cds 417. Influenza A virus 777 bp
AY962002.1 (A/Yilan/538/04(H3N2)) hemagglutinin (HA) linear mRNA
GI: 68138161 mRNA, partial cds 418. Influenza A virus 783 bp
AY973343.1 (A/Yilan/538/04(H3N2)) neuraminidase (NA) linear mRNA
GI: 70673242 mRNA, partial cds 419. Influenza A virus 882 bp
AY987003.1 (A/Yilan/538/04(H3N2)) nucleoprotein (NP) linear mRNA
GI: 70728133 mRNA, partial cds 420. Influenza A virus 788 bp
AY962003.1 (A/Yilan/549/04(H3N2)) hemagglutinin (HA) linear mRNA
GI: 68138163 mRNA, partial cds 421. Influenza A virus 779 bp
AY973344.1 (A/Yilan/549/04(H3N2)) neuraminidase (NA) linear mRNA
GI: 70673244 mRNA, partial cds 422. Influenza A virus 882 bp
AY987004.1 (A/Yilan/549/04(H3N2)) nucleoprotein (NP) linear mRNA
GI: 70728135 mRNA, partial cds 423. Influenza A virus 776 bp
AY962013.1 (A/Yilan/557/04(H3N2)) hemagglutinin (HA) linear mRNA
GI: 68138183 mRNA, partial cds 424. Influenza A virus 796 bp
AY973345.1 (A/Yilan/557/04(H3N2)) neuraminidase (NA) linear mRNA
GI: 70673246 mRNA, partial cds 425. Influenza A virus 882 bp
AY987005.1 (A/Yilan/557/04(H3N2)) nucleoprotein (NP) linear mRNA
GI: 70728137 mRNA, partial cds 426. Influenza A virus 753 bp
AY962014.1 (A/Yilan/566/04(H3N2)) hemagglutinin (HA) linear mRNA
GI: 68138185 mRNA, partial cds 427. Influenza A virus 808 bp
AY973346.1 (A/Yilan/566/04(H3N2)) neuraminidase (NA) linear mRNA
GI: 70673248 mRNA, partial cds 428. Influenza A virus 882 bp
AY987006.1 (A/Yilan/566/04(H3N2)) nucleoprotein (NP) linear mRNA
GI: 70728139 mRNA, partial cds 429. Influenza A virus 987 bp
AY138513.1 (A/zhejiang/06/99(H3N2)) hemagglutinin (HA) linear mRNA
GI: 24895131 mRNA, partial cds 430. Influenza A virus 987 bp
AY138515.1 (A/zhejiang/10/98(H3N2)) hemagglutinin (HA) linear mRNA
GI: 24895149 mRNA, partial cds 431. Influenza A virus 987 bp
AY138516.1 (A/zhejiang/11/2002(H3N2)) hemagglutinin linear mRNA GI:
24895159 (HA) mRNA, partial cds 432. Influenza A virus 987 bp
AY138514.1 (A/zhejiang/12/99(H3N2)) hemagglutinin-like linear mRNA
GI: 24895141 (HA) mRNA, partial sequence 433. Influenza A virus 987
bp AY138519.1 (A/zhejiang/8/2002(H3N2)) hemagglutinin (HA) linear
mRNA GI: 24895188 mRNA, partial cds 434. Influenza A virus H3N2
strain 840 bp U65670.1 A/Akita/1/94 nonstructural protein 1 and
linear mRNA GI: 3929405 nonstructural protein 2 mRNAs, complete cds
435. Influenza A virus H3N2 strain 840 bp U65671.1 A/Akita/1/95
nonstructural protein 1 and linear mRNA GI: 3929408 nonstructural
protein 2 mRNAs, complete cds 436. Influenza A virus H3N2 strain
840 bp U65673.1 A/Shiga/20/95 nonstructural protein 1 and linear
mRNA GI: 3929411 nonstructural protein 2 mRNAs, complete cds 437.
Influenza A virus H3N2 strain 840 bp U65674.1 A/Miyagi/69/95
nonstructural protein 1 and linear mRNA GI: 3929414 nonstructural
protein 2 mRNAs, complete cds 438. Influenza A virus H3N2 strain
840 bp U65672.1 A/Hebei/19/95 nonstructural protein 1 and linear
mRNA GI: 6468319 nonstructural protein 2 mRNAs, complete cds
A/Aichi/69/1994(H3N2) haemagglutinin U48446.1 A/Bangkok/1/1979
(H3N2) hemagglutinin (HA) AF201843.1 A/Beijing/353/89(H3)
hemagglutinin (HA) U97740.1 A/Beijing/353/1989(H3N2) haemagglutinin
Z46391.1 A/chicken/Singapore/2002(H3N2) M2 protein EU014143.1
A/Christ Hospital/231/82(H3N2)) U77830.1 hemagglutinin (HA)
A/duck/Eastern China/36/2002(H3N2) segment 6 EU429701.1
neuraminidase (NA) A/duck/Eastern China/160/2003(H3N2) segment
EU429732.1 6 neuraminidase (NA) A/duck/Eastern China/848/2003(H3N2)
segment EU429721.1 6 neuraminidase (NA) A/duck/Eastern
China/770/2003(H3N2) segment EU429736.1 6 neuraminidase (NA)
A/duck/Eastern China/855/2003(H3N2) segment EU429737.1 6
neuraminidase (NA) A/duck/Eastern China/875/2003(H3N2) segment
EU429738.1 6 neuraminidase (NA) A/duck/Eastern China/901/2003(H3N2)
segment EU429739.1 6 neuraminidase (NA) A/duck/Eastern
China/866/2003(H3N2) segment EU429756.1 6 neuraminidase (NA)
A/duck/Eastern China/857/2003(H3N2) segment EU429761.1 6
neuraminidase (NA) A/duck/Eastern China/852/2003(H3N2) segment
EU429767.1 6 neuraminidase (NA) A/duck/Eastern China/838/2003(H3N2)
segment EU429720.1 6 neuraminidase (NA) A/duck/Eastern
China/6/2004(H3N2) segment 6 EU429745.1 neuraminidase (NA)
A/duck/Eastern China/03/2005(H3N2) segment 6 EU429781.1
neuraminidase (NA) A/duck/Eastern China/02/2006(H3N2) segment 6
EU429769.1 neuraminidase (NA) A/duck/Eastern China/04/2006(H3N2)
segment 6 EU429770.1
neuraminidase (NA) A/duck/Eastern China/21/2006(H3N2) segment 6
EU429771.1 neuraminidase (NA) A/duck/Eastern China/23/2006(H3N2)
segment 6 EU429772.1 neuraminidase (NA) A/duck/Eastern
China/31/2006(H3N2) segment 6 EU429773.1 neuraminidase (NA)
A/duck/Eastern China/35/2006(H3N2) segment 6 EU429768.1
neuraminidase (NA) A/duck/Eastern China/42/2006(H3N2) segment 6
EU429774.1 neuraminidase (NA) A/duck/Eastern China/53/2006(H3N2)
segment 6 EU429775.1 neuraminidase (NA) A/duck/Eastern
China/60/2006(H3N2) segment 6 EU429776.1 neuraminidase (NA)
A/duck/Eastern China/62/2006(H3N2) segment 6 EU429784.1
neuraminidase (NA) A/duck/Eastern China/63/2006(H3N2) segment 6
EU429777.1 neuraminidase (NA) A/duck/Eastern China/142/2006(H3N2)
segment EU429742.1 6 neuraminidase (NA) A/Dunedin/4/1973 (H3N2)
hemagglutinin (HA) AF201842.1
TABLE-US-00013 TABLE 9 Influenza H5N1 Antigens GenBank/GI
Strain/Protein Length Accession No. 1. Influenza A virus
(A/chicken/Burkina 827 bp AM503036.1 Faso/01.03/2006(H5N1)) mRNA
for non- linear mRNA GI:147846308 structural protein (ns gene) 2.
Influenza A virus (A/chicken/Burkina 990 bp AM503007.1
Faso/13.1/2006(H5N1)) partial mRNA for linear mRNA GI:147846250
matrix protein 1 (m1 gene) 3. Influenza A virus (A/chicken/Burkina
1,529 bp AM503029.1 Faso/13.1/2006(H5N1)) mRNA for nucleoprotein
linear mRNA GI:147846294 (np gene) 4. Influenza A virus
(A/chicken/Burkina 827 bp AM503037.1 Faso/13.1/2006(H5N1)) mRNA for
non- linear mRNA GI:147846310 structural protein (ns gene) 5.
Influenza A virus (A/chicken/Burkina 2,169 bp AM503046.1
Faso/13.1/2006(H5N1)) partial mRNA for linear mRNA GI:147846328
polymerase (pa gene) 6. Influenza A virus (A/chicken/Burkina 2,259
bp AM503056.1 Faso/13.1/2006(H5N1)) partial mRNA for linear mRNA
GI:147846348 polymerase basic protein 1 (pb1 gene) 7. Influenza A
virus (A/chicken/Burkina 2,315 bp AM503067.1 Faso/13.1/2006(H5N1))
partial mRNA for linear mRNA GI:147846859 polymerase basic protein
2 (pb2 gene) 8. Influenza A virus 1,736 bp DQ023145.1
(A/chicken/China/1/02(H5N1)) hemagglutinin linear mRNA GI:66775624
(HA) mRNA, complete cds 9. Influenza A virus 1,509 bp DQ023146.1
(A/chicken/China/1/02(H5N1)) nucleoprotein linear mRNA GI:66775626
(NP) mRNA, complete cds 10. Influenza A virus 1,379 bp DQ023147.1
(A/chicken/China/1/02(H5N1)) neuraminidase linear mRNA GI:66775628
(NA) mRNA, complete cds 11. Influenza A virus 999 bp DQ650660.1
(A/chicken/Crimea/04/2005(H5N1)) matrix linear mRNA GI:109692767
protein (M) mRNA, complete cds 12. Influenza A virus 850 bp
DQ650662.1 (A/chicken/Crimea/04/2005(H5N1)) linear mRNA
GI:109692771 nonstructural protein (NS) mRNA, complete cds 13.
Influenza A virus 994 bp DQ650664.1
(A/chicken/Crimea/08/2005(H5N1)) matrix linear mRNA GI:109692775
protein (M) mRNA, complete cds 14. Influenza A virus 1,532 bp
DQ650666.1 (A/chicken/Crimea/08/2005(H5N1)) linear mRNA
GI:109692779 nucleoprotein (NP) mRNA, complete cds 15. Influenza A
virus 850 bp DQ65066 7.1 (A/chicken/Crimea/08/2005(H5N1)) linear
mRNA GI:109692781 nonstructural protein (NS) mRNA, complete cds 16.
Influenza A virus 2,208 bp DQ650668.1
(A/chicken/Crimea/08/2005(H5N1)) polymerase linear mRNA
GI:109692783 acidic protein (PA) mRNA, complete cds 17. Influenza A
virus 2,305 bp DQ650670.1 (A/chicken/Crimea/08/2005(H5N1))
polymerase linear mRNA GI:109692787 basic protein 2 (PB2) mRNA,
complete cds 18. Influenza A virus 1,015 bp DQ676838.1
(A/chicken/Dovolnoe/03/2005(H5N1)) linear mRNA GI:108782527
hemagglutinin (HA) mRNA, partial cds 20. Influenza A virus 2,341 bp
DQ366327.1 (A/chicken/Guangxi/12/2004(H5N1)) polymerase linear mRNA
GI:86753731 PB2 mRNA, complete cds 21. Influenza A virus 2,341 bp
DQ366328.1 (A/chicken/Guangxi/12/2004(H5N1)) polymerase linear mRNA
GI:86753741 PB1 mRNA, complete cds 22. Influenza A virus 2,233 bp
DQ366329.1 (A/chicken/Guangxi/12/2004(H5N1)) PA protein linear mRNA
GI:86753751 mRNA, complete cds 23. Influenza A virus 1,565 bp
DQ366331.1 (A/chicken/Guangxi/12/2004(H5N1)) linear mRNA
GI:86753771 nucleocapsid mRNA, complete cds 24. Influenza A virus
1,027 bp DQ366333.1 (A/chicken/Guangxi/12/2004(H5N1)) matrix linear
mRNA GI:86753791 protein mRNA, complete cds 25. Influenza A virus
(A/chicken/Hong 1,718 bp AF057291.1 Kong/258/97(H5N1))
hemagglutinin mRNA, linear mRNA GI:3068720 complete cds 26.
Influenza A virus (A/chicken/Hong 1,318 bp AF057292.1
Kong/258/97(H5N1)) neuraminidase mRNA, linear mRNA GI:3068722
partial cds 27. Influenza A virus (A/chicken/Hong 1,508 bp
AF057293.1 Kong/258/97(H5N1)) nucleoprotein mRNA, linear mRNA
GI:3068724 complete cds 28. Influenza A virus (A/Chicken/Hong 1,726
bp AF082034.1 Kong/728/97 (H5N1)) hemagglutinin H5 mRNA, linear
mRNA GI:4240435 complete cds 29. Influenza A virus (A/Chicken/Hong
1,726 bp AF082035.1 Kong/786/97 (H5N1)) hemagglutinin H5 mRNA,
linear mRNA GI:4240437 complete cds 30. Influenza A virus
(A/chicken/Hong 1,726 bp AF082036.1 Kong/915/97(H5N1))
hemagglutinin H5 mRNA, linear mRNA GI:4240439 complete cds 31.
Influenza A virus (A/chicken/Hong 1,091 bp AF082037.1 Kong/990/97
(H5N1)) hemagglutinin H5 mRNA, linear mRNA GI:4240441 partial cds
32. Influenza A virus 1,002 bp DQ676835.1
(A/chicken/Krasnodar/01/2006(H5N1)) matrix linear mRNA GI:108782521
protein 1 (M) mRNA, complete cds 33. Influenza A virus 850 bp
DQ676837.1 (A/chicken/Krasnodar/01/2006(H5N1)) linear mRNA
GI:108782525 nonstructural protein (NS) mRNA, complete cds 34.
Influenza A virus 1,754 bp DQ449632.1
(A/chicken/Kurgan/05/2005(H5N1)) linear mRNA GI:90289625
hemagglutinin (HA) mRNA, complete cds 35. Influenza A virus 1,002
bp DQ449633.1 (A/chicken/Kurgan/05/2005(H5N1)) matrix linear mRNA
GI:90289627 protein 1 (M) mRNA, complete cds 36. Influenza A virus
1,373 bp DQ449634.1 (A/chicken/Kurgan/05/2005(H5N1)) linear mRNA
GI:90289629 neuraminidase (NA) mRNA, complete cds 37. Influenza A
virus 1,540 bp DQ449635.1 (A/chicken/Kurgan/05/2005(H5N1)) linear
mRNA GI:90289631 nucleoprotein (NP) mRNA, complete cds 38.
Influenza A virus 850 bp DQ449636.1
(A/chicken/Kurgan/05/2005(H5N1)) linear mRNA GI:90289633
nonstructural protein (NS) mRNA, complete cds 39. Influenza A virus
2,208 bp DQ449637.1 (A/chicken/Kurgan/05/2005(H5N1)) polymerase
linear mRNA GI:90289635 acidic protein (PA) mRNA, complete cds 40.
Influenza A virus 2,316 bp DQ449638.1
(A/chicken/Kurgan/05/2005(H5N1)) polymerase linear mRNA GI:90289637
basic protein 1 (PB1) mRNA, complete cds 41. Influenza A virus
2,316 bp DQ449639.1 (A/chicken/Kurgan/05/2005(H5N1)) polymerase
linear mRNA GI:90289646 basic protein 2 (PB2) mRNA, complete cds
42. Influenza A virus 184 bp EU447276.1
(A/chicken/Lobzenko/01/2008(H5N1)) linear mRNA GI:168998217
hemagglutinin (HA) mRNA, partial cds 43. Influenza A virus 1,002 bp
DQ676831.1 (A/chicken/Mahachkala/05/2006(H5N1)) matrix linear mRNA
GI:108782513 protein 1 (M) mRNA, complete cds 44. Influenza A virus
850 bp DQ676833.1 (A/chicken/Mahachkala/05/2006(H5N1)) linear mRNA
GI:108782517 nonstructural protein (NS) mRNA, complete cds 45.
Influenza A virus 1,531 bp AM503030.1
(A/chicken/Nigeria/AB13/2006(H5N1)) mRNA for linear mRNA
GI:147846296 nucleoprotein (np gene) 46. Influenza A virus 827 bp
AM503040.1 (A/chicken/Nigeria/AB13/2006(H5N1)) mRNA for linear mRNA
GI:147846316 non-structural protein (ns gene) 47. Influenza A virus
2,169 bp AM503051.1 (A/chicken/Nigeria/AB13/2006(H5N1)) partial
linear mRNA GI:147846338 mRNA for polymerase (pa gene) 48.
Influenza A virus 2,259 bp AM503060.1
(A/chicken/Nigeria/AB13/2006(H5N1)) partial linear mRNA
GI:147846845 mRNA for polymerase basic protein 1 (pb1 gene) 49.
Influenza A virus 2,315 bp AM503071.1
(A/chicken/Nigeria/AB13/2006(H5N1)) partial linear mRNA
GI:147846867 mRNA for polymerase basic protein 2 (pb2 gene) 70.
Influenza A virus (A/chicken/Hong 1,055 bp DQ250158.1
Kong/3123.1/2002(H5N1)) neuraminidase (NA) linear mRNA GI:82412012
mRNA, partial cds 75. Influenza A virus 1,754 bp DQ676834.1
(A/chicken/Krasnodar/01/2006(H5N1)) linear mRNA GI:108782519
hemagglutinin (HA) mRNA, complete cds 78. Influenza A virus 1,373
bp DQ676836.2 (A/chicken/Krasnodar/01/2006(H5N1)) linear mRNA
GI:115520953 neuraminidase (NA) mRNA, complete cds 91. Influenza A
virus 184 bp EU447276.1 (A/chicken/Lobzenko/01/2008(H5N1)) linear
mRNA GI:168998217 hemagglutinin (HA) mRNA, partial cds 92.
Influenza A virus 1,683 bp DQ676830.1
(A/chicken/Mahachkala/05/2006(H5N1)) linear mRNA GI:108782511
hemagglutinin (HA) mRNA, complete cds 94. Influenza A virus 1,373
bp DQ676832.1 (A/chicken/Mahachkala/05/2006(H5N1)) linear mRNA
GI:108782515 neuraminidase (NA) mRNA, complete cds 96. Influenza A
virus 433 bp DQ096567.1 (A/chicken/Malaysia/01/2004(H5N1)) linear
mRNA GI:69145364 neuramidase (NA) mRNA, partial cds 97. Influenza A
virus 1,722 bp AM503002.1 (A/chicken/Nigeria/AB13/2006(H5N1))
partial linear mRNA GI:147846240 mRNA for hemagglutinin (ha gene)
98. Influenza A virus 1,329 bp AM503020.1
(A/chicken/Nigeria/AB13/2006(H5N1)) partial linear mRNA
GI:147846276 mRNA for neuraminidase (na gene) 105. Influenza A
virus 1,719 bp AM503003.1 (A/chicken/Nigeria/AB14/2006(H5N1))
partial linear mRNA GI:147846242 mRNA for hemagglutinin (ha gene)
106. Influenza A virus 953 bp AM503011.1
(A/chicken/Nigeria/AB14/2006(H5N1)) partial linear mRNA
GI:147846258 mRNA for matrix protein 1 (m1 gene) 107. Influenza A
virus 1,343 bp AM503025.1 (A/chicken/Nigeria/AB14/2006(H5N1))
partial linear mRNA GI:147846286 mRNA for neuraminidase (na gene)
108. Influenza A virus 827 bp AM503041.1
(A/chicken/Nigeria/AB14/2006(H5N1)) mRNA for linear mRNA
GI:147846318 non-structural protein (ns gene) 109. Influenza A
virus 2,169 bp AM503054.1 (A/chicken/Nigeria/AB14/2006(H5N1))
partial linear mRNA GI:147846344 mRNA for polymerase (pa gene) 110.
Influenza A virus 2,259 bp AM503061.1
(A/chicken/Nigeria/AB14/2006(H5N1)) partial linear mRNA
GI:147846847 mRNA for polymerase basic protein 1 (pb1 gene) 111.
Influenza A virus 2,315 bp AM503072.1
(A/chicken/Nigeria/AB14/2006(H5N1)) partial linear mRNA
GI:147846869 mRNA for polymerase basic protein 2 (pb2 gene) 112.
Influenza A virus 1,548 bp AM503034.2
(A/chicken/Nigeria/AB14/2006(H5N1)) mRNA for linear mRNA
GI:149773117 nucleoprotein (np gene) 113. Influenza A virus 1,342
bp AM503022.1 (A/chicken/Nigeria/BA210/2006(H5N1)) partial linear
mRNA GI:147846280 mRNA for neuraminidase (na gene) 114. Influenza A
virus 1,321 bp AM503021.1 (A/chicken/Nigeria/BA211/2006(H5N1))
partial linear mRNA GI:147846278 mRNA for neuraminidase (na gene)
115. Influenza A virus 2,315 bp AM503073.1
(A/chicken/Nigeria/BA211/2006(H5N1)) partial linear mRNA
GI:147846871 mRNA for polymerase basic protein 2 (pb2 gene) 116.
Influenza A virus 1,717 bp AM503004.1
(A/chicken/Nigeria/FA4/2006(H5N1)) partial linear mRNA GI:147846244
raRNA for hemagglutinin (ha gene) 117. Influenza A virus 989 bp
AM503013.1 (A/chicken/Nigeria/FA4/2006(H5N1)) partial linear mRNA
GI:147846262 mRNA for matrix protein 1 (m1 gene) 118. Influenza A
virus 1,321 bp AM503026.1 (A/chicken/Nigeria/FA4/2006(H5N1))
partial linear mRNA GI:147846288 mRNA for neuraminidase (na gene)
119. Influenza A virus 827 bp AM503045.1
(A/chicken/Nigeria/FA4/2006(H5N1)) mRNA for linear mRNA
GI:147846326 non-structural protein (ns gene) 120. Influenza A
virus 2,169 bp AM503055.1 (A/chicken/Nigeria/FA4/2006(H5N1))
partial linear mRNA GI:147846346 mRNA for polymerase (pa gene) 121.
Influenza A virus 2,259 bp AM503064.1
(A/chicken/Nigeria/FA4/2006(H5N1)) partial linear mRNA GI:147846853
mRNA for polymerase basic protein 1 (pb1 gene) 122. Influenza A
virus 2,224 bp AM503074.1 (A/chicken/Nigeria/FA4/2006(H5N1))
partial linear mRNA GI:147846873 mRNA for polymerase basic protein
2 (pb2 gene) 123. Influenza A virus 1,717 bp AM502998.1
(A/chicken/Nigeria/FA6/2006(H5N1)) partial linear mRNA GI:147846232
mRNA for hemagglutinin (ha gene) 124. Influenza A virus 965 bp
AM503012.1 (A/chicken/Nigeria/FA6/2006(H5N1)) partial linear mRNA
GI:147846260 mRNA for matrix protein 1 (m1 gene) 125. Influenza A
virus 1,327 bp AM503023.1 (A/chicken/Nigeria/FA6/2006(H5N1))
partial linear mRNA GI:147846282 mRNA for neuraminidase (na gene)
126. Influenza A virus 1,543 bp AM503031.1
(A/chicken/Nigeria/FA6/2006(H5N1)) mRNA for linear mRNA
GI:147846298 nucleoprotein (np gene) 127. Influenza A virus 2,169
bp AM503052.1 (A/chicken/Nigeria/FA6/2006(H5N1)) partial linear
mRNA GI:147846340 mRNA for polymerase (pa gene) 128. Influenza A
virus 2,259 bp AM503063.1 (A/chicken/Nigeria/FA6/2006(H5N1))
partial linear mRNA GI:147846851 mRNA for polymerase basic protein
1 (pb1 gene) 129. Influenza A virus 1,710 bp AM502999.1
(A/chicken/Nigeria/FA7/2006(H5N1)) partial linear mRNA GI:147846234
mRNA for hemagglutinin (ha gene) 130. Influenza A virus 1,001 bp
AM503009.1 (A/chicken/Nigeria/FA7/2006(H5N1)) partial linear mRNA
GI:147846254 mRNA for matrix protein 1 (m1 gene) 131. Influenza A
virus 1,331 bp AM503018.1 (A/chicken/Nigeria/FA7/2006(H5N1))
partial linear mRNA GI:147846272 mRNA for neuraminidase (na gene)
132. Influenza A virus 1,531 bp AM503035.1
(A/chicken/Nigeria/FA7/2006(H5N1)) mRNA for linear mRNA
GI:147846306 nucleoprotein (np gene) 133. Influenza A virus 827 bp
AM503042.1 (A/chicken/Nigeria/FA7/2006(H5N1)) mRNA for linear mRNA
GI:147846320 non-structural protein (ns gene) 134. Influenza A
virus 2,169 bp AM503049.1 (A/chicken/Nigeria/FA7/2006(H5N1))
partial linear mRNA GI:147846334 mRNA for polymerase (pa gene) 135.
Influenza A virus 2,259 bp AM503057.1
(A/chicken/Nigeria/FA7/2006(H5N1)) partial linear mRNA GI:147846350
raRNA for polymerase basic protein 1 (pb1 gene) 136. Influenza A
virus 2,315 bp AM503068.1 (A/chicken/Nigeria/FA7/2006(H5N1))
partial linear mRNA GI:147846861 mRNA for polymerase basic protein
2 (pb2 gene) 137. Influenza A virus 1,714 bp AM503001.1
(A/chicken/Nigeria/IF10/2006(H5N1)) partial linear mRNA
GI:147846238 mRNA for hemagglutinin (ha gene) 138. Influenza A
virus 990 bp AM503010.1 (A/chicken/Nigeria/IF10/2006(H5N1)) partial
linear mRNA GI:147846256 mRNA for matrix protein 1 (m1 gene) 139.
Influenza A virus 1,332 bp AM503024.1
(A/chicken/Nigeria/IF10/2006(H5N1)) partial linear mRNA
GI:147846284 mRNA for neuraminidase (na gene) 140. Influenza A
virus 827 bp AM503044.1 (A/chicken/Nigeria/IF10/2006(H5N1)) mRNA
for linear mRNA GI:147846324 non-structural protein (ns gene) 141.
Influenza A virus 2,169 bp AM503053.1
(A/chicken/Nigeria/IF10/2006(H5N1)) partial linear mRNA
GI:147846342 mRNA for polymerase (pa gene) 142. Influenza A virus
2,259 bp AM503059.1 (A/chicken/Nigeria/IF10/2006(H5N1)) partial
linear mRNA GI:147846843 mRNA for polymerase basic protein 1 (pb1
gene) 143. Influenza A virus 2,315 bp AM503069.1
(A/chicken/Nigeria/IF10/2006(H5N1)) partial linear mRNA
GI:147846863 mRNA for polymerase basic protein 2 (pb2 gene) 144.
Influenza A virus 1,550 bp AM503033.2
(A/chicken/Nigeria/IF10/2006(H5N1)) mRNA for linear mRNA
GI:149773115 nucleoprotein (np gene) 145. Influenza A virus 1,719
bp AM503005.1 (A/chicken/Nigeria/OD8/2006(H5N1)) partial linear
mRNA GI:147846246 mRNA for hemagglutinin (ha gene) 146. Influenza A
virus 989 bp AM503014.1 (A/chicken/Nigeria/OD8/2006(H5N1)) partial
linear mRNA GI:147846264 mRNA for matrix protein 1 (m1 gene) 147.
Influenza A virus 1,720 bp AM503000.1
(A/chicken/Nigeria/OD9/2006(H5N1)) partial linear mRNA GI:147846236
mRNA for hemagglutinin (ha gene) 148. Influenza A virus 988 bp
AM503015.1 (A/chicken/Nigeria/OD9/2006(H5N1)) partial linear mRNA
GI:147846266 mRNA for matrix protein 1 (m1 gene) 149. Influenza A
virus 1,330 bp AM503019.1 (A/chicken/Nigeria/OD9/2006(H5N1))
partial linear mRNA GI:147846274 mRNA for neuraminidase (na gene)
150. Influenza A virus 1,531 bp AM503032.1
(A/chicken/Nigeria/OD9/2006(H5N1)) mRNA for linear mRNA
GI:147846300 nucleoprotein (np gene) 151. Influenza A virus 827 bp
AM503043.1 (A/chicken/Nigeria/OD9/2006(H5N1)) mRNA for linear mRNA
GI:147846322 non-structural protein (ns gene) 152. Influenza A
virus 2,169 bp AM503050.1 (A/chicken/Nigeria/OD9/2006(H5N1))
partial linear mRNA GI:147846336 mRNA for polymerase (pa gene) 153.
Influenza A virus 2,259 bp AM503058.1
(A/chicken/Nigeria/OD9/2006(H5N1)) partial linear mRNA GI:147846841
raRNA for polymerase basic protein 1 (pb1 gene) 154. Influenza A
virus 2,315 bp AM503070.1 (A/chicken/Nigeria/OD9/2006(H5N1))
partial linear mRNA GI:147846865 mRNA for polymerase basic protein
2 (pb2 gene) 155. Influenza A virus 1,768 bp X07869.1
(A/chicken/Scotland/59(H5N1)) mRNA for linear mRNA GI:60482
haemaggiutinin precursor 156. Influenza A virus 1,445 bp AJ416625.1
(A/chicken/Scotland/59(H5N1)) N1 gene for linear mRNA GI:39840717
neuraminidase, genomic RNA 161. Influenza A virus 1,497 bp
DQ208502.1 (A/chicken/zz/02/2004(H5N1)) nucleoprotein linear mRNA
GI:77158587 mRNA, complete cds 162. Influenza A virus (A/common
1,707 bp EF110519.1 coot/Switzerland/V544/2006(H5N1)) linear mRNA
GI:119394676 hemagglutinin (HA) gene, complete cds 163. Influenza A
virus (A/domestic 1,735 bp EU190482.1 goose/Pavlodar/1/2005(H5N1))
hemagglutinin linear mRNA GI:158516739 (HA) mRNA, complete cds 164.
Influenza A virus (A/duck/Eastern 1,401 bp EU429750.1
China/145/2003(H5N1)) segment 6 linear mRNA GI:167859465
neuraminidase (NA) mRNA, complete cds 165. Influenza A virus
(A/duck/Eastern 1,407 bp EU429731.1 China/150/2003(H5N1)) segment 6
linear mRNA GI:167859427 neuraminidase (NA) mRNA, complete cds 166.
Influenza A virus (A/duck/Eastern 1,398 bp EU429783.1
China/22/2005(H5N1)) segment 6 neuraminidase linear mRNA
GI:167859531 (NA) mRNA, complete cds 167. Influenza A virus
(A/duck/Eastern 1,398 bp EU429747.1 China/304/2002(H5N1)) segment 6
linear mRNA GI:167859459 neuraminidase (NA) mRNA, complete cds 168.
Influenza A virus (A/duck/Eastern 1,401 bp EU429727.1
China/318/2002(H5N1)) segment 6 linear mRNA GI:167859419
neuraminidase (NA) mRNA, complete cds 169. Influenza A virus
(A/duck/Eastern 1,399 bp EU429778.1 China/37/2006(H5N1)) segment 6
neuraminidase linear mRNA GI:167859521 (NA) mRNA, complete cds 170.
Influenza A virus (A/duck/Eastern 1,398 bp EU429757.1
China/40/2005(H5N1)) segment 6 neuraminidase linear mRNA
GI:167859479 (NA) mRNA, complete cds 171. Influenza A virus
(A/duck/Eastern 1,398 bp EU429779.1 China/48/2006(H5N1)) segment 6
neuraminidase linear mRNA GI:167859523 (NA) mRNA, complete cds 172.
Influenza A virus (A/duck/Eastern 1,398 bp EU429763.1
China/51/2005(H5N1)) segment 6 neuraminidase linear mRNA
GI:167859491 (NA) mRNA, complete cds 173. Influenza A virus
(A/duck/Eastern 1,398 bp EU429758.1 China/54/2005(H5N1)) segment 6
neuraminidase linear mRNA GI:167859481 (NA) mRNA, complete cds 174.
Influenza A virus (A/duck/Eastern 1,398 bp EU429764.1
China/58/2005(H5N1)) segment 6 neuraminidase linear mRNA
GI:167859493 (NA) mRNA, complete cds 175. Influenza A virus
(A/duck/Eastern 1,398 bp EU429759.1 China/59/2005(H5N1)) segment 6
neuraminidase linear mRNA GI:167859483 (NA) mRNA, complete cds 176.
Influenza A virus (A/duck/Eastern 1,398 bp EU429765.1
China/89/2005(H5N1)) segment 6 neuraminidase linear mRNA
GI:167859495 (NA) mRNA, complete cds 177. Influenza A virus
(A/duck/Eastern 1,399 bp EU429785.1 China/89/2006(H5N1)) segment 6
neuraminidase linear mRNA GI:167859535 (NA) mRNA, complete cds 178.
Influenza A virus (A/duck/Eastern 1,398 bp EU429717.1
China/97/2001(H5N1)) segment 6 neuraminidase linear mRNA
GI:167859399 (NA) mRNA, complete cds 179. Influenza A virus 2,281
bp AY585504.1 (A/duck/Fujian/01/2002(H5N1)) polymerase linear mRNA
GI:47156226 basic protein 2 (PB2) mRNA, complete cds 180. Influenza
A virus 760 bp AY585378.1 (A/duck/Fujian/01/2002(H5N1)) matrix
protein linear mRNA GI:47156310 mRNA, complete cds 181. Influenza A
virus 1,357 bp AY585399.1 (A/duck/Fujian/01/2002(H5N1))
neuraminidase linear mRNA GI:47156352 (NA) mRNA, complete cds 182.
Influenza A virus 1,497 bp AY585420.1 (A/duck/Fujian/01/2002(H5N1))
nucleoprotein linear mRNA GI:47156394 (NP) mRNA, complete cds 183.
Influenza A virus 686 bp AY585441.1 (A/duck/Fujian/01/2002(H5N1))
nonstructural linear mRNA GI:47156436 protein 1 (NS1) mRNA, partial
cds 184. Influenza A virus 2,281 bp AY585505.1
(A/duck/Fujian/13/2002(H5N1)) polymerase linear mRNA GI:47156228
basic protein 2 (PB2) mRNA, complete cds 185. Influenza A virus 761
bp AY585379.1 (A/duck/Fujian/13/2002(H5N1)) matrix protein linear
mRNA GI:47156312 mRNA, complete cds 186. Influenza A virus 1,357 bp
AY585400.1 (A/duck/Fujian/13/2002(H5N1)) neuraminidase linear mRNA
GI:47156354 (NA) mRNA, complete cds 187. Influenza A virus 1,499 bp
AY585421.1 (A/duck/Fujian/13/2002(H5N1)) nucleoprotein linear mRNA
GI:47156396 (NP) mRNA, complete cds 188. Influenza A virus 685 bp
AY585442.1 (A/duck/Fujian/13/2002(H5N1)) nonstructural linear mRNA
GI:47156438 protein 1 (NS1) mRNA, partial cds 189. Influenza A
virus 2,281 bp AY585506.1 (A/duck/Fujian/17/2001(H5N1)) polymerase
linear mRNA GI:47156230 basic protein 2 (PB2) mRNA, complete cds
190. Influenza A virus 759 bp AY585380.1
(A/duck/Fujian/17/2001(H5N1)) matrix protein linear mRNA
GI:47156314 mRNA, complete cds 191. Influenza A virus 1,418 bp
AY585401.1 (A/duck/Fujian/17/2001(H5N1)) neuraminidase linear mRNA
GI:47156356 (NA) mRNA, complete cds 192. Influenza A virus 1,498 bp
AY585422.1 (A/duck/Fujian/17/2001(H5N1)) nucleoprotein linear mRNA
GI:47156398 (NP) mRNA, complete cds 193. Influenza A virus 686 bp
AY585443.1 (A/duck/Fujian/17/2001(H5N1)) nonstructural linear mRNA
GI:47156440 protein 1 (NS1) mRNA, complete cds 194. Influenza A
virus 2,281 bp AY585507.1 (A/duck/Fujian/19/2000(H5N1)) polymerase
linear mRNA GI:47156232 basic protein 2 (PB2) mRNA, complete cds
195. Influenza A virus 760 bp AY585381.1
(A/duck/Fujian/19/2000(H5N1)) matrix protein linear mRNA
GI:47156316 mRNA, complete cds 196. Influenza A virus 1,355 bp
AY585402.1 (A/duck/Fujian/19/2000(H5N1)) neuraminidase linear mRNA
GI:47156358 (NA) mRNA, complete cds 197. Influenza A virus 1,498 bp
AY585423.1 (A/duck/Fujian/19/2000(H5N1)) nucleoprotein linear mRNA
GI:47156400 (NP) mRNA, complete cds 198. Influenza A virus 687 bp
AY585444.1 (A/duck/Fujian/19/2000(H5N1)) nonstructural linear mRNA
GI:47156442 protein 1 (NS1) mRNA, complete cds 199. Influenza A
virus 2,281 bp AY585508.1 (A/duck/Guangdong/01/2001(H5N1))
polymerase linear mRNA GI:47156234 basic protein 2 (PB2) mRNA,
complete cds 200. Influenza A virus 760 bp AY585382.1
(A/duck/Guangdong/01/2001(H5N1)) matrix linear mRNA GI:47156318
protein mRNA, complete cds 201. Influenza A virus 1,414 bp
AY585403.1 (A/duck/Guangdong/01/2001(H5N1)) linear mRNA GI:47156360
neuraminidase (NA) mRNA, complete cds 202. Influenza A virus 1,497
bp AY585424.1 (A/duck/Guangdong/01/2001(H5N1)) linear mRNA
GI:47156402 nucleoprotein (NP) mRNA, complete cds 203. Influenza A
virus 687 bp AY585445.1 (A/duck/Guangdong/01/2001(H5N1)) linear
mRNA GI:47156444 nonstructural protein 1 (NS1) mRNA, complete cds
204. Influenza A virus 2,280 bp AY585509.1
(A/duck/Guangdong/07/2000(H5N1)) polymerase linear mRNA GI:47156236
basic protein 2 (PB2) mRNA, complete cds 205. Influenza A virus 759
bp AY585383.1 (A/duck/Guangdong/07/2000(H5N1)) matrix linear mRNA
GI:47156320 protein mRNA, complete cds 206. Influenza A virus 1,417
bp AY585404.1 (A/duck/Guangdong/07/2000(H5N1)) linear mRNA
GI:47156362 neuraminidase (NA) mRNA, complete cds 207. Influenza A
virus 1,497 bp AY585425.1 (A/duck/Guangdong/07/2000(H5N1)) linear
mRNA GI:47156404 nucleoprotein (NP) mRNA, complete cds 208.
Influenza A virus 690 bp AY585446.1
(A/duck/Guangdong/07/2000(H5N1)) linear mRNA GI:47156446
nonstructural protein 1 (NS1) mRNA, partial cds 209. Influenza A
virus 2,281 bp AY585510.1 (A/duck/Guangdong/12/2000(H5N1))
polymerase linear mRNA GI:47156238 basic protein 2 (PB2) mRNA,
complete cds 210. Influenza A virus 760 bp AY585384.1
(A/duck/Guangdong/12/2000(H5N1)) matrix linear mRNA GI:47156322
protein mRNA, complete cds 211. Influenza A virus 1,359 bp
AY585405.1 (A/duck/Guangdong/12/2000(H5N1)) linear mRNA GI:47156364
neuraminidase (NA) mRNA, complete cds 212. Influenza A virus 1,498
bp AY585426.1 (A/duck/Guangdong/12/2000(H5N1)) linear mRNA
GI:47156406 nucleoprotein (NP) mRNA, complete cds 213. Influenza A
virus 685 bp AY585447.1 (A/duck/Guangdong/12/2000(H5N1)) linear
mRNA GI:47156448 nonstructural protein 1 (NS1) mRNA, partial cds
214. Influenza A virus 2,281 bp AY585511.1
(A/duck/Guangdong/22/2002(H5N1)) polymerase linear mRNA GI:47156240
basic protein 2 (PB2) mRNA, complete cds 215. Influenza A virus 760
bp AY585385.1 (A/duck/Guangdong/22/2002(H5N1)) matrix linear mRNA
GI:47156324 protein mRNA, complete cds 216. Influenza A virus 1,412
bp AY585406.1 (A/duck/Guangdong/22/2002(H5N1)) linear mRNA
GI:47156366 neuraminidase (NA) mRNA, complete cds
217. Influenza A virus 1,499 bp AY585427.1
(A/duck/Guangdong/22/2002(H5N1)) linear mRNA GI:47156408
nucleoprotein (NP) mRNA, complete cds 218. Influenza A virus 682 bp
AY585448.1 (A/duck/Guangdong/22/2002(H5N1)) linear mRNA GI:47156450
nonstructural protein 1 (NS1) mRNA, complete cds 219. Influenza A
virus 2,281 bp AY585512.1 (A/duck/Guangdong/40/2000(H5N1))
polymerase linear mRNA GI:47156242 basic protein 2 (PB2) mRNA,
complete cds 220. Influenza A virus 760 bp AY585386.1
(A/duck/Guangdong/40/2000(H5N1)) matrix linear mRNA GI:47156326
protein mRNA, complete cds 221. Influenza A virus 1,401 bp
AY585407.1 (A/duck/Guangdong/40/2000(H5N1)) linear mRNA GI:47156368
neuraminidase (NA) mRNA, partial cds 222. Influenza A virus 1,499
bp AY585428.1 (A/duck/Guangdong/40/2000(H5N1)) linear mRNA
GI:47156410 nucleoprotein (NP) mRNA, complete cds 223. Influenza A
virus 689 bp AY585449.1 (A/duck/Guangdong/40/2000(H5N1)) linear
mRNA GI:47156452 nonstructural protein 1 (NS1) mRNA, partial cds
224. Influenza A virus 2,281 bp AY585513.1
(A/duck/Guangxi/07/1999(H5N1)) polymerase linear mRNA GI:47156244
basic protein 2 (PB2) mRNA, complete cds 225. Influenza A virus 760
bp AY585387.1 (A/duck/Guangxi/07/1999(H5N1)) matrix linear mRNA
GI:47156328 protein mRNA, complete cds 226. Influenza A virus 1,421
bp AY585408.1 (A/duck/Guangxi/07/1999(H5N1)) neuraminidase linear
mRNA GI:47156370 (NA) mRNA, complete cds 227. Influenza A virus
1,501 bp AY585429.1 (A/duck/Guangxi/07/1999(H5N1)) nucleoprotein
linear mRNA GI:47156412 (NP) mRNA, complete cds 228. Influenza A
virus 687 bp AY585450.1 (A/duck/Guangxi/07/1999(H5N1))
nonstructural linear mRNA GI:47156454 protein 1 (NS1) mRNA, partial
cds 229. Influenza A virus 875 bp DQ366342.1
(A/duck/Guangxi/13/2004(H5N1)) nonstructural linear mRNA
GI:86753723 protein 1 mRNA, complete cds 230. Influenza A virus
2,341 bp DQ366335.1 (A/duck/Guangxi/13/2004(H5N1)) polymerase
linear mRNA GI:86753733 PB2 mRNA, complete cds 231. Influenza A
virus 2,341 bp DQ366336.1 (A/duck/Guangxi/13/2004(H5N1)) polymerase
linear mRNA GI:86753743 PB1 mRNA, complete cds 232. Influenza A
virus 2,233 bp DQ366337.1 (A/duck/Guangxi/13/2004(H5N1)) PA protein
linear mRNA GI:86753753 mRNA, complete cds 233. Influenza A virus
1,776 bp DQ366338.1 (A/duck/Guangxi/13/2004(H5N1)) hemagglutinin
linear mRNA GI:86753763 mRNA, complete cds 234. Influenza A virus
1,565 bp DQ366339.1 (A/duck/Guangxi/13/2004(H5N1)) nucleocapsid
linear mRNA GI:86753773 mRNA, complete cds 235. Influenza A virus
1,378 bp DQ366340.1 (A/duck/Guangxi/13/2004(H5N1)) neuraminidase
linear mRNA GI:86753783 mRNA, complete cds 236. Influenza A virus
1,027 bp DQ366341.1 (A/duck/Guangxi/13/2004(H5N1)) matrix linear
mRNA GI:86753793 protein mRNA, complete cds 237. Influenza A virus
2,281 bp AY585514.1 (A/duck/Guangxi/22/2001(H5N1)) polymerase
linear mRNA GI:47156246 basic protein 2 (PB2) mRNA, complete cds
238. Influenza A virus 757 bp AY585388.1
(A/duck/Guangxi/22/2001(H5N1)) matrix linear mRNA GI:47156330
protein mRNA, partial cds 239. Influenza A virus 1,414 bp
AY585409.1 (A/duck/Guangxi/22/2001(H5N1)) neuraminidase linear mRNA
GI:47156372 (NA) mRNA, complete cds 240. Influenza A virus 1,498 bp
AY585430.1 (A/duck/Guangxi/22/2001(H5N1)) nucleoprotein linear mRNA
GI:47156414 (NP) mRNA, complete cds 241. Influenza A virus 687 bp
AY585451.1 (A/duck/Guangxi/22/2001(H5N1)) nonstructural linear mRNA
GI:47156456 protein 1 (NS1) mRNA, complete cds 242. Influenza A
virus 2,281 bp AY585515.1 (A/duck/Guangxi/35/2001(H5N1)) polymerase
linear mRNA GI:47156248 basic protein 2 (PB2) mRNA, complete cds
243. Influenza A virus 760 bp AY585389.1
(A/duck/Guangxi/35/2001(H5N1)) matrix linear mRNA GI:47156332
protein mRNA, complete cds 244. Influenza A virus 1,414 bp
AY585410.1 (A/duck/Guangxi/35/2001(H5N1)) neuraminidase linear mRNA
GI:47156374 (NA) mRNA, complete cds 245. Influenza A virus 1,498 bp
AY585431.1 (A/duck/Guangxi/35/2001(H5N1)) nucleoprotein linear mRNA
GI:47156416 (NP) mRNA, complete cds 246. Influenza A virus 685 bp
AY585452.1 (A/duck/Guangxi/35/2001(H5N1)) nonstructural linear mRNA
GI:47156458 protein 1 (NS1) mRNA, complete cds 247. Influenza A
virus 2,281 bp AY585516.1 (A/duck/Guangxi/50/2001(H5N1)) polymerase
linear mRNA GI:47156250 basic protein 2 (PB2) mRNA, complete cds
248. Influenza A virus 760 bp AY585398.1
(A/duck/Guangxi/50/2001(H5N1)) matrix linear mRNA GI:47156350
protein mRNA, complete cds 249. Influenza A virus 1,354 bp
AY585411.1 (A/duck/Guangxi/50/2001(H5N1)) neuraminidase linear mRNA
GI:47156376 (NA) mRNA, complete cds 250. Influenza A virus 1,498 bp
AY585432.1 (A/duck/Guangxi/50/2001(H5N1)) nucleoprotein linear mRNA
GI:47156418 (NP) mRNA, complete cds 251. Influenza A virus 686 bp
AY585453.1 (A/duck/Guangxi/50/2001(H5N1)) nonstructural linear mRNA
GI:47156460 protein 1 (NS1) mRNA, complete cds 252. Influenza A
virus 2,281 bp AY585517.1 (A/duck/Guangxi/53/2002(H5N1)) polymerase
linear mRNA GI:47156252 basic protein 2 (PB2) mRNA, complete cds
253. Influenza A virus 760 bp AY585390.1
(A/duck/Guangxi/53/2002(H5N1)) matrix linear mRNA GI:47156334
protein mRNA, complete cds 254. Influenza A virus 1,361 bp
AY585412.1 (A/duck/Guangxi/53/2002(H5N1)) neuraminidase linear mRNA
GI:47156378 (NA) mRNA, complete cds 255. Influenza A virus 1,498 bp
AY585433.1 (A/duck/Guangxi/53/2002(H5N1)) nucleoprotein linear mRNA
GI:47156420 (NP) mRNA, complete cds 256. Influenza A virus 687 bp
AY585454.1 (A/duck/Guangxi/53/2002(H5N1)) nonstructural linear mRNA
GI:47156462 protein 1 (NS1) mRNA, partial cds 257. Influenza A
virus 1,754 bp DQ449640.1 (A/duck/Kurgan/08/2005(H5N1))
hemagglutinin linear mRNA GI:90289674 (HA) mRNA, complete cds 258.
Influenza A virus 1,002 bp DQ449641.1 (A/duck/Kurgan/08/2005(H5N1))
matrix protein linear mRNA GI:90289689 1 (M) mRNA, complete cds
259. Influenza A virus 1,373 bp DQ449642.1
(A/duck/Kurgan/08/2005(H5N1)) neuraminidase linear mRNA GI:90289708
(NA) mRNA, complete cds 260. Influenza A virus 1,540 bp DQ449643.1
(A/duck/Kurgan/08/2005(H5N1)) nucleoprotein linear mRNA GI:90289731
(NP) mRNA, complete cds 261. Influenza A virus 850 bp DQ449644.1
(A/duck/Kurgan/08/2005(H5N1)) nonstructural linear mRNA GI:90289739
protein (NS) mRNA, complete cds 262. Influenza A virus 2,208 bp
DQ449645.1 (A/duck/Kurgan/08/2005(H5N1)) polymerase linear mRNA
GI:90289756 acidic protein (PA) mRNA, complete cds 263. Influenza A
virus 2,316 bp DQ449646.1 (A/duck/Kurgan/08/2005(H5N1)) polymerase
linear mRNA GI:90289774 basic protein 1 (PB1) mRNA, complete cds
264. Influenza A virus 2,316 bp DQ449647.1
(A/duck/Kurgan/08/2005(H5N1)) polymerase linear mRNA GI:90289783
basic protein 2 (PB2) mRNA, complete cds 266. Influenza A virus
2,281 bp AY585518.1 (A/duck/Shanghai/08/2001(H5N1)) polymerase
linear mRNA GI:47156254 basic protein 2 (PB2) mRNA, complete cds
267. Influenza A virus 760 bp AY585391.1
(A/duck/Shanghai/08/2001(H5N1)) matrix linear mRNA GI:47156336
protein mRNA, complete cds 268. Influenza A virus 1,357 bp
AY585413.1 (A/duck/Shanghai/08/2001(H5N1)) linear mRNA GI:47156380
neuraminidase (NA) mRNA, complete cds 269. Influenza A virus 1,498
bp AY585434.1 (A/duck/Shanghai/08/2001(H5N1)) linear mRNA
GI:47156422 nucleoprotein (NP) mRNA, complete cds 270. Influenza A
virus 685 bp AY585455.1 (A/duck/Shanghai/08/2001(H5N1)) linear mRNA
GI:47156464 nonstructural protein 1 (NS1) mRNA, partial cds 271.
Influenza A virus 2,281 bp AY585519.1
(A/duck/Shanghai/13/2001(H5N1)) polymerase linear mRNA GI:47156256
basic protein 2 (PB2) mRNA, complete cds 272. Influenza A virus 760
bp AY585392.1 (A/duck/Shanghai/13/2001(H5N1)) matrix linear mRNA
GI:47156338 protein mRNA, complete cds 273. Influenza A virus 1,417
bp AY585414.1 (A/duck/Shanghai/13/2001(H5N1)) linear mRNA
GI:47156382 neuraminidase (NA) mRNA, complete cds 274. Influenza A
virus 1,499 bp AY585435.1 (A/duck/Shanghai/13/2001(H5N1)) linear
mRNA GI:47156424 nucleoprotein (NP) mRNA, complete cds 275.
Influenza A virus 685 bp AY585456.1 (A/duck/Shanghai/13/2001(H5N1))
linear mRNA GI:47156466 nonstructural protein 1 (NS1) mRNA,
complete cds 276. Influenza A virus 2,281 bp AY585520.1
(A/duck/Shanghai/35/2002(H5N1)) polymerase linear mRNA GI:47156258
basic protein 2 (PB2) mRNA, complete cds 277. Influenza A virus 760
bp AY585393.1 (A/duck/Shanghai/35/2002(H5N1)) matrix linear mRNA
GI:47156340 protein mRNA, complete cds 278. Influenza A virus 1,363
bp AY585415.1 (A/duck/Shanghai/35/2002(H5N1)) linear mRNA
GI:47156384 neuraminidase (NA) mRNA, complete cds 279. Influenza A
virus 1,498 bp AY585436.1 (A/duck/Shanghai/35/2002(H5N1)) linear
mRNA GI:47156426 nucleoprotein (NP) mRNA, complete cds 280.
Influenza A virus 685 bp AY585457.1 (A/duck/Shanghai/35/2002(H5N1))
linear mRNA GI:47156468 nonstructural protein 1 (NS1) mRNA, partial
cds 281. Influenza A virus 2,281 bp AY585521.1
(A/duck/Shanghai/37/2002(H5N1)) polymerase linear mRNA GI:47156260
basic protein 2 (PB2) mRNA, complete cds 282. Influenza A virus 760
bp AY585394.1 (A/duck/Shanghai/37/2002(H5N1)) matrix linear mRNA
GI:47156342 protein mRNA, complete cds 283. Influenza A virus 1,361
bp AY585416.1 (A/duck/Shanghai/37/2002(H5N1)) linear mRNA
GI:47156386 neuraminidase (NA) mRNA, complete cds 284. Influenza A
virus 1,497 bp AY585437.1 (A/duck/Shanghai/37/2002(H5N1)) linear
mRNA GI:47156428 nucleoprotein (NP) mRNA, complete cds 285.
Influenza A virus 685 bp AY585458.1 (A/duck/Shanghai/37/2002(H5N1))
linear mRNA GI:47156470 nonstructural protein 1 (NS1) mRNA, partial
cds 286. Influenza A virus 2,282 bp AY585522.1
(A/duck/Shanghai/38/2001(H5N1)) polymerase linear mRNA GI:47156262
basic protein 2 (PB2) mRNA, complete cds 287. Influenza A virus 760
bp AY585395.1 (A/duck/Shanghai/38/2001(H5N1)) matrix linear mRNA
GI:47156344 protein mRNA, complete cds 288. Influenza A virus 1,355
bp AY585417.1 (A/duck/Shanghai/38/2001(H5N1)) linear mRNA
GI:47156388 neuraminidase (NA) mRNA, complete cds 289. Influenza A
virus 1,499 bp AY585438.1 (A/duck/Shanghai/38/2001(H5N1)) linear
mRNA GI:47156430 nucleoprotein (NP) mRNA, complete cds 290.
Influenza A virus 692 bp AY585459.1 (A/duck/Shanghai/38/2001(H5N1))
linear mRNA GI:47156472 nonstructural protein 1 (NS1) mRNA, partial
cds 291. Influenza A virus 875 bp DQ354059.1
(A/duck/Sheyang/1/2005(H5N1)) nonstructural linear mRNA GI:87128643
protein (NS) mRNA, complete cds 292. Influenza A virus 1,748 bp
DQ861291.1 (A/duck/Tuva/01/2006(H5N1)) hemagglutinin linear mRNA
GI:112820195 (HA) mRNA, complete cds 293. Influenza A virus 991 bp
DQ861292.1 (A/duck/Tuva/01/2006(H5N1)) matrix protein 1 linear mRNA
GI:112820197 (Ml) mRNA, complete cds 294. Influenza A virus 1,364
bp DQ861293.1 (A/duck/Tuva/01/2006(H5N1)) neuraminidase linear mRNA
GI:112820199 (NA) mRNA, complete cds 295. Influenza A virus 1,531
bp DQ861294.1 (A/duck/Tuva/01/2006(H5N1)) nucleoprotein linear mRNA
GI:112820201 (NP) mRNA, complete cds 296. Influenza A virus 842 bp
DQ861295.1 (A/duck/Tuva/01/2006(H5N1)) nonstructural linear mRNA
GI:112820203 protein (NS) mRNA, complete cds 297. Influenza A virus
890 bp DQ366310.1 (A/duck/Vietnam/1/2005(H5N1)) nonstructural
linear mRNA GI:86753715 protein 1 mRNA, complete cds 298. Influenza
A virus 2,341 bp DQ366303.1 (A/duck/Vietnam/1/2005(H5N1))
polymerase PB2 linear mRNA GI:86753725 mRNA, complete cds 299.
Influenza A virus 2,341 bp DQ366304.1 (A/duck/Vietnam/1/2005(H5N1))
polymerase PB1 linear mRNA GI:86753735 mRNA, complete cds 300.
Influenza A virus 2,233 bp DQ366305.1 (A/duck/Vietnam/1/2005(H5N1))
PA protein linear mRNA GI:86753745 mRNA, complete cds 301.
Influenza A virus 1,779 bp DQ366306.1 (A/duck/Vietnam/1/2005(H5N1))
hemagglutinin linear mRNA GI:86753755
mRNA, complete cds 302. Influenza A virus 1,565 bp DQ366307.1
(A/duck/Vietnam/1/2005(H5N1)) nucleocapsid linear mRNA GI:86753765
mRNA, complete cds 303. Influenza A virus 1,401 bp DQ366308.1
(A/duck/Vietnam/1/2005(H5N1)) neuraminidase linear mRNA GI:86753775
mRNA, complete cds 304. Influenza A virus 1,027 bp DQ366309.1
(A/duck/Vietnam/1/2005(H5N1)) matrix protein linear mRNA
GI:86753785 mRNA, complete cds 305. Influenza A virus 890 bp
DQ366326.1 (A/duck/Vietnam/8/05(H5N1)) nonstructural linear mRNA
GI:86753719 protein 1 mRNA, complete cds 306. Influenza A virus
2,341 bp DQ366319.1 (A/duck/Vietnam/8/05(H5N1)) polymerase PB2
linear mRNA GI:86753729 mRNA, complete cds 307. Influenza A virus
2,341 bp DQ366320.1 (A/duck/Vietnam/8/05(H5N1)) polymerase PB1
linear mRNA GI:86753739 mRNA, complete cds 308. Influenza A virus
2,233 bp DQ366321.1 (A/duck/Vietnam/8/05(H5N1)) PA protein mRNA,
linear mRNA GI:86753749 complete cds 309. Influenza A virus 1,779
bp DQ366322.1 (A/duck/Vietnam/8/05(H5N1)) hemagglutinin linear mRNA
GI:86753759 mRNA, complete cds 310. Influenza A virus 1,565 bp
DQ366323.1 (A/duck/Vietnam/8/05(H5N1)) nucleocapsid linear mRNA
GI:86753769 mRNA, complete cds 311. Influenza A virus 1,401 bp
DQ366324.1 (A/duck/Vietnam/8/05(H5N1)) neuraminidase linear mRNA
GI:86753779 mRNA, complete cds 312. Influenza A virus 1,027 bp
DQ366325.1 (A/duck/Vietnam/8/05(H5N1)) matrix protein linear mRNA
GI:86753789 mRNA, complete cds 313. Influenza A virus 876 bp
DQ354060.1 (A/duck/Yangzhou/232/2004(H5N1)) linear mRNA GI:87128645
nonfunctional nonstructural protein (NS) mRNA, complete sequence
314. Influenza A virus 2,281 bp AY585523.1
(A/duck/Zhejiang/11/2000(H5N1)) polymerase linear mRNA GI:47156264
basic protein 2 (PB2) mRNA, complete cds 315. Influenza A virus 760
bp AY585396.1 (A/duck/Zhejiang/11/2000(H5N1)) matrix linear mRNA
GI:47156346 protein mRNA, complete cds 316. Influenza A virus 1,352
bp AY585418.1 (A/duck/Zhejiang/11/2000(H5N1)) linear mRNA
GI:47156390 neuraminidase (NA) mRNA, complete cds 317. Influenza A
virus 1,498 bp AY585439.1 (A/duck/Zhejiang/11/2000(H5N1)) linear
mRNA GI:47156432 nucleoprotein (NP) mRNA, complete cds 318.
Influenza A virus 687 bp AY585460.1 (A/duck/Zhejiang/11/2000(H5N1))
linear mRNA GI:47156474 nonstructural protein 1 (NS1) mRNA, partial
cds 319. Influenza A virus 2,281 bp AY585524.1
(A/duck/Zhejiang/52/2000(H5N1)) polymerase linear mRNA GI:47156266
basic protein 2 (PB2) mRNA, complete cds 320. Influenza A virus 760
bp AY585397.1 (A/duck/Zhejiang/52/2000(H5N1)) matrix linear mRNA
GI:47156348 protein mRNA, complete cds 321. Influenza A virus 1,423
bp AY585419.1 (A/duck/Zhejiang/52/2000(H5N1)) linear mRNA
GI:47156392 neuraminidase (NA) mRNA, complete cds 322. Influenza A
virus 1,499 bp AY585440.1 (A/duck/Zhejiang/52/2000(H5N1)) linear
mRNA GI:47156434 nucleoprotein (NP) mRNA, complete cds 323.
Influenza A virus 686 bp AY585461.1 (A/duck/Zhejiang/52/2000(H5N1))
linear mRNA GI:47156476 nonstructural protein 1 (NS1) mRNA,
complete cds 324. Influenza A virus (A/Egypt/0636- 1,749 bp
EF382359.1 NAMRU3/2007(H5N1)) hemagglutinin (HA) mRNA, linear mRNA
GI:124244205 complete cds 325. Influenza A virus 1,707 bp
EF110518.1 (A/goosander/Switzerland/V82/06 (H5N1)) linear mRNA
GI:119394674 hemagglutinin (HA) gene, complete cds 326. Influenza A
virus 1,707 bp AF148678.1 (A/goose/Guangdong/1/96/(H5N1)) linear
mRNA GI:5007022 hemagglutinin mRNA, complete cds 327. Influenza A
virus 1,779 bp DQ201829.1 (A/Goose/Huadong/1/2000(H5N1))
hemagglutinin linear mRNA GI:76786306 (HA) mRNA, complete cds 328.
Influenza A virus 1,458 bp DQ201830.1
(A/Goose/Huadong/1/2000(H5N1)) neuraminidase linear mRNA
GI:76786308 (NA) mRNA, complete cds 329. Influenza A virus 2,287 bp
EF446768.1 (A/goose/Hungary/2823/2/2007(H5N1)) linear mRNA
GI:126428373 polymerase PB1 (PB1) mRNA, partial cds 330. Influenza
A virus 2,274 bp EF446769.1 (A/goose/Hungary/2823/2/2007(H5N1))
linear mRNA GI:126428375 polymerase PB2 (PB2) mRNA, partial cds
331. Influenza A virus 2,175 bp EF446770.1
(A/goose/Hungary/2823/2/2007(H5N1)) linear mRNA GI:126428377
polymerase PA (PA) mRNA, complete cds 332. Influenza A virus 1,735
bp EF446771.1 (A/goose/Hungary/2823/2/2007(H5N1)) linear mRNA
GI:126428379 hemagglutinin (HA) mRNA, complete cds 333. Influenza A
virus 1,473 bp EF446772.1 (A/goose/Hungary/2823/2/2007(H5N1))
linear mRNA GI:126428381 nucleocapsid protein (NP) mRNA, partial
cds 334. Influenza A virus 1,311 bp EF446773.1
(A/goose/Hungary/2823/2/2007(H5N1)) linear mRNA GI:126428383
neuraminidase (NA) mRNA, partial cds 335. Influenza A virus 971 bp
EF446774.1 (A/goose/Hungary/2823/2/2007(H5N1)) matrix linear mRNA
GI:126428385 protein 1 (M1) mRNA, partial cds 336. Influenza A
virus 795 bp EF446775.1 (A/goose/Hungary/2823/2/2007(H5N1)) linear
mRNA GI:126428387 nonstructural protein 1 (NS1) mRNA, partial cds
337. Influenza A virus 2,277 bp EF446776.1
(A/goose/Hungary/3413/2007(H5N1)) polymerase linear mRNA
GI:126428389 PB1 (PB1) mRNA, partial cds 338. Influenza A virus
2,274 bp EF446777.1 (A/goose/Hungary/3413/2007(H5N1)) polymerase
linear mRNA GI:126428391 PB2 (PB2) mRNA, partial cds 339. Influenza
A virus 2,163 bp EF446778.1 (A/goose/Hungary/3413/2007 (H5N1))
polymerase linear mRNA GI:126428393 PA (PA) mRNA, partial cds 340.
Influenza A virus 1,722 bp EF446779.1 (A/goose/Hungary/3413/2007
(H5N1)) linear mRNA GI:126428395 hemagglutinin (HA) mRNA, complete
cds 341. Influenza A virus 1,463 bp EF446780.1
(A/goose/Hungary/3413/2007 (H5N1)) linear mRNA GI:126428397
nucleocapsid protein (NP) mRNA, partial cds 342. Influenza A virus
1,289 bp EF446781.1 (A/goose/Hungary/3413/2007(H5N1)) linear mRNA
GI:126428399 neuraminidase (NA) mRNA, partial cds 343. Influenza A
virus 955 bp EF446782.1 (A/goose/Hungary/3413/2007(H5N1)) matrix
linear mRNA GI:126428401 protein 1 (M1) mRNA, partial cds 344.
Influenza A virus 805 bp EF446783.1
(A/goose/Hungary/3413/2007(H5N1)) linear mRNA GI:126428403
nonstructural protein 1 (NS1) mRNA, complete cds 345. Influenza A
virus 877 bp DQ354061.1 (A/goose/jiangsu/131/2002(H5N1)) linear
mRNA GI:87128646 nonfunctional nonstructural protein (NS) mRNA,
complete sequence 346. Influenza A virus 875 bp DQ354062.1
(A/goose/Jiangsu/220/2003(H5N1)) linear mRNA GI:87128647
nonstructural protein (NS) mRNA, complete cds 347. Influenza A
virus 1,754 bp DQ676840.1 (A/goose/Krasnoozerka/627/2005(H5N1))
linear mRNA GI:108782531 hemagglutinin (HA) mRNA, complete cds 348.
Influenza A virus 1,530 bp DQ676841.1
(A/goose/Krasnoozerka/627/2005(H5N1)) linear mRNA GI:108782533
nucleoprotein (NP) mRNA, complete cds 349. Influenza A virus 850 bp
DQ676842.1 (A/goose/Krasnoozerka/627/2005(H5N1)) linear mRNA
GI:108782535 nonstructural protein (NS) mRNA, complete cds 350.
Influenza A virus 890 bp DQ366318.1 (A/goose/Vietnam/3/05(H5N1))
nonstructural linear mRNA GI:86753717 protein 1 mRNA, complete cds
351. Influenza A virus 2,341 bp DQ366311.1
(A/goose/Vietnam/3/05(H5N1)) polymerase PB2 linear mRNA GI:86753727
mRNA, complete cds 352. Influenza A virus 2,341 bp DQ366312.1
(A/goose/Vietnam/3/05(H5N1)) polymerase PB1 linear mRNA GI:86753737
mRNA, complete cds 353. Influenza A virus 2,233 bp DQ366313.1
(A/goose/Vietnam/3/05(H5N1)) PA protein linear mRNA GI:86753747
mRNA, complete cds 354. Influenza A virus 1,779 bp DQ366314.1
(A/goose/Vietnam/3/05(H5N1)) hemagglutinin linear mRNA GI:86753757
mRNA, complete cds 355. Influenza A virus 1,565 bp DQ366315.1
(A/goose/Vietnam/3/05(H5N1)) nucleocapsid linear mRNA GI:86753767
mRNA, complete cds 356. Influenza A virus 1,401 bp DQ366316.1
(A/goose/Vietnam/3/05(H5N1)) neuraminidase linear mRNA GI:86753777
mRNA, complete cds 357. Influenza A virus 1,027 bp DQ366317.1
(A/goose/Vietnam/3/05(H5N1)) matrix protein linear mRNA GI:86753787
mRNA, complete cds 358. Influenza A virus 1,700 bp AF082043.1
(A/gull/Pennsylvania/4175/83(H5N1)) linear mRNA GI:4240453
hemagglutinin H5 mRNA, partial cds 360. Influenza A virus 1,388 bp
AF028708.1 (A/HongKong/156/97(H5N1)) neuraminidase linear mRNA
GI:2865377 mRNA, complete cds 361. Influenza A virus 1,741 bp
AF028709.1 (A/HongKong/156/97(H5N1)) hemagglutinin linear mRNA
GI:2865379 mRNA, complete cds 362. Influenza A virus 1,549 bp
AF028710.1 (A/HongKong/156/97(H5N1)) nucleoprotein linear mRNA
GI:2865381 mRNA, complete cds 363. Influenza A virus (A/hooded
1,451 bp AM503028.1 vulture/Burkina Faso/1/2006(H5N1)) partial
linear mRNA GI:147846292 mRNA for nucleoprotein (np gene) 364.
Influenza A virus (A/hooded 827 bp AM503038.1 vulture/Burkina
Faso/1/2006(H5N1)) mRNA for linear mRNA GI:147846312 non-structural
protein (ns gene) 365. Influenza A virus (A/hooded 2,169 bp
AM503047.1 vulture/Burkina Faso/1/2006(H5N1)) partial linear mRNA
GI:147846330 mRNA for polymerase (pa gene) 366. Influenza A virus
(A/hooded 1,686 bp AM503065.1 vulture/Burkina Faso/1/2006(H5N1))
partial linear mRNA GI:147846855 mRNA for polymerase basic protein
1 (pb1 gene) 367. Influenza A virus (A/hooded 977 bp AM503006.1
vulture/Burkina Faso/2/2006(H5N1)) partial linear mRNA GI:147846248
mRNA for matrix protein 1 (m1 gene) 368. Influenza A virus
(A/hooded 1,336 bp AM503017.1 vulture/Burkina Faso/2/2006(H5N1))
partial linear mRNA GI:147846270 mRNA for neuraminidase (na gene)
369. Influenza A virus (A/hooded 1,499 bp AM503027.1
vulture/Burkina Faso/2/2006(H5N1)) partial linear mRNA GI:147846290
mRNA for nucleoprotein (np gene) 370. Influenza A virus (A/hooded
827 bp AM503039.1 vulture/Burkina Faso/2/2006(H5N1)) mRNA for
linear mRNA GI:147846314 non-structural protein (ns gene) 371.
Influenza A virus (A/hooded 2,169 bp AM503048.1 vulture/Burkina
Faso/2/2006(H5N1)) partial linear mRNA GI:147846332 mRNA for
polymerase (pa gene) 372. Influenza A virus (A/hooded 2,259 bp
AM503062.1 vulture/Burkina Faso/2/2006(H5N1)) partial linear mRNA
GI:147846849 mRNA for polymerase basic protein 1 (pb1 gene) 373.
Influenza A virus (A/hooded 2,315 bp AM503066.1 vulture/Burkina
Faso/2/2006(H5N1)) partial linear mRNA GI:147846857 mRNA for
polymerase basic protein 2 (pb2 gene) 374. Influenza A virus 294 bp
EU014135.1 (A/Indonesia/CDC177/2005(H5N1)) M2 protein linear mRNA
GI:151336850 mRNA, complete cds 375. Influenza A virus 294 bp
EU014138.1 (A/Indonesia/CDC298/2005(H5N1)) M2 protein linear mRNA
GI:151336856 mRNA, complete cds 376. Influenza A virus 294 bp
EU014136.1 (A/Indonesia/CDC485/2006(H5N1)) M2 protein linear mRNA
GI:151336852 mRNA, complete cds 377. Influenza A virus 294 bp
EU014134.1 (A/Indonesia/CDC530/2006(H5N1)) M2 protein linear mRNA
GI:151336848 mRNA, complete cds 378. Influenza A virus 294 bp
EU014133.1 (A/Indonesia/CDC535/2006(H5N1)) M2 protein linear mRNA
GI:151336846 mRNA, complete cds 379. Influenza A virus 294 bp
EU014132.1 (A/Indonesia/CDC540/2006(H5N1)) M2 protein linear mRNA
GI:151336844 mRNA, complete cds 380. Influenza A virus 294 bp
EU014137.1 (A/Indonesia/CDC561/2006(H5N1)) M2 protein linear mRNA
GI:151336854 mRNA, complete cds 381. Influenza A virus 294 bp
EU014139.1 (A/Indonesia/CDC60/2005(H5N1)) M2 protein linear mRNA
GI:151336858 mRNA, complete cds 382. Influenza A virus 996 bp
U79453.1 (A/mallard/Wisconsin/428/75(H5N1)) linear mRNA GI:1840071
hemagglutinin mRNA, partial cds 383. Influenza A virus 441 bp
JN157759.1 (A/ostrich/VRLCU/Egypt/2011(H5N1)) segment 4 linear mRNA
GI:338223304 hemagglutinin (HA) mRNA, partial cds 384. Influenza A
virus 875 bp DQ354063.1 (A/quail/yunnan/092/2002(H5N1)) linear mRNA
GI:87128649 nonstructural protein (NS) mRNA, complete cds 385.
Influenza A virus 1,472 bp AB241613.1 (A/R(Turkey/Ontario/7732/66-
linear mRNA GI:82581222
Bellamy/42)(H5N1)) HA mRNA for hemagglutinin, partial cds 386.
Influenza A virus (A/Thailand/LFPN- 1,350 bp AY679513.1
2004/2004(H5N1)) neuraminidase mRNA, linear mRNA GI:50843945
complete cds 387. Influenza A virus (A/Thailand/LFPN- 1,704 bp
AY679514.1 2004/2004(H5N1)) hemagglutinin mRNA, linear mRNA
GI:50843949 complete cds 388. Influenza A virus
(A/tiger/Thailand/CU- 534 bp DQ017251.1 T4/04(H5N1)) polymerase
basic protein 2 linear mRNA GI:65329524 (PB2) mRNA, partial cds
389. Influenza A virus (A/tiger/Thailand/CU- 582 bp DQ017252.1
T5/04(H5N1)) polymerase basic protein 2 linear mRNA GI:65329536
(PB2) mRNA, partial cds 390. Influenza A virus
(A/tiger/Thailand/CU- 564 bp DQ017253.1 T6/04(H5N1)) polymerase
basic protein 2 linear mRNA GI:65329553 (PB2) mRNA, partial cds
391. Influenza A virus (A/tiger/Thailand/CU- 582 bp DQ017254.1
T8/04(H5N1)) polymerase basic protein 2 linear mRNA GI:65329568
(PB2) mRNA, partial cds 392. Influenza A virus 1,695 bp EF441263.1
(A/turkey/England/250/2007(H5N1)) linear mRNA GI:129307104
hemagglutinin (HA) mRNA, partial cds 393. Influenza A virus 943 bp
EF441264.1 (A/turkey/England/250/2007(H5N1)) matrix linear mRNA
GI:129307106 protein (M) mRNA, partial cds 394. Influenza A virus
812 bp EF441265.1 (A/turkey/England/250/2007(H5N1)) linear mRNA
GI:129307109 nonstructural protein 1 (NS1) mRNA, complete cds 395.
Influenza A virus 2,185 bp EF441266.1
(A/turkey/England/250/2007(H5N1)) polymerase linear mRNA
GI:129307111 PA (PA) mRNA, complete cds 396. Influenza A virus
2,272 bp EF441267.1 (A/turkey/England/250/2007(H5N1)) polymerase
linear mRNA GI:129307113 PB2 (PB2) mRNA, partial cds 397. Influenza
A virus 1,396 bp EF441268.1 (A/turkey/England/250/2007(H5N1))
linear mRNA GI:129307115 nucleocapsid (NP) mRNA, partial cds 398.
Influenza A virus 2,288 bp EF441269.1
(A/turkey/England/250/2007(H5N1)) polymerase linear mRNA
GI:129307117 PB1 (PB1) mRNA, partial cds 399. Influenza A virus
1,276 bp EF441270.1 (A/turkey/England/250/2007(H5N1)) linear mRNA
GI:129307119 neuraminidase (NA) mRNA, partial cds A/chicken/Burkina
Faso/13.1/2006(H5N1) AM503016.1 neuraminidase (NA)
A/chicken/Crimea/04/2005(H5N1) neuraminidase DQ650661.1 (NA)
A/chicken/Crimea/04/2005(H5N1) hemagglutinin DQ650659.1
A/chicken/Crimea/08/2005(H5N1) polymerase DQ650669.1 basic protein
1 (PB1) A/chicken/Crimea/08/2005(H5N1) neuraminidase DQ650665.1
(NA) A/chicken/Crimea/08/2005(H5N1) hemagglutinin DQ650663.1 (HA)
A/chicken/Guangxi/12/2004(H5N1) DQ366334.1 nonstructural protein 1
A/chicken/Guangxi/12/2004(H5N1) DQ366332.1 neuraminidase
A/chicken/Guangxi/12/2004(H5N1) DQ366330.1 hemagglutinin
A/duck/Kurgan/08/2005(H5N1) nucleoprotein DQ449643.1 (NP)
TABLE-US-00014 TABLE 10 Other Influenza A Antigens (H1N*, H2N*,
H3N*) GenBank/GI Strain/Protein Length Accession Nos. H1N*
Influenza A virus (A/duck/Hong 1,402 bp U49097.1
Kong/193/1977(H1N2)) nucleoprotein (NP) linear mRNA GI:1912392
mRNA, partial cds Influenza A virus (A/duck/Hong 258 bp U48285.1
Kong/193/1977(H1N2)) polymerase (PB1) mRNA, linear mRNA GI:1912374
partial cds Influenza A virus (A/England/2/2002(H1N2)) 795 bp
AJ519455.1 partial NS1 gene for non structural protein linear mRNA
GI:31096426 1 and partial NS2 gene for non structural protein 2,
genomic RNA Influenza A virus (A/England/3/02(H1N2)) 384 bp
AJ489497.1 partial mRNA for nucleoprotein (np gene) linear mRNA
GI:27526856 Influenza A virus (A/England/3/02(H1N2)) 442 bp
AJ489488.1 partial mRNA for polymerase subunit 2 (pb2 linear mRNA
GI:27526838 gene) Influenza A virus (A/England/5/02(H1N2)) 384 bp
AJ489498.1 partial mRNA for nucleoprotein (np gene) linear mRNA
GI:27526858 Influenza A virus (A/England/5/02(H1N2)) 442 bp
AJ489489.1 partial mRNA for polymerase subunit 2 (pb2 linear mRNA
GI:27526840 gene) Influenza A virus (A/England/57/02(H1N2)) 384 bp
AJ489499.1 partial mRNA for nucleoprotein (np gene) linear mRNA
GI:27526860 Influenza A virus (A/England/57/02(H1N2)) 442 bp
AJ489492.1 partial mRNA for polymerase subunit 2 (pb2 linear mRNA
GI:27526846 gene) Influenza A virus (A/England/691/01(H1N2)) 384 bp
AJ489496.1 partial mRNA for nucleoprotein (np gene) linear mRNA
GI:27526854 Influenza A virus (A/England/73/02(H1N2)) 384 bp
AJ489500.1 partial mRNA for nucleoprotein (np gene) linear mRNA
GI:27526862 Influenza A virus (A/England/73/02(H1N2)) 442 bp
AJ489493.1 partial mRNA for polymerase subunit 2 (pb2 linear mRNA
GI:27526848 gene) Influenza A virus (A/England/90/02(H1N2)) 384 bp
AJ489501.1 partial mRNA for nucleoprotein (np gene) linear mRNA
GI:27526864 Influenza A virus (A/England/90/02(H1N2)) 442 bp
AJ489490.1 partial mRNA for polymerase subunit 2 (pb2 linear mRNA
GI:27526842 gene) Influenza A virus (A/England/97/02(H1N2)) 384 bp
AJ489502.1 partial mRNA for nucleoprotein (np gene) linear mRNA
GI:27526866 Influenza A virus (A/England/97/02(H1N2)) 442 bp
AJ489491.1 partial mRNA for polymerase subunit 2 (pb2 linear mRNA
GI:27526844 gene) Influenza A virus (A/England/627/01(H1N2)) 384 bp
AJ489494.1 partial mRNA for nucleoprotein (np gene) linear mRNA
GI:27526850 Influenza A virus (A/England/627/01(H1N2)) 442 bp
AJ489485.1 partial mRNA for polymerase subunit 2 (pb2 linear mRNA
GI:27526832 gene) Influenza A virus (A/England/691/01(H1N2)) 442 bp
AJ489487.1 partial mRNA for polymerase subunit 2 (pb2 linear mRNA
GI:27526836 gene) Influenza A virus (A/Egypt/96/2002(H1N2)) 747 bp
AJ519457.1 partial NS1 gene for non structural protein linear mRNA
GI:31096432 1 and partial NS2 gene for non structural protein 2,
genomic RNA Influenza A virus (A/Israel/6/2002(H1N2)) 773 bp
AJ519456.1 partial NS1 gene for non structural protein linear mRNA
GI:31096429 1 and partial NS2 gene for non structural protein 2,
genomic RNA Influenza A virus (A/Saudi 772 bp AJ519453.1
Arabia/2231/2001(H1N2)) partial NS1 gene for linear mRNA
GI:31096420 non structural protein 1 and partial NS2 gene for non
structural protein 2, genomic RNA Influenza A virus
(A/Scotland/122/01(H1N2)) 384 bp AJ489495.1 partial mRNA for
nucleoprotein (np gene) linear mRNA GI:27526852 Influenza A virus
(A/Scotland/122/01(H1N2)) 442 bp AJ489486.1 partial mRNA for
polymerase subunit 2 (pb2 linear mRNA GI:27526834 gene) Influenza A
virus 832 bp AY861443.1 (A/swine/Bakum/1832/2000(H1N2)) linear mRNA
GI:57791765 hemagglutinin (HA) mRNA, partial cds Influenza A virus
467 bp AY870645.1 (A/swine/Bakum/1832/2000(H1N2)) linear mRNA
GI:58042754 neuraminidase mRNA, partial cds Influenza A virus
(A/swine/Cotes 1,039 bp AM503547.1 d'Armor/0040/2007(H1N2)) segment
4 partial linear mRNA GI:225578611 mRNA Influenza A virus
(A/swine/Cotes 1,136 bp AM490224.3 d'Armor/0136_17/2006(H1N2))
partial mRNA for linear mRNA GI:222062921 haemagglutinin precursor
(HA1 gene) Influenza A virus 1,778 bp AF085417.1
(A/swine/England/72685/96(H1N2)) linear mRNA GI:3831770
haemagglutinin precursor, mRNA, complete cds Influenza A virus
1,778 bp AF085416.1 (A/swine/England/17394/96(H1N2)) linear mRNA
GI:3831768 haemagglutinin precursor, mRNA, complete cds Influenza A
virus 1,778 bp AF085415.1 (A/swine/England/690421/95(H1N2)) linear
mRNA GI:3831766 haemagglutinin precursor, mRNA, complete cds
Influenza A virus 1,778 bp AF085414.1
(A/swine/England/438207/94(H1N2)) linear mRNA GI:3831764
haemagglutinin precursor, mRNA, complete cds Influenza A virus
1,427 bp AY129157.1 (A/Swine/Korea/CY02/02(H1N2)) neuraminidase
linear mRNA GI:24286064 (NA) mRNA, complete cds Influenza A virus
952 bp AY129158.1 (A/Swine/Korea/CY02/02(H1N2)) matrix protein
linear mRNA GI:24286066 (M) mRNA, complete cds Influenza A virus
1,542 bp AY129159.1 (A/Swine/Korea/CY02/02(H1N2)) nucleoprotein
linear mRNA GI:24286069 (NP) mRNA, complete cds Influenza A virus
842 bp AY129160.1 (A/Swine/Korea/CY02/02(H1N2)) nonstructural
linear mRNA GI:24286081 protein (NS) mRNA, complete cds Influenza A
virus 2,165 bp AY129161.1 (A/Swine/Korea/CY02/02(H1N2)) polymerase
linear mRNA GI:24286087 acidic protein 2 (PA) mRNA, complete cds
Influenza A virus 2,274 bp AY129162.1 (A/Swine/Korea/CY02/02(H1N2))
polymerase linear mRNA GI:24286096 subunit 1 (PB1) mRNA, complete
cds Influenza A virus 2,334 bp AY129163.1
(A/Swine/Korea/CY02/02(H1N2)) polymerase linear mRNA GI:24286100
subunit 2 (PB2) mRNA, complete cds Influenza A virus 1,778 bp
AF085413.1 (A/swine/Scotland/410440/94(H1N2)) linear mRNA
GI:3831762 haemagglutinin precursor, mRNA, complete cds Influenza A
virus (A/swine/Spain/80598- 291 bp EU305436.1 LP4/2007(H1N2))
matrix protein 2 (M2) mRNA, linear mRNA GI:168830657 partial cds
Influenza A virus 975 bp AJ517813.1 (A/Switzerland/3100/2002(H1N2))
partial HA linear mRNA GI:38422519 gene for Haemagglutinin, genomic
RNA Influenza A virus (A/duck/Hong 1,387 bp U49095.1
Kong/717/1979(H1N3)) nucleoprotein (NP) linear mRNA GI:1912388
mRNA, partial cds Influenza A virus (A/duck/Hong 265 bp U48281.1
Kong/717/1979(H1N3)) polymerase (PB1) mRNA, linear mRNA GI:1912366
partial cds Influenza A virus (A/herring gull/New 971 bp AY664422.1
Jersey/780/86 (H1N3)) nonfunctional matrix linear mRNA GI:51011826
protein mRNA, partial sequence Influenza A virus 997 bp AY664426.1
(A/mallard/Alberta/42/77(H1N6)) linear mRNA GI:51011830
nonfunctional matrix protein mRNA, partial sequence Influenza A
virus 1,020 bp U85985.1 (A/swine/England/191973/92(H1N7)) matrix
linear mRNA GI:1835733 protein Ml mRNA, complete cds Influenza A
virus 1,524 bp U85987.1 (A/swine/England/191973/92(H1N7)) linear
mRNA GI:1835737 nucleoprotein mRNA, complete cds Influenza A virus
1,458 bp U85988.1 (A/swine/England/191973/92(H1N7)) linear mRNA
GI:1835739 neuraminidase mRNA, complete cds Influenza A virus 1,698
bp U85986.1 (A/swine/England/191973/92 (H1N7) ) linear mRNA
GI:1835735 haemagglutinin HA mRNA, partial cds H2N* Influenza A
virus (A/ruddy 917 bp AY664465.1 turnstone/Delaware/81/93 (H2N1))
linear mRNA GI:51011869 nonfunctional matrix protein mRNA, partial
sequence Influenza A virus (A/ruddy 968 bp AY664429.1
turnstone/Delaware/34/93 (H2N1)) linear mRNA GI:51011833
nonfunctional matrix protein mRNA, partial sequence Influenza A
virus 925 bp AY 66 4 466.1 (A/Shorebird/Delaware/122/97(H2N1))
linear mRNA GI:51011870 nonfunctional matrix protein mRNA, partial
sequence Influenza A virus 958 bp AY664454.1
(A/shorebird/Delaware/138/97 (H2N1)) linear mRNA GI:51011858
nonfunctional matrix protein mRNA, partial sequence Influenza A
virus 958 bp AY664457.1 (A/shorebird/Delaware/111/97 (H2N1)) linear
mRNA GI:51011861 nonfunctional matrix protein mRNA, partial
sequence Influenza A virus 979 bp AY664442.1
(A/shorebird/Delaware/24/98 (H2N1)) linear mRNA GI:51011846
nonfunctional matrix protein mRNA, partial sequence Influenza virus
type A/Leningrad/134/17/57 2,233 bp M81579.1 (H2N2) PA RNA,
complete cds linear mRNA GI:324935 Influenza A virus (STRAIN
A/MALLARD/NEW 2,151 bp AJ243994.1 YORK/6750/78) partial mRNA for PA
protein linear mRNA GI:5918195 Influenza A virus (A/X-7(F1)/(H2N2))
1,467 bp M11205.1 neuraminidase mRNA, complete cds linear mRNA
GI:323969 Influenza A virus (A/mallard/Alberta/77/77 1,009 bp
AY664425.1 (H2N3)) nonfunctional matrix protein mRNA, linear mRNA
GI:51011829 partial sequence Influenza A virus 968 bp AY664447.1
(A/mallard/Alberta/226/98(H2N3)) linear mRNA GI:51011851
nonfunctional matrix protein mRNA, partial sequence Influenza A
virus (A/sanderling/New 846 bp AY664477.1 Jersey/766/86 (H2N7))
nonfunctional matrix linear mRNA GI:51011881 protein mRNA, partial
sequence Influenza A virus (A/laughing gull/New 907 bp AY664471.1
Jersey/798/86 (H2N7)) nonfunctional matrix linear mRNA GI:51011875
protein mRNA, partial sequence Influenza A virus (A/herring 960 bp
AY664440.1 gull/Delaware/471/1986(H2N7)) nonfunctional linear mRNA
GI:51011844 matrix protein mRNA, partial sequence Influenza A virus
(A/ruddy 1,011 bp AY664423.1 turnstone/Delaware/142/98 (H2N8))
linear mRNA GI:51011827 nonfunctional matrix protein mRNA, partial
sequence Influenza A virus (A/pintail/Alberta/293/77 906 bp
AY664473.1 (H2N9)) nonfunctional matrix protein mRNA, linear mRNA
GI:51011877 partial sequence Influenza A virus (A/blue-winged 961
bp AY664449.1 teal/Alberta/16/97 (H2N9)) nonfunctional linear mRNA
GI:51011853 matrix protein mRNA, partial sequence Influenza A virus
(A/Laughing gull/New 952 bp AY664437.1 Jersey/75/85 (H2N9))
nonfunctional matrix linear mRNA GI:51011841 protein mRNA, partial
sequence Influenza A virus (A/mallard/Alberta/205/98 959 bp
AY664450.1 (H2N9)) nonfunctional matrix protein mRNA, linear mRNA
GI:51011854 partial sequence H3N* Influenza A virus (A/duck/Eastern
1,458 bp EU429755.1 China/267/2003(H3N1)) segment 6 linear mRNA
GI:167859475 neuraminidase (NA) mRNA, complete cds Influenza A
virus (A/duck/Eastern 1,458 bp EU429754.1 China/253/2003(H3N1))
segment 6 linear mRNA GI:167859473 neuraminidase (NA) mRNA,
complete cds Influenza A virus (A/duck/Eastern 1,458 bp EU429753.1
China/252/2003(H3N1)) segment 6 linear mRNA GI:167859471
neuraminidase (NA) mRNA, complete cds Influenza A virus
(A/duck/Eastern 1,458 bp EU429752.1 China/243/2003(H3N1)) segment 6
linear mRNA GI:167859469 neuraminidase (NA) mRNA, complete cds
Influenza A virus (A/duck/Eastern 1,458 bp EU429734.1
China/262/2003(H3N1)) segment 6 linear mRNA GI:167859433
neuraminidase (NA) mRNA, complete cds Influenza A virus
(A/duck/Eastern 1,459 bp EU429733.1 China/233/2003(H3N1)) segment 6
linear mRNA GI:167859431 neuraminidase (NA) mRNA, complete cds
Influenza A virus (A/duck/Eastern 1,458 bp EU429723.1
China/213/2003(H3N1)) segment 6 linear mRNA GI:167859411
neuraminidase (NA) mRNA, complete cds Influenza A virus
(A/duck/Eastern 1,458 bp EU429719.1 China/341/2003(H3N1)) segment 6
linear mRNA GI:167859403 neuraminidase (NA) mRNA, complete cds
Influenza A virus (A/duck/Eastern 1,458 bp EU429718.1
China/01/2002(H3N1)) segment 6 neuraminidase linear mRNA
GI:167859401 (NA) mRNA, complete cds Influenza A virus
(A/mallard/Alberta/22/76 1,013 bp AY664434.1 (H3N6)) nonfunctional
matrix protein mRNA, linear mRNA GI:51011838 partial sequence
Influenza A virus 970 bp AY664443.1
(A/mallard/Alberta/199/99(H3N6)) linear mRNA GI:51011847
nonfunctional matrix protein mRNA, partial
sequence Influenza A virus 922 bp AY664461.1
(A/shorebird/Delaware/222/97 (H3N6)) linear mRNA GI:51011865
nonfunctional matrix protein mRNA, partial sequence Influenza A
virus (A/Duck/Hokkaido/8/80 984 bp AF079570.1 (H3N8)) hemagglutinin
precursor, mRNA, linear mRNA GI:3414978 partial cds Influenza A
virus (A/Duck/Hokkaido/8/80 1,497 bp AF079571.1 (H3N8))
nucleoprotein mRNA, complete cds linear mRNA GI:3414980 Influenza A
virus 1,461 bp EU429797.1 (A/duck/Ukraine/1/1963(H3N8)) segment 6
linear mRNA GI:167859559 neuraminidase (NA) mRNA, complete cds
Influenza A virus (A/duck/Eastern 1,460 bp EU429698.1
China/19/2004(H3N8)) segment 6 neuraminidase linear mRNA
GI:167859361 (NA) mRNA, complete cds Influenza A virus
(A/duck/Eastern 1,460 bp EU429700.1 China/90/2004(H3N8)) segment 6
neuraminidase linear mRNA GI:167859365 (NA) mRNA, complete cds
Influenza A virus (A/duck/Eastern 1,460 bp EU429787.1
China/18/2005(H3N8)) segment 6 neuraminidase linear mRNA
GI:167859539 (NA) mRNA, complete cds Influenza A virus
(A/duck/Eastern 1,460 bp EU429788.1 China/119/2005(H3N8)) segment 6
linear mRNA GI:167859541 neuraminidase (NA) mRNA, complete cds
Influenza A virus 1,061 bp AF197246.1
(A/equine/Argentina/1/96(H3N8)) linear mRNA GI:6651512
hemagglutinin precursor (HA1) mRNA, partial cds Influenza A virus
1,061 bp AF197245.1 (A/equine/Argentina/2/94(H3N8)) linear mRNA
GI:6651510 hemagglutinin precursor (HA1) mRNA, partial cds
Influenza A virus 1,061 bp AF197244.1
(A/equine/Argentina/1/95(H3N8)) linear mRNA GI:6651508
hemagglutinin precursor (HA1) mRNA, partial cds Influenza A virus
HA partial gene for 1,026 bp AJ223194.1 haemagglutinin, genomic
RNA, strain linear mRNA GI:2780201 A/equine/Berlin/3/89(H3N8)
Influenza A virus HA partial gene for 1,006 bp AJ223195.1
haemagglutinin, genomic RNA, strain linear mRNA GI:2780203
A/equine/Berlin/4/89(H3N8) Influenza A virus 1,061 bp AF197242.1
(A/equine/Florida/1/94(H3N8)) hemagglutinin linear mRNA GI:6651504
precursor (HA1) mRNA, partial cds Influenza A virus 695 bp
AY328471.1 (A/equine/Grobois/1/98(H3N8)) nonstructural linear mRNA
GI:32966577 protein NS1 mRNA, complete cds Influenza A virus
(A/equi 473 bp AY919314.1 2/Gotland/01(H3N8)) hemagglutinin HA1
linear mRNA GI:60250543 subunit mRNA, partial cds Influenza A virus
(A/eq/Kentucky/81(H3N8)) 1,763 bp U58195.1 hemagglutinin mRNA,
complete cds linear mRNA GI:1377873 Influenza A virus 1,061 bp
AF197247.1 (A/equine/Kentucky/9/95(H3N8)) hemagglutinin linear mRNA
GI:6651514 precursor (HA1) mRNA, partial cds Influenza A virus
1,061 bp AF197248.1 (A/equine/Kentucky/1/96(H3N8)) hemagglutinin
linear mRNA GI:6651516 precursor (HA1) mRNA, partial cds Influenza
A virus 1,061 bp AF197249.1 (A/equine/Kentucky/1/97(H3N8))
hemagglutinin linear mRNA GI:6651518 precursor (HA1) mRNA, partial
cds Influenza A virus 1,061 bp AF197241.1
(A/equine/Kentucky/1/98(H3N8)) hemagglutinin linear mRNA GI:6651502
precursor (HA1) mRNA, partial cds Influenza A virus 1,497 bp
AY383753.1 (A/equine/Santiago/85(H3N8)) nucleoprotein linear mRNA
GI:37223511 mRNA, complete cds Influenza A virus 1,698 bp
AY383755.1 (A/equine/Santiago/85(H3N8)) hemagglutinin linear mRNA
GI:37223515 mRNA, complete cds Influenza A virus 1,413 bp
AY383754.1 (A/equine/Santiago/85(H3N8)) neuraminidase linear mRNA
GI:37223513 mRNA, complete cds Influenza A virus 1,061 bp
AF197243.1 (A/equine/Saskatoon/1/90(H3N8)) linear mRNA GI:6651506
hemagglutinin precursor (HA1) mRNA, partial cds Influenza A virus
(A/mallard/Alberta/114/97 1,010 bp AY664432.1 (H3N8)) nonfunctional
matrix protein mRNA, linear mRNA GI:51011836 partial sequence
Influenza A virus (A/mallard/Alberta/167/98 961 bp AY664489.1
(H3N8)) nonfunctional matrix protein mRNA, linear mRNA GI:51011893
partial sequence Influenza A virus 970 bp AY664445.1
(A/pintail/Alberta/37/99(H3N8)) linear mRNA GI:51011849
nonfunctional matrix protein mRNA, partial sequence Influenza A
virus 922 bp AY664455.1 (A/sanderling/Delaware/65/99 (H3N8)) linear
mRNA GI:51011859 nonfunctional matrix protein mRNA, partial
sequence
TABLE-US-00015 TABLE 11 Other Influenza A Antigens (H4N*-H13N*)
GenBank Strain/Protein Access No. A/chicken/Singapore/1992(H4N1) M2
protein EU014144.1 A/mallard/Alberta/47/98(H4N1) nonfunctional
matrix protein AY664488.1 A/duck/Hong Kong/412/1978(H4N2)
polymerase (PB1) U48279.1 A/mallard/Alberta/300/77 (H4N3)
nonfunctional matrix protein AY664480.1
A/Duck/Czechoslovakia/56(H4N6) segment 4 hemagglutinin AF290436.1
A/duck/Eastern China/376/2004(H4N6) segment 6neuraminidase (NA)
EU429792.1 A/duck/Eastern China/01/2007(H4N6) segment 6
neuraminidase (NA) EU429790.1 A/duck/Eastern China/216/2007(H4N6)
segment 6 neuraminidase EU429789.1 (NA) A/duck/Eastern
China/166/2004(H4N6) segment 6 neuraminidase EU429746.1 (NA)
A/duck/Eastern China/02/2003(H4N6) segment 6 neuraminidase (NA)
EU429713.1 A/duck/Eastern China/160/2002(H4N6) segment 6
neuraminidase EU429706.1 (NA) A/mallard/Alberta/111/99(H4N6)
nonfunctional matrix protein AY664482.1 A/mallard/Alberta/213/99
(H4N6) nonfunctional matrix protein AY664460.1
A/mallard/Alberta/30/98 (H4N6) nonfunctional matrix protein
AY664484.1 A/blue-winged teal/Alberta/96/76 (H4N8) nonfunctional
matrix AY664420.1 protein A/chicken/Florida/25717/1993(H5N2)
hemagglutinin U05332.1 A/chicken/Hidalgo/26654-1368/1994(H5N2)
hemagglutinin (HA) U37172.1 A/chicken/Jalisco/14585-660/1994(H5N2)
hemagglutinin (HA) U37181.1 A/chicken/Mexico/26654-1374/1994(H5N2)
hemagglutinin (HA) U37173.1 A/chicken/Mexico/31381-3/1994(H5N2)
hemagglutinin (HA) U37176.1 A/chicken/Mexico/31381-6/1994(H5N2)
hemagglutinin (HA) U37175.1 A/chicken/Mexico/31381-4/1994(H5N2)
hemagglutinin (HA) U37174.1 A/chicken/Mexico/31381-5/1994(H5N2)
hemagglutinin (HA) U37169.1 A/chicken/Mexico/31381-8/1994(H5N2)
hemagglutinin (HA) U37170.1
A/Chicken/Mexico/31381-Avilab/94(H5N2)hemagglutinin (HA) L46585.1
A/chicken/Mexico/31382-1/1994(H5N2)hemagglutinin (HA) U37168.1
A/chicken/Mexico/31381-2/1994(H5N2) hemagglutinin (HA) U37167.1
A/chicken/Mexico/31381-1/1994(H5N2) hemagglutinin (HA) U37166.1
A/chicken/Mexico/31381-7/1994(H5N2) hemagglutinin (HA) U37165.1
A/chicken/Pennsylvania/13609/1993(H5N2) hemagglutinin U05331.1
A/chicken/Pennsylvania/1/1983(H5N2) hemagglutinin esterase M18001.1
precursor A/chicken/Pennsylvania/1370/1983(H5N2) hemagglutinin
esterase M10243.1 precursor A/Chicken/Puebla/8623-607/94(H5N2)
hemagglutinin (HA) L46586.1 A/chicken/Puebla/14586-654/1994(H5N2)
hemagglutinin (HA) U37180.1 A/chicken/Puebla/14585-622/1994(H5N2)
hemagglutinin (HA) U37179.1
A/chicken/Puebla/8623-607/1994(H5N2)hemagglutinin (HA) U37178.1
A/chicken/Puebla/8624-604/1994(H5N2) hemagglutinin (HA) U37177.1
A/Chicken/Queretaro/14588-19/95(H5N2) hemagglutinin (HA) L46587.1
A/chicken/Queretaro/7653-20/95(H5N2) hemagglutinin (HA) U79448.1
A/chicken/Queretaro/26654-1373/1994(H5N2) hemagglutinin (HA)
U37171.1 A/chicken/Queretaro/14588-19/1994(H5N2)hemagglutinin (HA)
U37182.1 A/chicken/Singapore/98(H5N2) matrix protein 2 (M2)
EF682127.1 A/chicken/Taiwan/1209/03(H5N2) hemagglutinin protein
(HA) AY573917.1 A/chicken/Taiwan/1209/03(H5N2) neuraminidase
AY573918.1 A/duck/Eastern China/64/2004(H5N2) segment 6
neuraminidase (NA) EU429791.1 A/duck/Eastern China/264/2002(H5N2)
segment 6 neuraminidase EU429744.1 (NA) A/duck/Eastern
China/01/2001(H5N2) segment 6 neuraminidase (NA) EU429728.1
A/duck/Eastern China/06/2000(H5N2) segment 6 neuraminidase
EU429722.1 (NA) A/duck/Hong Kong/342/78(H5N2) matrix protein 1 (M)
and matrix DQ107452.1 protein 2 (M) A/duck/Hong Kong/342/78(H5N2)
hemagglutinin precursor U20475.1 A/duck/Michigan/80(H5N2)
hemagglutinin 1 chain U20474.1 A/duck/Michigan/80(H5N2)
hemagglutinin U79449.1 A/duck/MN/1564/81(H5N2) matrix protein 1 (M)
and matrix protein DQ107467.1 2 (M) A/duck/Mongolia/54/2001(H5N2)
hemagglutinin (HA) AB241614.2 A/duck/Primorie/2621/01(H5N2)
hemagglutinin (HA) AJ621811.3
A/duck/Primorie/2621/01(H5N2)nucleoprotein (NP ) AJ621812.1
A/duck/Primorie/2621/01(H5N2) nonstructural protein (NS) AJ621813.1
A/duck/Pennsylvania/84(H5N2) hemagglutinin 1chain U20473.1
A/duck/Potsdam/1402-6/86(H5N2) hemagglutinin H5 AF082042.1
A/emu/Texas/39442/93(H5N2) hemaglutinin U28920.1
A/emu/Texas/39442/93(H5N2) hemaglutinin U28919.1
A/mallard/Alberta/645/80(H5N2) matrix protein 1 (M) and matrix
DQ107471.1 protein 2 (M) A/mallard/AR/1C/2001(H5N2) matrix protein
1 (M) and matrix DQ107463.1 protein 2 (M) A/mallard/NY/189/82(H5N2)
matrix protein 1 (M) and matrix DQ107465.1 protein 2 (M)
A/mallard/MN/25/80(H5N2) matrix protein 1 (M) and matrix DQ107473.1
protein 2 (M) A/mallard/MI/18/80(H5N2) matrix protein 1 (M) and
matrix DQ107470.1 protein 2 (M) A/mallard/Ohio/345/88(H5N2)
hemagglutinin U79450.1 A/parrot/CA/6032/04(H5N2) polymerase basic
protein 2 (PB2) DQ256390.1 A/parrot/CA/6032/04(H5N2) polymerase
basic protein 1 (PB1) DQ256389.1 A/parrot/CA/6032/04(H5N2) matrix
protein (M) DQ256384.2 A/parrot/CA/6032/04(H5N2) hemagglutinin (HA)
DQ256383.1 A/parrot/CA/6032/04(H5N2) neuraminidase (NA) DQ256385.1
A/parrot/CA/6032/04(H5N2) polymerase basic protein 2 (PB2)
DQ256390.1 A/parrot/CA/6032/04(H5N2) nucleoprotein (NP) DQ256386.1
A/parrot/CA/6032/04(H5N2)) polymerase (PA) DQ256388.1 A/ruddy
turnstone/Delaware/244/91 (H5N2) nonfunctional matrix AY664474.1
protein A/ruddy turnstone/Delaware/244/91 (H5N2) U05330.1
A/turkey/Colorado/72(H5N2) hemagglutinin 1 chain (HA) U20472.1
A/turkey/England/N28/73 (H5N2) hemagglutinin AY500365.1
A/turkey/TX/14082/81(H5N2) matrix protein 1 (M) and matrix
DQ107464.1 protein 2 (M) A/turkey/MN/1704/82(H5N2)) matrix protein
1 (M) and matrix DQ107472.1 protein 2 (M)
A/turkey/Minnesota/10734/95(H5N2)) hemagglutinin U79455.1
A/turkey/Minnesota/3689-1551/81(H5N2) hemagglutinin U79454.1
A/chicken/Singapore/1997(H5N3) M2 protein EU014141.1
A/duck/Hokkaido/299/04(H5N3) hemagglutinin (HA) AB241626.1
A/duck/Hokkaido/193/04(H5N3) hemagglutinin (HA) AB241625.1
A/duck/Hokkaido/101/04(H5N3) hemagglutinin (HA) AB241624.1
A/duck/Hokkaido/447/00(H5N3) hemagglutinin (HA) AB241620.1
A/duck/Hokkaido/69/00(H5N3) hemagglutinin (HA) AB241619.1
A/duck/Hong Kong/205/77(H5N3) hemagglutinin H5 AF082038.1
A/duck/Hong Kong/698/79(H5N3) hemagglutinin H5 AF082039.1
A/duck/Hong Kong/308/78(H5N3) matrix protein 1 (M) and matrix
DQ107457.1 protein 2 (M) A/duck/Hong Kong/825/80(H5N3) matrix
protein 1 (M) and matrix DQ107455.1 protein 2 (M) A/duck/Hong
Kong/820/80(H5N3) matrix protein 1 (M) and matrix DQ107453.1
protein 2 (M) A/duck/Hong Kong/205/77(H5N3) matrix protein 1 (M)
and matrix DQ107456.1 protein 2 (M) A/Duck/Ho Chi Minh/014/78(H5N3)
segment 4 hemagglutinin AF290443.1 A/duck/Jiangxi/6151/2003(H5N3)
matrix protein 1 (M) and matrix DQ107451.1 protein 2 (M)
A/duck/Malaysia/F119-3/97(H5N3) hemagglutinin AF303057.1
A/duck/Miyagi/54/76(H5N3)hemagglutinin (HA) AB241615.1
A/duck/Mongolia/596/01(H5N3) hemagglutinin HA) AB241622.1
A/duck/Mongolia/500/01(H5N3)hemagglutinin (HA) AB241621.1
A/duck/Primorie/2633/01(H5N3) matrix protein (M1) AJ621810.1
A/duck/Primorie/2633/01(H5N3)nucleoprotein (NP) AJ621808.1
A/duck/Primorie/2633/01(H5N3)hemagglutinin (HA) AJ621807.1
A/duck/Primorie/2633/01(H5N3)nucleoprotein (NP) AJ621809.1
A/goose/Hong Kong/23/78(H5N3) matrix protein 1 (M) and matrix
DQ107454.1 protein 2 (M) A/mallard/Wisconsin/169/75(H5N3)
hemagglutinin U79452.1 A/swan/Hokkaido/51/96(H5N3)hemagglutinin
(HA) AB241617.1 A/swan/Hokkaido/4/96(H5N3) hemagglutinin (HA)
AB241616.1 A/turkey/CA/6878/79(H5N3) matrix protein 1 (M) and
matrix DQ107469.1 protein 2 (M) A/tern/South Africa/61(H5N3)
hemagglutinin precursor (HA) U20460.1 A/gull/Delaware/5/2000(H5N4)
matrix protein 1 (M) and matrix DQ107459.1 protein 2 (M)
A/gull/Delaware/4/2000(H5N4) matrix protein 1 (M) and matrix
DQ107458.1 protein 2 (M) A/shorebird/Delaware/109/2000(H5N4) matrix
protein 1 (M) DQ107460.1 A/shorebird/Delaware/243/2000(H5N4) matrix
protein 1 (M) and DQ107462.1 matrix protein 2 (M)
A/shorebird/Delaware/230/2000(H5N4) matrix protein 1 (M) and
DQ107461.1 matrix protein 2 (M) A/mallard/Wisconsin/34/75(H5N6)
hemagglutinin U79451.1 A/duck/Potsdam/2216-4/1984(H5N6)
hemagglutinin H5 AF082041.1 A/shorebird/Delaware/207/98 (H5N8)
nonfunctional matrix protein AY664456.1 A/shorebird/Delaware/27/98
(H5N8) nonfunctional matrix protein AY664453.1 A/herring
gull/Delaware/281/98 (H5N8) nonfunctional matrix AY664452.1 protein
A/mallard/Ohio/556/1987(H5N9) hemagglutinin (HA) U67783.2
A/turkey/Wisconsin/68(H5N9) hemagglutinin U79456.1 A/blue-winged
teal/Alberta/685/82(H6N1) matrix protein 1 (M) DQ107448.1 and
matrix protein 2 (M) A/chicken/Taiwan/7-5/99(H6N1) nucleocapsid
protein (NP) AF261750.1 A/chicken/Taiwan/7-5/99(H6N1) matrix
protein AF262213.1 A/chicken/Taiwan/7-5/99(H6N1) nonstructural
protein AF262212.1 A/chicken/Taiwan/7-5/99(H6N1) polymerase (PA)
AF262211.1 A/chicken/Taiwan/7-5/99(H6N1) polymerase subunit PB1
AF262210.1 A/chicken/Taiwan/7-5/99(H6N1) nucleocapsid protein (NP)
AF261750.1 A/chicken/Taiwan/ns2/99(H6N1) segment 4 hemagglutinin
(HA1) AF310985.1 A/chicken/Taiwan/na3/98(H6N1) segment 4
hemagglutinin (HA1) AF310984.1 A/chicken/Taiwan/7-5/99(H6N1)
segment 4 hemagglutinin (HA1) AF310983.1 A/duck/Hong
Kong/D73/76(H6N1) matrix protein 1 (M) and matrix DQ107432.1
protein 2 (M) A/duck/Taiwan/9/23-3/2000(H6N1) matrix protein 1 (M)
and matrix DQ107407.1 protein 2 (M) A/pheasant/Hong
Kong/FY479/2000(H6N1) matrix protein 1 (M) and DQ107409.1 matrix
protein 2 (M) A/pheasant/Hong Kong/SSP44/2002(H6N1) matrix protein
1 (M) and DQ107412.1 matrix protein 2 (M) A/quail/Hong
Kong/YU421/2002(H6N1) matrix protein 1 (M) and DQ107414.1 matrix
protein 2 (M) A/avian/NY/17150-7/2000(H6N2) matrix protein 1 (M)
and matrix DQ107423.1 protein 2 (M) A/chicken/CA/285/2003(H6N2)
matrix protein 1 (M) and matrix DQ107429.1 protein 2 (M)
A/chicken/CA/375TR/2002(H6N2) matrix protein 1 (M) and matrix
DQ107428.1 protein 2 (M) A/chicken/CA/203/2003(H6N2) matrix protein
1 (M) and matrix DQ107426.1 protein 2 (M)
A/chicken/NY/101250-7/2001(H6N2) matrix protein 1 (M) and
DQ107419.1 matrix protein 2 (M) A/chicken/CA/625/2002(H6N2) matrix
protein 1 (M) and matrix DQ107418.1 protein 2 (M)
A/Chicken/California/0139/2001(H6N2)nucleoprotein (NP) AF474070.1
A/Chicken/California/650/2000(H6N2) nucleoprotein (NP) AF474069.1
A/Chicken/California/9420/2001(H6N2) neuraminidase N2 (N2)
AF474048.1 A/Chicken/California/9174/2001(H6N2) neuraminidase N2
(N2) AF474047.1 A/Chicken/California/8892/2001(H6N2)neuraminidase
N2 (N2) AF474046.1 A/Chicken/California/6643/2001(H6N2)
neuraminidase N2 (N2) AF474045.1
A/Chicken/California/1316/2001(H6N2)neuraminidase N2 (N2)
AF474044.1 A/Chicken/California/0139/2001(H6N2) neuraminidase N2
(N2) AF474043.1 A/Chicken/California/1002/2000(H6N2) neuraminidase
N2 (N2) AF474042.1 A/Chicken/California/650/2000(H6N2)
neuraminidase N2 (N2) AF474041.1
A/Chicken/California/465/2000(H6N2) neuraminidase N2 (N2)
AF474040.1 A/Chicken/California/431/2000(H6N2) neuraminidase N2
(N2) AF474039.1 A/Chicken/California/6643/2001(H6N2) hemagglutinin
H6 (H6) AF474035.1 A/Chicken/California/431/2000(H6N2)
hemagglutinin H6 (H6) AF474029.1
A/Chicken/California/9420/2001(H6N2) hemagglutinin H6 (H6)
AF474038.1 A/Chicken/California/9174/2001(H6N2) hemagglutinin H6
(H6) AF474037.1 A/Chicken/California/8892/2001(H6N2) hemagglutinin
H6 (H6) AF474036.1 A/Chicken/California/1316/2001(H6N2)
hemagglutinin H6 (H6) AF474034.1
A/Chicken/California/0139/2001(H6N2) hemagglutinin H6 (H6)
AF474033.1 A/Chicken/California/1002/2000(H6N2) hemagglutinin H6
(H6) AF474032.1 A/Chicken/California/650/2000(H6N2) hemagglutinin
H6 (H6) AF474031.1 A/Chicken/California/465/2000(H6N2)
hemagglutinin H6 (H6) AF474030.1 A/cornish cross/CA/139/2001(H6N2)
matrix protein 1 (M) and DQ107424.1 matrix protein 2 (M)
A/duck/Eastern China/164/2002(H6N2) segment 6 neuraminidase
EU429762.1 (NA) A/duck/Eastern China/729/2003(H6N2) segment 6
neuraminidase EU429760.1 (NA) A/duck/Eastern China/262/2002(H6N2)
segment 6 neuraminidase EU429743.1 (NA) A/duck/Eastern
China/74/2006(H6N2) segment 6 neuraminidase EU429741.1 (NA)
A/duck/Eastern China/161/2002(H6N2) segment 6 neuraminidase
EU429740.1 (NA) A/duck/Hong Kong/960/80(H6N2)) matrix protein 1 (M)
and matrix DQ107435.1 protein 2 (M) A/duck/Hong Kong/D134/77(H6N2))
matrix protein 1 (M) and matrix DQ107433.1 protein 2 (M)
A/duck/CA/10221/2002(H6N2) matrix protein 1 (M) and matrix
DQ107421.1 protein 2 (M) A/duck/Shantou/5540/2001(H6N2) matrix
protein 1 (M) and matrix DQ107431.1 protein 2 (M) A/guinea
fowl/Hong Kong/SSP99/2002(H6N2) matrix protein 1 (M) DQ107413.1 and
matrix protein 2 (M) A/mallard/NY/016/83(H6N2) matrix protein 1 (M)
and matrix DQ107449.1 protein 2 (M) A/mallard/NY/046/83(H6N2)
matrix protein 1 (M) and matrix DQ107450.1 protein 2 (M)
A/pintail/Alberta/644/81(H6N2) matrix protein 1 (M) and matrix
DQ107445.1
protein 2 (M) A/quail/Hong Kong/SF792/2000(H6N2) matrix protein 1
(M) and DQ107410.1 matrix protein 2 (M) A/ruddy
turnstone/Delaware/106/98 (H6N2) nonfunctional matrix AY664439.1
protein A/Shorebird/Delaware/127/97(H6N2) nonfunctional matrix
protein AY664467.1 A/shorebird/Delaware/124/2001(H6N2) matrix
protein 1 (M) and DQ107417.1 matrix protein 2 (M)
A/shorebird/Delaware/208/2001(H6N2) matrix protein 1 (M) and
DQ107427.1 matrix protein 2 (M) A/turkey/CA/527/2002(H6N2) matrix
protein 1 (M) and matrix DQ107420.1 protein 2 (M)
A/turkey/CA/1623CT/2002(H6N2) matrix protein 1 (M) and matrix
DQ107425.1 protein 2 (M) A/turkey/MN/836/80(H6N2) matrix protein 1
(M) and matrix DQ107440.1 protein 2 (M) A/turkey/MN/735/79(H6N2)
matrix protein 1 (M) and matrix DQ107437.1 protein 2 (M)
A/chicken/Hong Kong/17/77(H6N4)) matrix protein 1 (M) and
DQ107436.1 matrix protein 2 (M) A/chicken/Hong
Kong/CSW106/2001(H6N4) matrix protein 1 (M) and DQ107406.1 matrix
protein 2 (M) A/gull/Delaware/18/2000(H6N4) matrix protein 1 (M)
and matrix DQ107415.1 protein 2 (M) A/pheasant/Hong
Kong/CSW2573/2001(H6N4) matrix protein 1 (M) DQ107411.1 and matrix
protein 2 (M) A/quail/Hong Kong/CSW106/2001(H6N4) matrix protein 1
(M) and DQ107430.1 matrix protein 2 (M)
A/Shorebird/Delaware/194/98(H6N4) nonfunctional matrix protein
AY664424.1 A/shorebird/Delaware/259/2000(H6N4) matrix protein 1 (M)
and DQ107416.1 matrix protein 2 (M)
A/shearwater/Australia/1/1972(H6N5) segment 6 neuraminidase
EU429794.1 (NA) A/shearwater/Australia/1/1972(H6N5) polymerase A
(PA) L25832.1 A/pintail/Alberta/1040/79(H6N5) matrix protein 1 (M)
and matrix DQ107439.1 protein 2 (M) A/blue-winged
teal/MN/993/80(H6N6)) matrix protein 1 (M) and DQ107441.1 matrix
protein 2 (M) A/duck/NY/83779/2002(H6N6) matrix protein 1 (M) and
matrix DQ107422.1 protein 2 (M) A/duck/MN/1414/81(H6N6) matrix
protein 1 (M) and matrix DQ107444.1 protein 2 (M)
A/mallard/Alberta/289/82(H6N6) matrix protein 1 (M) and matrix
DQ107447.1 protein 2 (M) A/mallard duck/MN/1041/80(H6N6) matrix
protein 1 (M) and matrix DQ107442.1 protein 2 (M)
A/pintail/Alberta/189/82(H6N6) matrix protein 1 (M) and matrix
DQ107446.1 protein 2 (M) A/sanderling/Delaware/1258/86(H6N6)
nonfunctional matrix AY664436.1 protein A/blue-winged
teal/Alberta/368/78(H6N8)) matrix protein 1 (M) DQ107438.1 and
matrix protein 2 (M) A/ruddy turnstone/Delaware/105/98 (H6N8)
nonfunctional matrix AY664428.1 protein A/domestic
duck/NY/81(H6N8)) matrix protein (M) DQ107443.1 A/duck/Eastern
China/163/2002(H6N8) segment 6 neuraminidase EU429786.1 (NA)
A/duck/Hong Kong/D182/77(H6N9) matrix protein 1 (M) and matrix
DQ107434.1 protein 2 (M) A/chicken/Hong Kong/SF3/2001(H6) matrix
protein 1 (M) and DQ107408.1 matrix protein 2 (M) A/African
starling/England/983/79(H7N1) neuraminidase (N1) AJ416629.1
A/Afri.Star./Eng-Q/938/79(H7N1) hemagglutinin precurosr AF149295.1
A/chicken/Italy/1067/99(H7N1) matrix protein 1 (M1) AJ416630.1
A/chicken/Italy/1067/99(H7N1) neuraminidase (N1) AJ416627.1
A/chicken/Italy/4575/99 (H7N1) hemagglutinin (HA) AJ493469.1
A/chicken/Italy/13474/99(H7N1) haemagglutinin (HA) AJ491720.1
A/chicken/Italy/445/1999(H7N1) AX537385.1
A/Chicken/Italy/267/00(H7N1) hemagglutinin (HA) AJ493215.1
A/Chicken/Italy/13489/99(H7N1) hemagglutinin (HA) AJ493214.1
A/Chicken/Italy/13307/99(H7N1) hemagglutinin (HA) AJ493212.1
A/chicken/Singapore/1994(H7N1) M2 protein EU014140.1 A/duck/Hong
Kong/301/78(H7N1) matrix protein 1 (M) and matrix DQ107475.1
protein 2 (M) A/Hong Kong/301/78(H7N1) hemagglutinin (HA)
AY672090.1 A/fowl plaguq virus/Rostock/34 (H7N1) NP protein
AJ243993.1 A/fowl plaguq virus/Rostock/34 (H7N1) PA protein
AJ243992.1 A/fowl plaguq virus/Rostock/34 (H7N1) PB2 protein
AJ243991.1 A/fowl plaguq virus/Rostock/34 (H7N1) PB1 protein
AJ243990.1 A/ostrich/South Africa/5352/92(H7N1) hemagglutinin
precursor U20458.1 (HA) A/rhea/North Carolina/39482/93(H7N1)
hemagglutinin precursor U20468.1 (HA) A/turkey/Italy/3775/99 (H7N1)
hemagglutinin (HA) AJ493472.1 A/turkey/Italy/4603/99 (H7N1)
hemagglutinin (HA) AJ493471.1 A/turkey/Italy/4602/99 (H7N1)
hemagglutinin (HA) AJ493470.1 A/turkey/Italy/4169/99 (H7N1)
hemagglutinin (HA) AJ493468.1 A/turkey/Italy/4073/99 (H7N1)
hemagglutinin (HA) AJ493467.1 A/turkey/Italy/3889/99 (H7N1)
hemagglutinin (HA) AJ493466.1 A/turkey/Italy/12598/99(H7N1)
haemagglutinin (HA) AJ489520.1 A/turkey/Italy/4580/99(H7N1)
haemagglutinin (HA) AJ416628.1 A/Turkey/Italy/335/00(H7N1)
haemagglutinin (HA) AJ493217.1 A/Turkey/Italy/13468/99(H7N1)
haemagglutinin (HA) AJ493216.1 A/Turkey/Italy/13467/99(H7N1)
haemagglutinin (HA) AJ493213.1 A/chicken/CT/9407/2003(H7N2) matrix
protein 1 (M) and matrix DQ107478.1 protein 2 (M)
A/chicken/NY/116124/2003(H7N2) matrix protein 1 (M) and matrix
DQ107479.1 protein 2 (M) A/chicken/PA/143586/2002(H7N2) matrix
protein 1 (M) and matrix DQ107477.1 protein 2 (M) A/duck/Hong
Kong/293/78(H7N2) matrix protein 1 (M) and matrix DQ107474.1
protein 2 (M) A/duck/Hong Kong/293/78(H7N2) hemagglutinin precursor
(HA) U20461.1 A/laughing gull/Delaware/2838/87 (H7N2) nonfunctional
matrix AY664427.1 protein A/pheasant/NJ/30739-9/2000(H7N2) matrix
protein 1 (M) and DQ107481.1 matrix protein 2 (M) A/ruddy
turnstone/Delaware/130/99 (H7N2) onfunctional matrix AY664451.1
protein A/unknown/149717-12/2002(H7N2) matrix protein 1 (M) and
matrix DQ107480.1 protein 2 (M) A/unknown/NY/74211-5/2001(H7N2)
matrix protein 1 (M) and matrix DQ107476.1 protein 2 (M)
A/unknown/149717-12/2002(H7N2) matrix protein 1 (M) and matrix
DQ107480.1 protein 2(M) A/unknown/NY/74211-5/2001(H7N2) matrix
protein 1(M) and matrix DQ107476.1 protein 2 (M) A/chicken/British
Columbia/CN7-3/04 (H7N3) hemagglutinin (HA) AY644402.1
A/chicken/British Columbia/CN7-3/04 (H7N3) matrix protein (M1)
AY677732.1 A/chicken/Italy/270638/02(H7N3) hemagglutinin (HA)
EU158111.1 A/gadwall/MD/3495/83(H7N3) matrix protein 1 (M) and
matrix DQ107488.1 protein 2 (M) A/mallard/Alberta/22/2001(H7N3)
matrix protein 1 (M) and matrix DQ107482.1 protein 2 (M)
A/mallard/Alberta/699/81(H7N3) matrix protein 1 (M) and matrix
DQ107487.1 protein 2 (M) A/pintail/Alberta/25/2001(H7N3) matrix
protein 1 (M) and matrix DQ107483.1 protein 2 (M)
A/Quail/Arkansas/16309-7/94 (H7N3) hemagglutinin protein AF072401.1
subunit 1 precursor (HA1) A/ruddy turnstone/New Jersey/65/85(H7N3)
nonfunctional matrix AY664433.1 protein A/turkey/England/63(H7N3)
hemagglutinin precursor (HA) U20462.1 A/Turkey/Colorado/13356/91
(H7N3) hemagglutinin protein subunit AF072400.1 1 precursor (HA1)
A/turkey/MN/1200/80(H7N3)) matrix protein 1 (M) and matrix
DQ107486.1 protein 2 (M) A/turkey/MN/1818/82(H7N3) matrix protein 1
(M) and matrix DQ107489.1 protein 2 (M)
A/turkey/Minnesota/1237/80(H7N3) hemagglutinin precursor (HA)
U20466.1 A/turkey/TX/1/79(H7N3) matrix protein 1 (M) and matrix
protein DQ107484.1 2 (M) A/Turkey/0regon/71(H7N3) hemagglutinin
AF497557.1 A/Turkey/Utah/24721-10/95 (H7N3) hemagglutinin protein
subunit AF072402.1 1 precursor (HA1) A/softbill/South
Africa/142/92(H7N4) hemagglutinin precursor U20464.1 (HA) A/ruddy
turnstone/Delaware/2770/87 (H7N5) nonfunctional matrix AY664476.1
protein A/chicken/Brescia/1902(H7N7) hemagglutinin 1 chain (HA)
U20471.1 A/chicken/Jena/1816/87(H7N7) hemagglutinin precursor (HA)
U20469.1 A/chicken/Leipzig/79(H7N7) hemagglutinin precursor (HA)
U20459.1 A/duck/Heinersdorf/S495/6/86(H7N7) hemagglutinin precursor
(HA) U20465.1 A/equine/Prague/1/56 (H7N7) neuraminidase U85989.1
A/equine/Santiago/77(H7N7) nucleoprotein AY383752.1
A/equine/Santiago/77(H7N7) neuraminidase AY383757.1
A/equine/Santiago/77(H7N7) hemagglutinin AY383756.1
A/FPV/Weybridge(H7N7) matrix protein M38299.1
A/goose/Leipzig/187/7/1979(H7N7) hemagglutinin L43914.1
A/goose/Leipzig/192/7/1979(H7N7) hemagglutinin L43915.1
A/goose/Leipzig/137/8/1979(H7N7) hemagglutinin L43913.1 A/ruddy
turnstone/Delaware/134/99 (H7N7) nonfunctional matrix AY664468.1
protein A/seal/Mass/1/80 H7N7 recombinant S73497.1
A/swan/Potsdam/63/6/81(H7N7) hemagglutinin precursor (HA) U20467.1
A/tern/Potsdam/342/6/79(H7N7) hemagglutinin precursor (HA) U20470.1
A/pintail/Alberta/121/79(H7N8) matrix protein 1 (M) and matrix
DQ107485.1 protein 2 (M) A/Turkey/Minnesota/38429/88(H7N9)
hemagglutinin AF497551.1 A/turkey/Ontario/6118/1968(H8N4) segment 6
neuraminidase (NA) EU429793.1 A/Mallard Duck/Alberta/357/84(H8N4)
segment 4 hemagglutinin AF310988.1 (HA1) A/Pintail
Duck/Alberta/114/79(H8N4) segment 4 hemagglutinin AF310987.1 (HA1)
A/duck/Eastern China/01/2005(H8N4) segment 6 neuraminidase (NA)
EU429780.1 A/Red Kont/Delaware/254/94(H8N4) segment 4 hemagglutinin
(HA1) AF310989.1 A/chicken/Amioz/1527/03(H9N2) nucleoprotein
DQ116511.1 A/chicken/Amioz/1527/03(H9N2) neuraminidase DQ116081.1
A/chicken/Amioz/1527/03(H9N2) hemagglutinin DQ108911.1
A/chicken/Alonim/1953/104(H9N2) hemagglutinin DQ108928.1
A/chicken/Alonim/1552/03(H9N2) hemagglutinin DQ108914.1
A/chicken/Alonim/1552/03(H9N2) nucleoprotein DQ116514.1
A/chicken/Alonim/1965/04(H9N2) hemagglutinin DQ108929.1
A/Chicken/Anhui/1/98(H9N2) hemagglutinin (HA) AF461511.1
A/Chicken/Beijing/1/95(H9N2) nonfunctional matrix protein
AF536719.1 A/Chicken/Beijing/1/95(H9N2) nucleoprotein (NP)
AF536699.1 A/Chicken/Beijing/1/95(H9N2) nonfunctional nonstructural
AF536729.1 protein A/Chicken/Beijing/1/95(H9N2) segment 6
neuraminidase (NA) AF536709.1 A/Chicken/Beijing/2/97(H9N2)
nucleoprotein (NP) AF536700.1 A/Chicken/Beijing/2/97(H9N2)
nonfunctional matrix protein AF536720.1
A/Chicken/Beijing/2/97(H9N2) nonfunctional nonstructural AF536730.1
protein A/Chicken/Beijing/2/97(H9N2) segment 6 neuraminidase (NA)
AF536710.1 A/Chicken/Beijing/1/97(H9N2) hemagglutinin (HA)
AF461530.1 A/Chicken/Beijing/3/99(H9N2) nonfunctional matrix
protein AF536721.1 A/Chicken/Beijing/3/99(H9N2) nucleoprotein (NP)
AF536701.1 A/Chicken/Beijing/3/99(H9N2) nonfunctional nonstructural
AF536731.1 protein A/Chicken/Beijing/3/99(H9N2) segment 6
neuraminidase (NA) AF536711.1 A/chicken/Beit
Alfa/1282/03(H9N2)hemagglutinin DQ104476.1
A/chicken/Beit-Aran/29/05(H9N2) hemagglutinin DQ108931.1
A/chicken/Bnei Darom/1557/03(H9N2) hemagglutinin DQ108915.1
A/chicken/Ein Habsor/1808/04(H9N2) hemagglutinin DQ108925.1
A/Chicken/Gangxi/2/00(H9N2) hemagglutinin (HA) AF461514.1
A/Chicken/Gangxi/1/00(H9N2) hemagglutinin (HA) AF461513.1
A/chicken/Gan Shomron/1465/03(H9N2) hemagglutinin DQ104480.1
A/chicken/Gan Shomron/1292/03(H9N2) hemagglutinin DQ104478.1
A/chicken/Gan_Shomron/1465/03(H9N2) nucleoprotein DQ116506.1
A/chicken/Gan_Shomron/1465/03(H9N2) neuraminidase DQ116077.1
A/chicken/Gan Shomron/1543/04(H9N2) nucleoprotein DQ116512.1
A/chicken/Gan Shomron/1543/04(H9N2) hemagglutinin DQ108912.1
A/Chicken/Guangdong/97(H9N2) nonfunctional matrix protein
AF536722.1 A/Chicken/Guangdong/97(H9N2) nucleoprotein (NP)
AF536702.1 A/Chicken/Guangdong/97(H9N2) nonfunctional nonstructural
AF536732.1 protein A/Chicken/Guangdong/97(H9N2) segment 6
neuraminidase (NA) AF536712.1 A/Chicken/Gansu/1/99(H9N2)
hemagglutinin (HA) AF461512.1
A/chicken/Gujrat/India/3697/2004(H9N2) polymerase basic 2
DQ979865.1 (PB2) A/chicken/Haryana/India/2424/2004(H9N2) polymerase
basic 2 DQ979862.1 (PB2) A/Chicken/Henan/98(H9N2) nonfunctional
matrix protein AF536726.1 A/Chicken/Henan/98(H9N2) nucleoprotein
(NP) AF536706.1 A/Chicken/Henan/98(H9N2) nonfunctional
nonstructural protein AF536736.1 A/Chicken/Henan/2/98(H9N2)
hemagglutinin (HA) AF461517.1 A/Chicken/Henan/1/99(H9N2)
hemagglutinin (HA) AF461516.1 A/Chicken/Henan/98(H9N2) segment 6
neuraminidase (NA) AF536716.1 A/Chicken/Hebei/1/96(H9N2)
nonfunctional matrix protein AF536723.1 A/Chicken/Hebei/1/96(H9N2)
segment 6 nonfunctional AF536713.1 neuraminidase protein
A/Chicken/Hebei/1/96(H9N2) nucleoprotein (NP) AF536703.1
A/Chicken/Hebei/1/96(H9N2) nonfunctional nonstructural protein
AF536733.1 A/Chicken/Hebei/1/96(H9N2) segment 6 nonfunctional
AF536713.1 neuraminidase protein A/Chicken/Hebei/2/00(H9N2)
hemagglutinin (HA) AF461531.1 A/Chicken/Hebei/2/98(H9N2)
nonfunctional matrix protein AF536724.1 A/Chicken/Hebei/2/98(H9N2)
nucleoprotein (NP) AF536704.1 A/Chicken/Hebei/2/98(H9N2)
nonfunctional nonstructural protein AF536734.1
A/Chicken/Hebei/2/98(H9N2) segment 6 neuraminidase (NA) AF536714.1
A/Chicken/Hebei/1/00(H9N2) hemagglutinin (HA) AF461515.1
A/Chicken/Hebei/3/98(H9N2) nucleoprotein (NP) AF536705.1
A/Chicken/Hebei/3/98(H9N2) nonfunctional matrix protein AF536725.1
A/Chicken/Hebei/3/98(H9N2) nonfunctional onstructural protein
AF536735.1
A/Chicken/Hebei/3/98(H9N)) segment 6 neuraminidase (NA) AF536715.1
A/chicken/Hong Kong/FY313/2000(H9N2) matrix protein 1 (M) and
DQ107508.1 matrix protein 2 (M) A/chicken/Hong
Kong/WF208/2001(H9N2) matrix protein 1 (M) and DQ107513.1 matrix
protein 2 (M) A/chicken/Hong Kong/NT471/2002(H9N2) matrix protein 1
(M) and DQ107514.1 matrix protein 2 (M) A/chicken/Hong
Kong/WF2/99(H9N2) hemagglutinin AY206677.1
A/chicken/Iarah/1376/03(H9N2) nucleoprotein DQ116504.1
A/chicken/Iarah/1376/03(H9N2) neuraminidase DQ116075.1
A/chicken/Iarah/1376/03(H9N2) hemagglutinin DQ108910.1
A/chicken/India/2793/2003(H9N2) hemagglutinin (HA) AY336597.1
A/chicken/Iran/101/1998(H9N2) matrix protein 2 (M2) EU477375.1
A/Chicken/Jiangsu/1/99(H9N)) hemagglutinin (HA) AF461509.1
A/Chicken/Jiangsu/2/98(H9N2) hemagglutinin (HA) AF461510.1
A/chicken/Kfar Monash/636/02(H9N2) hemagglutinin DQ104464.1
A/chicken/Kalanit/1966/06.12.04(H9N2) hemagglutinin DQ108930.1
A/chicken/Kaianit/1946/04(H9N2) hemagglutinin DQ108927.1
A/chicken/Korea/S4/2003(H9N2) matrix protein 1 (M) and matrix
DQ107517.1 protein 2 (M) A/Chicken/Korea/MS96/96(H9N2) matrix
protein 1 and 2 (M) AF203788.1 A/Chicken/Korea/MS96/96(H9N2)
neuraminidase subtype 2 AF203786.1 A/Chicken/Korea/MS96/96(H9N2)
nucleoprotein AF203787.1 A/Chicken/Liaoning/99(H9N2) nonfunctional
matrix protein AF536727.1 A/Chicken/Liaoning/1/00(H9N2)
hemagglutinin (HA) AF461518.1 A/Chicken/Liaoning/99(H9N2)
nucleoprotein (NP) AF536707.1 A/Chicken/Liaoning/99(H9N2)
nonfunctional matrix protein AF536727.1 A/Chicken/Liaoning/99(H9N2)
nonfunctional onstructural protein AF536737.1
A/Chicken/Liaoning/2/00(H9N2) hemagglutinin (HA) AF461519.1
A/chicken/Liaoning/99(H9N2) segment 6 neuraminidase (NA) AF536717.1
A/chicken/Mudanjiang/0823/2000(H9N2) nucleoprotein (NP) AY496851.1
A/Chicken/Mudanjiang/0823/2000 (H9N2) nonstructural protein
AY631868.1 A/Chicken/Mudanjiang/0823/00 (H9N2) hemagglutinin (HA)
AY513715.1 A/chicken/Mudanjiang/0823/2000(H9N2) matrix protein (M1)
AY496852.1 A/chicken/Mudanjiang/0823/2000(H9N2) nucleoprotein (np)
AY496851.1 A/chicken/Maale HaHamisha/90658/00(H9N2) hemagglutinin
DQ104472.1 A/chicken/Maanit/1477/03(H9N2) hemagglutinin DQ104483.1
A/chicken/Maanit/1291/03(H9N2) hemagglutinin DQ104477.1
A/chicken/Maanit/1275/03(H9N2) hemagglutinin DQ104457.1
A/chicken/Maanit/1477/03(H9N2) nucleoprotein DQ116508.1
A/chicken/Netohah/1373/03 (H9N2) nucleoprotein DQ116503.1
A/chicken/Netohah/1373/03 (H9N2) neuraminidase DQ116074.1
A/chicken/Netohah/1373/03 (H9N2) hemagglutinin DQ108909.1
A/chicken/Neve Ilan/1504/03(H9N2) hemagglutinin DQ104484.1
A/chicken/Neve_Ilan/1504/03(H9N2) nucleoprotein DQ116509.1
A/chicken/Neve_Ilan/1504/03(H9N2) neuraminidase DQ116079.1
A/chicken/Orissa/India/2317/2004(H9N2) polymerase basic 2 (PB2)
DQ979861.1 A/chicken/Pardes-Hana-Carcur/1475/03(H9N2) hemagglutinin
DQ104482.1 A/chicken/Pardes-Hana-Carcur/1475/03(H9N2) neuraminidase
DQ116078.1 A/chicken/Saar/1456/03(H9N2) hemagglutinin DQ104479.1
A/chicken/Sde_Uziahu/1747/04(H9N2) neuraminidase DQ116068.1
A/chicken/Sede Uzziyyahu/1651/04(H9N2) hemagglutinin DQ108923.1
A/chicken/Sde Uziahu/1747/04(H9N2) DQ108905.1
A/chicken/Singapore/1998(H9N2) M2 protein EU014142.1
A/chicken/Singapore/1998(H9N2) M2 protein EU014142.1
A/Chicken/Shandong/98(H9N2) nonfunctional matrix protein AF536728.1
A/Chicken/Shandong/1/98(H9N2) hemagglutinin (HA) AF461520.1
A/Chicken/Shandong/98(H9N2) nucleoprotein (NP) AF536708.1
A/Chicken/Shandong/98(H9N2) nonfunctional nonstructural protein
AF536738.1 A/Chicken/Shandong/98(H9N2) segment 6 neuraminidase (NA)
AF536718.1 A/Chicken/Shandong/2/99(H9N2) hemagglutinin (HA)
AF461521.1 A/chicken/Shandong/1/02(H9N2) neuraminidase (NA)
AY295761.1 A/Chicken/Shanghai/F/98(H9N2) hemagglutinin AF461532.1
A/Chicken/Shanghai/1/02(H9N2) hemagglutinin AY281745.1
A/Chicken/Shanghai/2/99(H9N2)) hemagglutinin (HA) AF461522.1
A/Chicken/Shanghai/3/00(H9N2)) hemagglutinin (HA) AF461523.1
A/Chicken/Shanghai/F/98(H9N2) hemagglutinin (HA) AY743216.1
A/Chicken/Shanghai/4-2/01(H9N2) hemagglutinin (HA) AF461525.1
A/Chicken/Shanghai/4-1/01(H9N2) hemagglutinin (HA) AF461524.1
A/Chicken/Shanghai/4/01(H9N2) hemagglutinin (HA) AY083841.1
A/Chicken/Shanghai/3/01(H9N2) hemagglutinin HA) AY083840.1
A/chicken/Talmei_Elazar/1304/03(H9N2)nucleoprotein DQ116530.1
A/chicken/Talmei_Elazar/1304/03(H9N2) neuraminidase DQ116072.1
A/Chicken/Tianjing/2/96(H9N2) hemagglutinin AF461527.1
A/Chicken/Tianjing/1/96(H9N2) hemagglutinin (HA) AF461526.1
A/chicken/Tel Adashim/811/01 (H9N2) hemagglutinin DQ104467.1
A/chicken/Tel Adashim/811/01 (H9N2) nucleoprotein DQ116527.1
A/ck/Tel_Adashim/811/01(H9N2) neuraminidase DQ116064.1
A/chicken/Tel Adashim/812/01 (H9N2) nucleoprotein DQ116528.1
A/chicken/Tel Adashim/812/01 (H9N2) hemagglutinin DQ104468.1
A/ck/Tel_Adashim/812/01(H9N2) neuraminidase DQ116065.1
A/chicken/Tel Adashim/786/01 (H9N2) nucleoprotein DQ116524.1
A/chicken/Tel Adashim/809/01 (H9N2) hemagglutinin DQ104465.1
A/chicken/Tel Adashim/809/01 (H9N2) nucleoprotein DQ116525.1
A/chicken/Tel Adashim/1469/03 (H9N2) nucleoprotein DQ116507.1
A/chicken/Tel Adashim/1469/303(H9N2) hemagglutinin DQ104481.1
A/chicken/Tel Adashim/1506/03 (H9N2) neuraminidase DQ116080.1
A/chicken/Tel Adashim/1506/03(H9N2) hemagglutinin DQ104474.1
A/chicken/Tel Adashim/1506/03 (H9N2) nucleoprotein DQ116510.1
A/chicken/Tel Adashim/1332/03(H9N2) nucleoprotein DQ116501.1
A/chicken/Tel Adashim/1321/03(H9N2) nucleoprotein DQ116500.1
A/chicken/Tel Adashim/1332/03(H9N2) hemagglutinin DQ108907.1
A/chicken/Tel Adashim/1321/03(H9N2) hemagglutinin DQ108906.1
A/chicken/Telmond/1308/03(H9N2) nucleoprotein DQ116499.1
A/chicken/Telmond/1308/03(H9N2) neuraminidase DQ116073.1
A/chicken/Telmond/1308/03(H9N2) hemagglutinin DQ108921.1
A/chicken/Tzrofa/1568/04(H9N2) nucleoprotein DQ116519.1
A/chicken/Tzrofa/1568/04(H9N2) hemagglutinin DQ108919.1
A/chicken/UP/India/2544/2004(H9N2) polymerase basic 2 (PB2)
DQ979864.1 A/chicken/UP/India/2543/2004(H9N2) polymerase basic 2
(PB2) DQ979863.1 A/chicken/Wangcheng/4/2001(H9N2) nucleoprotein
AY268949.1 A/chicken/Ysodot/1362/03(H9N2) nucleoprotein DQ116502.1
A/chicken/Ysodot/1362/03(H9N2) hemagglutinin DQ108908.1
A/Chicken/Yunnan/2/00(H9N2) hemagglutinin (HA) AF461529.1
A/Chicken/Yunnan/1/99(H9N2) hemagglutinin (HA) AF461528.1
A/duck/Eastern China/01/2000(H9N2) segment 6 neuraminidase (NA)
EU429725.1 A/duck/Eastern China/48/2001(H9N2) segment 6
neuraminidase (NA) EU429707.1 A/duck/Eastern China/66/2003(H9N2)
segment 6 neuraminidase (NA) EU429699.1 A/duck/Eastern
China/80/2004(H9N2) segment 6 neuraminidase (NA) EU429726.1
A/duck/Hong Kong/448/78(H9N2) matrix protein 1 (M) and matrix
DQ107494.1 protein 2 (M) A/duck/Hong Kong/448/78(H9N2)
hemagglutinin precursor AY206673.1 A/duck/Hong Kong/366/78(H9N2)
hemagglutinin precursor AY206674.1 A/duck/Hong Kong/784/79(H9N2))
matrix protein 1(M) and matrix DQ107496.1 protein 2 (M) A/duck/Hong
Kong/702/79(H9N2) matrix protein 1 (M) and matrix DQ107495.1
protein 2 (M) /duck/Hong Kong/702/79(H9N2) hemagglutinin precursor
AY206672.1 A/duck/Hong Kong/610/79(H9N2) hemagglutinin precursor
AY206680.1 A/duck/Hong Kong/552/79(H9N2) hemagglutinin precursor
AY206679.1 A/duck/Hong Kong/644/79(H9N2) hemagglutinin precursor
AY206678.1 A/duck/Korea/S13/2003(H9N2) matrix protein 1 (M) and
matrix DQ107518.1 protein 2 (M) A/duck/Nanchang/4-361/2001(H9N2)
matrix protein 1 (M) and DQ107511.1 matrix protein 2 (M)
A/duck/NY/83793/2002(H9N2) matrix protein 1 (M) and matrix
DQ107499.1 protein 2 (M) A/goose/MN/5733-1243/80(H9N2) matrix
protein 1 (M) and matrix DQ107492.1 protein 2 (M) A/geese/Tel
Adashim/829/01(H9N2) hemagglutinin DQ104469.1 A/geese/Tel
Adashim/830/01(H9N2 hemagglutinin DQ104470.1
A/ostrich/Eshkol/1436/03(H9N2) neuraminidase DQ116076.1
A/ostrich/Eshkol/1436/03(H9N2) nucleoprotein DQ116505.1
A/pigeon/Hong Kong/WF286/2000(H9N2) matrix protein 1 (M) and
DQ107509.1 matrix protein 2 (M) A/quail/Hong Kong/YU415/2002(H9N2)
matrix protein 1 (M) and DQ107516.1 matrix protein 2 (M)
A/quail/Hong Kong/SSP225/2001(H9) matrix protein 1 (M) and
DQ107512.1 matrix protein 2 (M) A/quail/Hong Kong/YU1495/2000(H9N2)
matrix protein 1 (M) and DQ107510.1 matrix protein 2 (M)
A/quail/Hong Kong/A28945/88(H9N2) hemagglutinin precursor
AY206675.1 A/shorebird/Delaware/276/99 (H9N2) nonfunctional matrix
protein AY664464.1 A/shorebird/Delaware/113/2001(H9N2) matrix
protein 1 (M) and DQ107505.1 matrix protein 2 (M) A/silky
chicken/Hong Kong/WF266/2002(H9N2) matrix protein 2 (M) DQ107515.1
and matrix protein 1 (M) A/shorebird/Delaware/77/2001(H9N2) matrix
protein 1 (M) and DQ107497.1 matrix protein 2 (M) A/guinea
fowl/Hong Kong/WF10/99(H9N2) hemagglutinin precursor AY206676.1
A/swine/Hangzhou/1/2006(H9N2) nucleocapsid protein (NP) DQ907704.1
A/swine/Hangzhou/1/2006(H9N2)) matrix protein 1 (M1) EF055887.1
A/swine/Hangzhou/1/2006(H9N2)) nonstructural protein 1 (NS1)
DQ823385.1 A/Sw/ShanDong/1/2003(H9N2) hemagglutinin (HA) AY294658.1
A/turkey/CA/6889/80(H9N2) matrix protein 1 (M) and matrix
DQ107491.1 protein 2 (M) A/turkey/TX/28737/81(H9N2) matrix protein
1 (M) and matrix DQ107493.1 protein 2 (M) A/turkey/MN/511/78(H9N2)
matrix protein 1 (M) and matrix DQ107490.1 protein 2 (M)
A/turkey/Beit Herut/1267/03(H9N2) hemagglutinin DQ104485.1
A/turkey/Beit HaLevi/1009/02(H9N2) hemagglutinin DQ104473.1
A/turkey/Beit Herut/1265/03(H9N2) hemagglutinin DQ104456.1
A/turkey/Beit_HaLevi/1562/03(H9N2) nucleoprotein DQ116515.1
A/turkey/Beit_HaLevi/1566/04(H9N2) nucleoprotein DQ116517.1
A/turkey/Beit_HaLevi/1562/03(H9N2) neuraminidase DQ116083.1
A/turkey/Beit_HaLevi/1566/04(H9N2) neuraminidase DQ116084.1
A/turkey/Beit_Herut/1267/03(H9N2) neuraminidase DQ116070.1
A/turkey/Beit_Herut/1265/03(H9N2) neuraminidase DQ116069.1
A/turkey/Beit HaLevi/1566/04(H9N2) hemagglutinin DQ108917.1
A/turkey/Bezat/89/05(H9N2) hemagglutinin DQ108922.1
A/turkey/Brosh/1276/03(H9N2) hemagglutinin DQ104458.1
A/turkey/Brosh/1276/03(H9N2) neuraminidase DQ116071.1 A/turkey/Emek
Hefer/1272/03(H9N2) hemagglutinin DQ104475.1 A/turkey/Ein
Habsor/1804/04(H9N2) hemagglutinin DQ108924.1 A/turkey/Ein
Tzurim/1172/02(H9N2) hemagglutinin DQ104451.1 A/turkey/Ein
Tzurim/1738/04(H9N2) hemagglutinin DQ108920.1
A/turkey/Ein_Tzurim/1738/04(H9N2) neuraminidase DQ116085.1
A/turkey/Gyvat Haim Ehud/1544/03(H9N2)hemagglutinin DQ108913.1
A/turkey/Givat Haim/810/01 (H9N2) hemagglutinin DQ104466.1
A/turkey/Givat Haim/810/01 (H9N2) nucleoprotein DQ116526.1
A/turkey/Givat Haim/868/02(H9N2) hemagglutinin DQ104471.1
A/turkey/Givat Haim/622/02(H9N2) hemagglutinin DQ104462.1
A/turkey/Givat_Haim/965/02(H9N2) nucleoprotein DQ116498.1
A/turkey/Gyvat_Haim_Ehud/1544/03(H9N2) nucleoprotein DQ116513.1
A/turkey/Gyvat_Haim_Ehud/1544/03(H9N2) neuraminidase DQ116082.1
A/tk/Givat_Haim/810/25.12.01(H9N2) neuraminidase DQ116063.1
A/turkey/Givat_Haim/622/02(H9N2)) neuraminidase DQ116060.1
A/turkey/Givat_Haim/965/02(H9N2) neuraminidase DQ116057.1
A/turkey/Hod_Ezyon/699/02(H9N2) neuraminidase DQ116062.1
A/turkey/Mishmar Hasharon/619/02 (H9N2) hemagglutinin DQ104461.1
A/turkey/Mishmar_Hasharon/619/02(H9N2) neuraminidase DQ116059.1
A/turkey/Kfar_Vitkin/616/02(H9N2) neuraminidase DQ116058.1
A/turkey/Kfar Vitkin/616/02 (H9N2) hemagglutinin DQ104460.1
A/turkey/Kfar Vitkin/615/02 (H9N2)hemagglutinin DQ104459.1
A/turkey/Kfar Vitkin/615/02 (H9N2) nucleoprotein DQ116520.1
A/turkey/Kfar_Vitkin/616/02(H9N2)) nucleoprotein DQ116521.1
A/turkey/Kfar Warburg/1224/03(H9N2) hemagglutinin DQ104455.1
A/tk/Kfar_Vitkin/615/02(H9N)) neuraminidase DQ116067.1
A/turkey/Mishmar_Hasharon/619/02(H9N2) nucleoprotein DQ116522.1
A/turkey/Naharia/1013/02(H9N2) hemagglutinin DQ104449.1
A/turkey/Nahalal/1547/04(H9N2) hemagglutinin DQ108932.1
A/turkey/Neve Ilan/90710/00 (H9N2) nucleoprotein DQ116529.1
A/tk/Neve_Ilan/90710/00(H9N2) neuraminidase DQ116066.1
A/turkey/Qevuzat_Yavne/1242/03(H9N2) neuraminidase DQ116086.1
A/turkey/Sapir/1199/02(H9N2) hemagglutinin DQ104452.1
A/turkey/Shadmot Dvorah/1567/04(H9N2) nucleoprotein DQ116518.1
A/turkey/Shadmot Dvorah/1567/04(H9N2) hemagglutinin DQ108918.1
A/turkey/Tzur Moshe/1565/04(H9N2) nucleoprotein DQ116516.1
A/turkey/Tzur Moshe/1565/04(H9N2) hemagglutinin DQ108916.1
A/turkey/Yedidia/625/02 (H9N2) hemagglutinin DQ104463.1
A/turkey/Yedidia/625/02 (H9N2) nucleoprotein DQ116523.1
A/turkey/Yedidia/625/02 (H9N2) neuraminidase DQ116061.1
A/turkey/Yedidia/911/02(H9N2) hemagglutinin DQ104448.1
A/turkey/Avigdor/1215/03(H9N2) hemagglutinin DQ104454.1
A/turkey/Avigdor/1209/03(H9N2) hemagglutinin DQ104453.1
A/turkey/Avichail/1075/02(H9N2) hemagglutinin DQ104450.1
A/turkey/Avigdor/1920/04(H9N2) hemagglutinin DQ108926.1
A/pintail/Alberta/49/2003(H9N5) matrix protein 1 (M) and matrix
DQ107498.1 protein 2 (M) A/red knot/Delaware/2552/87 (H9N5)
nonfunctional matrix protein AY664472.1 A/duck/Hong
Kong/147/77(H9N6) hemagglutinin precursor AY206671.1
A/shorebird/Delaware/270/2001(H9N7) matrix protein 1 (M) and
DQ107504.1 matrix protein 2 (M) A/shorebird/Delaware/277/2000(H9N7)
matrix protein 1 (M) and DQ107507.1 matrix protein 2 (M)
A/shorebird/Delaware/275/2001(H9N7)) matrix protein 2 (M) and
DQ107506.1 matrix protein 1 (M) A/ruddy turnstone/Delaware/116/98
(H9N8) nonfunctional matrix AY664435.1 protein
A/shorebird/Delaware/141/2002(H9N9) matrix protein 1 (M) and
DQ107503.1 matrix protein 2 (M) A/ruddy
turnstone/Delaware/103/2002(H9N9) matrix protein 1 (M) DQ107502.1
and matrix protein 2 (M) A/shorebird/Delaware/29/2002(H9N9) matrix
protein 1 (M) and DQ107501.1 matrix protein 2 (M)
A/shorebird/Delaware/18/2002(H9N9) matrix protein 1 (M) and
DQ107500.1 matrix protein 2 (M) A/ruddy turnstone/Delaware/259/98
(H9N9) nonfunctional matrix AY664469.1 protein A/duck/Eastern
China/527/2003(H10N3) segment 6 neuraminidase EU429716.1
(NA) A/duck/Eastern China/495/2003(H10N3) segment 6 neuraminidase
EU429715.1 (NA) A/duck/Eastern China/372/2003(H10N3) segment 6
neuraminidase EU429714.1 (NA) A/duck/Eastern China/488/2003(H10N3)
segment 6 neuraminidase EU429712.1 (NA) A/duck/Eastern
China/453/2002(H10N3) segment 6 neuraminidase EU429711.1 (NA)
A/duck/Eastern China/412/2003(H10N3) segment 6 neuraminidase
EU429710.1 (NA) A/duck/Eastern China/404/2003(H10N3) segment 6
neuraminidase EU429709.1 (NA) A/duck/Eastern China/397/2003(H10N3)
segment 6 neuraminidase EU429708.1 (NA) A/duck/Eastern
China/502/2003(H10N3) segment 6 neuraminidase EU429705.1 (NA)
A/duck/Eastern China/395/2003(H10N3) segment 6 neuraminidase
EU429704.1 (NA) A/duck/Eastern China/356/2003(H10N3) segment 6
neuraminidase EU429703.1 (NA) A/duck/Eastern China/368/2003(H10N3)
segment 6 neuraminidase EU429702.1 (NA)
A/chicken/Singapore/1993(H10N5) M2 protein EU014145.1 A/red
knot/Delaware/2561/87 (H10N5) nonfunctional matrix AY664441.1
protein A/chicken/Germany/N/1949(H10N7) segment 6 neuraminidase
(NA) EU429796.1 A/ruddy turnstone/Delaware/2764/87 (H10N7)
nonfunctional matrix AY664462.1 protein A/mallard/Alberta/71/98
(H10N7) nonfunctional matrix protein AY664485.1
A/mallard/Alberta/90/97 (H10N7) nonfunctional matrix protein
AY664446.1 A/mallard/Alberta/110/99(Hl0N7) nonfunctional matrix
protein AY664481.1 A/mallard/Alberta/297/77 (H10N7) nonfunctional
matrix protein AY664430.1 A/mallard/Alberta/223/98 (H10N8)
nonfunctional matrix protein AY664486.1 A/ruddy turnstone/New
Jersey/51/85 (H11N1) nonfunctional matrix AY664479.1 protein
A/duck/Nanchang/1749/1992(H11N2) nucleoprotein (NP) U49094.1
A/duck/Hong Kong/62/1976(H11N2) polymerase (PB1) U48280.1
A/duck/Yangzhou/906/2002(H11N2) hemagglutinin DQ080993.1
A/shorebird/Delaware/86/99 (H11N2) nonfunctional matrix protein
AY664463.1 A/ruddy turnstone/Delaware
Bay/2762/1987(H11N2)polymerase PB2 CY126279.1 (PB2) A/ruddy
turnstone/Delaware/2762/87 (H11N2) nonfunctional AY664459.1 matrix
protein A/ruddy turnstone/Delaware Bay/2762/1987(H11N2) polymerase
PB1 CY126278.1 (PB1) and PB1-F2 protein (PB1-F2) A/ruddy
turnstone/Delaware/2589/87 (H11N4) nonfunctional matrix AY664478.1
protein A/duck/England/1/1956(H11N6) segment 6 neuraminidase (NA)
EU429795.1 A/mallard/Alberta/125/99 (H11N6) nonfunctional matrix
protein AY664483.1 A/duck/Memphis/546/1974(H11N9) segment 6
neuraminidase (NA) EU429798.1 A/mallard/Alberta/122/99 (H11N9)
nonfunctional matrix protein AY664444.1 A/Mallard
Duck/Alberta/342/83(H12N1) segment 4 hemagglutinin AF310991.1 (HA1)
A/ruddy turnstone/Delaware/67/98(H12N4) nonfunctional matrix
AY664470.1 protein A/Ruddy Turnstone/Delaware/67/98(H12N4) segment
4 hemagglutinin AF310990.1 (HA1) A/mallard/Alberta/52/97 (H12N5)
nonfunctional matrix protein AY664448.1 A/mallard/Alberta/223/77
(H12N5) nonfunctional matrix protein AY664431.1 A/Laughing Gull/New
Jersey/171/92(H12N5) segment 4 AF310992.1 hemagglutinin (HA1)
A/ruddy turnstone/Delaware/265/98 (H12N8) nonfunctional matrix
AY664438.1 protein A/herring gull/New Jersey/782/86 (H13N2)
nonfunctional matrix AY664475.1 protein A/shorebird/Delaware/224/97
(H13N6) nonfunctional matrix AY664421.1 protein A/PR/8/34 (H1N1)
.times. A/England/939/69 (H3N2) PB1 protein AJ564806.1 A/PR/8/34
(H1N1) .times. A/England/939/69 (H3N2)PB2 protein AJ564804.1
A/duck/Czechslovakia/56(H4N6) .times. A/USSR/90/77(H1N1))
EU643639.1 neuraminidase (NA) A/duck/Czechslovakia/56(H4N6) .times.
A/USSR/90/77(H1N1)) EU643638.1 neuraminidase (NA)
A/duck/Ukraine/63(H3N8) .times. A/USSR/90/77(H1N1)) neuraminidase
EU643637.1 (NA) A/duck/Ukraine/63(H3N8) .times. A/USSR/90/77(H1N1))
neuraminidase EU643636.1 (NA) RCB1-XXI: A/USSR/90/77(H1N1) .times.
A/Duck/Czechoslov 56 (H4N6) AF290438.1 segment 4 hemagglutinin
RCB1: A/USSR/90/77(H1N1) .times. A/Duck/Czechoslov 56 (H4N6)
AF290437.1 hemagglutinin PX14-XIII (A/USSR/90/77(H1N1) .times.
A/Pintail AF290442.1 Duck/Primorie/695/76(H2N3)) segment 4
hemagglutinin PX14(A/USSR/90/77(H1N1) .times. A/Pintail
Duck/Primorie/695/76(H2N3)) AF290441.1 segment 4 hemagglutinin
PX8-XIII(A/USSR/90/77(H1N1) .times. A/Pintail
Duck/Primorie/695/76(H2N3)) segment 4 hemagglutinin
PX8(A/USSR/90/77(H1N1) .times. A/Pintail
Duck/Primorie/695/76(H2N3)) AF290439.1 segment 4 hemagglutinin
A/swine/Schleswig-Holstein/1/93 hemagglutinin (HA) U72669.1
A/swine/England/283902/93 hemagglutinin (HA) U72668.1
A/swine/England/195852/92 hemagglutinin (HA) U72667.1
A/swine/England/117316/86 hemagglutinin (HA) U72666.1
A/turkey/Germany/2482/90) hemagglutinin (HA) U96766.1
TABLE-US-00016 TABLE 12 Influenza B Antigens GenBank Strain/Protein
Access No. B/Daeku/47/97 hemagglutinin AF521237.1 B/Daeku/45/97
hemagglutinin AF521236.1 B/Daeku/10/97 hemagglutinin AF521221.1
B/Daeku/9/97 hemagglutinin AF521220.1 B/Gyeonggi/592/2005
neuraminidase DQ231543.1 B/Gyeonggi/592/2005 hemagglutinin
DQ231538.1 B/Hong Kong/5/72 neuraminidase AF305220.1 B/Hong
Kong/5/72 hemagglutinin AF305219.1 B/Hong Kong/157/99 hemagglutinin
AF387503.1 B/Hong Kong/157/99 hemagglutinin AF387502.1 B/Hong
Kong/156/99 hemagglutinin AF387501.1 B/Hong Kong/156/99
hemagglutinin AF387500.1 B/Hong Kong/147/99 hemagglutinin
AF387499.1 B/Hong Kong/147/99 hemagglutinin AF387498.1 B/Hong
Kong/110/99 hemagglutinin AF387497.1 B/Hong Kong/110/99
hemagglutinin AF387496.1 B/Incheon/297/2005 hemagglutinin
DQ231539.1 B/Incheon/297/2005 neuraminidase DQ231542.1 B/Lee/40
polymerase protein (PB1) D00004.1 B/Michigan/22572/99 hemagglutinin
AY129961.1 B/Michigan/22723/99 hemagglutinin (HA) AY112992.1
B/Michigan/22631/99 hemagglutinin (HA) AY112991.1
B/Michigan/22587/99 hemagglutinin (HA) AY112990.1 B/New
York/20139/99 hemagglutinin AY129960.1 B/Panama/45/90 nucleoprotein
AF005739.1 B/Panama/45/90 polymerase (PA) AF005738.1 B/Panama/45/90
polymerase (PB2) AF005737.1 B/Panama/45/90 polymerase (PB1)
AF005736.1 B/Pusan/250/99 hemagglutinin AF521218.1 B/Pusan/255/99
hemagglutinin AF521226.1 B/Pusan/270/99 hemagglutinin AF521219.1
B/Pusan/285/99 hemagglutinin AF521217.1 B/Riyadh/01/2007 segment 8
nuclear export protein (NEP) GU135839.1 and non structural protein
1 (NS1) B/Seoul/6/88 hemagglutinin AF521238.1 B/Seoul/12/88
hemagglutinin AF521239.1 B/Seoul/1/89 hemagglutinin AF521230.1
B/Seoul/37/91 hemagglutinin AF521229.1 B/Seoul/38/91 hemagglutinin
AF521227.1 B/Seoul/40/91 hemagglutinin AF521235.1 B/Seoul/41/91
hemagglutinin AF521228.1 B/Seoul/13/95 hemagglutinin AF521225.1
B/Seoul/12/95 hemagglutinin AF521223.1 B/Seoul/17/95 hemagglutinin
AF521222.1 B/Seoul/21/95 hemagglutinin AF521224.1 B/Seoul/16/97
hemagglutinin AF521233.1 B/Seoul/19/97 hemagglutinin AF521231.1
B/Seoul/28/97 hemagglutinin AF521234.1 B/Seoul/31/97 hemagglutinin
AF521232.1 B/Seoul/232/2004 neuraminidase DQ231541.1
B/Seoul/1163/2004 neuraminidase DQ231540.1 B/Seoul/1163/2004
hemagglutinin DQ231537.1 B/Sichuan/379/99 hemagglutinin (HA)
AF319590.1 B/Sichuan/38/2000 hemagglutinin (HA) AF319589.1 B/South
Carolina/25723/99 hemagglutinin AY129962.1 B/Switzerland/4291/97
hemagglutinin AF387505.1 B/Switzerland/4291/97 hemagglutinin
AF387504.1 B/Taiwan/21706/97 nonstructural protein 1 (NS1)
AF492479.1 B/Taiwan/21706/97 hemagglutinin (HA) AF026162.1
B/Taiwan/3143/97 nonstructural protein 1 (NS1) AF492478.1
B/Taiwan/3143/97 haemagglutinin (HA) AF026161.1 B/Taiwan/2026/99
nonstructural protein 1 (NS1) AF492481.1 B/Taiwan/2026/99
hemagglutinin AY604741.1 B/Taiwan/2027/99 nonstructural protein 1
(NS1) AF492480.1 B/Taiwan/2027/99 hemagglutinin AY604742.1
B/Taiwan/1243/99 nonstructural protein NS1(NS1) AF380504.1
B/Taiwan/1243/99 hemagglutinin AY604740.1 B/Taiwan/2195/99
hemagglutinin AY604743.1 B/Taiwan/2195/99 nonstructural protein 1
(NS1) AF492482.1 B/Taiwan/1293/2000 nonstructural protein NS1(NS1)
AF380509.1 B/Taiwan/1293/00 hemagglutinin AY604746.1
B/Taiwan/1293/2000 hemagglutinin (HA) AF492477.1 B/Taiwan/1265/2000
nonstructural protein NS1 (NS1) AF380508.1 B/Taiwan/1265/00
hemagglutinin AY604745.1 B/Taiwan/4184/2000 nonstructural protein
NS1 (NS1) AF380507.1 B/Taiwan/4184/00 hemagglutinin (HA) AY604750.1
B/Taiwan/31511/2000 nonstructural protein NS1 (NS1) AF380505.1
B/Taiwan/31511/00 hemagglutinin (HA) AY604748.1 B/Taiwan/12192/2000
hemagglutinin AY604747.1 B/Taiwan/41010/00 hemagglutinin (HA)
AY604749.1 B/Taiwan/41010/2000 nonstructural protein NS1 (NS1)
AF380506.1 B/Taiwan/0409/00 hemagglutinin (HA) AY604744.1
B/Taiwan/202/2001 nonstructural protein 1 (NS1) AF380512.1
B/Taiwan/202/2001 hemagglutinin (HA) AF366076.1 B/Taiwan/11515/2001
nonstructural protein 1 (NS1) AF380511.1 B/Taiwan/11515/01
hemagglutinin AY604754.1 B/Taiwan/11515/2001 hemagglutinin (HA)
AF366075.1 B/Taiwan/1103/2001 nonstructural protein NS1 (NS1)
AF380510.1 B/Taiwan/1103/01 hemagglutinin AY604755.1
B/Taiwan/114/2001 hemagglutinin (HA), HA-4 allele AF492476.1
B/Taiwan/2805/2001 hemagglutinin (HA) AF400581.1 B/Taiwan/2805/01
hemagglutinin (HA) AY604752.1 B/Taiwan/0114/01 hemagglutinin (HA)
AY604753.1 B/Taiwan/0202/01 hemagglutinin (HA) AY604751.1
B/Taiwan/4119/02 hemagglutinin (HA) AY604778.1 B/Taiwan/4602/02
hemagglutinin (HA) AY604777.1 B/Taiwan/1950/02 hemagglutinin (HA)
AY604776.1 B/Taiwan/1949/02 hemagglutinin (HA) AY604775.1
B/Taiwan/1584/02 hemagglutinin (HA) AY604774.1 B/Taiwan/1561/02
hemagglutinin (HA) AY604773.1 B/Taiwan/1536/02 hemagglutinin (HA)
AY604772.1 B/Taiwan/1534/02 hemagglutinin (HA) AY604771.1
B/Taiwan/1503/02 hemagglutinin (HA) AY604770.1 B/Taiwan/1502/02
hemagglutinin (HA) AY604769.1 B/Taiwan/1013/02 hemagglutinin (HA)
AY604768.1 B/Taiwan/0993/02 hemagglutinin (HA) AY604766.1
B/Taiwan/0932/02 hemagglutinin (HA) AY604765.1 B/Taiwan/0927/02
hemagglutinin (HA) AY604764.1 B/Taiwan/0880/02 hemagglutinin (HA)
AY604763.1 B/Taiwan/0874/02 hemagglutinin (HA) AY604762.1
B/Taiwan/0730/02 hemagglutinin (HA) AY604761.1 B/Taiwan/0722/02
hemagglutinin (HA) AY604760.1 B/Taiwan/0702/02 hemagglutinin (HA)
AY604759.1 B/Taiwan/0654/02 hemagglutinin (HA) AY604758.1
B/Taiwan/0600/02 hemagglutinin (HA) AY604757.1 B/Taiwan/0409/02
hemagglutinin (HA) AY604756.1 B/Taiwan/0879/02 nonfunctional
hemagglutinin AY604767.1 B/Taiwan/3532/03 hemagglutinin (HA)
AY604794.1 B/Taiwan/2551/03 hemagglutinin (HA) AY604793.1
B/Taiwan/1618/03 hemagglutinin (HA) AY604792.1 B/Taiwan/1574/03
hemagglutinin (HA) AY604791.1 B/Taiwan/1013/03 hemagglutinin (HA)
AY604790.1 B/Taiwan/0833/03 hemagglutinin (HA) AY604789.1
B/Taiwan/0735/03 hemagglutinin (HA) AY604788.1 B/Taiwan/0699/03
hemagglutinin (HA) AY604787.1 B/Taiwan/0684/03 hemagglutinin (HA)
AY604786.1 B/Taiwan/0616/03 hemagglutinin (HA) AY604785.1
B/Taiwan/0615/03 hemagglutinin (HA) AY604784.1 B/Taiwan/0610/03
hemagglutinin (HA) AY604783.1 B/Taiwan/0576/03 hemagglutinin (HA)
AY604782.1 B/Taiwan/0569/03 hemagglutinin (HA) AY604781.1
B/Taiwan/0562/03 hemagglutinin (HA) AY604780.1 B/Taiwan/0002/03
hemagglutinin (HA) AY604779.1 B/Taiwan/773/2004 hemagglutinin (HA)
EU068195.1 B/Taiwan/187/2004 hemagglutinin (HA) EU068194.1
B/Taiwan/3892/2004 hemagglutinin (HA) EU068193.1 B/Taiwan/562/2004
hemagglutinin (HA) EU068191.1 B/Taiwan/234/2004 hemagglutinin (HA)
EU068188.1 B/Taiwan/4897/2004 hemagglutinin (HA) EU068186.1
B/Taiwan/8579/2004 hemagglutinin (HA) EU068184.1 B/Taiwan/184/2004
hemagglutinin (HA) EU068183.1 B/Taiwan/647/2005 hemagglutinin (HA)
EU068196.1 B/Taiwan/877/2005 hemagglutinin (HA) EU068198.1
B/Taiwan/521/2005 hemagglutinin (HA) EU068189.1 B/Taiwan/1064/2005
hemagglutinin (HA) EU068192.1 B/Taiwan/3722/2005 hemagglutinin (HA)
EU068197.1 B/Taiwan/5049/2005 hemagglutinin (HA) EU068190.1
B/Taiwan/5011/2005 hemagglutinin (HA) EU068187.1 B/Taiwan/4659/2005
hemagglutinin (HA) EU068185.1 B/Taiwan/25/2005 hemagglutinin (HA)
EU068182.1 B/Taiwan/1037/2005 hemagglutinin (HA) EU068181.1
B/Taiwan/62/2005 hemagglutinin (HA) EU068180.1 B/Taiwan/591/2005
hemagglutinin (HA) EU068179.1 B/Taiwan/649/2005 hemagglutinin (HA)
EU068178.1 B/Taiwan/4554/2005 hemagglutinin (HA) EU068177.1
B/Taiwan/987/2005 hemagglutinin (HA) EU068176.1 B/Taiwan/2607/2006
hemagglutinin (HA) EU068175.1 B/Vienna/1/99 hemagglutinin
AF387495.1 B/Vienna/1/99 hemagglutinin AF387494.1 B/Vienna/1/99
hemagglutinin AF387493.1 B/Vienna/1/99 hemagglutinin AF387492.1
TABLE-US-00017 TABLE 13 Influenza C Antigens GenBank Strain/Protein
Access No. C/JHB/1/66) hemagglutinin-esterase-fusion AY880247.1
protein (HEF) mRNA, complete cds. STRAIN C/ANN ARBOR/1/50)
persistent variant AF102027.1 segment 7 non-structural protein 1
(NS1) mRNA, complete cds (STRAIN C/ANN ARBOR/1/50) wild type
segment 7 AF102026.1 non-structural protein 1 (NS1) mRNA, complete
cds (C/JHB/1/66) hemagglutinin-esterase-fusion protein AY880247.1
(HEF) mRNA, complete cds (STRAIN C/BERLIN/1/85) mRNA for basic
polymerase X55992.1 2 precursor
TABLE-US-00018 TABLE 14 H7 Hemagglutinin Amino Acid Sequences
Accession No/ SEQ Strain/Protein Amino Acid Sequence ID NO:
AAM19228 ACVLVEAKGDKICLGHHAVVNGTKVNTLTEKGIEVVNATETVETA 1 A/turkey/
NIGKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEFESDLIIERR Minnesota/
EGNDVCYPGKFTNEESLRQILRGSGGIDKESMGFTYSGIITNGAT 38429/1988
SACRRSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPALIVW 1988// HA
GIHHSGSTTEQTKLYGSGNKLITVESSKYQQSFTPSPGARPQVNG 20335017
ESGRIDFHWMLLDPNDTVTFTFNGAFIAPDRASFFKGESLGVQSD
VPLDSSCGGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQPSLL
LATGMRNVPENPKTRGLFGAIAGFIEKDGGSHYG AAY46211
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 2 A/mallard/
NATETVERTNVPRICSRGKRTVDLGQCGLLGTITGPPQCDQFLEF Sweden/91/2002
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY 2002// HA
SGIRTNGAPSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 66394828
RNDPALIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSFVPS
PGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQIDANCEGDCYHSGGTIISNLPFQNINSRAVGKCP
RYVKQESLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI AMGLVFMCVKNGNMRCTICI
ABI84694 MNTQILVFIACVLVEAKGDKICLGHHAVVNGTKVNTLTEKGIEVV 3 A/turkey/
NATETVETANIGKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF Minnesota/
ESDLIIERREGNDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY 1/1988
SGIRTNGATSACRRSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNP 1988/07/13 HA
RNKPALIVWGIHHSGSTTEQTKLYGSGNKLITVGSSKYQQSFTPS 115278573
PGARPQVNGQSGRIDFHWMLLDPNDTVTFTFNGAFIAPDRASFFK
GESLGVQSDVPLDSSCGGDCFHSGGTIVSSLPFQNINPRTVGKCP
RYVKQPSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW
YGFKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI
DNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT
YDHAQYRAESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI AMGLVFICIKNGNMRCTICI
ABS89409 MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVV 4
A/blue-winged NATETVETANIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF
teal/Ohio/566/ DTDLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY 2006
2006// HA SGIRTNGATSACRRSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNP 155016324
RNKPALIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFTPS
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFER
GESLGVQSDVPLDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCP
RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI
DNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT
YDHTQYRTESLQNRIQIDPVRLSSGYKDIILWFSFGASCFLLLAI AMGLVFICIKNGNMRCTICI
ACD03594 MNTQILAFIACMLVGVRGDKICLGHHAVANGTKVNTLTEKGIEVV 5 A/ruddy
NATETVESANIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF turnstone/DE/
DSDLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY 1538/2000
SGIRTNGATSACRRLGSSFYAEMKWLLSNSDNAAFPQMTKSYRNP 2000// HA
RNKPALIIWGVHHSGSANEQTKLYGSGNKLITVGSSKYQQSFTPS 187384848
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFER
GESLGIQSDVPLDSSCGGDCFHSGGTIVSSLPFQNINPRTVGKCP
RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELM
DNEFNEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT
YDHTQYRTESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI AMGLIFICIKNGNMRCTICI
BAH22785 MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 6
A/duck/Mongolia/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
119/2008 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIGKETMGFTY 2008// HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 223717820
RKDPALIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSFVPS
PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHNGGTIISNLPFQNINSRTVGKCP
RYVKQESLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIERTNQQFELI
DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSNGYKDVILWFSFGASCFILLAI AMGLVFICVKNGNMRCTICI
CAY39406 MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 7
A/Anascrecca/ NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF Spain/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY 1460/2008
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2008/01/26 HA
RKDPALIIWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS 254674376
PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNINSRAVGKCP
RYVKQESLMLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFTEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI AMGLVFICVKNGNMRCTICI
ACX53683 MNIQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 8
A/goose/Czech NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
Republic/1848- SADLIIERRGGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY
K9/2009 SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2009/02/04 HA
RKDPALIIWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS 260907763
PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLK
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNINSRAVGKCP
RYVKQESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQINPVKLSSGYKDVILWFSFGASCFILLAI AMGLVFICVKNGNMRCTICI
ACZ48625 MNTQILVFIACVLVEAKGDKICLGHHAVVNGTKVNTLTEKGIEVV 9 A/turkey/
NATETVETANIGKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF Minnesota/
ESDLIIERREGNDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY 38429/1988
SGIRTNGATSACRRSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNP 1988// HA
RNKPALIVWGIHHSGSTTEQTKLYGSGNKLITVGSSKYQQSFTPS 269826341
PGARPQVNGQSGRIDFHWMLLDPNDTVTFTFNGAFIAPDRASFFK
GESLGVQSDVPLDSSCGGDCFHSGGTIVSSLPFQNINPRTVGKCP
RYVKQPSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW
YGFKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFEL ADC29485
STQSAIDQITGKLNRLIEKTNQQFELIDNEFTEVEKQIGNVINWT 10 A/mallard/Spain/
RDSMTEVWSYNAELLVAMENQHTIDLADSEMNKLYERVKRQLREN 08.00991.3/
AEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKYREEAMQNRIQID 2005 2005/11/
PVKLSSGYKDVILWFSFGASCFILL HA 284927336 ADK71137
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVV 11 A/blue-winged
NATETVETANIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF teal/Guatemala/
DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY CIP049-
SGIRTNGATSACRRSGSSSYAEMKWLLSNSDNAAFPQMTKSYRNP 01/2008
RNKPALIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFTPS 2008/02/07 HA
PGIRPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFLR 301333785
GKSLGIQSDVPLDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCP
RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQHFELI
DNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT
YDHTQYRTESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI AMGLVFICIKNGNMRCTICI
ADK71148 MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVV 12
A/blue-winged NXTETVETANIKKICTHGKRPTDLGQCGLLGTLIGPPQCDRFLEF
teal/Guatemala/ DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY
CIP049- SGIRTNGATSACRRSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNP 02/2008
RNKPALIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFTPS 2008/03/05 HA
PGIRPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFLR 301333804
GKSLGIQSDVPLDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCP
RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI
DNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT
YDHTQYRTESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI AMGLVFICIKNGNMRCTICI
ADN34727 MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 13
A/goose/Czech NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
Republic/1848- SADLIIERRGGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY
T14/2009 SGIRTNGXTSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2009/02/04
HA RKDPALIIWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS 307141869
PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLK
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNINSRAVGKCP
RYVKQESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQINPVKLSSGYKDVILWFSFGASCFILLAI AMGLVFICVKNGNMRCTICI
AEK84760 PAFIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSGGTIISNLP 14 A/wild
FQNINSRAVGKCPRYVKQESLMLATGMKNVPELPKGRGLFGAIAG bird/Korea/A14/
FIENGWEGLIDGWYGFRHQNAQGEGTAADYKSTQSAIDQITGKLN 2011 2011/02/
RLIEKTNQQFELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAEL HA 341610308
LVAMENQHTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFHK
CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILW
FSFGASCFILLAIAMGLVFICVKNGNMRCTICI AEK84761
ILVFALVAIIPTNANKIGLGHHAVSNGTKVNTLTERGVEVFNATE 15 A/wild
TVERTNVPRICSKGKKTVDLGQCGLRGTITGPPQCDQFLKFSPDL bird/Korea/A3/
IIERQKGSDVCYPGKFVNEKPLRQILRESGGIDKETMGFAYNGIK 2011 2011/02/
TNGPPIACRKSGSSFYAKMKWLLSNTDKAAFPQMTKSYKNTRRNP HA 341610310
ALIVWGIHHSGSTTKQTKLYGIGSNLITVGSSNYQQSFVPSPGAR
PQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIPPDRASFLRGKSM
GIQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVK
QESLMLATGMKNVPELPKGKGLFGAIAGFIENGWEGLIDGWYGFR
HQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEF
TEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLADSEM
NKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHS
KYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIAMGL VFICVKNGNMRCTICI
AEK84763 ILVFALVAIIPTNANKIGLGHHAVSNGTKVNTLTERGVEFFNATE 16 A/wild
TVEPINVPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEFSADL bird/Korea/A9/
IIERREGSDVCYPGKFVNEKALRQILRESGGIDKETMGFAYSGIK 2011 2011/02/
TNGPPIACRKSGSSFYAKMKWLLSNTDKAAFPQMTKSYKNTRRDP HA 341610314
ALIVWGIHHSGSTIKQINLYGIGSNLITVGSSNYQQSFVPSPGAR
PQVNGQSGRIDFHWLILNPNDTVIFIENGAFIAPDRASFLIGKSM
GIQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVK
QESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYGFR
HQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEF
TEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLADSEM
NKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHS
KYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIAMGL VFICVKNGNMRCTICI
AEK84765 LVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVNATET 17
A/spot-billed VERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEFSADLI
duck/Korea/447/ IERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTYSGIRT 2011
2011/04/ NGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRDPA HA 341610318
LIVWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPSPGARP
QVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLRGKSMG
IQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQ
ESLMLATGMKNVPEPPKGRGLFGAIAGFIENGWEGLIDGWYGFRH
QNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFT
EVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLADSEMN
KLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMARIRNNTYDHSK
YREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIAMGLV FICVKNGNMRCTICI
AEM98291 SILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVNAT 18 A/wild
ETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEFSAD duck/Mongolia/
LIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTYSGI 1-241/2008
RTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKD 2008/04/ HA
PALIIWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPSPGA 344196120
RPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLRGKS
MGIQSGVQVDANCEGDCYHSGGSIISNLPFQNINSRAVGKCPRYV
KQESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYGF
RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNE
FTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLADSE
MNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDH
SKYREEAMQNRIQINPVKLSSGYKDVILWFSFGASCFILLAIAMG LVFICVKNGNMRCTI
AFM09439 QILAFIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVVNAT 19 A/emperor
ETVETVNIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEFDAD goose/Alaska/
LIIERRKGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTYSGI 44063-061/2006
RTNGATSACRRSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNK 2006/05/23 HA
PALIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFVPSPGA 390535062
RPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPERASFERGES
LGVQSDVPLDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCPRYV
KQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGF
RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDNE
FSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLADSE
MNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNTYDH
TQYRTESLQNRIQINPVKLSSGYKDIILWFSFGASCFLLLAIAMG LVFICIKNGNMRCTICI
AFV33945 MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTERRIEVV 20
A/guinea NATETVETANIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF
fowl/Nebraska/ DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY
17096-1/2011 SGIRTNGATSACRRSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNP
2011/04/05 HA RNKPALIVWGVHHSGSATEQTKLYGSGSKLITVGSSKYQQSFTPS
409676820 PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR
GESLGVQSDVPLDSGCEGDCFHKGGTIVSSLPFQNINPRTVGKCP
RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI
DNEFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT
YDHTQYRAESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI AMGLVFICIKNGNMRCTICI
AFV33947 MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVV 21 A/goose/
NATETVETANIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF Nebraska/17097-
DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY 4/2011
SGIRTNGATSACRRSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNP 2011/04/05 HA
RNKPALIVWGVHHSASATEQTKLYGSGSKLITVGSSKYQQSFTPS 409676827
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR
GESLGVQSDVPLDSGCEGDCFHKGGTIVSSLPFQNINPRTVGKCP
RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI
DNEFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT
YDHTQYRAESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI AMGLVFICIKNGNMRCTICI
AFX85260 MNTQILAFIACMLIGINGDKICLGHHAVANGTKVNTLTERGIEVV 22 A/ruddy
NATETVETANIKRICTQGKRPIDLGQCGLLGTLIGPPQCDQFLEF turnstone/
DSDLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY Delaware
SGIRTNGATSACIRLGSSFYAEMKWLLSNSDNAAFPQMTKSYRNP Bay/220/1995
RNKPALIIWGVHHSGSANEQTKLYGSGNKLITVGSSKYQQSFTPS 1995/05/21 HA
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR 423514912
GESLGVQSDVPLDSSCGGDCFHSGGTIVSSLPFQNINPRTVGRCP
RYVKQTSLLLATGMKNVPENPKTRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI
DNEFNEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT
YDHTQYRTESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI AMGLVFICIKNGNMRCTICI
AGE08098 MNTQILTLIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVV 23
A/northern NATETVETANIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF shoverl/
DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY Mississippi/
SGIRTNGATSACRRSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNP 11OS145/2011
RNKPALIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFTPS 2011/01/08 HA
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR 444344488
GESLGVQSDVPLDSGCEGDCFHNGGTIVSSLPFQNINPRTVGKCP
RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI
DNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT
YDHTQYRAESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI AMGLVFICIKNGNMRCTICI
AGI60301 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 24
A/Hangzhou/1/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF 2013
2013/03/24 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY HA
475662454 SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGISGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AGI60292 MNTQILVFALIAIIPANADKICLGHHAVSNGTKVNTLTERGVEVV 25
A/Shanghai/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
4664T/2013 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2013/03/05
HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 476403560
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCHHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AGJ72861 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGGEVV 26
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQGGPRGTITGPPQCDQFLEF
Zhejiang/DTID- SADLIMERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
ZJU01/2013 SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2013/04/
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS HA 479280294
PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AGJ73503 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 27
A/Nanjing/1/ NATETVERTNIPRICSKGKMTVDLGQCGLLGTITGPPQCDQFLEF 2013
2013/03/28 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY HA
479285761 SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
BAN16711 MNIQVLVFALMAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 28
A/duck/Gunma/ NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
466/2011 2011// SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY HA
482661571 SGIRTNGITSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
RRDPALIAWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS
PGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCP
RYVKQESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRRQLRENAEEDDTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI AMGLVFICVKNGNMRCTICI
AGK84857 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 29
A/Hangzhou/2/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF 2013
2013/04/01 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY HA
485649824 SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQIIKSYKNT
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AGL44438 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 30
A/Shanghai/02/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF 2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2013/03/05 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 496493389
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AGL33692 GMIDGWYGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTN 31
A/Shanghai/ QQFELIDNEFTEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
4655T/2013 HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMA 2013/02/26
HA SIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASC 491874175
FILLAIAMGLVFICVKNGNMRCTICI AGL33693
GMIDGWYGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTN 32 A/Shanghai/
QQFELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ 4659T/2013
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMA 2013/02/27 HA
SIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASC 491874186
FILLAIVMGLVFICVKNGNMRCTICI AGL95088
VFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVNATETV 33 A/Taiwan/
ERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEFSADLII S02076/2013
ERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTYSGIRTN 2013/04/22 HA
GATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPAL 501485301
IVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPGARPQ
VNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGI
QSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQR
SLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQ
NAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFNE
VEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADSEMDK
LYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKY
REEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIVMGLVF ICVKNGNMR AGL95098
LVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVNATET 34 A/Taiwan/
VERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEFSADLI T02081/2013
IERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTYSGIRT 2013/04/22 HA
NGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA 501485319
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPGARP
QVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMG
IQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQ
RSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRH
QNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFN
EVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADSEMD
KLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSK
YREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIVMGLV FICVKNGNMRCT AGM53883
GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELID 35 A/Shanghai/
NEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLAD 5083T/2013
SEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTY 2013/04/20 HA
DHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIV 507593986
MGLVFICVKNGNMRCT AGM53884
AQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFNEV 36 A/Shanghai/
EKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADSEMDKL 5180T/2013
YERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKYR 2013/04/23 HA
EEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIVMGLVFI 507593988
CVKNGNMRCTICI AGM53885
QNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFN 37 A/Shanghai/
EVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADSEMD 5240T/2013
KLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSK 2013/04/25 HA
YREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIVMGLV 507593990
FICVKNGNMRCT AGM53886 NAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFNE
38 A/Shanghai/ VEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADSEMDK
4842T/2013 LYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKY 2013/04/13
HA REEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIVMGLVF 507593992
ICVKNGNMRCT AGM53887 NAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFNE
39 A/Shanghai/ VEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADSEMDK
4701T/2013 LYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKY 2013/04/06
HA REEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIVMGLVF 507593994
ICVKNGNMRCTIC AGN69462
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 40 A/Wuxi/2/2013
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF 2013/03/31 HA
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 511105778
SGIRTNGSTSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
RKSPALIVWGIHHSVSTAEQTKLYGSGSKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AGN69474 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 41
A/Wuxi/1/2013 NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
2013/03/31 HA SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
511105798 SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLINGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI
VMGLVFICVKNGNMRCTICI
AGO51387 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 42
A/Jiangsu/2/ NATETVERTNIPRICSKGKMTVDLGQCGLLGTITGPPQCDQFLEF 2013
2013/04/20 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY HA
514390990 SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYRKEAMKBXIQIDPVKLSSGYKDVXJWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
BAN59726 MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 43
A/duck/Mongolia/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
147/2008 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIGKETMGFTY 2008/08/29
HA SGIRTNGATSACRRSRSSFYAEMKWLLSNTDNAAFPQMIRSYKNT 519661951
RKDPALIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSFVPS
PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHNGGTIISNLPFQNINSRTVGKCP
RYVKQESLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIERTNQQFELI
DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSNGYKDVILWFSFGASCFILLAI AMGLVFICVKNGNMRCTICI
BAN59727 MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 44
A/duck/Mongolia/ NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
129/2010 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY 2010// HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 519661954
RKDPALIIWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS
PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCP
RYVKQESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQINPVKLSSGYKDVILWFSFGASCFILLAI AMGLVFICVKNGNMRCTICI
AGQ80952 MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 45
A/duck/Jiangxi/ NATETVERTSIPRICSKGKRAVDLGQCGLLGTITGPPQCDQFLEF
3096/2009 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY 2009// HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQTIKSYKNT 523788794
RKDPALIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSFVPS
PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHNGGTIISNLPFQNINSRAVGKCP
RYVKQESLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFTEVERQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI AMGLVFICVKNGNMRCTICI
AGQ80989 MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 46
A/duck/Jiangxi/ NATETVERTSIPRICSKGKRAVDLGQCGLLGTITGPPQCDQFLEF
3257/2009 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY 2009// HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQTIKSYKNT 523788868
RKDPALIIWGIHHSGSTTEQTKLYGSGNKLITVGXSNYQQSFVPS
PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHNGGTIISNLPFQNINSRAVGKCP
RYVKQESLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFTEVERQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI AMGLVFICVKNGNMRCTICI
AGQ81043 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 47
A/chicken/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
Rizhao/515/2013 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEEMGFTY
2013// HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 523788976
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AGR33894 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 48
A/chicken/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
Rizhao/719b/2013 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2013// HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 524845213
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDRSKYREEAMQNRXXXXXXXXXXXXKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AGR49399 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 49
A/chicken/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF Jiangxi/
SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY SD001/2013
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2013/05/03 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS 525338528
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AGR49495 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 50
A/chicken/ NATETVERTNIPRICSKGKMTVDLGQCGLLGTITGPPQCDQFLEF Shanghai/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY S1358/2013
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2013/04/03
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS HA 525338689
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIKNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AGR49506 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 51
A/chicken/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF Shanghai/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY S1410/2013
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2013/04/03
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS HA 525338708
PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AGR49554 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 52
A/chicken/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF Zhejiang/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY SD033/2013
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2013/04/11
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS HA 525338789
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AGR49566 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 53
A/duck/Anhui/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
SC702/2013 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2013/04/16
HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 525338809
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDNRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AGR49722 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 54 A/homing
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF pigeon/Jiangsu/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY SD184/2013
SEIRINGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2013/04/20 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS 525339071
PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AGR49734 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 55 A/pigeon/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF Shanghai/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY S1069/2013
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2013/04/02 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS 525339091
PGARPQVNGLSGRIDFHWLMLNPNDTITFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AGR49770 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 56 A/wild
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF pigeon/Jiangsu/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY SD001/2013
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2013/04/17 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS 525339151
PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AGY41893 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 57
A/Huizhou/01/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF 2013
2013/08/08 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY HA
552049496 SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AGY42258 FALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVNATETVE 58
A/mallard/ RTNVPRICSRGKRTVDLGQCGLLGTIXGPPQCDQFLEFSADLIIE
Sweden/91/2002 RREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTYSGIRTNG
2002/12/12 HA AXSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRNDPALI
552052155 IWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSFVPSPGARPQV
NGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQ
SGVQIDANCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQES
LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQN
AQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFTEV
EKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLADSEMNKL
YERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKYR
EEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIAMGLVFM CVKNGNMRCTICI
AHA11441 MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVV 59 A/guinea
NATETVETANIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF fowl/Nebraska/
DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY 17096/2011
SGIRTNGATSACRRSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNP 2011/04/10 HA
RNKPALIVWGVHHSGSATEQTKLYGSGSKLITVGSSKYQQSFTPS 557478572
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFER
GESLGVQSDVPLDSGCEGDCFHKGGTIVSSLPFQNINPRTVGKCP
RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI
DNEFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT
YDHIQYRAESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI
AMGLVFICIKNGNMRCTICI
AHA11452 MNTQILALIACMLVGIKGDKICLGHHAVANGTKVNTLTERGIEVV 60 A/turkey/
NATETVETANIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF Minnesota/
DADLIIERREGTDVCYPGKFTNEEPLRQILRGSGGIDKESMGFTY 32710/2011
SGIRTNGATSTCRRSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNP 2011/07/12
RNKPALIVWGVHHSGSATEQTKLYGSGSKLITVGSSKYQQSFTPS HA 557478591
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFER
GESLGVQSDVPLDSGCEGDCFHKGGTIVSSLPFQNINPRTVGKCP
RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFEMI
DNEFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT
YDHIQYRAESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI AMGLVFICIKNGNMRCTICI
AHA11461 MNTQILALIACMLVGIKGDKICLGHHAVANGTKVNTLTERGIEVV 61 A/turkey/
NATETVETANIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF Minnesota/
DADLIIERREGTDVCYPGKFTNEEPLRQILRGSGGIDKESMGFTY 31900/2011
SGIRTNGATSTCRRSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNP 2011/07/05
RNKPALIVWGVHHSGSATEQTKLYGSGSKLITVGSSKYQQSFTPS HA 557478606
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFER
GESLGVQSDVPLDSGCEGDCFHKGGTIVSSLPFQNINPRTVGKCP
RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI
DNEFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT
YDHIQYRAESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI AMGLVFICIKNGNMRCTICI
AHK10585 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 62
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF Guangdong/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY G1/2013
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2013/05/05 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS 587680636
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AGG53366 MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 63 A/wild
NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF duck/Korea/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGLTY CSM42-34/2011
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2011/03/
RRDPALIVWGIHHSGSSTEQTKLYGSGSKLITVGSSNYQQSFVPS HA 459252887
PGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCP
RYVKQESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVRLSSGYKDVILWFSFGASCFILLAI AMGLVFICVKNGNMRCTICI
AGG53377 MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 64 A/wild
NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF duck/Korea/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGLTY CSM42-1/2011
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2011/03/
RRDPALIVWGIHHSGSSTEQTKLYGSGSKLITVGSSNYQQSFVPS HA 459252925
PGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCP
RYVKQESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVRLSSGYKDVILWFSFGASCFILLAI AMGLVFICVKNGNMRCT
AGG53399 MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 65 A/wild
NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF duck/Korea/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY MHC39-26/2011
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2011/03/
RRDPALIVWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS HA 459253005
PGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCP
RYVKQESLMLATGMKNVPEPPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI AMGLVFICVKNGNMRCTICI
AGG53432 MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 66 A/wild
NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF duck/Korea/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY MHC35-41/2011
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2011/03/
RRDPALIVWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS HA 459253136
PGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCP
RYVKQESLMLATGMKNVPEPPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI AMGLVFICVKNGNMRCT
AGG53476 MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 67 A/wild
NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF duck/Korea/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY SH19-27/2010
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2010/12/
RRDPALIVWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS HA 459253257
PGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCP
RYVKQESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI AMGLVFICVKNGNMRCTI
AGG53487 MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 68 A/wild
NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF duck/Korea/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY SH19-50/2010
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2010/01/
RRDPALIVWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS HA 459253278
PGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDASCEGDCYHSGGTIISNLPFQNINSRAVGKCP
RYVKQESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI AMGLVFICVKNGNMRCTICI
AGG53520 QILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVNAT 69 A/wild
ETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCDQLLEFSAD duck/Korea/
LIIERREGTDVCYPGKFVNEEALRQILRESGGIEKETMGFTYSGI SH20-27/2008
RTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKD 2008/12/
PALIIWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPSPGA HA 459253409
RPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLRGKS
MGIQSGVQVDANCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYV
KQESLMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYGF
RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNE
FTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLADSE
MNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDH
SKYREEAMQNRIQINPVKLSSGYKDVILWFSFGASCFILLAIAMG LVFICVKNGNMR AGL43637
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 70 A/Taiwan/1/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF 2013 2013// HA
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 496297389
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGPSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIINNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AGL97639 IACMLVGAKGDKICLGHHAVANGTKVNTLTERGIEVVNATETVET 71
A/mallard/ ANIKKLCTQGKRPTDLGQCGLLGTLIGPPQCDQFLEFDADLIIER
Minnesota/AI09- REGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTYSGIRTNGA
3770/2009 TSACRRSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPALII 2009/09/12
HA WGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFTPSPGARPQVN 505555371
GQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFERGESLGVQS
DVPLDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTSL
LLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNA
QGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDNEFSEIE
QQIGNVINWTRDSMTELWSYNAELLVAMENQHTIDLADSEMNKLY
ERVRKQLRENAEEDGIGCFEIFHKCDDQCMESIRNNTYDHIQYRT ESLQNRIQIDPVKLS
AGO02477 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 72
A/Xuzhou/1/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF 2013
2013/04/25 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY HA
512403688 SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
RKSPALIVWGIHHSVSTAEQTKLYGSGSKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKSRNMRCTICI
AGR84942 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 73
A/Suzhou/5/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF 2013
2013/04/12 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY HA
526304561 SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
RKSPALIVWGIHHSVSTAEQTKLYGSGSKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AGR84954 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 74
A/Nanjing/6/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF 2013
2013/04/11 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY HA
526304594 SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNRNMRCTICI
AGR84978 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 75
A/Wuxi/4/2013 NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
2013/04/07 HA SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
526304656 SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKSRNMRCTICI
AGR84990 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 76
A/Wuxi/3/2013 NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
2013/04/07 HA SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
526304688 SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKSRNMRCTICI
AGR85002 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 77
A/Zhenjiang/1/ NATETVERTNIPRICSKGKMTVDLGQCGLLGTITGPPQCDQFLEF 2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2013/04/07 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 526304708
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI
VMGLVFICVKSRNKRCTICI
AGR85026 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 78
A/Nanjing/2/ NATETVERTNIPRICSKGKMTVDLGQCGLLGTITGPPQCDQFLEF 2013
2013/04/05 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY HA
526304762 SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKSRNMRCTICI
AGU02230 LVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGGEVVNATET 79
A/Zhejiang/ VERTNIPRICSKGKRTVDLGQCGLRGTITGPPQCDQFLEFSADLI
DTID-ZJU05/2013 IERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTYSGIRT
2013/04/ NGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA HA 532808765
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPGARP
QVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMG
IQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQ
RSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRH
QNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFN
EVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADSEMD
KLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSK
YREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIVMGLV FICVKNGNMRCT AGU02233
FALIAIIPTNADKICLGHHAVSNGTKVNTLTERGGEVVNATETVE 80 A/Zhejiang/
RINFPRICSKGKRTVDLGQCGLRGTITGPPQCDQFLEFSADLIIE DTID-ZJU08/2013
RREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTYSGIRTNG 2013/04/
ATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNIRKSPALI HA 532808788
VWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPGARPQV
NGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQ
SGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS
LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQN
AQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFNEV
EKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADSEMDKL
YERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKYR
EEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIVMGLVFI CVKNGNMRCT AGW82588
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 81 A/tree
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF sparrow/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY Shanghai/01/2013
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2013/05/09 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS 546235348
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTIGI
AGW82600 ALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVNATETVER 82
A/Shanghai/ TNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEFSADLIIER CN01/2013
REGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTYSGIRTNGA 2013/04/11 HA
TSACRRSRSSFYAEMKWLLSNTDNAAFPQMTKSYKNIRKSPALIV 546235368
WGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPGARPQVN
GLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQS
GVQVDANCEGDCYHSGGTIMSNLPFQNIDSRAVGKCPRYVKQRSL
LLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNA
QGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFNEVE
KQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADSEMDKLY
ERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKYRE
EAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIVMGLVFIC VKNGNMRCTICI AGW82612
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 83 A/Shanghai/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF JS01/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2013/04/03 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 546235388
RKNPALIVWGIHHSGSTAEQTKLYGSGNKLVTVGSSNYQQSFAPS
PGARTQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFTEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI AMGLVFICVKNGNMRCTICI
AHA11472 MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVV 84 A/turkey/
NATETVETANVKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF Minnesota/
DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY 31676/2009
SGIRTNGETSACRRSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNP 2009/12/08
RDKPALIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFTPS HA 557478625
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR
GESLGVQSDVPLDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCP
RYVKQTSLLLATGMRNVPEKPKTRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITNKLNRLIDKTNQQFELI
DNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT
YDHTQYRKESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI AMGLVFICIKNGNMRCTICI
AHA11483 MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVV 85 A/turkey/
NATETVETANVKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF Minnesota/
DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY 14135-2/2009
SGIRTNGATSACRRSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNP 2009/08/07 HA
RDKPALIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFTPS 557478644
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR
GESLGVQSDVPLDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCP
RYVKQTSLLLATGMRNVPEKPKTRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITSKLNRLIDKTNQQFELI
DNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT
YDHTQYRKESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI AMGLVFICIKNGNMRCTICI
AHA11500 TQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVNA 86
A/Zhejiang/ TETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEFSA
DTID-ZJU10/2013 DLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTYSG
2013/10/14 HA IRINGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNIRK
557478676 SPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPG
ARPPVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLRGK
SMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRY
VKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG
FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADS
EMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYD
HSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAIVM GLVFICVKN AHA57050
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVV 87 A/turkey/
NATETVETANVKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF Minnesota/
DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY 14659/2009
SGIRTNGATSACRRSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNP 2009/08/12
RDKPALIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFTPS HA 558484427
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR
GESLGVQSDVPLDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCP
RYVKQTSLLLATGMRNVPEKPKTRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITSKLNRLIDKTNQQFELI
DNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRKQLRENAEEDGTGCFEIFHNCDDQCMESIRNNT
YDHTQYRKESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI AMGLVFICIKNGNMRCTICI
AHA57072 MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIEVV 88 A/turkey/
NATETVETANVKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF Minnesota/
DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY 18421/2009
SGIRTNGATSACRRSGSSFYAEMKWLLSNSNDAAFPQMTKSYRNP 2009/09/09
RDKPALIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFTPS HA 558484465
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFFR
GESLGVQSDVPLDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCP
RYVKQTSLLLATGMRNVPEKPKTRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI
DNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT
YDHTQYRKESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI AMGLVFICIKNGNMRCTICI
AHD25003 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 89
A/Guangdong/02/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF 2013
2013/10/ SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY HA 568260567
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNM
AHF20528 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 90 A/Hong
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF Kong/470129/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2013/11/30
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT HA 570933555
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISSLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AHF20568 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 91
A/Shanghai/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF CN02/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2013/04/02 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 570933626
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIMSNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AHH25185 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 92
A/Guangdong/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF 04/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIEKEAMGFTY 2013/12/16 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 576106234
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AHJ57411 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 93
A/Shanghai/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
PD-01/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2014/01/17
HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 585478041
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVSS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCKGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRIIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AHJ57418 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 94
A/Shanghai/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
PD-02/2014 SADLIIERREGSDICYPGKFVNEEALRQILRESGGIDKEAMGFTY 2014/01/17
HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 585478256
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLK
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRIIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AHK10800 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 95
A/Shanghai/01/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF 2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2014/01/03 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 587681014
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRIIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI
VMGLVFICVKNGNMRCTICI AHM24224
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 96 A/Beijing/3/2013
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF 2013/04/16
SADLIIERREGSDVCYPGKEVKEEALRQILRESGGIDKEAMGFTY HA 594704802
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AHN96472 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 97
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Shanghai/PD-CN- SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
02/2014 SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2014/01/21 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS 602701641
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AHZ39686 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 98
A/Anhui/DEWH72- NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
01/2013 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2013// HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDDAAFPQMTKSYKNT 632807036
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AHZ39710 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 99
A/Anhui/DEWH72- NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
03/2013 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2013// HA
SGIRTDGATSACRRSGSSFYAEMKWLLSNTDDAAFPQMTKSYKNT 632807076
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AHZ39746 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 100
A/Anhui/DEWH72- NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
06/2013 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2013// HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 632807136
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGERPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AHZ41929 MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 101
A/mallard/ NATETVERTNVPRICSRGKRTVDLGQCGLLGTITGPPQCDQFLEF
Sweden/1621/2002 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKETMGFTY
2002/12/12 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
632810949 RNDPALIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSFVPS
PGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQIDANCEGDCYHSGGTIISNLPFQNINSRAVGKCP
RYVKQESLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI AMGLVFMCVKNGNMRCTICI
AHZ42537 MNTQILAFIACMLVGAKGDKICLGHHAVANGTKVNTLTERGIEVV 102
A/mallard/ NATETVETANIKKLCTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF Minnesota/
DADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY AI09-3770/2009
SGIRTNGATSACRRSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNP 2009/09/12 HA
RNKPALIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFTPS 632811964
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFER
GESLGVQSDVPLDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCP
RYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELI
DNEFSEIEQQIGNVINWTRDSMTELWSYNAELLVAMENQHTIDLA
DSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNNT
YDHTQYRTESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLAI AMGLVFICIKNGNMRCTICI
AHZ42549 MNTQILAFIACMLVGVRGDKICLGHHAVANGTKVNTLTEKGIEVV 103 A/ruddy
NATETVESANIKKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLEF turnstone/
DSDLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKESMGFTY Delaware/AI00-
SGIRTNGATSACRRLGSSSFYAEMKWLLSNSDNAAFPQMTKSYRN 1538/2000
PRNKPALIIWGVHHSGSANEQTKLYGSGNKLITVGSSKYQQSFTP 2000/05/20 HA
SPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIAPDRASFF 632811984
RGESLGIQSDVPLDSSCGGDCFHSGGTIVSSLPFQNINPRTVGKC
PRYVKQTSLLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDG
WYGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFEL
MDNEFNEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDL
ADSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESIRNN
TYDHTQYRTESLQNRIQIDPVKLSSGYKDIILWFSFGASCFLLLA IAMGLIFICIKNGNMRCTICI
AID70634 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 104
A/Shanghai/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF Mix1/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2014/01/03 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 660304650
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRIIEKTNQQFELI
DNEFNEVEKQISNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AIN76383 MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTERGVEVV 105
A/Zhejiang/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF LS01/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2014/02/08 HA
SGIRTNGITSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 684694637
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AIU46619 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 106
A/chicken/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
Zhejiang/DTID- SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
ZJU06/2013 SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2013/12/
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS HA 699978931
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVEVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AIU47013 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 107
A/chicken/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
Suzhou/040201H/ SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2013
2013/04/ SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT HA 699979673
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDMILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ90490 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 108
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Shenzhen/742/2013 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2013/12/10 HA SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755178094 RRSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ90526 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 109
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Shenzhen/898/2013 SADLIIERREGSDICYPGKFVNEEALRQILRESGGIDKEAMGFTY
2013/12/09 HA SGIRANGATSACKRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755178154 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISSLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSRGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ90538 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 110 A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF chicken/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY Shenzhen/918/2013
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2013/12/09 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS 755178174
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ90576 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 111
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Shenzhen/1665/2013 SADLIIERREGSDICYPGKFVNEEALRQILRESGGIDKEAMGFTY
2013/12/12 HA SGIRANGATSACKRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755178238 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSRGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ90588 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 112
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Shenzhen/2110/2013 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2013/12/13 HA SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755178258 RRSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSIGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ90661 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 113
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/2912/2013 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2013/12/18 HA SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755178380 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ90673 MNTQILVFALTAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 114 A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF chicken/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY Dongguan/3049/2013
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2013/12/18 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS 755178400
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ90795 MNTQILVFALIAIIPTNADKICLGHHAVPNGTKVNTLTERGVEVV 115 A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF chicken/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY Dongguan/3281/2013
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2013/12/18 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS 755178604
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ90891 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 116 A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF chicken/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY Dongguan/3520/2013
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2013/12/19 HA
RKXPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS 755178764
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ90951 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 117
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/3544/2013 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2013/12/19 HA SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYRNT
755178864 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ91035 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 118
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Shenzhen/3780/2013 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2013/12/19 HA SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755179004 RRSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDNRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ91155 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 119
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/4037/2013 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2013/12/19 HA SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755179204 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ92005 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 120
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Shenzhen/801/2013 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2013/12/09 HA SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755180629 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSRGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ94254 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 121
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/1374/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/02/21 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755184382 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPERASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ94606 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 122
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/191/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY
2014/02/20 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755184968 RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ96552 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 123
A/chicken/ NATETVERTNIPRICSKGKKTIDLGQCGLLGTITGPPQCDQFLEF
Jiangxi/12206/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/03/16 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755188219 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHNKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ96684 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKINTLTERGVEVV 124
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Jiangxi/13207/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/03/30 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755188439 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ96732 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 125
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Jiangxi/13223/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/03/30 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755188519 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJK00354 MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 126
A/duck/Zhejiang/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
LS02/2014 SADLIVERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2014/01/12
HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 755194469
RKDPALIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSFVPS
PGARPLVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNINSRAVGKCP
RYVKQESLLLATGMKNVPEVPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQVIGKLNRLIEKTNQQFELI
DHEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA
DSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ91264 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 127 A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF chicken/Dongguan/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 4129/2013
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2013/12/19 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS 755179386
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLMEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ91314 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 128
A/chicken/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
Shaoxing/2417/2013 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2013/10/20 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755179470 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPPVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ91402 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 129
A/chicken/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
Huzhou/4045/2013 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2013/10/24 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755179618 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKEVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ91476 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 130
A/chicken/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
Huzhou/4076/2013 SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY
2013/10/24 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755179743 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSRGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ91725 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 131
A/chicken/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
Shaoxing/5201/2013 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2013/10/28 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755180161 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ91885 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 132
A/Shenzhen/SP4/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF 2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2014/01/16 HA
SGIRANGVTSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 755180429
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSRGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ91909 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 133
A/Shenzhen/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF SP26/2014
SADLIIERREGSDICYPGKFVNEEALRQILRESGGIDKEAMGFTY 2014/01/20 HA
SGIRANGATSACKRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 755180469
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISSLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDGCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSRGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ91945 MNTQILAFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 134
A/Shenzhen/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF SP38/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2014/01/22 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 755180529
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIGGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ91957 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 135
A/Shenzhen/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF SP44/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2014/01/23 HA
SGIRANGTTSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 755180549
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISSLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ91969 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 136
A/Shenzhen/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF SP48/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2014/01/23 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 755180569
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ91993 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 137
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/4119/2013 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2013/12/19 HA SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755180609 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLLGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFTLLAI VMGLVFICVKNGNMRCTICI
AJJ92031 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 138
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/4064/2013 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2013/12/19 HA SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755180672 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVESSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ92967 MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTERGVEVV 139 A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF chicken/Jiangxi/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 9469/2014
SGIRTNGVISACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2014/02/16 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS 755182232
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ93027 MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTERGVEVV 140
A/chicken/Jiangxi/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
9558/2014 SADLIIERREGSDVCYPGKEVKEEALRQILRESGGIDKEAMGFTY 2014/02/16
HA SGIRTNGVISACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 755182332
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ93051 MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTERGVEVV 141
A/chicken/Jiangxi/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
10573/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2014/02/18
HA SGIRTNGVISACRRSGSSFYAEMKWLLSNIDDAAFPQMTKSYKNT 755182372
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ93845 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 142 A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF chicken/Dongguan/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 157/2014
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2014/02/20 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS 755183695
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ93857 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 143
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/169/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY
2014/02/20 HA SGIRTNGATSACMRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755183715 RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ93869 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 144
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTVTGPPQCDQFLEF
Dongguan/173/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/02/20 HA SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755183735 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ93881 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 145
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTVTGPPQCDQFLEF
Dongguan/189/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/02/20 HA SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755183755 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
KYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ93907 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 146
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/449/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/02/20 HA SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755183799 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPERASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ93931 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 147
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/536/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY
2014/02/20 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755183839 RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDADCEGDCYHSGGTIISKLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ93943 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 148
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/568/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIEKEAMGFTY
2014/02/20 HA SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755183859 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSGGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ93979 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 149 A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTVTGPPQCDQFLEF chicken/Dongguan/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 656/2014
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2014/02/20 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS 755183919
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFGLI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ94134 MNTQILVLALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 150
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/1051/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY
2014/02/21 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755184182 RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVXLSXGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ94158 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 151
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/1075/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/02/21 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755184222 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPERASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYRGEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ94182 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 152
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/1177/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/02/21 HA SGIRTNGATSACKRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755184262 RKSPALIVWGIHHSVSIAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ94194 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 153 A/silkie
NATETVERTNIPRICSKGKKTIDLGQCGLLGTITGPPQCDQFLEF chicken/Dongguan/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 1264/2014
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2014/02/21 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS 755184282
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPERASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFKHQNAQGEGTAADYKSTQSAIDQVIGKLNRLIEKTNQQFELI
DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYRGEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFMLLAI VMGLVFICVKNGNMRCTICI
AJJ94206 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 154 A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF chicken/Dongguan/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 1268/2014
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2014/02/21 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS 755184302
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPERASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISDLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ94344 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 155 A/silkie
NSTETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF chicken/Dongguan/
SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY 1451/2014
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2014/02/21 HA
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS 755184532
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRTVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ94356 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 156
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/1456/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/02/21 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755184552 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPERASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ94396 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 157
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/1494/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/02/21 HA SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755184618 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPETPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ94754 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 158
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/748/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIEKEAMGFTY
2014/02/20 HA SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755185215 RKSPALIVWGIHHSVSNAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSGGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ94838 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 159
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/835/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/02/20 HA SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755185356 RKSPALIVWGIHHSASTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFGFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ94862 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 160
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/843/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIEKEAMGFTY
2014/02/20 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755185396 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSGGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ94886 MNTQILAFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 161
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/851/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/02/20 HA SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755185436 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ94910 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 162
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/874/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/02/20 HA SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755185476 RKSPALIVWGIHHSASTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ94959 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 163 A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF chicken/Dongguan/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 967/2014
SGIRANGATSACXRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2014/02/21 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS 755185558
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ95048 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 164
A/chicken/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/1009/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/02/21 HA SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755185708 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPETPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDNDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ95171 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 165
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/1314/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/02/21 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755185913 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVIFNFNGAFIAPERASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ95227 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 166
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/1382/2014 SADLIIERREGSDICYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/02/21 HA SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755186006 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPERASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ95251 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 167
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/1401/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/02/21 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755186046 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYKRVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ95346 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 168
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/1548/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/02/21 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755186206 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYKRVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHNKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ95382 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 167
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/1690/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY
2014/02/21 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755186266 RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSIGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ95464 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 170
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Shenzhen/138/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/02/19 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755186404 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPERASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYRGEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFMLLAI VMGLVFICVKNGNMRCTICI
AJJ95572 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 171
A/chicken/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
Dongguan/1100/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIEKEAMGFTY
2014/02/21 HA SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755186584 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSGGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ95584 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 172 A/silkie
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF chicken/Dongguan/
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 1519/2014
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2014/02/21 HA
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS 755186604
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPERASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYRGEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFMLLAI VMGLVFICVKNGNMRCTICI
AJJ95596 MNTQILAFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 173
A/Shenzhen/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF SP58/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2014/01/25 HA
SGIRANGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 755186624
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ95620 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 174
A/Shenzhen/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF SP75/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2014/02/15 HA
SGIRTNGSTSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 755186664
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAV VMGLVFICVKNGNMRCTICI
AJJ95632 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 175
A/Shenzhen/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF SP62/2014
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2014/02/05 HA
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNATFPQMTKSYKNT 755186684
RKSPALIIWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ96720 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 176
A/chicken/Jiangxi/ NATETVERTTIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
13220/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2014/03/30
HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 755188499
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSRGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ96817 MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTERGVEVV 177
A/chicken/Jiangxi/ NATEIVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
9513/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2014/02/16
HA SGIRTNGVISACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 755188661
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ96841 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 178
A/Shenzhen/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
SP139/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY 2014/04/02
HA SGIRTNGATSTCRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 755188701
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRACFLR
GKSMGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVERQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ96889 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 179
A/chicken/ NATETVERIXIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Jiangxi/13496/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKXAMGFTY
2014/04/11 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755188781 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSXGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ96901 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 180
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Jiangxi/13502/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/04/11 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755188801 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSXGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ96925 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 181
A/chicken/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
Jiangxi/13513/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/04/11 HA NGIRINGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755188841 RKSPAIIVWGIHHTVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDLHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKINQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHRKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ97267 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 182
A/chicken/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
Jiangxi/13252/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/03/30 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755189411 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ97291 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 183
A/chicken/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
Jiangxi/13493/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/04/06 HA NGIRINGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755189451 RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKINQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHRKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ97331 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 184
A/chicken/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
Jiangxi/13512/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/04/06 HA NGIRINGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755189517 RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSIGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKINQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHRKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ97373 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 185
A/chicken/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
Jiangxi/13521/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/04/06 HA NGIRINGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755189587 RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPXRASFLR
GKSXGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKINQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHRKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ97443 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 186
A/chicken/ NATETVERTTIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
Jiangxi/13530/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/04/06 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755189702 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSRGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ97582 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 187
A/chicken/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
Jiangxi/14023/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/04/13 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755189933 RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKINQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHRKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ97697 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 188
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Jiangxi/14517/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/04/20 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755190125 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCDGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ97709 MNTQILVFALIAIIPANADKICLGHHAVSNGTKVNTLTERGVEVV 189
A/chicken/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
Jiangxi/14518/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/04/20 HA NGIRINGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755190145 RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGNCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKINQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHRKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ97745 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 190
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Jiangxi/14554/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY
2014/04/20 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755190205 RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELM
DNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ97757 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 191
A/chicken/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
Shantou/2537/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY
2014/04/16 HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT
755190225 RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ97841 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 192
A/duck/Jiangxi/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
15044/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2014/04/27
HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 755190365
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKINQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHRKYREEAMQNRIQIDPVRLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ97899 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 193
A/chicken/Jiangxi/ NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF
15524/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2014/05/05
HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 755190462
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKINQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHRKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFMCVKNGNMRCTICI
AJJ97925 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 194 A/silkie
NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF chicken/Shantou/
SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY 2050/2014
SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 2014/03/25 HA
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS 755190506
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEVPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ97973 MNTQILVFALISIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 195
A/chicken/Shantou/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
4325/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRKSGGIDKEAMGFTY 2014/07/01
HA SGIRTNGVTSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 755190586
RKSPAIIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQRSLLLATGMKNVPEVPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI VMGLVFICVKNGNMRCTICI
AJJ97998 MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTERGVEVV 196
A/chicken/Shantou/ NATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPPQCDQFLEF
4816/2014 SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAMGFTY 2014/07/22
HA SGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNT 755190628
RKSPALIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPS
PGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRASFLR
GKSMGIQSGVQVDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCP
RYVKQKSLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGW
YGFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELV
DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNT
YDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLAI
VMGLVFICVKNGNMRCTICI
TABLE-US-00019 TABLE 15 H10 Hemagglutinin Amino Acid Sequences SEQ
Accession No/ SEQ ID NO: Strain/Protein Amino Acid Sequence ID NO:
AAM19228 ACVLVEAKGDKICLGHHAVVNGTKVNTLTEKGIEVVN 197 A/turkey/
ATETVETANIGKICTQGKRPTDLGQCGLLGTLIGPPQ Minnesota/
CDQFLEFESDLIIERREGNDVCYPGKFTNEESLRQIL 38429/1988
RGSGGIDKESMGFTYSGIITNGATSACRRSGSSFYAE 1988// HA
MKWLLSNSDNAAFPQMTKSYRNPRNKPALIVWGIHHS 20335017
GSTTEQTKLYGSGNKLITVESSKYQQSFTPSPGARPQ
VNGESGRIDFHWMLLDPNDTVTFTFNGAFIAPDRASF
FKGESLGVQSDVPLDSSCGGDCFHSGGTIVSSLPFQN
INPRTVGKCPRYVKQPSLLLATGMRNVPENPKTRGLF GAIAGFIEKDGGSHYG AAY46211
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL 198 A/mallard/
TERGVEVVNATETVERTNVPRICSRGKRTVDLGQCGL Sweden/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 91/2002
NEEALRQILRESGGIDKETMGFTYSGIRTNGAPSACR 2002// HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRNDPA 66394828
LIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSF
VPSPGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQIDANCEGDCYHSGGT
IISNLPFQNINSRAVGKCPRYVKQESLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIAMGLVFMCVKNGNMR CTICI ABI84694
MNTQILVFIACVLVEAKGDKICLGHHAVVNGTKVNTL 199 A/turkey/
TEKGIEVVNATETVETANIGKICTQGKRPTDLGQCGL Minnesota/1/1988
LGTLIGPPQCDQFLEFESDLIIERREGNDVCYPGKFT 1988/07/13 HA
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR 115278573
RSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPA
LIVWGIHHSGSTTEQTKLYGSGNKLITVGSSKYQQSF
TPSPGARPQVNGQSGRIDFHWMLLDPNDTVTFTFNGA
FIAPDRASFFKGESLGVQSDVPLDSSCGGDCFHSGGT
IVSSLPFQNINPRTVGKCPRYVKQPSLLLATGMRNVP
ENPKTRGLFGAIAGFIENGWEGLIDGWYGFKHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN
EFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH
KCDDQCMESIRNNTYDHAQYRAESLQNRIQIDPVKLS
SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR CTICI ABS89409
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTL 200 A/blue-winged
TERGIEVVNATETVETANIKKICTQGKRPTDLGQCGL teal/Ohio/566/
LGTLIGPPQCDQFLEFDTDLIIERREGTDVCYPGKFT 2006 2006// HA
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR 155016324
RSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPA
LIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSF
TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA
FIAPDRASFERGESLGVQSDVPLDSGCEGDCFHSGGT
IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP
ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN
EFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH
KCDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVRLS
SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR CTICI ACD03594
MNTQILAFIACMLVGVRGDKICLGHHAVANGTKVNTL 201 A/ruddy
TEKGIEVVNATETVESANIKKICTQGKRPTDLGQCGL turnstone/DE/
LGTLIGPPQCDQFLEFDSDLIIERREGTDVCYPGKFT 1538/2000
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR 2000// HA
RLGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPA 187384848
LIIWGVHHSGSANEQTKLYGSGNKLITVGSSKYQQSF
TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA
FIAPDRASFERGESLGIQSDVPLDSSCGGDCFHSGGT
IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP
ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELMDN
EFNEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH
KCDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLS
SGYKDIILWFSFGASCFLLLAIAMGLIFICIKNGNMR CTICI BAH22785
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL 202 A/duck/Mongolia/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 119/2008
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2008// HA
NEEALRQILRESGGIGKETMGFTYSGIRTNGATSACR 223717820
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKDPA
LIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSF
VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHNGGT
IISNLPFQNINSRTVGKCPRYVKQESLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIERTNQQFELIDN
EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
NGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR CTICI CAY39406
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL 203 A/Anas crecca/
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL Spain/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 1460/2008
NEEALRQILRESGGIDKETMGFTYSGIRTNGATSACR 2008/01/26 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKDPA 254674376
LIIWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSF
VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFTEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR CTICI ACX53683
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL 204 A/goose/Czech
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL Republic/1848-
LGTITGPPQCDQFLEFSADLIIERRGGSDVCYPGKFV K9/2009
NEEALRQILRESGGIDKETMGFTYSGIRTNGATSACR 2009/02/04 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKDPA 260907763
LIIWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSF
VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLKGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP
ELPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQINPVKLS
SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR CTICI ACZ48625
MNTQILVFIACVLVEAKGDKICLGHHAVVNGTKVNTL 205 A/turkey/
TEKGIEVVNATETVETANIGKICTQGKRPTDLGQCGL Minnesota/38429/
LGTLIGPPQCDQFLEFESDLIIERREGNDVCYPGKFT 1988 1988// HA
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR 269826341
RSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPA
LIVWGIHHSGSTTEQTKLYGSGNKLITVGSSKYQQSF
TPSPGARPQVNGQSGRIDFHWMLLDPNDTVTFTFNGA
FIAPDRASFFKGESLGVQSDVPLDSSCGGDCFHSGGT
IVSSLPFQNINPRTVGKCPRYVKQPSLLLATGMRNVP
ENPKTRGLFGAIAGFIENGWEGLIDGWYGFKHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFEL ADC29485
STQSAIDQITGKLNRLIEKTNQQFELIDNEFTEVEKQ 206 A/mallard/Spain/
IGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLADS 08.00991.3/
EMNKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMA 2005 2005/11/
SIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVIL HA 284927336 WFSFGASCFILL
ADK71137 MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTL 207 A/blue-winged
TERGIEVVNATETVETANIKKICTQGKRPTDLGQCGL teal/Guatemala/
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT CIP049-
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR 01/2008
RSGSSSYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPA 2008/02/07 HA
LIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSF 301333785
TPSPGIRPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA
FIAPDRASFLRGKSLGIQSDVPLDSGCEGDCFHSGGT
IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP
ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIDKTNQHFELIDN
EFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH
KCDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLS
SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR CTICI ADK71148
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTL 208 A/blue-winged
TERGIEVVNXTETVETANIKKICTHGKRPTDLGQCGL teal/Guatemala/
LGTLIGPPQCDRFLEFDADLIIERREGTDVCYPGKFT CIP049-
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR 02/2008
RSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPA 2008/03/05 HA
LIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSF 301333804
TPSPGIRPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA
FIAPDRASFLRGKSLGIQSDVPLDSGCEGDCFHSGGT
IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP
ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN
EFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH
KCDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLS
SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR CTICI ADN34727
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL 209 A/goose/Czech
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL Republic/1848-
LGTITGPPQCDQFLEFSADLIIERRGGSDVCYPGKFV T14/2009
NEEALRQILRESGGIDKETMGFTYSGIRINGXTSACR 2009/02/04 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKDPA 307141869
LIIWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSF
VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLKGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP
ELPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQINPVKLS
SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR CTICI AEK84760
PAFIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSG 210 A/wild
GTIISNLPFQNINSRAVGKCPRYVKQESLMLATGMKN bird/Korea/A14/
VPELPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNA 2011 2011/02/
QGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI HA 341610308
DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAME
NQHTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEI
FHKCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVK
LSSGYKDVILWFSFGASCFILLAIAMGLVFICVKNGN MRCTICI AEK84761
ILVFALVAIIPTNANKIGLGHHAVSNGTKVNTLTERG 211 A/wild
VEVFNATETVERTNVPRICSKGKKTVDLGQCGLRGTI bird/Korea/A3/
TGPPQCDQFLKFSPDLIIERQKGSDVCYPGKFVNEKP 2011 2011/02/
LRQILRESGGIDKETMGFAYNGIKTNGPPIACRKSGS HA 341610310
SFYAKMKWLLSNTDKAAFPQMTKSYKNTRRNPALIVW
GIHHSGSTTKQTKLYGIGSNLITVGSSNYQQSFVPSP
GARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIPP
DRASFLRGKSMGIQSGVQVDASCEGDCYHSGGTIISN
LPFQNINSRAVGKCPRYVKQESLMLATGMKNVPELPK
GKGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTA
ADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFTE
VEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTID
LADSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDD
DCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYK
DVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTIC I AEK84763
ILVFALVAIIPTNANKIGLGHHAVSNGTKVNTLTERG 212 A/wild
VEFFNATETVEPINVPRICSKGKKTVDLGQCGLLGTI bird/Korea/A9/
TGPPQCDQFLEFSADLIIERREGSDVCYPGKFVNEKA 2011 2011/02/
LRQILRESGGIDKETMGFAYSGIKTNGPPIACRKSGS HA 341610314
SFYAKMKWLLSNTDKAAFPQMTKSYKNTRRDPALIVW
GIHHSGSTIKQINLYGIGSNLITVGSSNYQQSFVPSP
GARPQVNGQSGRIDFHWLILNPNDTVTFIFNGAFIAP
DRASFLIGKSMGIQSGVQVDASCEGDCYHSGGTIISN
LPFQNINSRAVGKCPRYVKQESLMLATGMKNVPELPK
GRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTA
ADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFTE
VEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTID
LADSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDD
DCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYK
DVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTIC I AEK84765
LVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGV 213
A/spot-billed EVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTIT duck/Korea/447/
GPPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEAL 2011 2011/04/
RQILRESGGIDKETMGFTYSGIRTNGATSACRRSGSS HA 341610318
FYAEMKWLLSNTDNAAFPQMTKSYKNTRRDPALIVWG
IHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPSPG
ARPQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPD
RASFLRGKSMGIQSGVQVDASCEGDCYHSGGTIISNL
PFQNINSRAVGKCPRYVKQESLMLATGMKNVPEPPKG
RGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTAA
DYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFTEV
EKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDL
ADSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDD
CMARIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKD
VILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI AEM98291
SILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER 214 A/wild
GVEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGT duck/Mongolia/
ITGPPQCDQFLEFSADLIIERREGSDVCYPGKFVNEE 1-241/2008
ALRQILRESGGIDKETMGFTYSGIRTNGATSACRRSG 2008/04/ HA
SSFYAEMKWLLSNTDNAAFPQMTKSYKNIRKDPALII 344196120
WGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS
PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIA
PDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGSIIS
NLPFQNINSRAVGKCPRYVKQESLMLATGMKNVPELP
KGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGT
AADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFT
EVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTI
DLADSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCD
DDCMASIRNNTYDHSKYREEAMQNRIQINPVKLSSGY
KDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTI AFM09439
QILAFIACMLIGAKGDKICLGHHAVANGTKVNTLTER 215 A/emperor
GIEVVNATETVETVNIKKICTQGKRPTDLGQCGLLGT goose/Alaska/
LIGPPQCDQFLEFDADLIIERRKGTDVCYPGKFTNEE 44063-061/2006
SLRQILRGSGGIDKESMGFTYSGIRTNGATSACRRSG 2006/05/23 HA
SSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPALII 390535062
WGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSFVPS
PGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGAFIA
PERASFFRGESLGVQSDVPLDSGCEGDCFHSGGTIVS
SLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVPENP
KTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGT
AADYKSTQSAIDQITGKLNRLIDKTNQQFELIDNEFS
EIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTI
DLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCD
DQCMESIRNNTYDHTQYRTESLQNRIQINPVKLSSGY
KDIILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTI CI AFV33945
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTL 216 A/guinea
TERRIEVVNATETVETANIKKICTQGKRPTDLGQCGL fowl/Nebraska/
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT 17096-1/2011
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR 2011/04/05 HA
RSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNPRNKPA 409676820
LIVWGVHHSGSATEQTKLYGSGSKLITVGSSKYQQSF
TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA
FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHKGGT
IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP
ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN
EFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH
KCDDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLS
SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR CTICI AFV33947
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTL 217 A/goose/
TERGIEVVNATETVETANIKKICTQGKRPTDLGQCGL Nebraska/17097-
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT 4/2011
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR 2011/04/05 HA
RSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPA 409676827
LIVWGVHHSASATEQTKLYGSGSKLITVGSSKYQQSF
TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA
FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHKGGT
IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP
ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN
EFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH
KCDDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLS
SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR CTICI AFX85260
MNTQILAFIACMLIGINGDKICLGHHAVANGTKVNTL 218 A/ruddy
TERGIEVVNATETVETANIKRICTQGKRPIDLGQCGL turnstone/
LGTLIGPPQCDQFLEFDSDLIIERREGTDVCYPGKFT Delaware
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACI Bay/220/1995
RLGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPA 1995/05/21 HA
LIIWGVHHSGSANEQTKLYGSGNKLITVGSSKYQQSF 423514912
TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA
FIAPDRASFFRGESLGVQSDVPLDSSCGGDCFHSGGT
IVSSLPFQNINPRTVGRCPRYVKQTSLLLATGMKNVP
ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN
EFNEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH
KCDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLS
SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR CTICI AGE08098
MNTQILTLIACMLIGAKGDKICLGHHAVANGTKVNTL 219 A/northern
TERGIEVVNATETVETANIKKICTQGKRPTDLGQCGL shoverl/
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT Mississippi/
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR 11OS145/2011
RSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPA 2011/01/08 HA
LIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSF 444344488
TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA
FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHNGGT
IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP
ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN
EFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH
KCDDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLS
SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR CTICI AGI60301
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 220 A/Hangzhou/1/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 2013 2013/03/24
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV HA 475662454
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGISGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AGI60292
MNTQILVFALIAIIPANADKICLGHHAVSNGTKVNTL 221 A/Shanghai/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 4664T/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/03/05 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 476403560
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCHHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AGJ72861
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 222 A/chicken/
TERGGEVVNATETVERTNIPRICSKGKKTVDLGQGGP Zhejiang/DTID-
RGTITGPPQCDQFLEFSADLIMERREGSDVCYPGKFV ZJU01/2013
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 2013/04/
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA HA 479280294
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AGJ73503
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 223 A/Nanjing/1/
TERGVEVVNATETVERTNIPRICSKGKMTVDLGQCGL 2013 2013/03/28
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV HA 479285761
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI BAN16711
MNIQVLVFALMAIIPTNADKICLGHHAVSNGTKVNTL 224 A/duck/Gunma/
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL 466/2011 2011//
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV HA 482661571
NEEALRQILRESGGIDKETMGFTYSGIRINGITSACR
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRDPA
LIAWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSF
VPSPGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSGGT
IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP
ELPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRRQLRENAEEDDTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR CTICI AGK84857
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 225 A/Hangzhou/2/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 2013 2013/04/01
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV HA 485649824
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR
RSGSSFYAEMKWLLSNTDNAAFPQIIKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AGL44438
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 226 A/Shanghai/02/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/03/05 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 496493389
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AGL33692
GMIDGWYGFRHQNAQGEGTAADYKSTQSAIDQITGKL 227 A/Shanghai/
NRLIEKTNQQFELIDNEFTEVEKQIGNVINWTRDSIT 4655T/2013
EVWSYNAELLVAMENQHTIDLADSEMDKLYERVKRQL 2013/02/26 HA
RENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKYR 491874175
EEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLA IAMGLVFICVKNGNMRCTICI
AGL33693 GMIDGWYGFRHQNAQGEGTAADYKSTQSAIDQITGKL 228 A/Shanghai/
NRLIEKTNQQFELIDNEFNEVEKQIGNVINWTRDSIT 4659T/2013
EVWSYNAELLVAMENQHTIDLADSEMDKLYERVKRQL 2013/02/27 HA
RENAEEDGTGCFEIFHKCDDDCMASIRNNTYDHSKYR 491874186
EEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILLA IVMGLVFICVKNGNMRCTICI
AGL95088 VFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVE 229 A/Taiwan/
VVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITG
S02076/2013 PPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALR 2013/04/22 HA
QILRESGGIDKEAMGFTYSGIRTNGATSACRRSGSSF 501485301
YAEMKWLLSNTDNAAFPQMTKSYKNTRKSPALIVWGI
HHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPGA
RPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDR
ASFLRGKSMGIQSGVQVDANCEGDCYHSGGTIISNLP
FQNIDSRAVGKCPRYVKQRSLLLATGMKNVPEIPKGR
GLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTAAD
YKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFNEVE
KQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA
DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDC
MASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDV
ILWFSFGASCFILLAIVMGLVFICVKNGNMR AGL95098
LVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGV 230 A/Taiwan/
EVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTIT T02081/2013
GPPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEAL 2013/04/22 HA
RQILRESGGIDKEAMGFTYSGIRTNGATSACRRSGSS 501485319
FYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPALIVWG
IHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPG
ARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPD
RASFLRGKSMGIQSGVQVDANCEGDCYHSGGTIISNL
PFQNIDSRAVGKCPRYVKQRSLLLATGMKNVPEIPKG
RGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTAA
DYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFNEV
EKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDL
ADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDD
CMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKD
VILWFSFGASCFILLAIVMGLVFICVKNGNMRCT AGM53883
GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKT 231 A/Shanghai/
NQQFELIDNEFNEVEKQIGNVINWTRDSITEVWSYNA 5083T/2013
ELLVAMENQHTIDLADSEMDKLYERVKRQLRENAEED 2013/04/20 HA
GTGCFEIFHKCDDDCMASIRNNTYDHSKYREEAMQNR 507593986
IQIDPVKLSSGYKDVILWFSFGASCFILLAIVMGLVF ICVKNGNMRCT AGM53884
AQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFEL 232 A/Shanghai/
IDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAM 5180T/2013
ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFE 2013/04/23 HA
IFHKCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPV 507593988
KLSSGYKDVILWFSFGASCFILLAIVMGLVFICVKNG NMRCTICI AGM53885
QNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF 233 A/Shanghai/
ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLV 5240T/2013
AMENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGC 2013/04/25 HA
FEIFHKCDDDCMASIRNNTYDHSKYREEAMQNRIQID 507593990
PVKLSSGYKDVILWFSFGASCFILLAIVMGLVFICVK NGNMRCT AGM53886
NAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFE 234 A/Shanghai/
LIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVA 4842T/2013
MENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCF 2013/04/13 HA
EIFHKCDDDCMASIRNNTYDHSKYREEAMQNRIQIDP 507593992
VKLSSGYKDVILWFSFGASCFILLAIVMGLVFICVKN GNMRCT AGM53887
NAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFE 235 A/Shanghai/
LIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVA 4701T/2013
MENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCF 2013/04/06 HA
EIFHKCDDDCMASIRNNTYDHSKYREEAMQNRIQIDP 507593994
VKLSSGYKDVILWFSFGASCFILLAIVMGLVFICVKN GNMRCTIC AGN69462
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 236 A/Wuxi/2/2013
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 2013/03/31 HA
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 511105778
NEEALRQILRESGGIDKEAMGFTYSGIRTNGSTSACR
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGSKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AGN69474
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 236 A/Wuxi/1/2013
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 2013/03/31 HA
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 511105798
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLINGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AGO51387
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 238 A/Jiangsu/2/
TERGVEVVNATETVERTNIPRICSKGKMTVDLGQCGL 2013 2013/04/20
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV HA 514390990
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYRXEAMXBXIQIDPVKLS
SGYKDVXJWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI BAN59726
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL 239 A/duck/Mongolia/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 147/2008
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2008/08/29 HA
NEEALRQILRESGGIGKETMGFTYSGIRTNGATSACR 519661951
RSRSSFYAEMKWLLSNTDNAAFPQMTRSYKNTRKDPA
LIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSF
VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHNGGT
IISNLPFQNINSRTVGKCPRYVKQESLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIERTNQQFELIDN
EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
NGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR CTICI BAN59727
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL 240 A/duck/Mongolia/
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL 129/2010
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2010// HA
NEEALRQILRESGGIDKETMGFTYSGIRTNGATSACR 519661954
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKDPA
LIIWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSF
VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSGGT
IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP
ELPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQINPVKLS
SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR CTICI AGQ80952
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL 241 A/duck/Jiangxi/
TERGVEVVNATETVERTSIPRICSKGKRAVDLGQCGL 3096/2009
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2009// HA
NEEALRQILRESGGIDKETMGFTYSGIRTNGATSACR 523788794
RSGSSFYAEMKWLLSNTDNAAFPQTTKSYKNTRKDPA
LIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSF
VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHNGGT
IISNLPFQNINSRAVGKCPRYVKQESLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFTEVERQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR CTICI AGQ80989
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL 242 A/duck/Jiangxi/
TERGVEVVNATETVERTSIPRICSKGKRAVDLGQCGL 3257/2009
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2009// HA
NEEALRQILRESGGIDKETMGFTYSGIRTNGATSACR 523788868
RSGSSFYAEMKWLLSNTDNAAFPQTTKSYKNTRKDPA
LIIWGIHHSGSTTEQTKLYGSGNKLITVGXSNYQQSF
VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHNGGT
IISNLPFQNINSRAVGKCPRYVKQESLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFTEVERQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR CTICI AGQ81043
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 243 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL Rizhao/515/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013// HA
NEEALRQILRESGGIDKEEMGFTYSGIRTNGATSACR 523788976
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AGR33894
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 244 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL Rizhao/719b/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013// HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 524845213
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDRSKYREEAMQNRXXXXXXXXX
XXXKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AGR49399
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 245 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL Jiangxi/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV SD001/2013
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSACR 2013/05/03 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA 525338528
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AGR49495
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 246 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKMTVDLGQCGL Shanghai/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV S1358/2013
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 2013/04/03
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA HA 525338689
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIKNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI
AGR49506 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 247 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL Shanghai/S1410/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013 2013/04/03
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR HA 525338708
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AGR49554
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 248 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL Zhejiang/SD033/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013 2013/04/11
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR HA 525338789
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVRRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AGR49566
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 249 A/duck/Anhui/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL SC702/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/04/16 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 525338809
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDNRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AGR49722
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 250 A/homing
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL pigeon/Jiangsu/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV SD184/2013
NEEALRQILRESGGIDKEAMGFTYSEIRTNGATSACR 2013/04/20 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA 525339071
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AGR49734
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 251 A/pigeon/Shanghai/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL S1069/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/04/02 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 525339091
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTITFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AGR49770
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 252 A/wild
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL pigeon/Jiangsu/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV SD001/2013
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 2013/04/17 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA 525339151
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AGY41893
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 253 A/Huizhou/01/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL 2013 2013/08/08
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV HA 552049496
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDADCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AGY42258
FALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEV 254 A/mallard/
VNATETVERTNVPRICSRGKRTVDLGQCGLLGTIXGP Sweden/91/2002
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQ 2002/12/12 HA
ILRESGGIDKETMGFTYSGIRTNGAXSACRRSGSSFY 552052155
AEMKWLLSNTDNAAFPQMTKSYKNTRNDPALIIWGIH
HSGSTTEQTKLYGSGNKLITVGSSNYQQSFVPSPGAR
PQVNGQSGRIDFHWLILNPNDTVTFSFNGAFIAPDRA
SFLRGKSMGIQSGVQIDANCEGDCYHSGGTIISNLPF
QNINSRAVGKCPRYVKQESLLLATGMKNVPEIPKGRG
LFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTAADY
KSTQSAIDQITGKLNRLIEKTNQQFELIDNEFTEVEK
QIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLAD
SEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCM
ASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVI
LWFSFGASCFILLAIAMGLVFMCVKNGNMRCTICI AHA11441
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTL 255 A/guinea
TERGIEVVNATETVETANIKKICTQGKRPTDLGQCGL fowl/Nebraska/
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT 17096/2011
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR 2011/04/10 HA
RSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNPRNKPA 557478572
LIVWGVHHSGSATEQTKLYGSGSKLITVGSSKYQQSF
TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA
FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHKGGT
IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP
ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN
EFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH
KCDDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLS
SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR CTICI AHA11452
MNTQILALIACMLVGIKGDKICLGHHAVANGTKVNTL 256 A/turkey/Minnesota/
TERGIEVVNATETVETANIKKICTQGKRPTDLGQCGL 32710/2011
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT 2011/07/12
NEEPLRQILRGSGGIDKESMGFTYSGIRTNGATSTCR HA 557478591
RSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNPRNKPA
LIVWGVHHSGSATEQTKLYGSGSKLITVGSSKYQQSF
TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA
FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHKGGT
IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP
ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFEMIDN
EFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH
KCDDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLS
SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR CTICI AHA11461
MNTQILALIACMLVGIKGDKICLGHHAVANGTKVNTL 257 A/turkey/Minnesota/
TERGIEVVNATETVETANIKKICTQGKRPTDLGQCGL 31900/2011
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT 2011/07/05
NEEPLRQILRGSGGIDKESMGFTYSGIRTNGATSTCR HA 557478606
RSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNPRNKPA
LIVWGVHHSGSATEQTKLYGSGSKLITVGSSKYQQSF
TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA
FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHKGGT
IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP
ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN
EFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH
KCDDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLS
SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR CTICI AHK10585
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 258 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Guangdong/G1/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/05/05 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 587680636
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AGG53366
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL 259 A/wild
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL duck/Korea/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV CSM42-34/2011
NEEALRQILRESGGIDKETMGLTYSGIRTNGATSACR 2011/03/
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRDPA HA 459252887
LIVWGIHHSGSSTEQTKLYGSGSKLITVGSSNYQQSF
VPSPGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSGGT
IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP
ELPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVRLS
SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR CTICI AGG53377
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL 260 A/wild
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL duck/Korea/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV CSM42-1/2011
NEEALRQILRESGGIDKETMGLTYSGIRTNGATSACR 2011/03/
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRDPA HA 459252925
LIVWGIHHSGSSTEQTKLYGSGSKLITVGSSNYQQSF
VPSPGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSGGT
IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP
ELPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVRLS
SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR CT AGG53399
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL 261 A/wild
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL duck/Korea/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV MHC39-26/2011
NEEALRQILRESGGIDKETMGFTYSGIRTNGATSACR 2011/03/
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRDPA HA 459253005
LIVWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSF
VPSPGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSGGT
IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP
EPPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR CTICI AGG53432
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL 262 A/wild
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL duck/Korea/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV MHC35-41/2011
NEEALRQILRESGGIDKETMGFTYSGIRTNGATSACR 2011/03/
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRDPA HA 459253136
LIVWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSF
VPSPGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSGGT
IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP
EPPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR CT AGG53476
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL 263 A/wild
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL duck/Korea/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV SH19-27/2010
NEEALRQILRESGGIDKETMGFTYSGIRTNGATSACR 2010/12/
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRDPA HA 459253257
LIVWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSF
VPSPGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSGGT
IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP
ELPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR CTI AGG53487
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL 264 A/wild
TERGVEVVNATETVERTNVPRICSKGKRTVDLGQCGL duck/Korea/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV SH19-50/2010
NEEALRQILRESGGIDKETMGFTYSGIRTNGATSACR 2010/01/
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRDPA HA 459253278
LIVWGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSF
VPSPGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSGGT
IISNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVP
ELPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR CTICI AGG53520
QILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER 265 A/wild
GVEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGT duck/Korea/
ITGPPQCDQLLEFSADLIIERREGTDVCYPGKEVNEE SH20-27/2008
ALRQILRESGGIEKETMGFTYSGIRTNGATSACRRSG 2008/12/
SSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKDPALII HA 459253409
WGIHHSGSTTEQTKLYGSGSKLITVGSSNYQQSFVPS
PGARPQVNGQSGRIDFHWLMLNPNDTVTFSFNGAFIA
PDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGTIIS
NLPFQNINSRAVGKCPRYVKQESLMLATGMKNVPELP
KGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGT
AADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFT
EVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTI
DLADSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCD
DDCMASIRNNTYDHSKYREEAMQNRIQINPVKLSSGY
KDVILWFSFGASCFILLAIAMGLVFICVKNGNMR AGL43637
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 266 A/Taiwan/1/2013
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 2013// HA
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 496297389
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGPSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IINNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AGL97639
IACMLVGAKGDKICLGHHAVANGTKVNTLTERGIEVV 267 A/mallard/
NATETVETANIKKLCTQGKRPTDLGQCGLLGTLIGPP Minnesota/AI09-
QCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQI 3770/2009
LRGSGGIDKESMGFTYSGIRTNGATSACRRSGSSFYA 2009/09/12 HA
EMKWLLSNSDNAAFPQMTKSYRNPRNKPALIIWGVHH 505555371
SGSATEQTKLYGSGNKLITVGSSKYQQSFTPSPGARP
QVNGQSGRIDFHWLLLDPNDTVIFTFNGAFIAPDRAS
FFRGESLGVQSDVPLDSGCEGDCFHSGGTIVSSLPFQ
NINPRTVGKCPRYVKQTSLLLATGMRNVPENPKTRGL
FGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTAADYK
STQSAIDQITGKLNRLIDKTNQQFELIDNEFSEIEQQ
IGNVINWTRDSMTELWSYNAELLVAMENQHTIDLADS
EMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCME SIRNNTYDHTQYRTESLQNRIQIDPVKLS
AGO02477 MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 268 A/Xuzhou/1/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 2013 2013/04/25
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV HA 512403688
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGSKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKSRNMR CTICI AGR84942
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 269 A/Suzhou/5/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 2013 2013/04/12
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV HA 526304561
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGSKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AGR84954
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 270 A/Nanjing/6/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 2013 2013/04/11
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV HA 526304594
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNRNMR CTICI AGR84978
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 271 A/Wuxi/4/2013
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL 2013/04/07 HA
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 526304656
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKSRNMR CTICI AGR84990
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 272 A/Wuxi/3/2013
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 2013/04/07 HA
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 526304688
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKSRNMR CTICI AGR85002
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 273 A/Zhenjiang/1/
TERGVEVVNATETVERTNIPRICSKGKMTVDLGQCGL 2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/04/07 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 526304708
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKSRNKR CTICI AGR85026
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 274 A/Nanjing/2/
TERGVEVVNATETVERTNIPRICSKGKMTVDLGQCGL 2013 2013/04/05
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV HA 526304762
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKSRNMR CTICI AGU02230
LVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGG 275 A/Zhejiang/
EVVNATETVERTNIPRICSKGKRTVDLGQCGLRGTIT DTID-ZJU05/2013
GPPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEAL 2013/04/
RQILRESGGIDKEAMGFTYSGIRTNGATSACRRSGSS HA 532808765
FYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPALIVWG
IHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPG
ARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPD
RASFLRGKSMGIQSGVQVDANCEGDCYHSGGTIISNL
PFQNIDSRAVGKCPRYVKQRSLLLATGMKNVPEIPKG
RGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTAA
DYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFNEV
EKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDL
ADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDD
CMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKD
VILWFSFGASCFILLAIVMGLVFICVKNGNMRCT AGU02233
FALIAIIPTNADKICLGHHAVSNGTKVNTLTERGGEV 276 A/Zhejiang/
VNATETVERTNFPRICSKGKRTVDLGQCGLRGTITGP DTID-ZJU08/2013
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQ 2013/04/
ILRESGGIDKEAMGFTYSGIRTNGATSACRRSGSSFY HA 532808788
AEMKWLLSNTDNAAFPQMTKSYKNTRKSPALIVWGIH
HSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPGAR
PQVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRA
SFLRGKSMGIQSGVQVDANCEGDCYHSGGTIISNLPF
QNIDSRAVGKCPRYVKQRSLLLATGMKNVPEIPKGRG
LFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTAADY
KSTQSAIDQITGKLNRLIEKTNQQFELIDNEFNEVEK
QIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLAD
SEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCM
ASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVI
LWFSFGASCFILLAIVMGLVFICVKNGNMRCT AGW82588
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 277 A/tree
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL sparrow/Shanghai/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 01/2013
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 2013/05/09 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA 546235348
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTIGI AGW82600
ALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV 278 A/Shanghai/
NATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP CN01/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQI 2013/04/11 HA
LRESGGIDKEAMGFTYSGIRTNGATSACRRSRSSFYA 546235368
EMKWLLSNTDNAAFPQMTKSYKNTRKSPALIVWGIHH
SVSTAEQTKLYGSGNKLVTVGSSNYQQSFVPSPGARP
QVNGLSGRIDFHWLMLNPNDTVTFSFNGAFIAPDRAS
FLRGKSMGIQSGVQVDANCEGDCYHSGGTIMSNLPFQ
NIDSRAVGKCPRYVKQRSLLLATGMKNVPEIPKGRGL
FGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTAADYK
STQSAIDQITGKLNRLIEKTNQQFELIDNEFNEVEKQ
IGNVINWTRDSITEVWSYNAELLVAMENQHTIDLADS
EMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMA
SIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVIL
WFSFGASCFILLAIVMGLVFICVKNGNMRCTICI AGW82612
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 280 A/Shanghai/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL JS01/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/04/03 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 546235388
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKNPA
LIVWGIHHSGSTAEQTKLYGSGNKLVTVGSSNYQQSF
APSPGARTQVNGQSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDADCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFTEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMR CTICI AHA11472
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTL 281 A/turkey/
TERGIEVVNATETVETANVKKICTQGKRPTDLGQCGL Minnesota/31676/
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT 2009 2009/12/08
NEESLRQILRGSGGIDKESMGFTYSGIRTNGETSACR HA 557478625
RSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNPRDKPA
LIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSF
TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA
FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHSGGT
IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP
EKPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITNKLNRLIDKTNQQFELIDN
EFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH
KCDDQCMESIRNNTYDHTQYRKESLQNRIQIDPVKLS
SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR CTICI AHA11483
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTL 282 A/turkey/
TERGIEVVNATETVETANVKKICTQGKRPTDLGQCGL Minnesota/14135-
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT 2/2009
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR 2009/08/07 HA
RSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNPRDKPA 557478644
LIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSF
TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA
FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHSGGT
IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP
EKPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITSKLNRLIDKTNQQFELIDN
EFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH
KCDDQCMESIRNNTYDHTQYRKESLQNRIQIDPVKLS
SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR CTICI AHA11500
TQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTE 283 A/Zhejiang/
RGVEVVNATETVERTNIPRICSKGKRTVDLGQCGLLG DTID-ZJU10/2013
TITGPPQCDQFLEFSADLIIERREGSDVCYPGKFVNE 2013/10/14 HA
EALRQILRESGGIDKEAMGFTYSGIRTNGATSACRRS 557478676
GSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPALI
VWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSFVP
SPGARPPVNGLSGRIDFHWLMLNPNDTVTFSFNGAFI
APDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGTII
SNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVPEI
PKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEG
TAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEF
NEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHT
IDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKC
DDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG
YKDVILWFSFGASCFILLAIVMGLVFICVKN AHA57050
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTL 284 A/turkey/
TERGIEVVNATETVETANVKKICTQGKRPTDLGQCGL Minnesota/14659/
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT 2009 2009/08/12
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR HA 558484427
RSGSSFYAEMKWLLSNSNNAAFPQMTKSYRNPRDKPA
LIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSF
TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA
FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHSGGT
IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP
EKPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITSKLNRLIDKTNQQFELIDN
EFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH
NCDDQCMESIRNNTYDHTQYRKESLQNRIQIDPVKLS
SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR CTICI AHA57072
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTL 285 A/turkey/
TERGIEVVNATETVETANVKKICTQGKRPTDLGQCGL Minnesota/18421/
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT 2009 2009/09/09
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR HA 558484465
RSGSSFYAEMKWLLSNSNDAAFPQMTKSYRNPRDKPA
LIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSF
TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA
FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHSGGT
IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP
EKPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN
EFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH
KCDDQCMESIRNNTYDHTQYRKESLQNRIQIDPVKLS
SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR CTICI AHD25003
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 286 A/Guangdong/02/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL 2013 2013/10/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV HA 568260567
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNM AHF20528
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 287 A/Hong
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL Kong/470129/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013 2013/11/30
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR HA 570933555
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISSLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AHF20568
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 288 A/Shanghai/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL CN02/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/04/02 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 570933626
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IMSNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AHH25185
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 289 A/Guangdong/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL 04/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/12/16 HA
NEEALRQILRESGGIEKEAMGFTYSGIRANGATSACR 576106234
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AHJ57411
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 290 A/Shanghai/PD-
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 01/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/01/17 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 585478041
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VSSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCKGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRIIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AHJ57418
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 291 A/Shanghai/PD-
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 02/2014
LGTITGPPQCDQFLEFSADLIIERREGSDICYPGKFV 2014/01/17 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 585478256
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLKGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRIIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AHK10800
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 292 A/Shanghai/01/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/01/03 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 587681014
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRIIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AHM24224
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 293 A/Beijing/3/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 2013 2013/04/16
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV HA 594704802
KEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AHN96472
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 294 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Shanghai/PD-CN-
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 02/2014
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 2014/01/21 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA 602701641
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AHZ39686
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 295 A/Anhui/DEWH72-
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 01/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013// HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 632807036
RSGSSFYAEMKWLLSNTDDAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AHZ39710
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 296 A/Anhui/DEWH72-
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 03/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013// HA
NEEALRQILRESGGIDKEAMGFTYSGIRTDGATSACR 632807076
RSGSSFYAEMKWLLSNTDDAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AHZ39746
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 297 A/Anhui/DEWH72-
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 06/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013// HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 632807136
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGERPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AHZ41929
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL 298 A/mallard/Sweden/
TERGVEVVNATETVERTNVPRICSRGKRTVDLGQCGL 1621/2002
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2002/12/12 HA
NEEALRQILRESGGIDKETMGFTYSGIRTNGATSACR 632810949
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRNDPA
LIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSF
VPSPGARPQVNGQSGRIDFHWLILNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQIDANCEGDCYHSGGT
IISNLPFQNINSRAVGKCPRYVKQESLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIAMGLVFMCVKNGNMR CTICI AHZ42537
MNTQILAFIACMLVGAKGDKICLGHHAVANGTKVNTL 299 A/mallard/
TERGIEVVNATETVETANIKKLCTQGKRPTDLGQCGL Minnesota/AI09-
LGTLIGPPQCDQFLEFDADLIIERREGTDVCYPGKFT 3770/2009
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR 2009/09/12 HA
RSGSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKPA 632811964
LIIWGVHHSGSATEQTKLYGSGNKLITVGSSKYQQSF
TPSPGARPQVNGQSGRIDFHWLLLDPNDTVTFTFNGA
FIAPDRASFFRGESLGVQSDVPLDSGCEGDCFHSGGT
IVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNVP
ENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDN
EFSEIEQQIGNVINWTRDSMTELWSYNAELLVAMENQ
HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH
KCDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLS
SGYKDIILWFSFGASCFLLLAIAMGLVFICIKNGNMR CTICI AHZ42549
MNTQILAFIACMLVGVRGDKICLGHHAVANGTKVNTL 300 A/ruddy
TEKGIEVVNATETVESANIKKICTQGKRPTDLGQCGL turnstone/
LGTLIGPPQCDQFLEFDSDLIIERREGTDVCYPGKFT Delaware/AI00-
NEESLRQILRGSGGIDKESMGFTYSGIRTNGATSACR 1538/2000
RLGSSSFYAEMKWLLSNSDNAAFPQMTKSYRNPRNKP 2000/05/20 HA
ALIIWGVHHSGSANEQTKLYGSGNKLITVGSSKYQQS 632811984
FTPSPGARPQVNGQSGRIDFHWLLLDPNDTVIFTENG
AFIAPDRASFFRGESLGIQSDVPLDSSCGGDCFHSGG
TIVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRNV
PENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQ
GEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELMD
NEFNEIEQQIGNVINWTRDSMTEVWSYNAELLVAMEN
QHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIF
HKCDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKL
SSGYKDIILWFSFGASCFLLLAIAMGLIFICIKNGNM RCTICI AID70634
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 301 A/Shanghai/Mix1/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/01/03 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 660304650
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRIIEKTNQQFELIDN
EFNEVEKQISNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AIN76383
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTL 302 A/Zhejiang/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL LS01/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/08 HA
NEEALRQILRESGGIDKEAMGFTYSGIRINGITSACR 684694637
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AIU46619
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 303 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL Zhejiang/DTID-
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV ZJU06/2013
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 2013/12/ HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA 699978931
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVEVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AIU47013
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 304 A/chicken/Suzhou/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 040201H/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/04/
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR HA 699979673
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDMILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ90490
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 305 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Shenzhen/742/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/12/10 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 755178094
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ90526
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 306 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Shenzhen/898/2013
LGTITGPPQCDQFLEFSADLIIERREGSDICYPGKFV 2013/12/09 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACK 755178154
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISSLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
RGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ90538
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 307 A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL chicken/Shenzhen/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 918/2013
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 2013/12/09 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA 755178174
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ90576
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 308 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Shenzhen/1665/2013
LGTITGPPQCDQFLEFSADLIIERREGSDICYPGKFV 2013/12/12 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACK 755178238
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
RGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ90588
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 309 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Shenzhen/2110/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/12/13 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 755178258
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSIGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ90661
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 310 A/chicken/Dongguan/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL 2912/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/12/18 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 755178380
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ90673
MNTQILVFALTAIIPTNADKICLGHHAVSNGTKVNTL 311 A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL chicken/Dongguan/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 3049/2013
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 2013/12/18 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA 755178400
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ90795
MNTQILVFALIAIIPTNADKICLGHHAVPNGTKVNTL 312 A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL chicken/Dongguan/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 3281/2013
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 2013/12/18 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA 755178604
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ90891
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 313 A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL chicken/Dongguan/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 3520/2013
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 2013/12/19 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKXPA 755178764
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ90951
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 314 A/chicken/Dongguan/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL 3544/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/12/19 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 755178864
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYRNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ91035
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 315 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Shenzhen/3780/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/12/19 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 755179004
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRRSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDNRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ91155
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 316 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/4037/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/12/19 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 755179204
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ92005
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 317 A/chicken/Shenzhen/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL 801/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/12/09 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 755180629
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
RGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ94254
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 318 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/1374/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/21 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755184382
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPERASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFKHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ94606
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 319 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/191/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/20 HA
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSACR 755184968
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDADCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ96552
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 320 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTIDLGQCGL Jiangxi/12206/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/03/16 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755188219
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHNKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ96684
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKINTL 321 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Jiangxi/13207/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/03/30 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755188439
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ96732
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 322 A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL 13223/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/03/30 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755188519
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJK00354
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTL 323 A/duck/Zhejiang/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL LS02/2014
LGTITGPPQCDQFLEFSADLIVERREGSDVCYPGKFV 2014/01/12 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755194469
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKDPA
LIIWGIHHSGSTTEQTKLYGSGNKLITVGSSNYQQSF
VPSPGARPLVNGQSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNINSRAVGKCPRYVKQESLLLATGMKNVP
EVPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQVIGKLNRLIEKTNQQFELIDH
EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ
HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFH
KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ91264
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 324 A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL chicken/Dongguan/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 4129/2013
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 2013/12/19 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA 755179386
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLMEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ91314
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 325 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL Shaoxing/2417/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/10/20 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755179470
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPPVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ91402
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 326 A/chicken/Huzhou/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 4045/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/10/24 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755179618
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKEVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ91476
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 327 A/chicken/Huzhou/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 4076/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/10/24 HA
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSACR 755179743
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSRGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ91725
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 328 A/chicken/Shaoxing/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 5201/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/10/28 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755180161
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ91885
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 329 A/Shenzhen/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL SP4/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/01/16 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGVISACR 755180429
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
RGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ91909
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 330 A/Shenzhen/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL SP26/2014
LGTITGPPQCDQFLEFSADLIIERREGSDICYPGKFV 2014/01/20 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACK 755180469
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISSLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDGCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
RGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ91945
MNTQILAFALIAIIPTNADKICLGHHAVSNGTKVNTL 331 A/Shenzhen/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL SP38/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/01/22 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 755180529
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIGGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ91957
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 332 A/Shenzhen/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL SP44/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/01/23 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGTTSACR 755180549
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISSLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ91969
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 333 A/Shenzhen/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL SP48/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/01/23 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755180569
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ91993
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 334 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/4119/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/12/19 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 755180609
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLLGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFTLLAIVMGLVFICVKNGNMR CTICI AJJ92031
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 335 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/4064/2013
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2013/12/19 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 755180672
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVESSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ92967
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTL 336 A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL chicken/Jiangxi/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 9469/2014
NEEALRQILRESGGIDKEAMGFTYSGIRINGVISACR 2014/02/16 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA 755182232
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ93027
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTL 337
A/chicken/ TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Jiangxi/9558/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/16 HA
KEEALRQILRESGGIDKEAMGFTYSGIRINGVISACR 755182332
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ93051
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTL 338 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Jiangxi/10573/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/18 HA
NEEALRQILRESGGIDKEAMGFTYSGIRINGVISACR 755182372
RSGSSFYAEMKWLLSNTDDAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ93845
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 339 A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL chicken/Dongguan/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 157/2014
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 2014/02/20 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA 755183695
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ93857
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 340 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/169/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/20 HA
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSACM 755183715
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDADCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ93869
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 341 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/173/2014
LGTVTGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/20 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 755183735
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ93881
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 342 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/189/2014
LGTVTGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/20 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 755183755
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPKYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ93907
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 343 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/449/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/20 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 755183799
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPERASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ93931
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 344 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/536/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/20 HA
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSACR 755183839
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDADCEGDCYHSGGT
IISKLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ93943
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 345 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/568/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/20 HA
NEEALRQILRESGGIEKEAMGFTYSGIRANGATSACR 755183859
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
GGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ93979
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 346 A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL chicken/Dongguan/
LGTVTGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 656/2014
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 2014/02/20 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA 755183919
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFGLIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ94134
MNTQILVLALIAIIPTNADKICLGHHAVSNGTKVNTL 347 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/1051/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/21 HA
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSACR 755184182
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDADCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVXLS
XGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ94158
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 348 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/1075/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/21 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755184222
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPERASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFKHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYRGEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ94182
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 349 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/1177/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/21 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACK 755184262
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSIAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ94194
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 350 A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTIDLGQCGL chicken/Dongguan/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 1264/2014
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 2014/02/21 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA 755184282
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPERASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFKHQNAQG
EGTAADYKSTQSAIDQVIGKLNRLIEKTNQQFELIDN
EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYRGEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFMLLAIVMGLVFICVKNGNMR CTICI AJJ94206
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 351 A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL chicken/Dongguan/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 1268/2014
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 2014/02/21 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA 755184302
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPERASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISDLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ94344
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 352 A/silkie
TERGVEVVNSTETVERTNIPRICSKGKKTVDLGQCGL chicken/Dongguan/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 1451/2014
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSACR 2014/02/21 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA 755184532
IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDADCEGDCYHSGGT
IISNLPFQNIDSRTVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ94356
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 353 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/1456/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/21 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755184552
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPERASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ94396
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 354 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/1494/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/21 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 755184618
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
ETPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ94754
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 355 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/748/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/20 HA
NEEALRQILRESGGIEKEAMGFTYSGIRANGATSACR 755185215
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSNAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
GGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ94838
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 356 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/835/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/20 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 755185356
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSASTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFGFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ94862
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 357 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/843/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/20 HA
NEEALRQILRESGGIEKEAMGFTYSGIRTNGATSACR 755185396
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
GGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ94886
MNTQILAFALIAIIPTNADKICLGHHAVSNGTKVNTL 358 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/851/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/20 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 755185436
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ94910
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 359 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/874/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/20 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 755185476
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSASTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ94959
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 360 A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL chicken/Dongguan/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 967/2014
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACX 2014/02/21 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA 755185558
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ95048
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 361 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL Dongguan/1009/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/21 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 755185708
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
ETPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ95171
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 362 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/1314/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/21 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755185913
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVIFNFNGA
FIAPERASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFKHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ95227
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 363 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/1382/2014
LGTITGPPQCDQFLEFSADLIIERREGSDICYPGKFV 2014/02/21 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 755186006
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPERASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ95251
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 364 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/1401/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/21 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755186046
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYKRVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ95346
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 365 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/1548/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/21 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755186206
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYKRVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHNKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ95382
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 366 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Dongguan/1690/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/21 HA
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSACR 755186266
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSIGIQSGVQVDADCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ95464
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 367 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL Shenzhen/138/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/19 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755186404
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPERASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFKHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYRGEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFMLLAIVMGLVFICVKNGNMR CTICI AJJ95572
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 368 A/chicken/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL Dongguan/1100/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/21 HA
NEEALRQILRESGGIEKEAMGFTYSGIRANGATSACR 755186584
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
GGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ95584
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 369 A/silkie
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL chicken/Dongguan/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 1519/2014
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 2014/02/21 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA 755186604
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPERASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFKHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYRGEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFMLLAIVMGLVFICVKNGNMR CTICI AJJ95596
MNTQILAFALIAIIPTNADKICLGHHAVSNGTKVNTL 370 A/Shenzhen/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL SP58/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/01/25 HA
NEEALRQILRESGGIDKEAMGFTYSGIRANGATSACR 755186624
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ95620
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 371 A/Shenzhen/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL SP75/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/15 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGSTSACR 755186664
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAVVMGLVFICVKNGNMR CTICI AJJ95632
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 372 A/Shenzhen/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL SP62/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/05 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755186684
RSGSSFYAEMKWLLSNTDNATFPQMTKSYKNTRKSPA
LIIWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVETQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ96720
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 373 A/chicken/
TERGVEVVNATETVERTTIPRICSKGKKTVDLGQCGL Jiangxi/13220/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/03/30 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755188499
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSRGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ96817
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTL 374 A/chicken/
TERGVEVVNATEIVERTNIPRICSKGKKTVDLGQCGL Jiangxi/9513/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/02/16 HA
NEEALRQILRESGGIDKEAMGFTYSGIRINGVISACR 755188661
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ96841
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 375 A/Shenzhen/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL SP139/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/04/02 HA
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSTCR 755188701
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRACFLRGKSMGIQSGVQVDADCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVERQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ96889
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 376 A/chicken/Jiangxi/
TERGVEVVNATETVERTXIPRICSKGKKTVDLGQCGL 13496/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/04/11 HA
NEEALRQILRESGGIDKXAMGFTYSGIRTNGATSACR 755188781
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSXGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ96901
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 377 A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL 13502/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/04/11 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755188801
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSXGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ96925
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 378 A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 13513/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/04/11 HA
NEEALRQILRESGGIDKEAMGFTYNGIRTNGATSACR 755188841
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
IIVWGIHHTVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDLHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIAKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ97267
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 379 A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 13252/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/03/30 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755189411
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ97291
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 380 A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 13493/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/04/06 HA
NEEALRQILRESGGIDKEAMGFTYNGIRTNGATSACR 755189451
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIAKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ97331
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 381 A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 13512/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/04/06 HA
NEEALRQILRESGGIDKEAMGFTYNGIRTNGATSACR 755189517
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSIGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIAKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ97373
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 382 A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 13521/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/04/06 HA
NEEALRQILRESGGIDKEAMGFTYNGIRTNGATSACR 755189587
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPXRASFLRGKSXGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIAKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ97443
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 383 A/chicken/Jiangxi/
TERGVEVVNATETVERTTIPRICSKGKRTVDLGQCGL 13530/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/04/06 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755189702
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSRGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ97582
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 384 A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 14023/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/04/13 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755189933
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIAKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ97697
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 385 A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL 14517/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/04/20 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755190125
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCDGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ97709
MNTQILVFALIAIIPANADKICLGHHAVSNGTKVNTL 386 A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 14518/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/04/20 HA
NEEALRQILRESGGIDKEAMGFTYNGIRTNGATSACR 755190145
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGNCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIAKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ97745
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 387 A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL 14554/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/04/20 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755190205
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELMDN
EFNEVEKQIGNVINWTRDSITELWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ97757
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 388 A/chicken/Shantou/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL 2537/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/04/16 HA
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSACR 755190225
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDADCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFKHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ97841
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 389 A/duck/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 15044/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/04/27 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755190365
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIAKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVRLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ97899
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 390 A/chicken/Jiangxi/
TERGVEVVNATETVERTNIPRICSKGKRTVDLGQCGL 15524/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/05/05 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755190462
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIAKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFMCVKNGNMR CTICI AJJ97925
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTL 391 A/silkie
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL chicken/Shantou/
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2050/2014
NEEALRQILRKSGGIDKEAMGFTYSGIRTNGATSACR 2014/03/25 HA
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA 755190506
IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDADCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EVPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ97973
MNTQILVFALISIIPTNADKICLGHHAVSNGTKVNTL 392 A/chicken/Shantou/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL 4325/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/07/01 HA
NEEALRQILRKSGGIDKEAMGFTYSGIRINGVISACR 755190586
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
IIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDADCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQRSLLLATGMKNVP
EVPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI AJJ97998
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTL 393 A/chicken/Shantou/
TERGVEVVNATETVERTNIPRICSKGKKTVDLGQCGL 4816/2014
LGTITGPPQCDQFLEFSADLIIERREGSDVCYPGKFV 2014/07/22 HA
NEEALRQILRESGGIDKEAMGFTYSGIRTNGATSACR 755190628
RSGSSFYAEMKWLLSNTDNAAFPQMTKSYKNTRKSPA
LIVWGIHHSVSTAEQTKLYGSGNKLVTVGSSNYQQSF
VPSPGARPQVNGLSGRIDFHWLMLNPNDTVTFSFNGA
FIAPDRASFLRGKSMGIQSGVQVDANCEGDCYHSGGT
IISNLPFQNIDSRAVGKCPRYVKQKSLLLATGMKNVP
EIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG
EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELVDN
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ
HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLS
SGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMR CTICI
TABLE-US-00020 TABLE 16 Exemplary Influenza HA Stem Antigens SEQ ID
SEQ ID Strain Foldon version NO: AA seq NO: H1N1
DTVDTVLEKNVTVTHSVNL 394 METPAQLLFLLLLWLPDTTGDT 403 A/Puerto
LEDSHGSANSSLPYQNTHP VDTVLEKNVTVTHSVNLLEDSH Rico/8/
TTNGESPKYVRSAKLRMVT GSANSSLPYQNTHPTTNGESPK 1934 GLRNGSAGSATQNAINGIT
YVRSAKLRMVTGLRNGSAGSAT NKVNTVIEKMNIQDTATGK QNAINGITNKVNTVIEKMNIQD
EFNKDEKRMENLNKKVDDG TATGKEFNKDEKRMENLNKKVD FLDIWTYNAELLVLLENER
DGFLDIWTYNAELLVLLENERT TLDAHDSQGTgggyipeap LDAHDSQGTGGGYIPEAPRDGQ
rdgqayvrkdgewvllstf AYVRKDGEWVLLSTFL l H1N1 DTVDTVLEKNVTVTHSVNL 395
METPAQLLFLLLLWLPDTTGDT 404 A/VietNam/ LEDKHGSANTSLPFQNTHP
VDTVLEKNVTVTHSVNLLEDKH 850/2009 TTNGKCPKYVKSTKLRLAT
GSANTSLPFQNTHPTTNGKCPK GLRNGSAGSATQNAIDEIT YVKSTKLRLATGLRNGSAGSAT
NKVNSVIEKMNTQDTATGK QNAIDEITNKVNSVIEKMNTQD EFNHDEKRIENLNKKVDDG
TATGKEFNHDEKRIENLNKKVD FLDIWTYNAELLVLLENER DGFLDIWTYNAELLVLLENERT
TLDAHDSQGTgggyipeap LDAHDSQGTGGGYIPEAPRDGQ rdgqayvrkdgewvllstf
AYVRKDGEWVLLSTFL l H1N1 DTVDTVLEKNVTVTHSVNL 396
METPAQLLFLLLLWLPDTTGDT 405 A/New LEDSHGSANSSLPFQNTHP
VDTVLEKNVTVTHSVNLLEDSH Caledonia/ TTNGESPKYVRSAKLRMVT
GSANSSLPFQNTHPTTNGESPK 20/99 GLRNGSAGSATQNAINGIT
YVRSAKLRMVTGLRNGSAGSAT NKVNSVIEKMNTQDTAVGK QNAINGITNKVNSVIEKMNTQD
EFNKDERRMENLNKKVDDG TAVGKEFNKDERRMENLNKKVD FLDIWTYNAELLVLLENER
DGFLDIWTYNAELLVLLENERT TLDAHDSQGTgggyipeap LDAHDSQGTGGGYIPEAPRDGQ
rdgqayvrkdgewvllstf AYVRKDGEWVLLSTFL l H1N1 DTVDTVLEKNVTVTHSVNL 397
METPAQLLFLLLLWLPDTTGDT 406 A/ LEDKHGSANTSLPFQNTHP
VDTVLEKNVTVTHSVNLLEDKH California/ TTNGKSPKYVKSTKLRLAT
GSANTSLPFQNTHPTTNGKSPK 04/2009 GLRNGSAGSATQNAIDEIT
YVKSTKLRLATGLRNGSAGSAT NKVNSVIEKMNTQDTAVGK QNAIDEITNKVNSVIEKMNTQD
EFNHDEKRIENLNKKVDDG TAVGKEFNHDEKRIENLNKKVD FLDIWTYNAELLVLLENER
DGFLDIWTYNAELLVLLENERT TLDAHDSQGTgggyipeap LDAHDSQGTGGGYIPEAPRDGQ
rdgqayvrkdgewvllstf AYVRKDGEWVLLSTFL l H3N2 HAVPNGTIVKTITNDQIEV 398
METPAQLLFLLLLWLPDTTGHA 407 A/ TNATEgsaPNDKPFQNtNR
VPNGTIVKTITNDQIEVTNATE Wisconsin/ tTtGACPRYVKQNTLKLAT
GSAPNDKPFQNTNRTTTGACPR 67/2005 GMRNgsagsaTQAAINQIN
YVKQNTLKLATGMRNGSAGSAT GKLNRLIGKTNEKdHQdEK QAAINQINGKLNRLIGKTNEKD
EFSEdEGRIQDLEKYVEDT HQDEKEFSEDEGRIQDLEKYVE KIDLWSYNAELLVALENQH
DTKIDLWSYNAELLVALENQHT TIDaTDSQGTgggyipeap IDATDSQGTGGGYIPEAPRDGQ
rdgqayvrkdgewvllstf AYVRKDGEWVLLSTFL l H5N1 EQVDTIMEKNVTVTHAQDI 399
METPAQLLFLLLLWLPDTTGEQ 408 A/Vietnam/ LEKTHGSANSSMPFHNTHP
VDTIMEKNVTVTHAQDILEKTH 1203/2004 NTTGESPKYVKSNRLVLAT
GSANSSMPFHNTHPNTTGESPK GLRNGSAGSATQKAIDGVT YVKSNRLVLATGLRNGSAGSAT
NKVNSIIDKMNTQFEADGR QKAIDGVTNKVNSIIDKMNTQF EFNNDERRIENLNKKMEDG
EADGREFNNDERRIENLNKKME FLDVWTYNAELLVLMENER DGFLDVWTYNAELLVLMENERT
TLDAHDSQGTgggyipeap LDAHDSQGTGGGYIPEAPRDGQ rdgqayvrkdgewvllstf
AYVRKDGEWVLLSTFL l H7N9 TKVNTLTERGVEVVNATET 400
METPAQLLFLLLLWLPDTTGTK 409 (A/Anhui/ VERTgsaISNLPFQNtDSt
VNTLTERGVEVVNATETVERTG 1/2013) AnGKCPRYVKQRSLLLATG
SAISNLPFQNTDSTANGKCPRY MKNgsagsaTQSAIDQITG VKQRSLLLATGMKNGSAGSATQ
KLNRLIEKTNQQdELtDNE SAIDQITGKLNRLIEKTNQQDE FNEdEKQIGNVINWTRDSI
LTDNEFNEDEKQIGNVINWTRD TEVWSYNAELLVAMENQHT SITEVWSYNAELLVAMENQHTI
IDaADSQGTgggyipeapr DAADSQGTGGGYIPEAPRDGQA dgqayvrkdgewvllstfl
YVRKDGEWVLLSTFL H9N2 ETVDTLTETNVPVTHAKEL 401 METPAQLLFLLLLWLPDTTGET
410 A/Hong LHTEHgsaNSTLPFHNtSK VDTLTETNVPVTHAKELLHTEH Kong/1073/
tAnGTCPKYVRVNSLKLAV GSANSTLPFHNTSKTANGTCPK 99 GLRNgsagsaTQKAIDKIT
YVRVNSLKLAVGLRNGSAGSAT SKVNNIVDKMNKQdEItDH QKAIDKITSKVNNIVDKMNKQD
EFSEdETRLNMINNKIDDQ EITDHEFSEDETRLNMINNKID IQDVWAYNAELLVLLENQK
DQIQDVWAYNAELLVLLENQKT TLDaHDSQGTgggyipeap LDAHDSQGTGGGYIPEAPRDGQ
rdgqayvrkdgewvllstf AYVRKDGEWVLLSTFL l H10N8 TIVKTLTNEQEEVTNATET
402 METPAQLLFLLLLWLPDTTGTI 411 A/JX346/ VESTGgsaNTRLPFQNtSP
VKTLTNEQEEVTNATETVESTG 2013 tTnGQCPKYVNRRSLMLAT
GSANTRLPFQNTSPTTNGQCPK GMRNgsagsaTQAAIDQIT YVNRRSLMLATGMRNGSAGSAT
GKLNRLVEKTNTEdSItSE QAAIDQITGKLNRLVEKTNTED FSEIEHQIGNVINWTKDSI
SITSEFSEIEHQIGNVINWTKD TDIWTYQAELLVAMENQHT SITDIWTYQAELLVAMENQHTI
IDaADSQGTgggyipeapr DAADSQGTGGGYIPEAPRDGQA dgqayvrkdgewvllstfl
YVRKDGEWVLLSTFL H3N2 METPAQLLFLLLLWLPDTTGAS 412 A/Hong
PNGTLVKTITDDQIEVTNATEL Kong/1/ VQSSGSAGSANDKPFQNTNKRT 1968 stem
SGASPKYVKQNTLKLATGQRGS RNA AGSAATDQINGKLNRVIEKTNE
KDHQIEKEFSEDEGRIQDLEKY VEDTKIDLWSYNAELLVALENQ
HTIDLTDSQGTGGGYIPEAPRD GQAYVRKDGEWVLLSTFL
The first underlined sequence for each of the amino acid sequences
listed in Table 16, indicates a signal or secretory sequence, which
may be substituted by an alternative sequence that achieves the
same or similar function, or the signal or secretory sequence may
be deleted. The second underlined sequence for the amino acid
sequences listed in Table 16, indicates a foldon sequence, which is
a heterologous sequence that naturally trimerizes, to bring 3 HA
stems together in a trimer. Such foldon sequence may be substituted
by an alternative sequence, which achieves the same or similar
function.
TABLE-US-00021 TABLE 17 Exemplary Influenza Constructs Construct
SEQ Description ORF ID NO: Influenza
METPAQLLFLLLLWLPDTTGGLFGAIAGFIENGWEGMIDGWYGFRH 413 H3HA6
QNSEGTGQAADLKSTQAAIDQINGKLNRVIEKTNEKDHQIEKEFSE
DEGRIQDLEKYVEDTKIDLWSYNAELLVALENQHTIDLTDSEMNKL
FEKTRRQLRENAEEMGNGCFKIYHKCDNACIESIRNGTYDHDVYRD
EALNNRFQGSAGSAGDNSTATLCLGHHAVPNGTLVKTITDDQIEVT
NATELVQSSGSAGSANDKPFQNTNKETTGATPKYVKQNTLKLATGM R Influenza
METPAQLLFLLLLWLPDTTGGLFGAIAGFIEGGWTGMIDGWYGYHH 414 H1HA6
QNEQGSGYAADQKSTQNAINGITNKVNTVIEKMNIQDTATGKEFNK
DEKRMENLNKKVDDGFLDIWTYNAELLVLLENERTLDFHDSNVKNL
YEKVKSQLKNNAKEIGNGCFEFYHKCDNECMESVRNGTYDYPKYSE
ESKLNREKGSAGSAAADADTICIGYHANNSTDTVDTVLEKNVTVTH
SVNLLEDSHGSANSSLPYQNTHPTTNGESPKYVRSAKLRMVTGLRN IP Influenza
METPAQLLFLLLLWLPDTTGDTVDTVLEKNVTVTHSVNLLEDSHGS 415 H1HA10-
ANSSLPYQNTHPTTNGESPKYVRSAKLRMVTGLRNGGAGSATQNAI Foldon_.DELTA.Ngly1
NGITNKVNTVIEKMNIQDTATGKEFNKDEKRMENLNKKVDDGFLDI
WTYNAELLVLLENERTLDAHDSQGTGGGYIPEAPRDGQAYVRKDGE WVLLSTFL Influenza
METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDTVDTVLEKNVTV 416 eH1HA
THSVNLLEDSHNGKLCRLKGIAPLQLGKCNIAGWLLGNPECDPLLP
VRSWSYIVETPNSENGICYPGDFIDYEELREQLSSVSSFERFEIFP
KESSWPNHNTNGVTAACSHEGKSSFYRNLLWLTEKEGSYPNLKNSY
VNKKGKEVLVLWGIHHPSNSKEQQNLYQNENAYVSVVTSNYNRRFT
PEIAERPKVRDQAGRMNYYWTLLKPGDTIIFEANGNLIAPMYAFAL
SRGFGSGIITSNASMHECNTKCQTPLGAINSSLPYQNIHPVTIGEC
PKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGFIEGGWTGMIDGWY
GYHHQNEQGSGYAADQKSTQNAINGITNKVNTVIEKMNIQFTAVGK
EFNKLEKRMENLNKKVDDGFLDIWTYNAELLVLLENERTLDFHDSN
VKNLYEKVKSQLKNNAKEIGNGCFEFYHKCDNECMESVRNGTYDYP
KYSEESKLNREKVDGVKLESMGIGSAGSAGYIPEAPRDGQAYVRKD GEWVLLSTFL Influenza
MKANLLVLLCALAAADADTICIGYHANNSTDTVDTVLEKNVTVTHS 417 eH1HA_Native
VNLLEDSHNGKLCRLKGIAPLQLGKCNIAGWLLGNPECDPLLPVRS SS
WSYIVETPNSENGICYPGDFIDYEELREQLSSVSSFERFEIFPKES
SWPNHNTNGVTAACSHEGKSSFYRNLLWLTEKEGSYPNLKNSYVNK
KGKEVLVLWGIHHPSNSKEQQNLYQNENAYVSVVTSNYNRRFTPEI
AERPKVRDQAGRMNYYWTLLKPGDTIIFEANGNLIAPMYAFALSRG
FGSGIITSNASMHECNTKCQTPLGAINSSLPYQNIHPVTIGECPKY
VRSAKLRMVTGLRNIPSIQSRGLFGAIAGFIEGGWTGMIDGWYGYH
HQNEQGSGYAADQKSTQNAINGITNKVNTVIEKMNIQFTAVGKEFN
KLEKRMENLNKKVDDGFLDIWTYNAELLVLLENERTLDFHDSNVKN
LYEKVKSQLKNNAKEIGNGCFEFYHKCDNECMESVRNGTYDYPKYS
EESKLNREKVDGVKLESMGIGSAGSAGYIPEAPRDGQAYVRKDGEW VLLSTFL H1HA10TM-
METPAQLLFLLLLWLPDTTGDTVDTVLEKNVTVTHSVNLLEDSHGS 418 PR8 (H1
ANSSLPYQNTHPTTNGESPKYVRSAKLRMVTGLRNGSAGSATQNAI A/Puerto
NGITNKVNTVIEKMNIQDTATGKEFNKDEKRMENLNKKVDDGFLDI Rico/8/34 HA),
WTYNAELLVLLENERTLDAHDSQGTGGILAIYSTVASSLVLLVSLG with TM
AISFWMCSNGSLQCRICI domain, without foldon (with IgG Kappa leader)
H1HA10-PR8- METPAQLLFLLLLWLPDTTGDTVDTVCEKNVTVTHSVNLLEDSHGS 419 DS
(H1 ANSSLPYQNTHPTTNGESPKYVRSAKLRMVTGLRNGSAGSATQNAI A/Puerto
NCITNKVNTVIEKMNIQDTATGKEFNKDEKRMENLNKKVDDGFLDI Rico/8/34 HA),
WTYNAELLVLLENERTLDAHDS ds bond, without foldon (with IgG Kappa
leader) pH1HA10- METPAQLLFLLLLWLPDTTGDTVDTVCEKNVTVTHSVNLLEDKHGS 420
Cal04-DS (H1 ANTSLPFQNTHPTTNGKSPKYVKSTKLRLATGLRNGSAGSATQNAI
A/California/04/ DCITNKVNSVIEKMNTQDTAVGKEFNHDEKRIENLNKKVDDGFLDI
2009 HA), ds WTYNAELLVLLENERTLDAHDS bond, without foldon (with IgG
Kappa leader) Nucleoprotein
MASQGTKRSYEQMETDGERQNATEIRASVGKMIDGIGRFYIQMCTE 421 from H3N2 (no
LKLSDYEGRLIQNSLTIERMVLSAFDERRNRYLEEHPSAGKDPKKT IgG Kappa
GGPIYKRVDGRWMRELVLYDKEEIRRIWRQANNGDDATAGLTHMMI leader)
WHSNLNDTTYQRTRALVRTGMDPRMCSLMQGSTLPRRSGAAGAAVK
GIGTMVMELIRMIKRGINDRNFWRGENGRKTRSAYERMCNILKGKF
QTAAQRAMMDQVRESRNPGNAEIEDLIFSARSALILRGSVAHKSCL
PACVYGPAVSSGYNFEKEGYSLVGIDPFKLLQNSQVYSLIRPNENP
AHKSQLVWMACHSAAFEDLRLLSFIRGTKVSPRGKLSTRGVQIASN
ENMDNMESSTLELRSRYWAIRTRSGGNTNQQRASAGQISVQPTFSV
QRNLPFEKSTVMAAFTGNTEGRTSDMRAEIIRMMEGAKPEEVSFRG
RGVFELSDEKATNPIVPSFDMSNEGSYFFGDNAEEYDN HA10 version
METPAQLLFLLLLWLPDTTGHVVKTATQGEVNVTGVIPLTTTPTGS 422 for Influenza B
ANKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYGSAGSATQEAI strain
NKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADT
ISSQIELAVLLSNEGIINSEDEGTGGGYIPEAPRDGQAYVRKDGEW VLLSTFL
B/Yamagata/16/ MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIP 423
1988 mHA LTTTPTKSHFANLKGTKTRGKLCPNCLNCTDLDVALGRPMCMGTIP
SAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYENIRLSTHN
VINAERAPGGPYRLGTSGSCPNVTSRNGFFATMAWAVPRDNKTATN
PLTVEVPYICTKGEDQITVWGFHSDDKTQMKNLYGDSNPQKFTSSA
NGVTTHYVSQIGDFPNQTEDGGLPQSGRIVVDYMVQKPGKTGTIVY
QRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPY
YTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAG
FLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNS
LSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAV
LLSNEGIINSEDEHLLALERKLKKMLGPSAVDIGNGCFETKHKCNQ
TCLDRIAAGTFNAGEFSLPTFDSLNITAASLNDDGLDNHTILLYYS
TAASSLAVTLMIAIFIVYMVSRDNVSCSICL B/Yamagata/16/
MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIP 424 1988 sHA
LTTTPTKSHFANLKGTKTRGKLCPNCLNCTDLDVALGRPMCMGTIP
SAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYENIRLSTHN
VINAERAPGGPYRLGTSGSCPNVTSRNGFFATMAWAVPRDNKTATN
PLTVEVPYICTKGEDQITVWGFHSDDKTQMKNLYGDSNPQKFTSSA
NGVTTHYVSQIGDFPNQTEDGGLPQSGRIVVDYMVQKPGKTGTIVY
QRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPY
YTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAG
FLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNS
LSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAV
LLSNEGIINSEDEHLLALERKLKKMLGPSAVDIGNGCFETKHKCNQ
TCLDRIAAGTFNAGEFSLPTFDSLNITAASLNDDGLDNHT B/Victoria/02/
MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIP 425 1987 mHA
LTTTPTKSHFANLKGTKTRGKLCPKCLNCTDLDVALGRPKCTGTIP
SAKASILHEVKPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHN
VINAETAPGGPYKVGTSGSCPNVTNGNGFFATMAWAVPKNDNNKTA
TNPLTVEVPYICTEGEDQITVWGFHSDNEAQMVKLYGDSKPQKFTS
SANGVTTHYVSQIGGFPNQAEDGGLPQSGRIVVDYMVQKSGKTGTI
TYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSK
PYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKEKGFFGAI
AGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNL
NSLSELEVKNLQRLSGAMDELHNKILELDEKVDDLRADTISSQIEL
AVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKC
NQTCLDRIAAGTFNAGEFSLPTFDSLNITAASLNDDGLDNHTILLY
YSTAASSLAVTLMIAIFIVYMVSRDNVSCSICl B/Victoria/02/
MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIP 426 1987 sHA
LTTTPTKSHFANLKGTKTRGKLCPKCLNCTDLDVALGRPKCTGTIP
SAKASILHEVKPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHN
VINAETAPGGPYKVGTSGSCPNVTNGNGFFATMAWAVPKNDNNKTA
TNPLTVEVPYICTEGEDQITVWGFHSDNEAQMVKLYGDSKPQKFTS
SANGVTTHYVSQIGGFPNQAEDGGLPQSGRIVVDYMVQKSGKTGTI
TYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSK
PYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKEKGFFGAI
AGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNL
NSLSELEVKNLQRLSGAMDELHNKILELDEKVDDLRADTISSQIEL
AVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKC
NQTCLDRIAAGTFNAGEFSLPTFDSLNITAASLNDDGLDNHT B/Brisbane/60/
MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIP 427 2008 mHA
LTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIP
SARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHN
VINAENAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPKNDKNKTA
TNPLTIEVPYICTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTS
SANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTI
TYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSK
PYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAI
AGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNL
NSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIEL
AVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKC
NQTCLDRIAAGTFDAGEFSLPTFDSLNITAASLNDDGLDNHTILLY
YSTAASSLAVTLMIAIFVVYMVSRDNVSCSICL B/Brisbane/60/
MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIP 428 2008 sHA
LTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIP
SARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHN
VINAENAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPKNDKNKTA
TNPLTIEVPYICTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTS
SANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTI
TYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSK
PYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAI
AGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNL
NSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIEL
AVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKC
NQTCLDRIAAGTFDAGEFSLPTFDSLNITAASLNDDGLDNHT B/Phuket/3073/
MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIP 429 2013 mHA
LTTTPTKSYFANLKGTRTRGKLCPDCLNCTDLDVALGRPMCVGTTP
SAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEKIRLSTQN
VIDAEKAPGGPYRLGTSGSCPNATSKIGFFATMAWAVPKDNYKNAT
NPLTVEVPYICTEGEDQITVWGFHSDNKTQMKSLYGDSNPQKFTSS
ANGVTTHYVSQIGDFPDQTEDGGLPQSGRIVVDYMMQKPGKTGTIV
YQRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKP
YYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIA
GFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLN
SLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELA
VLLSNEGIINSEDEHLLALERKLKKMLGPSAVDIGNGCFETKHKCN
QTCLDRIAAGTFDAGEFSLPTFDSLNITAASLNDDGLDNHTILLYY
STAASSLAVTLMLAIFIVYMVSRDNVSCSICL B/Phuket/3073/
MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIP 430 2013 sHA
LTTTPTKSYFANLKGTRTRGKLCPDCLNCTDLDVALGRPMCVGTTP
SAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEKIRLSTQN
VIDAEKAPGGPYRLGTSGSCPNATSKIGFFATMAWAVPKDNYKNAT
NPLTVEVPYICTEGEDQITVWGFHSDNKTQMKSLYGDSNPQKFTSS
ANGVTTHYVSQIGDFPDQTEDGGLPQSGRIVVDYMMQKPGKTGTIV
YQRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKP
YYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIA
GFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLN
SLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELA
VLLSNEGIINSEDEHLLALERKLKKMLGPSAVDIGNGCFETKHKCN
QTCLDRIAAGTFDAGEFSLPTFDSLNITAASLNDDGLDNHT Pandemic
METPAQLLFLLLLWLPDTTGDTVDTVLEKNVTVTHSVNLLEDKHGS 431 H1HA10 from
ANTSLPFQNTHPTTNGKSPKYVKSTKLRLATGLRNGSAGSATQNAI California 04
DEITNKVNSVIEKMNTQDTAVGKEFNHDEKRIENLNKKVDDGFLDI strain, without
WTYNAELLVLLENERTLDAHDSQGTGGDIIKLLNEQVNKEMQSSNL foldon and with
YMSMSSWCYTHSLDGAGLFLFDHAAEEYEHAKKLIIFLNENNVPVQ ferritin fusion
LTSISAPEHKFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKDHA for particle
TFNFLQWYVAEQHEEEVLFKDILDKIELIGNENHGLYLADQYVKGI formation AKSRKS
Gen6 HA SS METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDTVDTVLEKNVTV 432
construct with THSVNLGSGLRMVTGLRNIPQRETRGLFGAIAGFIEGGWTGMVDGW
ferritin YGYHHQNEQGSGYAADQKSTQNAINGITNMVNSVIEKMGSGGSGTD
LAELLVLLLNERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGCFEF
YHKCNNECMESVKNGTYDYPKYSEESKLNREKIDSGGDIIKLLNEQ
VNKEMQSSNLYMSMSSWCYTHSLDGAGLFLFDHAAEEYEHAKKLII
FLNENNVPVQLTSISAPEHKFEGLTQIFQKAYEHEQHISESINNIV
DHAIKSKDHATFNFLQWYVAEQHEEEVLFKDILDKIELIGNENHGL YLADQYVKGIAKSRKS
Gen6 HA SS METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDTVDTVLEKNVTV 433
construct with THSVNLGSGLRMVTGLRNIPQRETRGLFGAIAGFIEGGWTGMVDGW
foldon YGYHHQNEQGSGYAADQKSTQNAINGITNMVNSVIEKMGSGGSGTD
LAELLVLLLNERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGCFEF
YHKCNNECMESVKNGTYDYPKYSEESKLNREKIDPGSGYIPEAPRD GQAYVRKDGEWVLLSTFL
#4900 construct METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDTVDTVLEKNVTV 434
without THSVNLLENGGGGKYVCSAKLRMVTGLRNKPSKQSQGLFGAIAGFT cleavage
site EGGWTGMVDGWYGYHHQNEQGSGYAADQKSTQNAINGITNKVNSVI and tag
EKMNTQYTAIGCEYNKSERCMKQIEDKIEEIESKIWCYNAELLVLL
ENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGCFEFYHKCNDEC
MESVKNGTYDYPKYSEESKLNREKIDGVKLESMGVYQ Pandemic
METPAQLLFLLLLWLPDTTGDTVDTVLEKNVTVTHSVNLLEDKHGS 435 H1HA10 from
ANTSLPFQNTHPTTNGKSPKYVKSTKLRLATGLRNGSAGSATQNAI California 04
DEITNKVNSVIEKMNTQDTAVGKEFNHDEKRIENLNKKVDDGFLDI strain, without
WTDLAELLVLLENERTLDAHDS foldon and with Y94D/N95L mutation for
trimerization Pandemic
METPAQLLFLLLLWLPDTTGDTVDTVLEKNVTVTHSVNLLEDKHGS 436 H1HA10 from
ANTSLPFQNTHPTTNGKSPKYVKSTKLRLATGLRNGSAGSATQNAI California 04
DEITNKVNSVIEKMNTQDTAVGCEFNHDEKCIENLNKKVDDGFLDI strain, without
WTYNAELLVLLENERTLDAHDS foldon and with K68C/R76C mutation for
trimerization H1HA10 from
METPAQLLFLLLLWLPDTTGDTVDTVLEKNVTVTHSVNLLEDSHGS 437 A/Puerto
ANSSLPYQNTHPTTNGESPKYVRSAKLRMVTGLRNGSAGSATQNAI Rico/8/34
NGITNKVNTVIEKMNIQDTATGKEFNKDEKRMENLNKKVDDGFLDI strain, without
WTDLAELLVLLENERTLDAHDS foldon and with Y94D/N95L mutation for
trimerization H1HA10 from
METPAQLLFLLLLWLPDTTGDTVDTVLEKNVTVTHSVNLLEDSHGS 438 A/Puerto
ANSSLPYQNTHPTTNGESPKYVRSAKLRMVTGLRNGSAGSATQNAI Rico/8/34
NGITNKVNTVIEKMNIQDTATGCEFNKDEKCMENLNKKVDDGFLDI strain, without
WTYNAELLVLLENERTLDAHDS foldon and with K68C/R76C mutation for
trimerization >sp|P06821|M2_
MSLLTEVETPIRNEWGCRCNGSSDPLAIAANIIGILHLILWILDRL 439 I34A1 Matrix
FFKCIYRRFKYGLKGGPSTEGVPKSMREEYRKEQQSAVDADDGHFV protein 2 SIELE OS =
Influenza A virus (strain A/Puerto Rico/8/1934 H1N1) GN = M PE = 3
SV = 1 A Matrix 1 MSLLTEVETYVLSIIPSGPLKAEIAQRLESVFAGKNTDLEALMEWL
440 (A/California/ KTRPILSPLTKGILGFVFTLTVPSERGLQRRRFVQNALNGNGDPNN
04/2009 (H1N1), MDRAVKLYKKLKREITFHGAKEVSLSYSTGALASCMGLIYNRMGTV
ACP44152) TTEAAFGLVCATCEQIADSQHRSHRQMATTTNPLIRHENRMVLAST
TAKAMEQMAGSSEQAAEAMEVANQTRQMVHAMRTIGTHPSSSAGLK
DDLLENLQAYQKRMGVQMQRFK BHA10-2
METPAQLLFLLLLWLPDTTGHVVKTATQGEVNVTGVIPLTTTPTGS 441
ANKSKPYYTGEHAKATGNCPIWVKTPLKLANGTKYGSAGSATQEAI
NKITKNLNSLSELEVKNLQRLSGASDETHNEILELDEKVDDLRADT
ISSQIELAVLLSNEGIINSEDEGTGGGYIPEAPRDGQAYVRKDGEW VLLSTFL BHA10-2*
HVVKTATQGEVNVTGVIPLTTTPTGSANKSKPYYTGEHAKATGNCP 442
IWVKTPLKLANGTKYGSAGSATQEAINKITKNLNSLSELEVKNLQR
LSGASDETHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSE
DEGTGGGYIPEAPRDGQAYVRKDGEWVLLSTFL BHA10-3
METPAQLLFLLLLWLPDTTGHVVKTATQGEVNVTGVIPLTTTPTGS 443
ANKSKPYYTGEHAKATGNCPIWVKTPLKLANGTKYGSAGSATQEAI
NKITKNLNSLSELEVKNLQRLSCASDETHNCILELDEKVDDLRADT
ISSLIELAVLLSNEGIINSEDE BHA10-3*
HVVKTATQGEVNVTGVIPLTTTPTGSANKSKPYYTGEHAKATGNCP 444
IWVKTPLKLANGTKYGSAGSATQEAINKITKNLNSLSELEVKNLQR
LSCASDETHNCILELDEKVDDLRADTISSLIELAVLLSNEGIINSE DE 5'UTR for each
construct:
TCAAGCTTTTGGACCCTCGTACAGAAGCTAATACGACTCACTATAGGGAAATAAGAGAGAAAAGAAGAGTA
AGAAGAAATATAAGAGCCACC (SEQ ID NO: 445) 3'UTR for each construct:
TGATAATAGGCTGGAGCCTCGGTGGCCATGCTTCTTGCCCCTTGGGCCTCCCCCCAGCCCCTCCTCCCCTT
CCTGCACCCGTACCCCCGTGGTCTTTGAATAAAGTCTGAGTGGGCGGC (SEQ ID NO:
446)
The first underlined sequence for each of the amino acid sequences
listed in Table 17, indicates a signal or secretory sequence, which
may be substituted by an alternative sequence that achieves the
same or similar function, or the signal or secretory sequence may
be deleted.
TABLE-US-00022 TABLE 18 Influenza Nucleic Acids Construct SEQ
Description ORF ID NO: B/Yamagata/16/
ATGAAGGCAATAATTGTACTACTCATGGTAGTAACATCCAACGCAG 447 1988 mHA
ATCGAATCTGCACTGGGATAACATCTTCAAACTCACCTCATGTGGT
CAAAACAGCTACTCAAGGGGAAGTTAATGTGACTGGTGTGATACCA
CTGACAACAACACCAACAAAATCTCATTTTGCAAATCTCAAAGGAA
CAAAGACCAGAGGGAAACTATGCCCAAACTGTCTCAACTGCACAGA
TCTGGATGTGGCCTTGGGCAGACCAATGTGTATGGGGACCATACCT
TCGGCAAAAGCTTCAATACTCCACGAAGTCAGACCTGTTACATCCG
GGTGCTTTCCTATAATGCACGACAGAACAAAAATCAGACAGCTACC
CAATCTTCTCAGAGGATATGAAAATATCAGATTATCAACCCATAAC
GTTATCAACGCAGAAAGGGCACCAGGAGGACCCTACAGACTTGGAA
CCTCAGGATCTTGCCCTAACGTTACCAGTAGAAACGGATTCTTCGC
AACAATGGCTTGGGCTGTCCCAAGGGACAACAAAACAGCAACGAAT
CCACTAACAGTAGAAGTACCATACATTTGCACAAAAGGAGAAGACC
AAATTACTGTTTGGGGGTTCCATTCTGATGACAAAACCCAAATGAA
AAACCTCTATGGAGACTCAAATCCTCAAAAGTTCACCTCATCTGCC
AATGGAGTAACCACACATTATGTTTCTCAGATTGGTGACTTCCCAA
ATCAAACAGAAGACGGAGGGCTACCACAAAGCGGCAGAATTGTTGT
TGATTACATGGTGCAAAAACCTGGGAAAACAGGAACAATTGTCTAT
CAAAGAGGTGTTTTGTTGCCTCAAAAGGTGTGGTGCGCAAGTGGCA
GGAGCAAGGTAATAAAAGGGTCCTTGCCTTTAATTGGTGAAGCAGA
TTGCCTTCACGAAAAATACGGTGGATTAAACAAAAGCAAGCCTTAC
TACACAGGAGAACATGCAAAAGCCATAGGAAATTGCCCAATATGGG
TGAAAACACCTTTGAAGCTTGCCAATGGAACCAAATATAGACCTCC
TGCAAAACTATTAAAGGAAAGGGGTTTCTTCGGAGCTATTGCTGGT
TTCTTAGAGGGAGGATGGGAAGGAATGATTGCAGGTTGGCACGGAT
ACACATCTCATGGAGCACATGGAGTGGCAGTGGCAGCAGACCTTAA
GAGCACGCAAGAAGCCATAAACAAGATAACAAAAAATCTCAATTCT
TTGAGTGAGCTAGAAGTAAAGAATCTTCAAAGACTAAGTGGTGCCA
TGGATGAACTCCACAACGAAATACTCGAGCTGGATGAGAAAGTGGA
TGATCTCAGAGCTGACACAATAAGCTCGCAAATAGAGCTTGCAGTC
TTGCTTTCCAACGAAGGAATAATAAACAGTGAAGATGAGCATCTAT
TGGCACTTGAGAGAAAACTAAAGAAAATGCTGGGTCCCTCTGCTGT
AGACATAGGGAATGGATGCTTCGAAACCAAACACAAGTGCAACCAG
ACCTGCTTAGACAGGATAGCTGCTGGCACCTTTAATGCAGGAGAAT
TTTCTCTTCCCACTTTTGATTCACTGAATATTACTGCTGCATCTTT
AAATGATGATGGATTGGATAATCATACTATACTGCTCTACTACTCA
ACTGCTGCTTCTAGTTTGGCCGTAACATTGATGATAGCTATTTTTA
TTGTTTATATGGTCTCCAGAGACAATGTTTCTTGCTCCATCTGTCT A B/Yamagata/16/
ATGAAGGCAATAATTGTACTACTCATGGTAGTAACATCCAACGCAG 448 1988 sHA
ATCGAATCTGCACTGGGATAACATCTTCAAACTCACCTCATGTGGT
CAAAACAGCTACTCAAGGGGAAGTTAATGTGACTGGTGTGATACCA
CTGACAACAACACCAACAAAATCTCATTTTGCAAATCTCAAAGGAA
CAAAGACCAGAGGGAAACTATGCCCAAACTGTCTCAACTGCACAGA
TCTGGATGTGGCCTTGGGCAGACCAATGTGTATGGGGACCATACCT
TCGGCAAAAGCTTCAATACTCCACGAAGTCAGACCTGTTACATCCG
GGTGCTTTCCTATAATGCACGACAGAACAAAAATCAGACAGCTACC
CAATCTTCTCAGAGGATATGAAAATATCAGATTATCAACCCATAAC
GTTATCAACGCAGAAAGGGCACCAGGAGGACCCTACAGACTTGGAA
CCTCAGGATCTTGCCCTAACGTTACCAGTAGAAACGGATTCTTCGC
AACAATGGCTTGGGCTGTCCCAAGGGACAACAAAACAGCAACGAAT
CCACTAACAGTAGAAGTACCATACATTTGCACAAAAGGAGAAGACC
AAATTACTGTTTGGGGGTTCCATTCTGATGACAAAACCCAAATGAA
AAACCTCTATGGAGACTCAAATCCTCAAAAGTTCACCTCATCTGCC
AATGGAGTAACCACACATTATGTTTCTCAGATTGGTGACTTCCCAA
ATCAAACAGAAGACGGAGGGCTACCACAAAGCGGCAGAATTGTTGT
TGATTACATGGTGCAAAAACCTGGGAAAACAGGAACAATTGTCTAT
CAAAGAGGTGTTTTGTTGCCTCAAAAGGTGTGGTGCGCAAGTGGCA
GGAGCAAGGTAATAAAAGGGTCCTTGCCTTTAATTGGTGAAGCAGA
TTGCCTTCACGAAAAATACGGTGGATTAAACAAAAGCAAGCCTTAC
TACACAGGAGAACATGCAAAAGCCATAGGAAATTGCCCAATATGGG
TGAAAACACCTTTGAAGCTTGCCAATGGAACCAAATATAGACCTCC
TGCAAAACTATTAAAGGAAAGGGGTTTCTTCGGAGCTATTGCTGGT
TTCTTAGAGGGAGGATGGGAAGGAATGATTGCAGGTTGGCACGGAT
ACACATCTCATGGAGCACATGGAGTGGCAGTGGCAGCAGACCTTAA
GAGCACGCAAGAAGCCATAAACAAGATAACAAAAAATCTCAATTCT
TTGAGTGAGCTAGAAGTAAAGAATCTTCAAAGACTAAGTGGTGCCA
TGGATGAACTCCACAACGAAATACTCGAGCTGGATGAGAAAGTGGA
TGATCTCAGAGCTGACACAATAAGCTCGCAAATAGAGCTTGCAGTC
TTGCTTTCCAACGAAGGAATAATAAACAGTGAAGATGAGCATCTAT
TGGCACTTGAGAGAAAACTAAAGAAAATGCTGGGTCCCTCTGCTGT
AGACATAGGGAATGGATGCTTCGAAACCAAACACAAGTGCAACCAG
ACCTGCTTAGACAGGATAGCTGCTGGCACCTTTAATGCAGGAGAAT
TTTCTCTTCCCACTTTTGATTCACTGAATATTACTGCTGCATCTTT
AAATGATGATGGATTGGATAATCATACT B/Victoria/02/
ATGAAGGCAATAATTGTACTACTCATGGTAGTAACATCCAATGCAG 449 1987 mHA
ATCGAATCTGCACTGGGATAACATCGTCAAACTCACCCCATGTGGT
CAAAACTGCTACTCAAGGGGAAGTCAATGTGACTGGTGTGATACCA
CTGACAACAACACCCACCAAATCTCATTTTGCAAATCTCAAAGGAA
CAAAAACCAGAGGGAAACTATGCCCAAAGTGTCTCAACTGCACAGA
TCTGGACGTGGCCTTGGGCAGACCAAAGTGCACGGGGACCATACCT
TCGGCAAAAGCTTCAATACTCCACGAAGTCAAACCTGTTACATCTG
GGTGCTTTCCTATAATGCACGACAGAACAAAAATTAGACAGCTACC
CAATCTTCTCAGAGGATACGAACATATCAGGTTATCAACCCATAAC
GTTATCAACGCAGAAACGGCACCAGGAGGACCCTACAAAGTTGGAA
CCTCAGGGTCTTGCCCTAACGTTACCAATGGAAACGGATTCTTCGC
AACAATGGCTTGGGCTGTCCCAAAAAACGACAACAACAAAACAGCA
ACAAATCCATTAACAGTAGAAGTACCATACATTTGTACAGAAGGAG
AAGACCAAATTACTGTTTGGGGGTTCCACTCTGATAACGAAGCCCA
AATGGTAAAACTCTATGGAGACTCAAAGCCTCAGAAGTTCACCTCA
TCTGCCAACGGAGTGACCACACATTACGTTTCACAGATTGGTGGCT
TCCCAAATCAAGCAGAAGACGGAGGGCTACCACAAAGCGGTAGAAT
TGTTGTTGATTACATGGTGCAAAAATCTGGAAAAACAGGAACAATT
ACCTACCAAAGAGGTATTTTATTGCCTCAAAAAGTGTGGTGCGCAA
GTGGCAGGAGCAAGGTAATAAAAGGGTCCTTGCCTTTAATTGGCGA
AGCAGATTGCCTCCACGAAAAATACGGTGGATTAAACAAAAGCAAG
CCTTACTACACAGGGGAACATGCAAAAGCCATAGGAAATTGCCCAA
TATGGGTGAAAACACCCTTGAAGCTGGCCAATGGAACCAAATATAG
ACCTCCTGCAAAACTATTAAAGGAAAAGGGTTTCTTCGGAGCTATT
GCTGGTTTCTTAGAAGGAGGATGGGAAGGAATGATTGCAGGTTGGC
ACGGATACACATCCCATGGAGCACATGGAGTAGCAGTGGCAGCAGA
CCTTAAGAGTACGCAAGAAGCCATAAACAAGATAACAAAAAATCTC
AATTCTTTGAGTGAGCTGGAAGTAAAGAATCTTCAAAGACTAAGCG
GTGCCATGGATGAACTCCACAACAAAATACTCGAACTGGATGAGAA
AGTGGATGATCTCAGAGCTGATACAATAAGCTCGCAAATAGAGCTC
GCAGTCTTGCTTTCCAACGAAGGAATAATAAACAGTGAAGATGAGC
ATCTCTTGGCGCTTGAAAGAAAACTGAAGAAAATGCTGGGCCCCTC
TGCTGTAGAGATAGGGAATGGATGCTTCGAAACCAAACACAAGTGC
AACCAGACCTGCCTCGACAGAATAGCTGCTGGCACCTTTAATGCAG
GAGAATTTTCTCTCCCCACCTTTGATTCACTAAATATTACTGCTGC
ATCTTTAAATGATGATGGATTGGATAATCATACTATACTGCTTTAC
TACTCAACTGCTGCTTCCAGTTTGGCTGTAACATTGATGATAGCTA
TCTTTATTGTTTATATGGTCTCCAGAGACAATGTTTCTTGCTCCAT CTGTCTA
B/Victoria/02/ ATGAAGGCAATAATTGTACTACTCATGGTAGTAACATCCAATGCAG 450
1987 sHA ATCGAATCTGCACTGGGATAACATCGTCAAACTCACCCCATGTGGT
CAAAACTGCTACTCAAGGGGAAGTCAATGTGACTGGTGTGATACCA
CTGACAACAACACCCACCAAATCTCATTTTGCAAATCTCAAAGGAA
CAAAAACCAGAGGGAAACTATGCCCAAAGTGTCTCAACTGCACAGA
TCTGGACGTGGCCTTGGGCAGACCAAAGTGCACGGGGACCATACCT
TCGGCAAAAGCTTCAATACTCCACGAAGTCAAACCTGTTACATCTG
GGTGCTTTCCTATAATGCACGACAGAACAAAAATTAGACAGCTACC
CAATCTTCTCAGAGGATACGAACATATCAGGTTATCAACCCATAAC
GTTATCAACGCAGAAACGGCACCAGGAGGACCCTACAAAGTTGGAA
CCTCAGGGTCTTGCCCTAACGTTACCAATGGAAACGGATTCTTCGC
AACAATGGCTTGGGCTGTCCCAAAAAACGACAACAACAAAACAGCA
ACAAATCCATTAACAGTAGAAGTACCATACATTTGTACAGAAGGAG
AAGACCAAATTACTGTTTGGGGGTTCCACTCTGATAACGAAGCCCA
AATGGTAAAACTCTATGGAGACTCAAAGCCTCAGAAGTTCACCTCA
TCTGCCAACGGAGTGACCACACATTACGTTTCACAGATTGGTGGCT
TCCCAAATCAAGCAGAAGACGGAGGGCTACCACAAAGCGGTAGAAT
TGTTGTTGATTACATGGTGCAAAAATCTGGAAAAAGAGGAACAATT
ACCTACCAAAGAGGTATTTTATTGCCTCAAAAAGTGTGGTGCGCAA
GTGGCAGGAGCAAGGTAATAAAAGGGTCCTTGCCTTTAATTGGCGA
AGCAGATTGCCTCCACGAAAAATACGGTGGATTAAACAAAAGCAAG
CCTTACTACACAGGGGAACATGCAAAAGCCATAGGAAATTGCCCAA
TATGGGTGAAAACACCCTTGAAGCTGGCCAATGGAACCAAATATAG
ACCTCCTGCAAAACTATTAAAGGAAAAGGGTTTCTTCGGAGCTATT
GCTGGTTTCTTAGAAGGAGGATGGGAAGGAATGATTGCAGGTTGGC
ACGGATACACATCCCATGGAGCACATGGAGTAGCAGTGGCAGCAGA
CCTTAAGAGTACGCAAGAAGCCATAAACAAGATAACAAAAAATCTC
AATTCTTTGAGTGAGCTGGAAGTAAAGAATCTTCAAAGACTAAGCG
GTGCCATGGATGAACTCCACAACAAAATACTCGAACTGGATGAGAA
AGTGGATGATCTCAGAGCTGATACAATAAGCTCGCAAATAGAGCTC
GCAGTCTTGCTTTCCAACGAAGGAATAATAAACAGTGAAGATGAGC
ATCTCTTGGCGCTTGAAAGAAAACTGAAGAAAATGCTGGGCCCCTC
TGCTGTAGAGATAGGGAATGGATGCTTCGAAACCAAACACAAGTGC
AACCAGACCTGCCTCGACAGAATAGCTGCTGGCACCTTTAATGCAG
GAGAATTTTCTCTCCCCACCTTTGATTCACTAAATATTACTGCTGC
ATCTTTAAATGATGATGGATTGGATAATCATACT B/Brisbane/60/
ATGAAGGCAATAATTGTACTACTCATGGTAGTAACATCCAATGCAG 451 2008 mHA
ATCGAATCTGCACTGGGATAACATCGTCAAACTCACCACATGTCGT
CAAAACTGCTACTCAAGGGGAGGTCAATGTGACTGGTGTAATACCA
CTGACAACAACACCCACCAAATCTCATTTTGCAAATCTCAAAGGAA
CAGAAACCAGGGGGAAACTATGCCCAAAATGCCTCAACTGCACAGA
TCTGGACGTAGCCTTGGGCAGACCAAAATGCACGGGGAAAATACCC
TCGGCAAGAGTTTCAATACTCCATGAAGTCAGACCTGTTACATCTG
GGTGCTTTCCTATAATGCACGACAGAACAAAAATTAGACAGCTGCC
TAACCTTCTCCGAGGATACGAACATATCAGGTTATCAACCCATAAC
GTTATCAATGCAGAAAATGCACCAGGAGGACCCTACAAAATTGGAA
CCTCAGGGTCTTGCCCTAACATTACCAATGGAAACGGATTTTTCGC
AACAATGGCTTGGGCCGTCCCAAAAAACGACAAAAACAAAACAGCA
ACAAATCCATTAACAATAGAAGTACCATACATTTGTACAGAAGGAG
AAGACCAAATTACCGTTTGGGGGTTCCACTCTGACGACGAGACCCA
AATGGCAAAGCTCTATGGGGACTCAAAGCCCCAGAAGTTCACCTCA
TCTGCCAACGGAGTGACCACACATTACGTTTCACAGATTGGTGGCT
TCCCAAATCAAACAGAAGACGGAGGACTACCACAAAGTGGTAGAAT
TGTTGTTGATTACATGGTGCAAAAATCTGGGAAAACAGGAACAATT
ACCTATCAAAGGGGTATTTTATTGCCTCAAAAGGTGTGGTGCGCAA
GTGGCAGGAGCAAGGTAATAAAAGGATCCTTGCCTTTAATTGGAGA
AGCAGATTGCCTCCACGAAAAATACGGTGGATTAAACAAAAGCAAG
CCTTACTACACAGGGGAACATGCAAAGGCCATAGGAAATTGCCCAA
TATGGGTGAAAACACCCTTGAAGCTGGCCAATGGAACCAAATATAG
ACCTCCTGCAAAACTATTAAAGGAAAGGGGTTTCTTCGGAGCTATT
GCTGGTTTCTTAGAAGGAGGATGGGAAGGAATGATTGCAGGTTGGC
ACGGATACACATCCCATGGGGCACATGGAGTAGCGGTGGCAGCAGA
CCTTAAGAGCACTCAAGAGGCCATAAACAAGATAACAAAAAATCTC
AACTCTTTGAGTGAGCTGGAAGTAAAGAATCTTCAAAGACTAAGCG
GTGCCATGGATGAACTCCACAACGAAATACTAGAACTAGATGAGAA
AGTGGATGATCTCAGAGCTGATACAATAAGCTCACAAATAGAACTC
GCAGTCCTGCTTTCCAATGAAGGAATAATAAACAGTGAAGATGAAC
ATCTCTTGGCGCTTGAAAGAAAGCTGAAGAAAATGCTGGGCCCCTC
TGCTGTAGAGATAGGGAATGGATGCTTTGAAACCAAACACAAGTGC
AACCAGACCTGTCTCGACAGAATAGCTGCTGGTACCTTTGATGCAG
GAGAATTTTCTCTCCCCACCTTTGATTCACTGAATATTACTGCTGC
ATCTTTAAATGACGATGGATTGGATAATCATACTATACTGCTTTAC
TACTCAACTGCTGCCTCCAGTTTGGCTGTAACACTGATGATAGCTA
TCTTTGTTGTTTATATGGTCTCCAGAGACAATGTTTCTTGCTCCAT CTGTCTA
B/Brisbane/60/ ATGAAGGCAATAATTGTACTACTCATGGTAGTAACATCCAATGCAG 452
2008 sHA ATCGAATCTGCACTGGGATAACATCGTCAAACTCACCACATGTCGT
CAAAACTGCTACTCAAGGGGAGGTCAATGTGACTGGTGTAATACCA
CTGACAACAACACCCACCAAATCTCATTTTGCAAATCTCAAAGGAA
CAGAAACCAGGGGGAAACTATGCCCAAAATGCCTCAACTGCACAGA
TCTGGACGTAGCCTTGGGCAGACCAAAATGCACGGGGAAAATACCC
TCGGCAAGAGTTTCAATACTCCATGAAGTCAGACCTGTTACATCTG
GGTGCTTTCCTATAATGCACGACAGAACAAAAATTAGACAGCTGCC
TAACCTTCTCCGAGGATACGAACATATCAGGTTATCAACCCATAAC
GTTATCAATGCAGAAAATGCACCAGGAGGACCCTACAAAATTGGAA
CCTCAGGGTCTTGCCCTAACATTACCAATGGAAACGGATTTTTCGC
AACAATGGCTTGGGCCGTCCCAAAAAACGACAAAAACAAAACAGCA
ACAAATCCATTAACAATAGAAGTACCATACATTTGTACAGAAGGAG
AAGACCAAATTACCGTTTGGGGGTTCCACTCTGACGACGAGACCCA
AATGGCAAAGCTCTATGGGGACTCAAAGCCCCAGAAGTTCACCTCA
TCTGCCAACGGAGTGACCACACATTACGTTTCACAGATTGGTGGCT
TCCCAAATCAAACAGAAGACGGAGGACTACCACAAAGTGGTAGAAT
TGTTGTTGATTACATGGTGCAAAAATCTGGGAAAACAGGAACAATT
ACCTATCAAAGGGGTATTTTATTGCCTCAAAAGGTGTGGTGCGCAA
GTGGCAGGAGCAAGGTAATAAAAGGATCCTTGCCTTTAATTGGAGA
AGCAGATTGCCTCCACGAAAAATACGGTGGATTAAACAAAAGCAAG
CCTTACTACACAGGGGAACATGCAAAGGCCATAGGAAATTGCCCAA
TATGGGTGAAAACACCCTTGAAGCTGGCCAATGGAACCAAATATAG
ACCTCCTGCAAAACTATTAAAGGAAAGGGGTTTCTTCGGAGCTATT
GCTGGTTTCTTAGAAGGAGGATGGGAAGGAATGATTGCAGGTTGGC
ACGGATACACATCCCATGGGGCACATGGAGTAGCGGTGGCAGCAGA
CCTTAAGAGCACTCAAGAGGCCATAAACAAGATAACAAAAAATCTC
AACTCTTTGAGTGAGCTGGAAGTAAAGAATCTTCAAAGACTAAGCG
GTGCCATGGATGAACTCCACAACGAAATACTAGAACTAGATGAGAA
AGTGGATGATCTCAGAGCTGATACAATAAGCTCACAAATAGAACTC
GCAGTCCTGCTTTCCAATGAAGGAATAATAAACAGTGAAGATGAAC
ATCTCTTGGCGCTTGAAAGAAAGCTGAAGAAAATGCTGGGCCCCTC
TGCTGTAGAGATAGGGAATGGATGCTTTGAAACCAAACACAAGTGC
AACCAGACCTGTCTCGACAGAATAGCTGCTGGTACCTTTGATGCAG
GAGAATTTTCTCTCCCCACCTTTGATTCACTGAATATTACTGCTGC
ATCTTTAAATGACGATGGATTGGATAATCATACT B/Phuket/3073/
ATGAAGGCAATAATTGTACTACTCATGGTAGTAACATCCAATGCAG 453 2013 mHA
ATCGAATCTGCACTGGGATAACATCTTCAAACTCACCTCATGTGGT
CAAAACAGCTACTCAAGGGGAGGTCAATGTGACTGGCGTGATACCA
CTGACAACAACACCAACAAAATCTTATTTTGCAAATCTCAAAGGAA
CAAGGACCAGAGGGAAACTATGCCCGGACTGTCTCAACTGTACAGA
TCTGGATGTGGCCTTGGGCAGGCCAATGTGTGTGGGGACCACACCT
TCTGCTAAAGCTTCAATACTCCACGAGGTCAGACCTGTTACATCCG
GGTGCTTTCCTATAATGCACGACAGAACAAAAATCAGGCAACTACC
CAATCTTCTCAGAGGATATGAAAAGATCAGGTTATCAACCCAAAAC
GTTATCGATGCAGAAAAAGCACCAGGAGGACCCTACAGACTTGGAA
CCTCAGGATCTTGCCCTAACGCTACCAGTAAAATCGGATTTTTCGC
AACAATGGCTTGGGCTGTCCCAAAGGACAACTACAAAAATGCAACG
AACCCACTAACAGTAGAAGTACCATACATTTGTACAGAAGGGGAAG
ACCAAATTACTGTTTGGGGGTTCCATTCAGACAACAAAACCCAAAT
GAAGAGCCTCTATGGAGACTCAAATCCTCAAAAGTTCACCTCATCT
GCTAATGGAGTAACCACACATTATGTTTCTCAGATTGGCGACTTCC
CAGATCAAACAGAAGACGGAGGACTACCACAAAGCGGCAGAATTGT
TGTTGATTACATGATGCAAAAACCTGGGAAAACAGGAACAATTGTC
TATCAAAGAGGTGTTTTGTTGCCTCAAAAGGTGTGGTGCGCGAGTG
GCAGGAGCAAAGTAATAAAAGGGTCATTGCCTTTAATTGGTGAAGC
AGATTGCCTTCATGAAAAATACGGTGGATTAAACAAAAGCAAGCCT
TACTACACAGGAGAACATGCAAAAGCCATAGGAAATTGCCCAATAT
GGGTAAAAACACCTTTGAAGCTTGCCAATGGAACCAAATATAGACC
TCCTGCAAAACTATTGAAGGAAAGGGGTTTCTTCGGAGCTATTGCT
GGTTTCCTAGAAGGAGGATGGGAAGGAATGATTGCAGGTTGGCACG
GATACACATCTCACGGAGCACATGGAGTGGCAGTGGCGGCAGACCT
TAAGAGTACACAAGAAGCTATAAATAAGATAACAAAAAATCTCAAT
TCTTTGAGTGAGCTAGAAGTAAAGAACCTTCAAAGACTAAGTGGTG
CCATGGATGAACTCCACAACGAAATACTCGAGCTGGATGAGAAAGT
GGATGATCTCAGAGCTGACACTATAAGCTCACAAATAGAACTTGCA
GTCTTGCTTTCCAACGAAGGAATAATAAACAGTGAAGACGAGCATC
TATTGGCACTTGAGAGAAAACTAAAGAAAATGCTGGGTCCCTCTGC
TGTAGACATAGGAAACGGATGCTTCGAAACCAAACACAAATGCAAC
CAGACCTGCTTAGACAGGATAGCTGCTGGCACCTTTGATGCAGGAG
AATTTTCTCTCCCCACTTTTGATTCATTGAACATTACTGCTGCATC
TTTAAATGATGATGGATTGGATAACCATACTATACTGCTCTATTAC
TCAACTGCTGCTTCTAGTTTGGCTGTAACATTAATGCTAGCTATTT
TTATTGTTTATATGGTCTCCAGAGACAACGTTTCATGCTCCATCTG TCTA 5'UTR for each
construct:
TCAAGCTTTTGGACCCTCGTACAGAAGCTAATACGACTCACTATAGGGAAATAAGAGAGAAAAGAAGA
GTAAGAAGAAATATAAGAGCCACC (SEQ ID NO: 445) 3'UTR for each construct:
TGATAATAGGCTGGAGCCTCGGTGGCCATGCTTCTTGCCCCTTGGGCCTCCCCCCAGCCCCTCCTCCC
CTTCCTGCACCCGTACCCCCGTGGTCTTTGAATAAAGTCTGAGTGGGCGGC (SEQ ID NO:
446)
It should be understood that the 5' and/or 3' UTR for each
construct may be omitted, modified or substituted for a different
UTR sequences in any one of the vaccines as provided herein.
TABLE-US-00023 TABLE 19 Examples of Wild Type Hemagglutinin
Antigens Protein/ SEQ Strain Nucleic Acid Sequence ID NO: H1
AGCAAAAGCAGGGGAAAATAAAAACAACCAAAATGAAGGCAAACCTACTG 454
GTCCTGTTATGTGCACTTGCAGCTGCAGATGCAGACACAATATGTATAGG
CTACCATGCGAACAATTCAACCGACACTGTTGACACAGTGCTCGAGAAGA
ATGTGACAGTGACACACTCTGTTAACCTGCTCGAAGACAGCCACAACGGA
AAACTATGTAGATTAAAAGGAATAGCCCCACTACAATTGGGGAAATGTAA
CATCGCCGGATGGCTCTTGGGAAACCCAGAATGCGACCCACTGCTTCCAG
TGAGATCATGGTCCTACATTGTAGAAACACCAAACTCTGAGAATGGAATA
TGTTATCCAGGAGATTTCATCGACTATGAGGAGCTGAGGGAGCAATTGAG
CTCAGTGTCATCATTCGAAAGATTCGAAATATTTCCCAAAGAAAGCTCAT
GGCCCAACCACAACACAACCAAAGGAGTAACGGCAGCATGCTCCCATGCG
GGGAAAAGCAGTTTTTACAGAAATTTGCTATGGCTGACGGAGAAGGAGGG
CTCATACCCAAAGCTGAAAAATTCTTATGTGAACAAGAAAGGGAAAGAAG
TCCTTGTACTGTGGGGTATTCATCACCCGTCTAACAGTAAGGATCAACAG
AATATCTATCAGAATGAAAATGCTTATGTCTCTGTAGTGACTTCAAATTA
TAACAGGAGATTTACCCCGGAAATAGCAGAAAGACCCAAAGTAAGAGATC
AAGCTGGGAGGATGAACTATTACTGGACCTTGCTAAAACCCGGAGACACA
ATAATATTTGAGGCAAATGGAAATCTAATAGCACCAAGGT
ATGCTTTCGCACTGAGTAGAGGCTTTGGGTCCGGCATCATCACCTCAAAC
GCATCAATGCATGAGTGTAACACGAAGTGTCAAACACCCCTGGGAGCTAT
AAACAGCAGTCTCCCTTTCCAGAATATACACCCAGTCACAATAGGAGAGT
GCCCAAAATACGTCAGGAGTGCCAAATTGAGGATGGTTACAGGACTAAGG
AACATTCCGTCCATTCAATCCAGAGGTCTATTTGGAGCCATTGCCGGTTT
TATTGAAGGGGGATGGACTGGAATGATAGATGGATGGTACGGTTATCATC
ATCAGAATGAACAGGGATCAGGCTATGCAGCGGATCAAAAAAGCACACAA
AATGCCATTAACGGGATTACAAACAAGGTGAACTCTGTTATCGAGAAAAT
GAACATTCAATTCACAGCTGTGGGTAAAGAATTCAACAAATTAGAAAAAA
GGATGGAAAATTTAAATAAAAAAGTTGATGATGGATTTCTGGACATTTGG
ACATATAATGCAGAATTGTTAGTTCTACTGGAAAATGAAAGGACTCTGGA
TTTCCATGACTCAAATGTGAAGAATCTGTATGAGAAAGTAAAAAGCCAAT
TAAAGAATAATGCCAAAGAAATCGGAAATGGATGTTTTGAGTTCTACCAC
AAGTGTGACAATGAATGCATGGAAAGTGTAAGAAATGGGACTTATGATTA
TCCCAAATATTCAGAAGAGTCAAAGTTGAACAGGGAAAAGGTAGATGGAG
TGAAATTGGAATCAATGGGGATCTATCAGATTCTGGCGATCTACTCAACT
GTCGCCAGTTCACTGGTGCTTTTGGTCTCCCTGGGGGCAATCAGTTTCTG
GATGTGTTCTAATGGATCTTTGCAGTGCAGAATATGCATCTGAGATTAGA
ATTTCAGAAATATGAGGAAAAACACCCTTGTTTCTACT H7
AGCGAAAGCAGGGGATACAAAATGAACACTCAAATCCTGGTATTCGCTCT 455
GATTGCGATCATTCCAACAAATGCAGACAAAATCTGCCTCGGACATCATG
CCGTGTCAAACGGAACCAAAGTAAACACATTAACTGAAAGAGGAGTGGAA
GTCGTCAATGCAACTGAAACAGTGGAACGAACAAACATCCCCAGGATCTG
CTCAAAAGGGAAAAGGACAGTTGACCTCGGTCAATGTGGACTCCTGGGGA
CAATCACTGGACCACCTCAATGTGACCAATTCCTAGAATTTTCAGCCGAT
TTAATTATTGAGAGGCGAGAAGGAAGTGATGTCTGTTATCCTGGGAAATT
CGTGAATGAAGAAGCTCTGAGGCAAATTCTCAGAGAATCAGGCGGAATTG
ACAAGGAAGCAATGGGATTCACATACAGTGGAATAAGAACTAATGGAGCA
ACCAGTGCATGTAGGAGATCAGGATCTTCATTCTATGCAGAAATGAAATG
GCTCCTGTCAAACACAGATGATGCTGCATTCCCGCAGATGACTAAGTCAT
ATAAAAATACAAGAAAAAGCCCAGCTCTAATAGTATGGGGGATCCATCAT
TCCGTATCAACTGCAGAGCAAACCAAGCTATATGGGAGTGGAAACAAACT
GGTGACAGTTGGGAGTTCTAATTATCAACAATCTTTTGTACCGAGTCCAG
GAGCGAGACCACAAGTTAATGGTCTATCTGGAAGAATTGACTTTCATTGG
CTAATGCTAAATCCCAATGATACAGTCACTTTCAGTTTCAATGGGGCTTT
CATAGCTCCAGACCGTGCAAGCTTCCTGAGAGGAAAATCTATGGGAATCC
AGAGTGGAGTACAGGTTGATGCCAATTGTGAAGGGGACTGCTATCATAGT
GGAGGGACAATAATAAGTAACTTGCCATTTCAGAACATAGATAGCAGGGC
AGTTGGAAAATGTCCGAGATATGTTAAGCAAAGGAGTCTGCTGCTAGCAA
CAGGGATGAAGAATGTTCCTGAGATTCCAAAGGGAAGAGGCCTATTTGGT
GCTATAGCGGGTTTCATTGAAAATGGATGGGAAGGCCTAATTGATGGTTG
GTATGGTTTCAGACACCAGAATGCACAGGGAGAGGGAACTGCTGCAGATT
ACAAAAGCACTCAATCGGCAATTGATCAAATAACAGGAAAATTAAACCGG
CTTATAGAAAAAACCAACCAACAATTTGAGTTGATAGACAATGAATTCAA
TGAGGTAGAGAAGCAAATCGGTAATGTGATAAATTGGACCAGAGATTCTA
TAACAGAAGTGTGGTCATACAATGCTGAACTCTTGGTAGCAATGGAGAAC
CAGCATACAATTGATCTGGCTGATTCAGAAATGGACAAACTGTACGAACG
AGTGAAAAGACAGCTGAGAGAGAATGCTGAAGAAGATGGCACTGGTTGCT
TTGAAATATTTCACAAGTGTGATGATGACTGTATGGCCAGTATTAGAAAT
AACACCTATGATCACAGCAAATACAGGGAAGAGGCAATGCAAAATAGAAT
ACAGATTGACCCAGTCAAACTAAGCAGCGGCTACAAAGATGTGATACTTT
GGTTTAGCTTCGGGGCATCATGTTTCATACTTCTAGCCATTGTAATGGGC
CTTGTCTTCATATGTGTAAAGAATGGAAACATGCGGTGCACTATTTGTAT
ATAAGTTTGGAAAAAAACACCCTTGTTTCTAC H10
ATGTACAAAATAGTAGTGATAATCGCGCTCCTTGGAGCTGTGAAAGGTCT 456
TGATAAAATCTGTCTAGGACATCATGCAGTGGCTAATGGGACCATCGTAA
AGACTCTCACAAACGAACAGGAAGAGGTAACCAACGCTACTGAAACAGTG
GAGAGTACAGGCATAAACAGATTATGTATGAAAGGAAGAAAACATAAAGA
CCTGGGCAACTGCCATCCAATAGGGATGCTAATAGGGACTCCAGCTTGTG
ATCTGCACCTTACAGGGATGTGGGACACTCTCATTGAACGAGAGAATGCT
ATTGCTTACTGCTACCCTGGAGCTACTGTAAATGTAGAAGCACTAAGGCA
GAAGATAATGGAGAGTGGAGGGATCAACAAGATAAGCACTGGCTTCACTT
ATGGATCTTCCATAAACTCGGCCGGGACCACTAGAGCGTGCATGAGGAAT
GGAGGGAATAGCTTTTATGCAGAGCTTAAGTGGCTGGTATCAAAGAGCAA
AGGACAAAACTTCCCTCAGACCACGAACACTTACAGAAATACAGACACGG
CTGAACACCTCATAATGTGGGGAATTCATCACCCTTCTAGCACTCAAGAG
AAGAATGATCTATATGGAACACAATCACTGTCCATATCAGTCGGGAGTTC
CACTTACCGGAACAATTTTGTTCCGGTTGTTGGAGCAAGACCTCAGGTCA
ATGGACAAAGTGGCAGAATTGATTTTCACTGGACACTAGTACAGCCAGGT
GACAACATCACCTTCTCACACAATGGGGGCCTGATAGCACCGAGCCGAGT
TAGCAAATTAATTGGGAGGGGATTGGGAATCCAATCAGACGCACCAATAG
ACAATAATTGTGAGTCCAAATGTTTTTGGAGAGGGGGTTCTATAAATACA
AGGCTTCCCTTTCAAAATTTGTCACCAAGAACAGTGGGTCAGTGTCCTAA
ATATGTGAACAGAAGAAGCTTGATGCTTGCAACAGGAATGAGAAACGTAC
CAGAACTAATACAAGGGAGAGGTCTATTTGGTGCAATAGCAGGGTTTTTA
GAGAATGGGTGGGAAGGAATGGTAGATGGCTGGTATGGTTTCAGACATCA
AAATGCTCAGGGCACAGGCCAGGCCGCTGATTACAAGAGTACTCAGGCAG
CTATTGATCAAATCACTGGGAAACTGAATAGACTTGTTGAAAAAACCAAT
ACTGAGTTCGAGTCAATAGAATCTGAGTTCAGTGAGATCGAACACCAAAT
CGGTAACGTCATCAATTGGACTAAGGATTCAATAACCGACATTTGGACTT
ATCAGGCTGAGCTGTTGGTGGCAATGGAGAACCAGCATACAATCGACATG
GCTGACTCAGAGATGTTGAATCTATATGAAAGAGTGAGGAAACAACTAAG
GCAGAATGCAGAAGAAGATGGGAAAGGATGTTTTGAGATATATCATGCTT
GTGATGATTCATGCATGGAGAGCATAAGAAACAACACCTATGACCATTCA
CAGTACAGAGAGGAAGCTCTTTTGAACAGATTGAATATCAACCCAGTGAC
ACTCTCTTCTGGATATAAAGACATCATTCTCTGGTTTAGCTTCGGGGCAT
CATGTTTTGTTCTTCTAGCCGTTGTCATGGGTCTTTTCTTTTTCTGTCTG
AAGAATGGAAACATGCGATGCACAATCTGTATTTAG
TABLE-US-00024 TABLE 20 Additional Flu Constructs SEQ Name Sequence
ID NO: MRK_LZ_ ATGGCCAGCCAGGGCACCAAGAGAAGCTACGAGCAGATGGAG 457
NP-H3N2 ACCGACGGCGAGAGACAGAACGCCACCGAGATCAGAGCCAGC SQ-031687
GTGGGCAAGATGATCGACGGCATCGGCAGATTCTACATCCAGA CX-003145
TGTGCACCGAGCTCAAGCTGAGCGACTACGAGGGCAGACTGAT
CCAGAACAGCCTGACCATCGAAAGAATGGTTCTGAGCGCCTTC
GACGAGAGAAGAAACAGATACCTGGAGGAGCACCCCAGCGCC
GGCAAGGACCCCAAGAAGACCGGCGGCCCCATCTACAAGAGA
GTGGACGGCAGATGGATGAGAGAGCTGGTGCTGTACGACAAGG
AGGAGATCAGAAGAATCTGGAGACAGGCCAACAACGGCGACG
ACGCCACCGCCGGCCTGACCCACATGATGATCTGGCACAGCAA
CCTGAACGACACCACCTACCAGAGAACCAGAGCCCTGGTGAGA
ACCGGCATGGACCCCAGAATGTGCAGCTTAATGCAGGGCAGCA
CCCTGCCCAGAAGATCCGGCGCCGCTGGTGCCGCCGTCAAGGG
CATCGGCACCATGGTGATGGAGCTGATCCGCATGATCAAGCGC
GGCATCAACGACAGAAACTTCTGGAGAGGCGAAAACGGCAGA
AAGACCAGAAGCGCCTACGAGAGAATGTGCAACATCCTGAAGG
GCAAGTTCCAGACCGCCGCCCAAAGAGCCATGATGGACCAGGT
GAGAGAGAGCAGAAACCCCGGCAACGCCGAGATCGAAGACCT
GATCTTCAGCGCCAGATCGGCCCTGATCCTGAGAGGCAGCGTG
GCCCACAAGAGCTGCCTGCCCGCCTGCGTGTATGGCCCCGCCGT
GAGCAGCGGCTACAACTTCGAGAAGGAGGGCTACAGCCTGGTG
GGCATCGACCCCTTCAAGCTGCTGCAGAACTCTCAGGTGTATAG
CCTGATCAGACCCAACGAGAACCCCGCCCACAAGAGCCAGCTG
GTGTGGATGGCCTGCCACAGCGCCGCCTTCGAGGACCTGAGAC
TGCTGAGCTTCATCAGAGGTACCAAGGTGTCCCCCAGAGGCAA
GCTGAGCACCAGAGGTGTGCAGATCGCCAGCAATGAGAACATG
GACAATATGGAGAGCAGCACCCTGGAGCTAAGAAGCAGGTACT
GGGCCATCCGGACCAGAAGCGGCGGCAATACCAACCAGCAGA
GAGCCAGCGCCGGCCAGATCAGCGTGCAGCCCACCTTCAGCGT
GCAGAGAAACCTGCCCTTTGAGAAGAGCACCGTGATGGCCGCC
TTCACCGGCAACACCGAGGGCAGAACCAGCGACATGAGAGCCG
AGATCATCAGAATGATGGAGGGCGCCAAGCCCGAGGAGGTGA
GCTTTAGAGGCAGAGGCGTGTTCGAGCTGAGCGACGAGAAGGC
CACCAACCCAATTGTGCCCAGCTTCGACATGTCGAACGAGGGC
AGCTACTTCTTCGGCGACAACGCCGAGGAGTACGACAAC MRK_LZ_
MASQGTKRSYEQMETDGERQNATEIRASVGKMIDGIGRFYIQMCT 458 NP-H3N2
ELKLSDYEGRLIQNSLTIERMVLSAFDERRNRYLEEHPSAGKDPKK SQ-031687
TGGPIYKRVDGRWMRELVLYDKEEIRRIWRQANNGDDATAGLTH CX-003145
MMIWHSNLNDTTYQRTRALVRTGMDPRMCSLMQGSTLPRRSGA
AGAAVKGIGTMVMELIRMIKRGINDRNFWRGENGRKTRSAYERM
CNILKGKFQTAAQRAMMDQVRESRNPGNAEIEDLIFSARSALILRG
SVAHKSCLPACVYGPAVSSGYNFEKEGYSLVGIDPFKLLQNSQVY
SLIRPNENPAHKSQLVWMACHSAAFEDLRLLSFIRGTKVSPRGKLS
TRGVQIASNENMDNMESSTLELRSRYWAIRTRSGGNTNQQRASAG
QISVQPTFSVQRNLPFEKSTVMAAFTGNTEGRTSDMRAEIIRMMEG
AKPEEVSFRGRGVFELSDEKATNPIVPSFDMSNEGSYFFGDNAEEY DN MRK_LZ_
ATGGAGACCCCCGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGCT 459 NIHGen6H
GCCCGACACCACCGGCGACACCATCTGCATCGGCTACCACGCC ASS-TM2
AACAACAGCACCGACACCGTGGACACCGTGCTGGAGAAGAAC SQ-034074
GTGACCGTGACCCACAGCGTGAACCTGGGCAGCGGCCTGAGGA CX-000553
TGGTGACCGGCCTGAGGAACATCCCCCAGAGGGAGACCAGGGG
CCTGTTCGGCGCCATCGCCGGCTTCATCGAGGGCGGCTGGACC
GGCATGGTGGACGGCTGGTACGGCTACCACCACCAGAACGAGC
AGGGCAGCGGCTACGCCGCCGACCAGAAGAGCACCCAGAACG
CCATCAACGGCATCACCAACATGGTGAACAGCGTGATCGAGAA
GATGGGCAGCGGCGGCAGCGGCACCGACCTGGCCGAGCTGCTG
GTGCTGCTGCTGAACGAGAGGACCCTGGACTTCCACGACAGCA
ACGTGAAGAACCTGTACGAGAAGGTGAAGAGCCAGCTGAAGA
ACAACGCCAAGGAGATCGGCAACGGCTGCTTCGAGTTCTACCA
CAAGTGCAACAACGAGTGCATGGAGAGCGTGAAGAACGGCAC
CTACGACTACCCCAAGTACAGCGAGGAGAGCAAGCTGAACAGG
GAGAAGATCGACGGAGTGAAATTGGAATCAATGGGGGTCTATC
AGATCCTGGCCATCTACAGCACCGTGGCCAGCAGCCTGGTGCT
GCTGGTGAGCCTGGGCGCCATCAGCTTCTGGATGTGCAGCAAC
GGCAGCCTGCAGTGCAGAATCTGCATC MRK_LZ_
METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDTVDTVLEKNVT 460 NIHGen6H
VTHSVNLGSGLRMVTGLRNIPQRETRGLFGAIAGFIEGGWTGMVD ASS-TM2
GWYGYHHQNEQGSGYAADQKSTQNAINGITNMVNSVIEKMGSG SQ-034074
GSGTDLAELLVLLLNERTLDFHDSNVKNLYEKVKSQLKNNAKEIG CX-000553
NGCFEFYHKCNNECMESVKNGTYDYPKYSEESKLNREKIDGVKLE
SMGVYQILAIYSTVASSLVLLVSLGAISFWMCSNGSLQCRICI MRK_LZ_
ATGGAGACCCCCGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGCT 461 NIHGen6H
GCCCGACACCACCGGCGACACCATCTGCATCGGCTACCACGCC ASS-foldon
AACAACAGCACCGACACCGTGGACACCGTGCTGGAGAAGAAC SQ-032106
GTGACCGTGACCCACAGCGTGAACCTGGGCAGCGGCCTGAGGA CX-000596
TGGTGACCGGCCTGAGGAACATCCCCCAGAGGGAGACCAGGGG
CCTGTTCGGCGCCATCGCCGGCTTCATCGAGGGCGGCTGGACC
GGCATGGTGGACGGCTGGTACGGCTACCACCACCAGAACGAGC
AGGGCAGCGGCTACGCCGCCGACCAGAAGAGCACCCAGAACG
CCATCAACGGCATCACCAACATGGTGAACAGCGTGATCGAGAA
GATGGGCAGCGGCGGCAGCGGCACCGACCTGGCCGAGCTGCTG
GTGCTGCTGCTGAACGAGAGGACCCTGGACTTCCACGACAGCA
ACGTGAAGAACCTGTACGAGAAGGTGAAGAGCCAGCTGAAGA
ACAACGCCAAGGAGATCGGCAACGGCTGCTTCGAGTTCTACCA
CAAGTGCAACAACGAGTGCATGGAGAGCGTGAAGAACGGCAC
CTACGACTACCCCAAGTACAGCGAGGAGAGCAAGCTGAACAGG
GAGAAGATCGACCCCGGCAGCGGCTACATCCCCGAGGCCCCCA
GGGACGGCCAGGCCTACGTGAGGAAGGACGGCGAGTGGGTGC TGCTGAGCACCTTCCTG
MRK_LZ_ METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDTVDTVLEKNVT 462 NIHGen6H
VTHSVNLGSGLRMVTGLRNIPQRETRGLFGAIAGFIEGGWTGMVD ASS-foldon
GWYGYHHQNEQGSGYAADQKSTQNAINGITNMVNSVIEKMGSG SQ-032106
GSGTDLAELLVLLLNERTLDFHDSNVKNLYEKVKSQLKNNAKEIG CX-000596
NGCFEFYHKCNNECMESVKNGTYDYPKYSEESKLNREKIDPGSGY
IPEAPRDGQAYVRKDGEWVLLSTFL
The underlined sequence for each of the amino acid sequences listed
in Table 20, indicates a signal or secretory sequence, which may be
substituted by an alternative sequence that achieves the same or
similar function, or the signal or secretory sequence may be
deleted.
TABLE-US-00025 TABLE 21 Additional Flu Sequences SEQ Name Sequence
ID NO: BHA10-2: HA10 version for METPAQLLFLLLLWLPDTTGHVVKTATQGEVNVT
463 Influenza B strain, with GVIPLTTTPTGSANKSKPYYTGEHAKATGNCPIWV
exposed hydrophobic KTPLKLANGTKYGSAGSATQEAINKITKNLNSLSEL residues
mutated EVKNLQRLSGASDETHNEILELDEKVDDLRADTISS
QIELAVLLSNEGIINSEDEGTGGGYIPEAPRDGQAY VRKDGEWVLLSTFL BHA10-3: HA10
version for METPAQLLFLLLLWLPDTTGHVVKTATQGEVNVT 464 Influenza B
strain, with GVIPLTTTPTGSANKSKPYYTGEHAKATGNCPIWV exposed
hydrophobic KTPLKLANGTKYGSAGSATQEAINKITKNLNSLSEL residues mutated,
with EVKNLQRLSCASDETHNCILELDEKVDDLRADTISS K68C/R76C/N95L
LIELAVLLSNEGIINSEDE mutations for trimerization NIHGen6HASS-TM:
Gen6 METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDT 465 HA SS construct
without VDTVLEKNVTVTHSVNLGSGLRMVTGLRNIPQRET foldon or ferritin,
with RGLFGAIAGFIEGGWTGMVDGWYGYHHQNEQGS transmembrane domain,
GYAADQKSTQNAINGITNMVNSVIEKMGSGGSGT version 1
DLAELLVLLLNERTLDFHDSNVKNLYEKVKSQLK
NNAKEIGNGCFEFYHKCNNECMESVKNGTYDYPK
YSEESKLNREKIDQGTGGILAIYSTVASSLVLLVSL GAISFWMCSNGSLQCRICI
NIHGen6HASS-TM2: Gen6 METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDT 466 HA SS
construct without VDTVLEKNVTVTHSVNLGSGLRMVTGLRNIPQRET foldon or
ferritin, with RGLFGAIAGFIEGGWTGMVDGWYGYHHQNEQGS transmembrane
domain, GYAADQKSTQNAINGITNMVNSVIEKMGSGGSGT version 2
DLAELLVLLLNERTLDFHDSNVKNLYEKVKSQLK
NNAKEIGNGCFEFYHKCNNECMESVKNGTYDYPK
YSEESKLNREKIDGVKLESMGVYQILAIYSTVASSL VLLVSLGAISFWMCSNGSLQCRICI
H1HA10-PR8-DS-ferritin: METPAQLLFLLLLWLPDTTGDTVDTVCEKNVTVT 467
H1HA10 from PR8 strain, HSVNLLEDSHGSANSSLPYQNTHPTTNGESPKYVR with
additional disulfide SAKLRMVTGLRNGSAGSATQNAINCITNKVNTVIE mutation,
without foldon KMNIQDTATGKEFNKDEKRMENLNKKVDDGFLDI and with ferritin
fusion for WTYNAELLVLLENERTLDAHDSQGTGGDIIKLLNE particle formation
QVNKEMQSSNLYMSMSSWCYTHSLDGAGLFLFD
HAAEEYEHAKKLIIFLNENNVPVQLTSISAPEHKFE
GLTQIFQKAYEHEQHISESINNIVDHAIKSKDHATF
NFLQWYVAEQHEEEVLFKDILDKIELIGNENHGLY LADQYVKGIAKSRKS ConH1:
consensus HA MKAKLLVLLCAFTATDADTICIGYHANNSTDTVDT 468 sequence for
subtype H1 VLEKNVTVTHSVNLLEDSHNGKLCKLKGIAPLQLG
KCNIAGWILGNPECESLISKRSWSYIVETPNSENGT
CYPGDFADYEELREQLSSVSSFERFEIFPKESSWPN
HNVTKGVTAACSHAGKSSFYRNLLWLTEKNGSYP
KLSKSYVNNKEKEVLVLWGVHHPSNITDQRTLYQ
NENAYVSVVSSHYNRRFTPEIAKRPKVRGQAGRIN
YYWTLLEPGDTIIFEANGNLIAPWYAFALSRGFGSG
IITSNAPMHECDTKCQTPQGAINSSLPFQNVHPVTI
GECPKYVRSTKLRMVTGLRNIPSIQSRGLFGAIAGF
IEGGWTGMIDGWYGYHHQNEQGSGYAADQKSTQ
NAINGITNKVNSVIEKMNTQFTAVGKEFNKLEKRM
ENLNKKVDDGFLDIWTYNAELLVLLENERTLDFH
DSNVKNLYEKVKSQLKNNAKEIGNGCFEFYHKCN
NECMESVKNGTYDYPKYSEESKLNREKIDGVKLES
MGVYQILAIYSTVASSLVLLVSLGAISFWMCSNGS LQCRICI ConH3: consensus HA
MKTIIALSYIFCLVFAQKLPGNDNSTATLCLGHHAV 469 sequence for subtype H3
PNGTLVKTITNDQIEVTNATELVQSSSTGRICDSPH
RILDGTNCTLIDALLGDPHCDGFQNKEWDLFVERS
KAYSNCYPYDVPDYASLRSLVASSGTLEFNNEGFN
WTGVTQNGGSSACKRGSDKSFFSRLNWLHKLKYK
YPALNVTMPNNDKFDKLYIWGVHHPSTDSDQTSL
YVQASGRVTVSTKRSQQTVIPNIGSRPWVRGLSSRI
SIYWTIVKPGDILLINSTGNLIAPRGYFKIRSGKSSIM
RSDAPIGTCNSECITPNGSIPNDKPFQNVNRITYGAC
PRYVKQNTLKLATGMRNVPEKQTRGIFGAIAGFIE
NGWEGMVDGWYGFRHQNSEGTGQAADLKSTQA
AIDQINGKLNRLIEKTNEKFHQIEKEFSEVEGRIQDL
EKYVEDTKIDLWSYNAELLVALENQHTIDLTDSEM
NKLFERTRKQLRENAEDMGNGCFKIYHKCDNACI
GSIRNGTYDHDVYRDEALNNRFQIKGVELKSGYK
DWILWISFAISCFLLCVVLLGFIMWACQKGNIRCNI CI MRK_pH1_Con: consensus
MKAILVVLLYTFATANADTLCIGYHANNSTDTVDT 470 HA sequence for pandemic
VLEKNVTVTHSVNLLEDKHNGKLCKLRGVAPLHL H1 strains
GKCNIAGWILGNPECESLSTASSWSYIVETSSSDNG
TCYPGDFIDYEELREQLSSVSSFERFEIFPKTSSWPN
HDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYP
KLSKSYINDKGKEVLVLWGIHHPSTSADQQSLYQN
ADAYVFVGTSRYSKKFKPEIAIRPKVRDQEGRMNY
YWTLVEPGDKITFEATGNLVVPRYAFAMERNAGS
GIIISDTPVHDCNTTCQTPKGAINTSLPFQNIHPITIG
KCPKYVKSTKLRLATGLRNVPSIQSRGLFGAIAGFI
EGGWTGMVDGWYGYHHQNEQGSGYAADLKSTQ
NAIDKITNKVNSVIEKMNTQFTAVGKEFNHLEKRIE
NLNKKVDDGFLDIWTYNAELLVLLENERTLDYHD
SNVKNLYEKVRSQLKNNAKEIGNGCFEFYHKCDN
TCMESVKNGTYDYPKYSEEAKLNREEIDGVKLEST
RIYQILAIYSTVASSLVLVVSLGAISFWMCSNGSLQ CRICI MRK_sH1_Con: consensus
MKVKLLVLLCTFTATYADTICIGYHANNSTDTVDT 471 HA sequence for seasonal
VLEKNVTVTHSVNLLEDSHNGKLCLLKGIAPLQLG H1 strains
NCSVAGWILGNPECELLISKESWSYIVETPNPENGT
CYPGYFADYEELREQLSSVSSFERFEIFPKESSWPN
HTVTGVSASCSHNGKSSFYRNLLWLTGKNGLYPN
LSKSYANNKEKEVLVLWGVHHPPNIGDQRALYHT
ENAYVSVVSSHYSRRFTPEIAKRPKVRDQEGRINY
YWTLLEPGDTIIFEANGNLIAPRYAFALSRGFGSGII
TSNAPMDECDAKCQTPQGAINSSLPFQNVHPVTIG
ECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGFI
EGGWTGMVDGWYGYHHQNEQGSGYAADQKSTQ
NAINGITNKVNSVIEKMNTQFTAVGKEFNKLERRM
ENLNKKVDDGFLDIWTYNAELLVLLENERTLDFH
DSNVKNLYEKVKSQLKNNAKEIGNGCFEFYHKCN
DECMESVKNGTYDYPKYSEESKLNREKIDGVKLES
MGVYQILAIYSTVASSLVLLVSLGAISFWMCSNGS LQCRICI Cobra_P1: consensus HA
MKARLLVLLCALAATDADTICIGYHANNSTDTVDT 472 sequence P1 for H1 subtype
VLEKNVTVTHSVNLLEDSHNGKLCKLKGIAPLQLG
KCNIAGWLLGNPECESLLSARSWSYIVETPNSENG
TCYPGDFIDYEELREQLSSVSSFERFEIFPKESSWPN
HNTTKGVTAACSHAGKSSFYRNLLWLTKKGGSYP
KLSKSYVNNKGKEVLVLWGVHHPSTSTDQQSLYQ
NENAYVSVVSSNYNRRFTPEIAERPKVRGQAGRM
NYYWTLLEPGDTIIFEATGNLIAPWYAFALSRGSGS
GIITSNASMHECNTKCQTPQGAINSSLPFQNIHPVTI
GECPKYVRSTKLRMVTGLRNIPSIQSRGLFGAIAGF
IEGGWTGMIDGWYGYHHQNEQGSGYAADQKSTQ
NAINGITNKVNSVIEKMNTQFTAVGKEFNNLEKRM
ENLNKKVDDGFLDIWTYNAELLVLLENERTLDFH
DSNVKNLYEKVKSQLRNNAKEIGNGCFEFYHKCD
NECMESVKNGTYDYPKYSEESKLNREKIDGVKLES
MGVYQILAIYSTVASSLVLLVSLGAISFWMCSNGS LQCRICI Cobra_X3: consensus HA
MEARLLVLLCAFAATNADTICIGYHANNSTDTVDT 473 sequence X3 for H1 subtype
VLEKNVTVTHSVNLLEDSHNGKLCRLKGIAPLQLG
NCSVAGWILGNPECESLFSKESWSYIAETPNPENGT
CYPGYFADYEELREQLSSVSSFERFEIFPKESSWPN
HTVTKGVTASCSHNGKSSFYRNLLWLTEKNGLYP
NLSKSYVNNKEKEVLVLWGVHHPSNIGDQRAIYH
TENAYVSVVSSHYSRRFTPEIAKRPKVRDQEGRIN
YYWTLLEPGDTIIFEANGNLIAPWYAFALSRGFGSG
IITSNASMDECDAKCQTPQGAINSSLPFQNVHPVTI
GECPKYVRSTKLRMVTGLRNIPSIQSRGLFGAIAGF
IEGGWTGMIDGWYGYHHQNEQGSGYAADQKSTQ
NAINGITNKVNSVIEKMNTQFTAVGKEFNKLERRM
ENLNKKVDDGFLDIWTYNAELLVLLENERTLDFH
DSNVKNLYEKVKSQLKNNAKEIGNGCFEFYHKCN
NECMESVKNGTYDYPKYSEESKLNREKIDGVKLES
MGVYQILAIYSTVASSLVLLVSLGAISFWMCSNGS LQCRICI ConH1_ferritin:
consensus MKAKLLVLLCAFTATDADTICIGYHANNSTDTVDT 474 HA sequence for
subtype VLEKNVTVTHSVNLLEDSHNGKLCKLKGIAPLQLG H1, with ferritin for
KCNIAGWILGNPECESLISKRSWSYIVETPNSENGT particle formation
CYPGDFADYEELREQLSSVSSFERFEIFPKESSWPN
HNVTKGVTAACSHAGKSSFYRNLLWLTEKNGSYP
KLSKSYVNNKEKEVLVLWGVHHPSNITDQRTLYQ
NENAYVSVVSSHYNRRFTPEIAKRPKVRGQAGRIN
YYWTLLEPGDTIIFEANGNLIAPWYAFALSRGFGSG
IITSNAPMHECDTKCQTPQGAINSSLPFQNVHPVTI
GECPKYVRSTKLRMVTGLRNIPSIQSRGLFGAIAGF
IEGGWTGMIDGWYGYHHQNEQGSGYAADQKSTQ
NAINGITNKVNSVIEKMNTQFTAVGKEFNKLEKRM
ENLNKKVDDGFLDIWTYNAELLVLLENERTLDFH
DSNVKNLYEKVKSQLKNNAKEIGNGCFEFYHKCN
NECMESVKNGTYDYPKYSEESKLNREKIDSGGDII
KLLNEQVNKEMQSSNLYMSMSSWCYTHSLDGAG
LFLFDHAAEEYEHAKKLIIFLNENNVPVQLTSISAPE
HKFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKD
HATFNFLQWYVAEQHEEEVLFKDILDKIELIGNEN HGLYLADQYVKGIAKSRKS
ConH3_ferritin: consensus MKTIIALSYIFCLVFAQKLPGNDNSTATLCLGHHAV 475
HA sequence for subtype PNGTLVKTITNDQIEVTNATELVQSSSTGRICDSPH H3,
with ferritin for RILDGTNCTLIDALLGDPHCDGFQNKEWDLFVERS particle
formation KAYSNCYPYDVPDYASLRSLVASSGTLEFNNEGFN
WTGVTQNGGSSACKRGSDKSFFSRLNWLHKLKYK
YPALNVTMPNNDKFDKLYIWGVHHPSTDSDQTSL
YVQASGRVTVSTKRSQQTVIPNIGSRPWVRGLSSRI
SIYWTIVKPGDILLINSTGNLIAPRGYFKIRSGKSSIM
RSDAPIGTCNSECITPNGSIPNDKPFQNVNRITYGAC
PRYVKQNTLKLATGMRNVPEKQTRGIFGAIAGFIE
NGWEGMVDGWYGFRHQNSEGTGQAADLKSTQA
AIDQINGKLNRLIEKTNEKFHQIEKEFSEVEGRIQDL
EKYVEDTKIDLWSYNAELLVALENQHTIDLTDSEM
NKLFERTRKQLRENAEDMGNGCFKIYHKCDNACI
GSIRNGTYDHDVYRDEALNNRFQIKSGGDIIKLLNE
QVNKEMQSSNLYMSMSSWCYTHSLDGAGLFLFD
HAAEEYEHAKKLIIFLNENNVPVQLTSISAPEHKFE
GLTQIFQKAYEHEQHISESINNIVDHAIKSKDHATF
NFLQWYVAEQHEEEVLFKDILDKIELIGNENHGLY LADQYVKGIAKSRKS
Merck_pH1_Con_ferritin: MKAILVVLLYTFATANADTLCIGYHANNSTDTVDT 476
consensus HA sequence for VLEKNVTVTHSVNLLEDKHNGKLCKLRGVAPLHL
pandemic H1 strains, with GKCNIAGWILGNPECESLSTASSWSYIVETSSSDNG
ferritin for particle TCYPGDFIDYEELREQLSSVSSFERFEIFPKTSSWPN
formation HDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYP
KLSKSYINDKGKEVLVLWGIHHPSTSADQQSLYQN
ADAYVFVGTSRYSKKFKPEIAIRPKVRDQEGRMNY
YWTLVEPGDKITFEATGNLVVPRYAFAMERNAGS
GIIISDTPVHDCNTTCQTPKGAINTSLPFQNIHPITIG
KCPKYVKSTKLRLATGLRNVPSIQSRGLFGAIAGFI
EGGWTGMVDGWYGYHHQNEQGSGYAADLKSTQ
NAIDKITNKVNSVIEKMNTQFTAVGKEFNHLEKRIE
NLNKKVDDGFLDIWTYNAELLVLLENERTLDYHD
SNVKNLYEKVRSQLKNNAKEIGNGCFEFYHKCDN
TCMESVKNGTYDYPKYSEEAKLNREEIDSGGDIIK
LLNEQVNKEMQSSNLYMSMSSWCYTHSLDGAGLF
LFDHAAEEYEHAKKLIIFLNENNVPVQLTSISAPEH
KFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKDH
ATFNFLQWYVAEQHEEEVLFKDILDKIELIGNENH GLYLADQYVKGIAKSRKS
Merck_sH1_Con_ferritin: MKVKLLVLLCTFTATYADTICIGYHANNSTDTVDT 477
consensus HA sequence for VLEKNVTVTHSVNLLEDSHNGKLCLLKGIAPLQLG
seasonal H1 strains, with NCSVAGWILGNPECELLISKESWSYIVETPNPENGT
ferritin for particle CYPGYFADYEELREQLSSVSSFERFEIFPKESSWPN
formation HTVTGVSASCSHNGKSSFYRNLLWLTGKNGLYPN
LSKSYANNKEKEVLVLWGVHHPPNIGDQRALYHT
ENAYVSVVSSHYSRRFTPEIAKRPKVRDQEGRINY
YWTLLEPGDTIIFEANGNLIAPRYAFALSRGFGSGII
TSNAPMDECDAKCQTPQGAINSSLPFQNVHPVTIG
ECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGFI
EGGWTGMVDGWYGYHHQNEQGSGYAADQKSTQ
NAINGITNKVNSVIEKMNTQFTAVGKEFNKLERRM
ENLNKKVDDGFLDIWTYNAELLVLLENERTLDFH
DSNVKNLYEKVKSQLKNNAKEIGNGCFEFYHKCN
DECMESVKNGTYDYPKYSEESKLNREKIDSGGDII
KLLNEQVNKEMQSSNLYMSMSSWCYTHSLDGAG
LFLFDHAAEEYEHAKKLIIFLNENNVPVQLTSISAPE
HKFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKD
HATFNFLQWYVAEQHEEEVLFKDILDKIELIGNEN HGLYLADQYVKGIAKSRKS
Cobra_P1_ferritin: MKARLLVLLCALAATDADTICIGYHANNSTDTVDT 478
consensus HA sequence P1 VLEKNVTVTHSVNLLEDSHNGKLCKLKGIAPLQLG for H1
subtype, with ferritin KCNIAGWLLGNPECESLLSARSWSYIVETPNSENG for
particle formation TCYPGDFIDYEELREQLSSVSSFERFEIFPKESSWPN
HNTTKGVTAACSHAGKSSFYRNLLWLTKKGGSYP
KLSKSYVNNKGKEVLVLWGVHHPSTSTDQQSLYQ
NENAYVSVVSSNYNRRFTPEIAERPKVRGQAGRM
NYYWTLLEPGDTIIFEATGNLIAPWYAFALSRGSGS
GIITSNASMHECNTKCQTPQGAINSSLPFQNIHPVTI
GECPKYVRSTKLRMVTGLRNIPSIQSRGLFGAIAGF
IEGGWTGMIDGWYGYHHQNEQGSGYAADQKSTQ
NAINGITNKVNSVIEKMNTQFTAVGKEFNNLEKRM
ENLNKKVDDGFLDIWTYNAELLVLLENERTLDFH
DSNVKNLYEKVKSQLRNNAKEIGNGCFEFYHKCD
NECMESVKNGTYDYPKYSEESKLNREKIDSGGDII
KLLNEQVNKEMQSSNLYMSMSSWCYTHSLDGAG
LFLFDHAAEEYEHAKKLIIFLNENNVPVQLTSISAPE
HKFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKD
HATFNFLQWYVAEQHEEEVLFKDILDKIELIGNEN HGLYLADQYVKGIAKSRKS
Cobra_X3_ferritin: MEARLLVLLCAFAATNADTICIGYHANNSTDTVDT 479
consensus HA sequence X3 VLEKNVTVTHSVNLLEDSHNGKLCRLKGIAPLQLG for H1
subtype, with ferritin NCSVAGWILGNPECESLFSKESWSYIAETPNPENGT for
particle formation CYPGYFADYEELREQLSSVSSFERFEIFPKESSWPN
HTVTKGVTASCSHNGKSSFYRNLLWLTEKNGLYP
NLSKSYVNNKEKEVLVLWGVHHPSNIGDQRAIYH
TENAYVSVVSSHYSRRFTPEIAKRPKVRDQEGRIN
YYWTLLEPGDTIIFEANGNLIAPWYAFALSRGFGSG
IITSNASMDECDAKCQTPQGAINSSLPFQNVHPVTI
GECPKYVRSTKLRMVTGLRNIPSIQSRGLFGAIAGF
IEGGWTGMIDGWYGYHHQNEQGSGYAADQKSTQ
NAINGITNKVNSVIEKMNTQFTAVGKEFNKLERRM
ENLNKKVDDGFLDIWTYNAELLVLLENERTLDFH
DSNVKNLYEKVKSQLKNNAKEIGNGCFEFYHKCN
NECMESVKNGTYDYPKYSEESKLNREKIDSGGDII
KLLNEQVNKEMQSSNLYMSMSSWCYTHSLDGAG
LFLFDHAAEEYEHAKKLIIFLNENNVPVQLTSISAPE
HKFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKD
HATFNFLQWYVAEQHEEEVLFKDILDKIELIGNEN HGLYLADQYVKGIAKSRKS
TABLE-US-00026 TABLE 22 Signal Peptides SEQ Description Sequence ID
NO: HuIgG.sub.k signal METPAQLLFLLLLWLPDTTG 480 peptide IgE heavy
chain MDWTWILFLVAAATRVHS 481 epsilon -1 signal peptide Japanese
MLGSNSGQRVVFTILLLLVA 482 encephalitis PRM PAYS signal sequence VSVg
protein MKCLLYLAFLFIGVNCA 483 signal sequence Japanese
MWLVSLAIVTACAGA 484 encephalitis JEV signal sequence
TABLE-US-00027 TABLE 23 Flagellin Nucleic Acid Sequences SEQ Name
Sequence ID NO: NT (5' TCAAGCTTTTGGACCCTCGTACAGAAGCTAATACGACTCA 485
UTR, ORF, CTATAGGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAA 3' UTR)
ATATAAGAGCCACCATGGCACAAGTCATTAATACAAACA
GCCTGTCGCTGTTGACCCAGAATAACCTGAACAAATCCC
AGTCCGCACTGGGCACTGCTATCGAGCGTTTGTCTTCCGG
TCTGCGTATCAACAGCGCGAAAGACGATGCGGCAGGACA
GGCGATTGCTAACCGTTTTACCGCGAACATCAAAGGTCT
GACTCAGGCTTCCCGTAACGCTAACGACGGTATCTCCATT
GCGCAGACCACTGAAGGCGCGCTGAACGAAATCAACAAC
AACCTGCAGCGTGTGCGTGAACTGGCGGTTCAGTCTGCG
AATGGTACTAACTCCCAGTCTGACCTCGACTCCATCCAGG
CTGAAATCACCCAGCGCCTGAACGAAATCGACCGTGTAT
CCGGCCAGACTCAGTTCAACGGCGTGAAAGTCCTGGCGC
AGGACAACACCCTGACCATCCAGGTTGGTGCCAACGACG
GTGAAACTATCGATATTGATTTAAAAGAAATCAGCTCTA
AAACACTGGGACTTGATAAGCTTAATGTCCAAGATGCCT
ACACCCCGAAAGAAACTGCTGTAACCGTTGATAAAACTA
CCTATAAAAATGGTACAGATCCTATTACAGCCCAGAGCA
ATACTGATATCCAAACTGCAATTGGCGGTGGTGCAACGG
GGGTTACTGGGGCTGATATCAAATTTAAAGATGGTCAAT
ACTATTTAGATGTTAAAGGCGGTGCTTCTGCTGGTGTTTA
TAAAGCCACTTATGATGAAACTACAAAGAAAGTTAATAT
TGATACGACTGATAAAACTCCGTTGGCAACTGCGGAAGC
TACAGCTATTCGGGGAACGGCCACTATAACCCACAACCA
AATTGCTGAAGTAACAAAAGAGGGTGTTGATACGACCAC
AGTTGCGGCTCAACTTGCTGCAGCAGGGGTTACTGGCGC
CGATAAGGACAATACTAGCCTTGTAAAACTATCGTTTGA
GGATAAAAACGGTAAGGTTATTGATGGTGGCTATGCAGT
GAAAATGGGCGACGATTTCTATGCCGCTACATATGATGA
GAAAACAGGTGCAATTACTGCTAAAACCACTACTTATAC
AGATGGTACTGGCGTTGCTCAAACTGGAGCTGTGAAATT
TGGTGGCGCAAATGGTAAATCTGAAGTTGTTACTGCTACC
GATGGTAAGACTTACTTAGCAAGCGACCTTGACAAACAT
AACTTCAGAACAGGCGGTGAGCTTAAAGAGGTTAATACA
GATAAGACTGAAAACCCACTGCAGAAAATTGATGCTGCC
TTGGCACAGGTTGATACACTTCGTTCTGACCTGGGTGCGG
TTCAGAACCGTTTCAACTCCGCTATCACCAACCTGGGCAA
TACCGTAAATAACCTGTCTTCTGCCCGTAGCCGTATCGAA
GATTCCGACTACGCAACCGAAGTCTCCAACATGTCTCGC
GCGCAGATTCTGCAGCAGGCCGGTACCTCCGTTCTGGCG
CAGGCGAACCAGGTTCCGCAAAACGTCCTCTCTTTACTGC
GTTGATAATAGGCTGGAGCCTCGGTGGCCATGCTTCTTGC
CCCTTGGGCCTCCCCCCAGCCCCTCCTCCCCTTCCTGCAC
CCGTACCCCCGTGGTCTTTGAATAAAGTCTGAGTGGGCG GC ORF
ATGGCACAAGTCATTAATACAAACAGCCTGTCGCTGTTG 486 Sequence,
ACCCAGAATAACCTGAACAAATCCCAGTCCGCACTGGGC NT
ACTGCTATCGAGCGTTTGTCTTCCGGTCTGCGTATCAACA
GCGCGAAAGACGATGCGGCAGGACAGGCGATTGCTAACC
GTTTTACCGCGAACATCAAAGGTCTGACTCAGGCTTCCCG
TAACGCTAACGACGGTATCTCCATTGCGCAGACCACTGA
AGGCGCGCTGAACGAAATCAACAACAACCTGCAGCGTGT
GCGTGAACTGGCGGTTCAGTCTGCGAATGGTACTAACTC
CCAGTCTGACCTCGACTCCATCCAGGCTGAAATCACCCA
GCGCCTGAACGAAATCGACCGTGTATCCGGCCAGACTCA
GTTCAACGGCGTGAAAGTCCTGGCGCAGGACAACACCCT
GACCATCCAGGTTGGTGCCAACGACGGTGAAACTATCGA
TATTGATTTAAAAGAAATCAGCTCTAAAACACTGGGACT
TGATAAGCTTAATGTCCAAGATGCCTACACCCCGAAAGA
AACTGCTGTAACCGTTGATAAAACTACCTATAAAAATGG
TACAGATCCTATTACAGCCCAGAGCAATACTGATATCCA
AACTGCAATTGGCGGTGGTGCAACGGGGGTTACTGGGGC
TGATATCAAATTTAAAGATGGTCAATACTATTTAGATGTT
AAAGGCGGTGCTTCTGCTGGTGTTTATAAAGCCACTTATG
ATGAAACTACAAAGAAAGTTAATATTGATACGACTGATA
AAACTCCGTTGGCAACTGCGGAAGCTACAGCTATTCGGG
GAACGGCCACTATAACCCACAACCAAATTGCTGAAGTAA
CAAAAGAGGGTGTTGATACGACCACAGTTGCGGCTCAAC
TTGCTGCAGCAGGGGTTACTGGCGCCGATAAGGACAATA
CTAGCCTTGTAAAACTATCGTTTGAGGATAAAAACGGTA
AGGTTATTGATGGTGGCTATGCAGTGAAAATGGGCGACG
ATTTCTATGCCGCTACATATGATGAGAAAACAGGTGCAA
TTACTGCTAAAACCACTACTTATACAGATGGTACTGGCGT
TGCTCAAACTGGAGCTGTGAAATTTGGTGGCGCAAATGG
TAAATCTGAAGTTGTTACTGCTACCGATGGTAAGACTTAC
TTAGCAAGCGACCTTGACAAACATAACTTCAGAACAGGC
GGTGAGCTTAAAGAGGTTAATACAGATAAGACTGAAAAC
CCACTGCAGAAAATTGATGCTGCCTTGGCACAGGTTGAT
ACACTTCGTTCTGACCTGGGTGCGGTTCAGAACCGTTTCA
ACTCCGCTATCACCAACCTGGGCAATACCGTAAATAACC
TGTCTTCTGCCCGTAGCCGTATCGAAGATTCCGACTACGC
AACCGAAGTCTCCAACATGTCTCGCGCGCAGATTCTGCA
GCAGGCCGGTACCTCCGTTCTGGCGCAGGCGAACCAGGT
TCCGCAAAACGTCCTCTCTTTACTGCGT mRNA
G*GGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAU 487 Sequence
AUAAGAGCCACCAUGGCACAAGUCAUUAAUACAAACAG (assumes
CCUGUCGCUGUUGACCCAGAAUAACCUGAACAAAUCCC T100 tail)
AGUCCGCACUGGGCACUGCUAUCGAGCGUUUGUCUUCC
GGUCUGCGUAUCAACAGCGCGAAAGACGAUGCGGCAGG
ACAGGCGAUUGCUAACCGUUUUACCGCGAACAUCAAAG
GUCUGACUCAGGCUUCCCGUAACGCUAACGACGGUAUC
UCCAUUGCGCAGACCACUGAAGGCGCGCUGAACGAAAU
CAACAACAACCUGCAGCGUGUGCGUGAACUGGCGGUUC
AGUCUGCGAAUGGUACUAACUCCCAGUCUGACCUCGAC
UCCAUCCAGGCUGAAAUCACCCAGCGCCUGAACGAAAU
CGACCGUGUAUCCGGCCAGACUCAGUUCAACGGCGUGA
AAGUCCUGGCGCAGGACAACACCCUGACCAUCCAGGUU
GGUGCCAACGACGGUGAAACUAUCGAUAUUGAUUUAAA
AGAAAUCAGCUCUAAAACACUGGGACUUGAUAAGCUUA
AUGUCCAAGAUGCCUACACCCCGAAAGAAACUGCUGUA
ACCGUUGAUAAAACUACCUAUAAAAAUGGUACAGAUCC
UAUUACAGCCCAGAGCAAUACUGAUAUCCAAACUGCAA
UUGGCGGUGGUGCAACGGGGGUUACUGGGGCUGAUAUC
AAAUUUAAAGAUGGUCAAUACUAUUUAGAUGUUAAAG
GCGGUGCUUCUGCUGGUGUUUAUAAAGCCACUUAUGAU
GAAACUACAAAGAAAGUUAAUAUUGAUACGACUGAUA
AAACUCCGUUGGCAACUGCGGAAGCUACAGCUAUUCGG
GGAACGGCCACUAUAACCCACAACCAAAUUGCUGAAGU
AACAAAAGAGGGUGUUGAUACGACCACAGUUGCGGCUC
AACUUGCUGCAGCAGGGGUUACUGGCGCCGAUAAGGAC
AAUACUAGCCUUGUAAAACUAUCGUUUGAGGAUAAAAA
CGGUAAGGUUAUUGAUGGUGGCUAUGCAGUGAAAAUG
GGCGACGAUUUCUAUGCCGCUACAUAUGAUGAGAAAAC
AGGUGCAAUUACUGCUAAAACCACUACUUAUACAGAUG
GUACUGGCGUUGCUCAAACUGGAGCUGUGAAAUUUGGU
GGCGCAAAUGGUAAAUCUGAAGUUGUUACUGCUACCGA
UGGUAAGACUUACUUAGCAAGCGACCUUGACAAACAUA
ACUUCAGAACAGGCGGUGAGCUUAAAGAGGUUAAUACA
GAUAAGACUGAAAACCCACUGCAGAAAAUUGAUGCUGC
CUUGGCACAGGUUGAUACACUUCGUUCUGACCUGGGUG
CGGUUCAGAACCGUUUCAACUCCGCUAUCACCAACCUG
GGCAAUACCGUAAAUAACCUGUCUUCUGCCCGUAGCCG
UAUCGAAGAUUCCGACUACGCAACCGAAGUCUCCAACA
UGUCUCGCGCGCAGAUUCUGCAGCAGGCCGGUACCUCC
GUUCUGGCGCAGGCGAACCAGGUUCCGCAAAACGUCCU
CUCUUUACUGCGUUGAUAAUAGGCUGGAGCCUCGGUGG
CCAUGCUUCUUGCCCCUUGGGCCUCCCCCCAGCCCCUCC
UCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAUA
AAGUCUGAGUGGGCGGCAAAAAAAAAAAAAAAAAAAA
AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAUCUAG
[0962] The first underlined sequence is representative of the 5'
UTR, which may be included in or omitted from any of the constructs
listed in Table 1, or it may be modified or substituted with
another 5' UTR comprising a different sequence. The second
underlined sequence is representative of the 3' UTR, which may be
included in or omitted from any of the constructs listed in Table
1, or it may be modified or substituted with another 3' UTR
comprising a different sequence.
TABLE-US-00028 TABLE 24 Flagellin Amino Acid Sequences SEQ Name
Sequence ID NO: ORF MAQVINTNSLSLLTQNNLNKSQSAL 488 Sequence,
GTAIERLSSGLRINSAKDDAAGQAI AA ANRFTANIKGLTQASRNANDGISIA
QTTEGALNEINNNLQRVRELAVQSA NGTNSQSDLDSIQAEITQRLNEIDR
VSGQTQFNGVKVLAQDNTLTIQVGA NDGETIDIDLKEISSKTLGLDKLNV
QDAYTPKETAVTVDKTTYKNGTDPI TAQSNTDIQTAIGGGATGVTGADIK
FKDGQYYLDVKGGASAGVYKATYDE TTKKVNIDTTDKTPLATAEATAIRG
TATITHNQIAEVTKEGVDTTTVAAQ LAAAGVTGADKDNTSLVKLSFEDKN
GKVIDGGYAVKMGDDFYAATYDEKT GAITAKTTTYTDGTGVAQTGAVKFG
GANGKSEVVTATDGKTYLASDLDKH NFRTGGELKEVNTDKTENPLQKIDA
ALAQVDTLRSDLGAVQNRFNSAITN LGNTVNNLSSARSRIEDSDYATEVS
NMSRAQILQQAGTSVLAQANQVPQN VLSLLR Flagellin-
MAQVINTNSLSLLTQNNLNKSQSAL 489 GS linker- GTAIERLSSGLRINSAKDDAAGQAI
circumspor- ANRFTANIKGLTQASRNANDGISIA ozoite
QTTEGALNEINNNLQRVRELAVQSA protein NSTNSQSDLDSIQAEITQRLNEIDR (CSP)
VSGQTQFNGVKVLAQDNTLTIQVGA NDGETIDIDLKQINSQTLGLDTLNV
QQKYKVSDTAATVTGYADTTIALDN STFKASATGLGGTDQKIDGDLKFDD
TTGKYYAKVTVTGGTGKDGYYEVSV DKTNGEVTLAGGATSPLTGGLPATA
TEDVKNVQVANADLTEAKAALTAAG VTGTASVVKMSYTDNNGKTIDGGLA
VKVGDDYYSATQNKDGSISINTTKY TADDGTSKTALNKLGGADGKTEVVS
IGGKTYAASKAEGHNFKAQPDLAEA AATTTENPLQKIDAALAQVDTLRSD
LGAVQNRFNSAITNLGNTVNNLTSA RSRIEDSDYATEVSNMSRAQILQQA
GTSVLAQANQVPQNVLSLLRGGGGS GGGGSMMAPDPNANPNANPNANPNA
NPNANPNANPNANPNANPNANPNAN PNANPNANPNANPNANPNANPNANP
NANPNANPNANPNKNNQGNGQGHNM PNDPNRNVDENANANNAVKNNNNEE
PSDKHIEQYLKKIKNSISTEWSPCS VTCGNGIQVRIKPGSANKPKDELDY
ENDIEKKICKMEKCSSVFNVVNS Flagellin- MMAPDPNANPNANPNANPNANPNAN 490
RPVT PNANPNANPNANPNANPNANPNANP linker- NANPNANPNANPNANPNANPNANPN
circumspor- ANPNANPNKNNQGNGQGHNMPNDPN ozoite
RNVDENANANNAVKNNNNEEPSDKH protein IEQYLKKIKNSISTEWSPCSVTCGN (CSP)
GIQVRIKPGSANKPKDELDYENDIE KKICKMEKCSSVFNVVNSRPVTMAQ
VINTNSLSLLTQNNLNKSQSALGTA IERLSSGLRINSAKDDAAGQAIANR
FTANIKGLTQASRNANDGISIAQTT EGALNEINNNLQRVRELAVQSANST
NSQSDLDSIQAEITQRLNEIDRVSG QTQFNGVKVLAQDNTLTIQVGANDG
ETIDIDLKQINSQTLGLDTLNVQQK YKVSDTAATVTGYADTTIALDNSTF
KASATGLGGTDQKIDGDLKFDDTTG KYYAKVTVTGGTGKDGYYEVSVDKT
NGEVTLAGGATSPLTGGLPATATED VKNVQVANADLTEAKAALTAAGVTG
TASVVKMSYTDNNGKTIDGGLAVKV GDDYYSATQNKDGSISINTTKYTAD
DGTSKTALNKLGGADGKTEVVSIGG KTYAASKAEGHNFKAQPDLAEAAAT
TTENPLQKIDAALAQVDTLRSDLGA VQNRFNSAITNLGNTVNNLTSARSR
IEDSDYATEVSNMSRAQILQQAGTS VLAQANQVPQNVLSLLR
TABLE-US-00029 TABLE 25 Influenza mRNA Constructs Influenza mRNA
Sequences Construct SEQ Description ORF ID NO: B/Yamagata/16/
AUGAAGGCAAUAAUUGUACUACUCAUGGUAGUAACAUC 491 1988 mHA
CAACGCAGAUCGAAUCUGCACUGGGAUAACAUCUUCAAA
CUCACCUCAUGUGGUCAAAACAGCUACUCAAGGGGAAGU
UAAUGUGACUGGUGUGAUACCACUGACAACAACACCAAC
AAAAUCUCAUUUUGCAAAUCUCAAAGGAACAAAGACCA
GAGGGAAACUAUGCCCAAACUGUCUCAACUGCACAGAUC
UGGAUGUGGCCUUGGGCAGACCAAUGUGUAUGGGGACC
AUACCUUCGGCAAAAGCUUCAAUACUCCACGAAGUCAGA
CCUGUUACAUCCGGGUGCUUUCCUAUAAUGCACGACAGA
ACAAAAAUCAGACAGCUACCCAAUCUUCUCAGAGGAUAU
GAAAAUAUCAGAUUAUCAACCCAUAACGUUAUCAACGC
AGAAAGGGCACCAGGAGGACCCUACAGACUUGGAACCUC
AGGAUCUUGCCCUAACGUUACCAGUAGAAACGGAUUCU
UCGCAACAAUGGCUUGGGCUGUCCCAAGGGACAACAAAA
CAGCAACGAAUCCACUAACAGUAGAAGUACCAUACAUUU
GCACAAAAGGAGAAGACCAAAUUACUGUUUGGGGGUUC
CAUUCUGAUGACAAAACCCAAAUGAAAAACCUCUAUGG
AGACUCAAAUCCUCAAAAGUUCACCUCAUCUGCCAAUGG
AGUAACCACACAUUAUGUUUCUCAGAUUGGUGACUUCCC
AAAUCAAACAGAAGACGGAGGGCUACCACAAAGCGGCA
GAAUUGUUGUUGAUUACAUGGUGCAAAAACCUGGGAAA
ACAGGAACAAUUGUCUAUCAAAGAGGUGUUUUGUUGCC
UCAAAAGGUGUGGUGCGCAAGUGGCAGGAGCAAGGUAA
UAAAAGGGUCCUUGCCUUUAAUUGGUGAAGCAGAUUGC
CUUCACGAAAAAUACGGUGGAUUAAACAAAAGCAAGCC
UUACUACACAGGAGAACAUGCAAAAGCCAUAGGAAAUU
GCCCAAUAUGGGUGAAAACACCUUUGAAGCUUGCCAAU
GGAACCAAAUAUAGACCUCCUGCAAAACUAUUAAAGGA
AAGGGGUUUCUUCGGAGCUAUUGCUGGUUUCUUAGAGG
GAGGAUGGGAAGGAAUGAUUGCAGGUUGGCACGGAUAC
ACAUCUCAUGGAGCACAUGGAGUGGCAGUGGCAGCAGA
CCUUAAGAGCACGCAAGAAGCCAUAAACAAGAUAACAA
AAAAUCUCAAUUCUUUGAGUGAGCUAGAAGUAAAGAAU
CUUCAAAGACUAAGUGGUGCCAUGGAUGAACUCCACAAC
GAAAUACUCGAGCUGGAUGAGAAAGUGGAUGAUCUCAG
AGCUGACACAAUAAGCUCGCAAAUAGAGCUUGCAGUCU
UGCUUUCCAACGAAGGAAUAAUAAACAGUGAAGAUGAG
CAUCUAUUGGCACUUGAGAGAAAACUAAAGAAAAUGCU
GGGUCCCUCUGCUGUAGACAUAGGGAAUGGAUGCUUCG
AAACCAAACACAAGUGCAACCAGACCUGCUUAGACAGGA
UAGCUGCUGGCACCUUUAAUGCAGGAGAAUUUUCUCUU
CCCACUUUUGAUUCACUGAAUAUUACUGCUGCAUCUUUA
AAUGAUGAUGGAUUGGAUAAUCAUACUAUACUGCUCUA
CUACUCAACUGCUGCUUCUAGUUUGGCCGUAACAUUGAU
GAUAGCUAUUUUUAUUGUUUAUAUGGUCUCCAGAGACA AUGUUUCUUGCUCCAUCUGUCUA
B/Yamagata/16/ AUGAAGGCAAUAAUUGUACUACUCAUGGUAGUAACAUC 492 1988 sHA
CAACGCAGAUCGAAUCUGCACUGGGAUAACAUCUUCAAA
CUCACCUCAUGUGGUCAAAACAGCUACUCAAGGGGAAGU
UAAUGUGACUGGUGUGAUACCACUGACAACAACACCAAC
AAAAUCUCAUUUUGCAAAUCUCAAAGGAACAAAGACCA
GAGGGAAACUAUGCCCAAACUGUCUCAACUGCACAGAUC
UGGAUGUGGCCUUGGGCAGACCAAUGUGUAUGGGGACC
AUACCUUCGGCAAAAGCUUCAAUACUCCACGAAGUCAGA
CCUGUUACAUCCGGGUGCUUUCCUAUAAUGCACGACAGA
ACAAAAAUCAGACAGCUACCCAAUCUUCUCAGAGGAUAU
GAAAAUAUCAGAUUAUCAACCCAUAACGUUAUCAACGC
AGAAAGGGCACCAGGAGGACCCUACAGACUUGGAACCUC
AGGAUCUUGCCCUAACGUUACCAGUAGAAACGGAUUCU
UCGCAACAAUGGCUUGGGCUGUCCCAAGGGACAACAAAA
CAGCAACGAAUCCACUAACAGUAGAAGUACCAUACAUUU
GCACAAAAGGAGAAGACCAAAUUACUGUUUGGGGGUUC
CAUUCUGAUGACAAAACCCAAAUGAAAAACCUCUAUGG
AGACUCAAAUCCUCAAAAGUUCACCUCAUCUGCCAAUGG
AGUAACCACACAUUAUGUUUCUCAGAUUGGUGACUUCCC
AAAUCAAACAGAAGACGGAGGGCUACCACAAAGCGGCA
GAAUUGUUGUUGAUUACAUGGUGCAAAAACCUGGGAAA
ACAGGAACAAUUGUCUAUCAAAGAGGUGUUUUGUUGCC
UCAAAAGGUGUGGUGCGCAAGUGGCAGGAGCAAGGUAA
UAAAAGGGUCCUUGCCUUUAAUUGGUGAAGCAGAUUGC
CUUCACGAAAAAUACGGUGGAUUAAACAAAAGCAAGCC
UUACUACACAGGAGAACAUGCAAAAGCCAUAGGAAAUU
GCCCAAUAUGGGUGAAAACACCUUUGAAGCUUGCCAAU
GGAACCAAAUAUAGACCUCCUGCAAAACUAUUAAAGGA
AAGGGGUUUCUUCGGAGCUAUUGCUGGUUUCUUAGAGG
GAGGAUGGGAAGGAAUGAUUGCAGGUUGGCACGGAUAC
ACAUCUCAUGGAGCACAUGGAGUGGCAGUGGCAGCAGA
CCUUAAGAGCACGCAAGAAGCCAUAAACAAGAUAACAA
AAAAUCUCAAUUCUUUGAGUGAGCUAGAAGUAAAGAAU
CUUCAAAGACUAAGUGGUGCCAUGGAUGAACUCCACAAC
GAAAUACUCGAGCUGGAUGAGAAAGUGGAUGAUCUCAG
AGCUGACACAAUAAGCUCGCAAAUAGAGCUUGCAGUCU
UGCUUUCCAACGAAGGAAUAAUAAACAGUGAAGAUGAG
CAUCUAUUGGCACUUGAGAGAAAACUAAAGAAAAUGCU
GGGUCCCUCUGCUGUAGACAUAGGGAAUGGAUGCUUCG
AAACCAAACACAAGUGCAACCAGACCUGCUUAGACAGGA
UAGCUGCUGGCACCUUUAAUGCAGGAGAAUUUUCUCUU
CCCACUUUUGAUUCACUGAAUAUUACUGCUGCAUCUUUA AAUGAUGAUGGAUUGGAUAAUCAUACU
B/Victoria/02/ AUGAAGGCAAUAAUUGUACUACUCAUGGUAGUAACAUC 493 1987 mHA
CAAUGCAGAUCGAAUCUGCACUGGGAUAACAUCGUCAA
ACUCACCCCAUGUGGUCAAAACUGCUACUCAAGGGGAAG
UCAAUGUGACUGGUGUGAUACCACUGACAACAACACCCA
CCAAAUCUCAUUUUGCAAAUCUCAAAGGAACAAAAACCA
GAGGGAAACUAUGCCCAAAGUGUCUCAACUGCACAGAUC
UGGACGUGGCCUUGGGCAGACCAAAGUGCACGGGGACCA
UACCUUCGGCAAAAGCUUCAAUACUCCACGAAGUCAAAC
CUGUUACAUCUGGGUGCUUUCCUAUAAUGCACGACAGA
ACAAAAAUUAGACAGCUACCCAAUCUUCUCAGAGGAUAC
GAACAUAUCAGGUUAUCAACCCAUAACGUUAUCAACGCA
GAAACGGCACCAGGAGGACCCUACAAAGUUGGAACCUCA
GGGUCUUGCCCUAACGUUACCAAUGGAAACGGAUUCUUC
GCAACAAUGGCUUGGGCUGUCCCAAAAAACGACAACAAC
AAAACAGCAACAAAUCCAUUAACAGUAGAAGUACCAUA
CAUUUGUACAGAAGGAGAAGACCAAAUUACUGUUUGGG
GGUUCCACUCUGAUAACGAAGCCCAAAUGGUAAAACUCU
AUGGAGACUCAAAGCCUCAGAAGUUCACCUCAUCUGCCA
ACGGAGUGACCACACAUUACGUUUCACAGAUUGGUGGC
UUCCCAAAUCAAGCAGAAGACGGAGGGCUACCACAAAGC
GGUAGAAUUGUUGUUGAUUACAUGGUGCAAAAAUCUGG
AAAAACAGGAACAAUUACCUACCAAAGAGGUAUUUUAU
UGCCUCAAAAAGUGUGGUGCGCAAGUGGCAGGAGCAAG
GUAAUAAAAGGGUCCUUGCCUUUAAUUGGCGAAGCAGA
UUGCCUCCACGAAAAAUACGGUGGAUUAAACAAAAGCA
AGCCUUACUACACAGGGGAACAUGCAAAAGCCAUAGGA
AAUUGCCCAAUAUGGGUGAAAACACCCUUGAAGCUGGCC
AAUGGAACCAAAUAUAGACCUCCUGCAAAACUAUUAAA
GGAAAAGGGUUUCUUCGGAGCUAUUGCUGGUUUCUUAG
AAGGAGGAUGGGAAGGAAUGAUUGCAGGUUGGCACGGA
UACACAUCCCAUGGAGCACAUGGAGUAGCAGUGGCAGCA
GACCUUAAGAGUACGCAAGAAGCCAUAAACAAGAUAAC
AAAAAAUCUCAAUUCUUUGAGUGAGCUGGAAGUAAAGA
AUCUUCAAAGACUAAGCGGUGCCAUGGAUGAACUCCACA
ACAAAAUACUCGAACUGGAUGAGAAAGUGGAUGAUCUC
AGAGCUGAUACAAUAAGCUCGCAAAUAGAGCUCGCAGU
CUUGCUUUCCAACGAAGGAAUAAUAAACAGUGAAGAUG
AGCAUCUCUUGGCGCUUGAAAGAAAACUGAAGAAAAUG
CUGGGCCCCUCUGCUGUAGAGAUAGGGAAUGGAUGCUU
CGAAACCAAACACAAGUGCAACCAGACCUGCCUCGACAG
AAUAGCUGCUGGCACCUUUAAUGCAGGAGAAUUUUCUC
UCCCCACCUUUGAUUCACUAAAUAUUACUGCUGCAUCUU
UAAAUGAUGAUGGAUUGGAUAAUCAUACUAUACUGCUU
UACUACUCAACUGCUGCUUCCAGUUUGGCUGUAACAUUG
AUGAUAGCUAUCUUUAUUGUUUAUAUGGUCUCCAGAGA CAAUGUUUCUUGCUCCAUCUGUCUA
B/Victoria/02/ AUGAAGGCAAUAAUUGUACUACUCAUGGUAGUAACAUC 494 1987 sHA
CAAUGCAGAUCGAAUCUGCACUGGGAUAACAUCGUCAA
ACUCACCCCAUGUGGUCAAAACUGCUACUCAAGGGGAAG
UCAAUGUGACUGGUGUGAUACCACUGACAACAACACCCA
CCAAAUCUCAUUUUGCAAAUCUCAAAGGAACAAAAACCA
GAGGGAAACUAUGCCCAAAGUGUCUCAACUGCACAGAUC
UGGACGUGGCCUUGGGCAGACCAAAGUGCACGGGGACCA
UACCUUCGGCAAAAGCUUCAAUACUCCACGAAGUCAAAC
CUGUUACAUCUGGGUGCUUUCCUAUAAUGCACGACAGA
ACAAAAAUUAGACAGCUACCCAAUCUUCUCAGAGGAUAC
GAACAUAUCAGGUUAUCAACCCAUAACGUUAUCAACGCA
GAAACGGCACCAGGAGGACCCUACAAAGUUGGAACCUCA
GGGUCUUGCCCUAACGUUACCAAUGGAAACGGAUUCUUC
GCAACAAUGGCUUGGGCUGUCCCAAAAAACGACAACAAC
AAAACAGCAACAAAUCCAUUAACAGUAGAAGUACCAUA
CAUUUGUACAGAAGGAGAAGACCAAAUUACUGUUUGGG
GGUUCCACUCUGAUAACGAAGCCCAAAUGGUAAAACUCU
AUGGAGACUCAAAGCCUCAGAAGUUCACCUCAUCUGCCA
ACGGAGUGACCACACAUUACGUUUCACAGAUUGGUGGC
UUCCCAAAUCAAGCAGAAGACGGAGGGCUACCACAAAGC
GGUAGAAUUGUUGUUGAUUACAUGGUGCAAAAAUCUGG
AAAAACAGGAACAAUUACCUACCAAAGAGGUAUUUUAU
UGCCUCAAAAAGUGUGGUGCGCAAGUGGCAGGAGCAAG
GUAAUAAAAGGGUCCUUGCCUUUAAUUGGCGAAGCAGA
UUGCCUCCACGAAAAAUACGGUGGAUUAAACAAAAGCA
AGCCUUACUACACAGGGGAACAUGCAAAAGCCAUAGGA
AAUUGCCCAAUAUGGGUGAAAACACCCUUGAAGCUGGCC
AAUGGAACCAAAUAUAGACCUCCUGCAAAACUAUUAAA
GGAAAAGGGUUUCUUCGGAGCUAUUGCUGGUUUCUUAG
AAGGAGGAUGGGAAGGAAUGAUUGCAGGUUGGCACGGA
UACACAUCCCAUGGAGCACAUGGAGUAGCAGUGGCAGCA
GACCUUAAGAGUACGCAAGAAGCCAUAAACAAGAUAAC
AAAAAAUCUCAAUUCUUUGAGUGAGCUGGAAGUAAAGA
AUCUUCAAAGACUAAGCGGUGCCAUGGAUGAACUCCACA
ACAAAAUACUCGAACUGGAUGAGAAAGUGGAUGAUCUC
AGAGCUGAUACAAUAAGCUCGCAAAUAGAGCUCGCAGU
CUUGCUUUCCAACGAAGGAAUAAUAAACAGUGAAGAUG
AGCAUCUCUUGGCGCUUGAAAGAAAACUGAAGAAAAUG
CUGGGCCCCUCUGCUGUAGAGAUAGGGAAUGGAUGCUU
CGAAACCAAACACAAGUGCAACCAGACCUGCCUCGACAG
AAUAGCUGCUGGCACCUUUAAUGCAGGAGAAUUUUCUC
UCCCCACCUUUGAUUCACUAAAUAUUACUGCUGCAUCUU
UAAAUGAUGAUGGAUUGGAUAAUCAUACU B/Brisbane/60/
AUGAAGGCAAUAAUUGUACUACUCAUGGUAGUAACAUC 495 2008 mHA
CAAUGCAGAUCGAAUCUGCACUGGGAUAACAUCGUCAA
ACUCACCACAUGUCGUCAAAACUGCUACUCAAGGGGAGG
UCAAUGUGACUGGUGUAAUACCACUGACAACAACACCCA
CCAAAUCUCAUUUUGCAAAUCUCAAAGGAACAGAAACCA
GGGGGAAACUAUGCCCAAAAUGCCUCAACUGCACAGAUC
UGGACGUAGCCUUGGGCAGACCAAAAUGCACGGGGAAA
AUACCCUCGGCAAGAGUUUCAAUACUCCAUGAAGUCAGA
CCUGUUACAUCUGGGUGCUUUCCUAUAAUGCACGACAGA
ACAAAAAUUAGACAGCUGCCUAACCUUCUCCGAGGAUAC
GAACAUAUCAGGUUAUCAACCCAUAACGUUAUCAAUGC
AGAAAAUGCACCAGGAGGACCCUACAAAAUUGGAACCUC
AGGGUCUUGCCCUAACAUUACCAAUGGAAACGGAUUUU
UCGCAACAAUGGCUUGGGCCGUCCCAAAAAACGACAAAA
ACAAAACAGCAACAAAUCCAUUAACAAUAGAAGUACCA
UACAUUUGUACAGAAGGAGAAGACCAAAUUACCGUUUG
GGGGUUCCACUCUGACGACGAGACCCAAAUGGCAAAGCU
CUAUGGGGACUCAAAGCCCCAGAAGUUCACCUCAUCUGC
CAACGGAGUGACCACACAUUACGUUUCACAGAUUGGUG
GCUUCCCAAAUCAAACAGAAGACGGAGGACUACCACAAA
GUGGUAGAAUUGUUGUUGAUUACAUGGUGCAAAAAUCU
GGGAAAACAGGAACAAUUACCUAUCAAAGGGGUAUUUU
AUUGCCUCAAAAGGUGUGGUGCGCAAGUGGCAGGAGCA
AGGUAAUAAAAGGAUCCUUGCCUUUAAUUGGAGAAGCA
GAUUGCCUCCACGAAAAAUACGGUGGAUUAAACAAAAG
CAAGCCUUACUACACAGGGGAACAUGCAAAGGCCAUAGG
AAAUUGCCCAAUAUGGGUGAAAACACCCUUGAAGCUGG
CCAAUGGAACCAAAUAUAGACCUCCUGCAAAACUAUUAA
AGGAAAGGGGUUUCUUCGGAGCUAUUGCUGGUUUCUUA
GAAGGAGGAUGGGAAGGAAUGAUUGCAGGUUGGCACGG
AUACACAUCCCAUGGGGCACAUGGAGUAGCGGUGGCAGC
AGACCUUAAGAGCACUCAAGAGGCCAUAAACAAGAUAA
CAAAAAAUCUCAACUCUUUGAGUGAGCUGGAAGUAAAG
AAUCUUCAAAGACUAAGCGGUGCCAUGGAUGAACUCCAC
AACGAAAUACUAGAACUAGAUGAGAAAGUGGAUGAUCU
CAGAGCUGAUACAAUAAGCUCACAAAUAGAACUCGCAG
UCCUGCUUUCCAAUGAAGGAAUAAUAAACAGUGAAGAU
GAACAUCUCUUGGCGCUUGAAAGAAAGCUGAAGAAAAU
GCUGGGCCCCUCUGCUGUAGAGAUAGGGAAUGGAUGCU
UUGAAACCAAACACAAGUGCAACCAGACCUGUCUCGACA
GAAUAGCUGCUGGUACCUUUGAUGCAGGAGAAUUUUCU
CUCCCCACCUUUGAUUCACUGAAUAUUACUGCUGCAUCU
UUAAAUGACGAUGGAUUGGAUAAUCAUACUAUACUGCU
UUACUACUCAACUGCUGCCUCCAGUUUGGCUGUAACACU
GAUGAUAGCUAUCUUUGUUGUUUAUAUGGUCUCCAGAG ACAAUGUUUCUUGCUCCAUCUGUCUA
B/Brisbane/60/ AUGAAGGCAAUAAUUGUACUACUCAUGGUAGUAACAUC 496 2008 sHA
CAAUGCAGAUCGAAUCUGCACUGGGAUAACAUCGUCAA
ACUCACCACAUGUCGUCAAAACUGCUACUCAAGGGGAGG
UCAAUGUGACUGGUGUAAUACCACUGACAACAACACCCA
CCAAAUCUCAUUUUGCAAAUCUCAAAGGAACAGAAACCA
GGGGGAAACUAUGCCCAAAAUGCCUCAACUGCACAGAUC
UGGACGUAGCCUUGGGCAGACCAAAAUGCACGGGGAAA
AUACCCUCGGCAAGAGUUUCAAUACUCCAUGAAGUCAGA
CCUGUUACAUCUGGGUGCUUUCCUAUAAUGCACGACAGA
ACAAAAAUUAGACAGCUGCCUAACCUUCUCCGAGGAUAC
GAACAUAUCAGGUUAUCAACCCAUAACGUUAUCAAUGC
AGAAAAUGCACCAGGAGGACCCUACAAAAUUGGAACCUC
AGGGUCUUGCCCUAACAUUACCAAUGGAAACGGAUUUU
UCGCAACAAUGGCUUGGGCCGUCCCAAAAAACGACAAAA
ACAAAACAGCAACAAAUCCAUUAACAAUAGAAGUACCA
UACAUUUGUACAGAAGGAGAAGACCAAAUUACCGUUUG
GGGGUUCCACUCUGACGACGAGACCCAAAUGGCAAAGCU
CUAUGGGGACUCAAAGCCCCAGAAGUUCACCUCAUCUGC
CAACGGAGUGACCACACAUUACGUUUCACAGAUUGGUG
GCUUCCCAAAUCAAACAGAAGACGGAGGACUACCACAAA
GUGGUAGAAUUGUUGUUGAUUACAUGGUGCAAAAAUCU
GGGAAAACAGGAACAAUUACCUAUCAAAGGGGUAUUUU
AUUGCCUCAAAAGGUGUGGUGCGCAAGUGGCAGGAGCA
AGGUAAUAAAAGGAUCCUUGCCUUUAAUUGGAGAAGCA
GAUUGCCUCCACGAAAAAUACGGUGGAUUAAACAAAAG
CAAGCCUUACUACACAGGGGAACAUGCAAAGGCCAUAGG
AAAUUGCCCAAUAUGGGUGAAAACACCCUUGAAGCUGG
CCAAUGGAACCAAAUAUAGACCUCCUGCAAAACUAUUAA
AGGAAAGGGGUUUCUUCGGAGCUAUUGCUGGUUUCUUA
GAAGGAGGAUGGGAAGGAAUGAUUGCAGGUUGGCACGG
AUACACAUCCCAUGGGGCACAUGGAGUAGCGGUGGCAGC
AGACCUUAAGAGCACUCAAGAGGCCAUAAACAAGAUAA
CAAAAAAUCUCAACUCUUUGAGUGAGCUGGAAGUAAAG
AAUCUUCAAAGACUAAGCGGUGCCAUGGAUGAACUCCAC
AACGAAAUACUAGAACUAGAUGAGAAAGUGGAUGAUCU
CAGAGCUGAUACAAUAAGCUCACAAAUAGAACUCGCAG
UCCUGCUUUCCAAUGAAGGAAUAAUAAACAGUGAAGAU
GAACAUCUCUUGGCGCUUGAAAGAAAGCUGAAGAAAAU
GCUGGGCCCCUCUGCUGUAGAGAUAGGGAAUGGAUGCU
UUGAAACCAAACACAAGUGCAACCAGACCUGUCUCGACA
GAAUAGCUGCUGGUACCUUUGAUGCAGGAGAAUUUUCU
CUCCCCACCUUUGAUUCACUGAAUAUUACUGCUGCAUCU
UUAAAUGACGAUGGAUUGGAUAAUCAUACU B/Phuket/3073/
AUGAAGGCAAUAAUUGUACUACUCAUGGUAGUAACAUC 497 2013 mHA
CAAUGCAGAUCGAAUCUGCACUGGGAUAACAUCUUCAA
ACUCACCUCAUGUGGUCAAAACAGCUACUCAAGGGGAGG
UCAAUGUGACUGGCGUGAUACCACUGACAACAACACCAA
CAAAAUCUUAUUUUGCAAAUCUCAAAGGAACAAGGACC
AGAGGGAAACUAUGCCCGGACUGUCUCAACUGUACAGA
UCUGGAUGUGGCCUUGGGCAGGCCAAUGUGUGUGGGGA
CCACACCUUCUGCUAAAGCUUCAAUACUCCACGAGGUCA
GACCUGUUACAUCCGGGUGCUUUCCUAUAAUGCACGACA
GAACAAAAAUCAGGCAACUACCCAAUCUUCUCAGAGGAU
AUGAAAAGAUCAGGUUAUCAACCCAAAACGUUAUCGAU
GCAGAAAAAGCACCAGGAGGACCCUACAGACUUGGAACC
UCAGGAUCUUGCCCUAACGCUACCAGUAAAAUCGGAUUU
UUCGCAACAAUGGCUUGGGCUGUCCCAAAGGACAACUAC
AAAAAUGCAACGAACCCACUAACAGUAGAAGUACCAUAC
AUUUGUACAGAAGGGGAAGACCAAAUUACUGUUUGGGG
GUUCCAUUCAGACAACAAAACCCAAAUGAAGAGCCUCUA
UGGAGACUCAAAUCCUCAAAAGUUCACCUCAUCUGCUAA
UGGAGUAACCACACAUUAUGUUUCUCAGAUUGGCGACU
UCCCAGAUCAAACAGAAGACGGAGGACUACCACAAAGCG
GCAGAAUUGUUGUUGAUUACAUGAUGCAAAAACCUGGG
AAAACAGGAACAAUUGUCUAUCAAAGAGGUGUUUUGUU
GCCUCAAAAGGUGUGGUGCGCGAGUGGCAGGAGCAAAG
UAAUAAAAGGGUCAUUGCCUUUAAUUGGUGAAGCAGAU
UGCCUUCAUGAAAAAUACGGUGGAUUAAACAAAAGCAA
GCCUUACUACACAGGAGAACAUGCAAAAGCCAUAGGAA
AUUGCCCAAUAUGGGUAAAAACACCUUUGAAGCUUGCC
AAUGGAACCAAAUAUAGACCUCCUGCAAAACUAUUGAA
GGAAAGGGGUUUCUUCGGAGCUAUUGCUGGUUUCCUAG
AAGGAGGAUGGGAAGGAAUGAUUGCAGGUUGGCACGGA
UACACAUCUCACGGAGCACAUGGAGUGGCAGUGGCGGCA
GACCUUAAGAGUACACAAGAAGCUAUAAAUAAGAUAAC
AAAAAAUCUCAAUUCUUUGAGUGAGCUAGAAGUAAAGA
ACCUUCAAAGACUAAGUGGUGCCAUGGAUGAACUCCACA
ACGAAAUACUCGAGCUGGAUGAGAAAGUGGAUGAUCUC
AGAGCUGACACUAUAAGCUCACAAAUAGAACUUGCAGU
CUUGCUUUCCAACGAAGGAAUAAUAAACAGUGAAGACG
AGCAUCUAUUGGCACUUGAGAGAAAACUAAAGAAAAUG
CUGGGUCCCUCUGCUGUAGACAUAGGAAACGGAUGCUUC
GAAACCAAACACAAAUGCAACCAGACCUGCUUAGACAGG
AUAGCUGCUGGCACCUUUGAUGCAGGAGAAUUUUCUCU
CCCCACUUUUGAUUCAUUGAACAUUACUGCUGCAUCUUU
AAAUGAUGAUGGAUUGGAUAACCAUACUAUACUGCUCU
AUUACUCAACUGCUGCUUCUAGUUUGGCUGUAACAUUA
AUGCUAGCUAUUUUUAUUGUUUAUAUGGUCUCCAGAGA CAACGUUUCAUGCUCCAUCUGUCUA H1
AGCAAAAGCAGGGGAAAAUAAAAACAACCAAAAUGAAG 498
GCAAACCUACUGGUCCUGUUAUGUGCACUUGCAGCUGCA
GAUGCAGACACAAUAUGUAUAGGCUACCAUGCGAACAA
UUCAACCGACACUGUUGACACAGUGCUCGAGAAGAAUG
UGACAGUGACACACUCUGUUAACCUGCUCGAAGACAGCC
ACAACGGAAAACUAUGUAGAUUAAAAGGAAUAGCCCCA
CUACAAUUGGGGAAAUGUAACAUCGCCGGAUGGCUCUU
GGGAAACCCAGAAUGCGACCCACUGCUUCCAGUGAGAUC
AUGGUCCUACAUUGUAGAAACACCAAACUCUGAGAAUG
GAAUAUGUUAUCCAGGAGAUUUCAUCGACUAUGAGGAG
CUGAGGGAGCAAUUGAGCUCAGUGUCAUCAUUCGAAAG
AUUCGAAAUAUUUCCCAAAGAAAGCUCAUGGCCCAACCA
CAACACAACCAAAGGAGUAACGGCAGCAUGCUCCCAUGC
GGGGAAAAGCAGUUUUUACAGAAAUUUGCUAUGGCUGA
CGGAGAAGGAGGGCUCAUACCCAAAGCUGAAAAAUUCU
UAUGUGAACAAGAAAGGGAAAGAAGUCCUUGUACUGUG
GGGUAUUCAUCACCCGUCUAACAGUAAGGAUCAACAGA
AUAUCUAUCAGAAUGAAAAUGCUUAUGUCUCUGUAGUG
ACUUCAAAUUAUAACAGGAGAUUUACCCCGGAAAUAGC
AGAAAGACCCAAAGUAAGAGAUCAAGCUGGGAGGAUGA
ACUAUUACUGGACCUUGCUAAAACCCGGAGACACAAUAA
UAUUUGAGGCAAAUGGAAAUCUAAUAGCACCAAGGU
AUGCUUUCGCACUGAGUAGAGGCUUUGGGUCCGGCAUC
AUCACCUCAAACGCAUCAAUGCAUGAGUGUAACACGAAG
UGUCAAACACCCCUGGGAGCUAUAAACAGCAGUCUCCCU
UUCCAGAAUAUACACCCAGUCACAAUAGGAGAGUGCCCA
AAAUACGUCAGGAGUGCCAAAUUGAGGAUGGUUACAGG
ACUAAGGAACAUUCCGUCCAUUCAAUCCAGAGGUCUAUU
UGGAGCCAUUGCCGGUUUUAUUGAAGGGGGAUGGACUG
GAAUGAUAGAUGGAUGGUACGGUUAUCAUCAUCAGAAU
GAACAGGGAUCAGGCUAUGCAGCGGAUCAAAAAAGCAC
ACAAAAUGCCAUUAACGGGAUUACAAACAAGGUGAACU
CUGUUAUCGAGAAAAUGAACAUUCAAUUCACAGCUGUG
GGUAAAGAAUUCAACAAAUUAGAAAAAAGGAUGGAAAA
UUUAAAUAAAAAAGUUGAUGAUGGAUUUCUGGACAUUU
GGACAUAUAAUGCAGAAUUGUUAGUUCUACUGGAAAAU
GAAAGGACUCUGGAUUUCCAUGACUCAAAUGUGAAGAA
UCUGUAUGAGAAAGUAAAAAGCCAAUUAAAGAAUAAUG
CCAAAGAAAUCGGAAAUGGAUGUUUUGAGUUCUACCAC
AAGUGUGACAAUGAAUGCAUGGAAAGUGUAAGAAAUGG
GACUUAUGAUUAUCCCAAAUAUUCAGAAGAGUCAAAGU
UGAACAGGGAAAAGGUAGAUGGAGUGAAAUUGGAAUCA
AUGGGGAUCUAUCAGAUUCUGGCGAUCUACUCAACUGU
CGCCAGUUCACUGGUGCUUUUGGUCUCCCUGGGGGCAAU
CAGUUUCUGGAUGUGUUCUAAUGGAUCUUUGCAGUGCA
GAAUAUGCAUCUGAGAUUAGAAUUUCAGAAAUAUGAGG AAAAACACCCUUGUUUCUACU H7
AGCGAAAGCAGGGGAUACAAAAUGAACACUCAAAUCCU 499
GGUAUUCGCUCUGAUUGCGAUCAUUCCAACAAAUGCAG
ACAAAAUCUGCCUCGGACAUCAUGCCGUGUCAAACGGAA
CCAAAGUAAACACAUUAACUGAAAGAGGAGUGGAAGUC
GUCAAUGCAACUGAAACAGUGGAACGAACAAACAUCCCC
AGGAUCUGCUCAAAAGGGAAAAGGACAGUUGACCUCGG
UCAAUGUGGACUCCUGGGGACAAUCACUGGACCACCUCA
AUGUGACCAAUUCCUAGAAUUUUCAGCCGAUUUAAUUA
UUGAGAGGCGAGAAGGAAGUGAUGUCUGUUAUCCUGGG
AAAUUCGUGAAUGAAGAAGCUCUGAGGCAAAUUCUCAG
AGAAUCAGGCGGAAUUGACAAGGAAGCAAUGGGAUUCA
CAUACAGUGGAAUAAGAACUAAUGGAGCAACCAGUGCA
UGUAGGAGAUCAGGAUCUUCAUUCUAUGCAGAAAUGAA
AUGGCUCCUGUCAAACACAGAUGAUGCUGCAUUCCCGCA
GAUGACUAAGUCAUAUAAAAAUACAAGAAAAAGCCCAG
CUCUAAUAGUAUGGGGGAUCCAUCAUUCCGUAUCAACU
GCAGAGCAAACCAAGCUAUAUGGGAGUGGAAACAAACU
GGUGACAGUUGGGAGUUCUAAUUAUCAACAAUCUUUUG
UACCGAGUCCAGGAGCGAGACCACAAGUUAAUGGUCUA
UCUGGAAGAAUUGACUUUCAUUGGCUAAUGCUAAAUCC
CAAUGAUACAGUCACUUUCAGUUUCAAUGGGGCUUUCA
UAGCUCCAGACCGUGCAAGCUUCCUGAGAGGAAAAUCUA
UGGGAAUCCAGAGUGGAGUACAGGUUGAUGCCAAUUGU
GAAGGGGACUGCUAUCAUAGUGGAGGGACAAUAAUAAG
UAACUUGCCAUUUCAGAACAUAGAUAGCAGGGCAGUUG
GAAAAUGUCCGAGAUAUGUUAAGCAAAGGAGUCUGCUG
CUAGCAACAGGGAUGAAGAAUGUUCCUGAGAUUCCAAA
GGGAAGAGGCCUAUUUGGUGCUAUAGCGGGUUUCAUUG
AAAAUGGAUGGGAAGGCCUAAUUGAUGGUUGGUAUGGU
UUCAGACACCAGAAUGCACAGGGAGAGGGAACUGCUGC
AGAUUACAAAAGCACUCAAUCGGCAAUUGAUCAAAUAA
CAGGAAAAUUAAACCGGCUUAUAGAAAAAACCAACCAA
CAAUUUGAGUUGAUAGACAAUGAAUUCAAUGAGGUAGA
GAAGCAAAUCGGUAAUGUGAUAAAUUGGACCAGAGAUU
CUAUAACAGAAGUGUGGUCAUACAAUGCUGAACUCUUG
GUAGCAAUGGAGAACCAGCAUACAAUUGAUCUGGCUGA
UUCAGAAAUGGACAAACUGUACGAACGAGUGAAAAGAC
AGCUGAGAGAGAAUGCUGAAGAAGAUGGCACUGGUUGC
UUUGAAAUAUUUCACAAGUGUGAUGAUGACUGUAUGGC
CAGUAUUAGAAAUAACACCUAUGAUCACAGCAAAUACA
GGGAAGAGGCAAUGCAAAAUAGAAUACAGAUUGACCCA
GUCAAACUAAGCAGCGGCUACAAAGAUGUGAUACUUUG
GUUUAGCUUCGGGGCAUCAUGUUUCAUACUUCUAGCCA
UUGUAAUGGGCCUUGUCUUCAUAUGUGUAAAGAAUGGA
AACAUGCGGUGCACUAUUUGUAUAUAAGUUUGGAAAAA AACACCCUUGUUUCUAC H10
AUGUACAAAAUAGUAGUGAUAAUCGCGCUCCUUGGAGC 500
UGUGAAAGGUCUUGAUAAAAUCUGUCUAGGACAUCAUG
CAGUGGCUAAUGGGACCAUCGUAAAGACUCUCACAAACG
AACAGGAAGAGGUAACCAACGCUACUGAAACAGUGGAG
AGUACAGGCAUAAACAGAUUAUGUAUGAAAGGAAGAAA
ACAUAAAGACCUGGGCAACUGCCAUCCAAUAGGGAUGCU
AAUAGGGACUCCAGCUUGUGAUCUGCACCUUACAGGGA
UGUGGGACACUCUCAUUGAACGAGAGAAUGCUAUUGCU
UACUGCUACCCUGGAGCUACUGUAAAUGUAGAAGCACU
AAGGCAGAAGAUAAUGGAGAGUGGAGGGAUCAACAAGA
UAAGCACUGGCUUCACUUAUGGAUCUUCCAUAAACUCGG
CCGGGACCACUAGAGCGUGCAUGAGGAAUGGAGGGAAU
AGCUUUUAUGCAGAGCUUAAGUGGCUGGUAUCAAAGAG
CAAAGGACAAAACUUCCCUCAGACCACGAACACUUACAG
AAAUACAGACACGGCUGAACACCUCAUAAUGUGGGGAA
UUCAUCACCCUUCUAGCACUCAAGAGAAGAAUGAUCUAU
AUGGAACACAAUCACUGUCCAUAUCAGUCGGGAGUUCCA
CUUACCGGAACAAUUUUGUUCCGGUUGUUGGAGCAAGA
CCUCAGGUCAAUGGACAAAGUGGCAGAAUUGAUUUUCA
CUGGACACUAGUACAGCCAGGUGACAACAUCACCUUCUC
ACACAAUGGGGGCCUGAUAGCACCGAGCCGAGUUAGCAA
AUUAAUUGGGAGGGGAUUGGGAAUCCAAUCAGACGCAC
CAAUAGACAAUAAUUGUGAGUCCAAAUGUUUUUGGAGA
GGGGGUUCUAUAAAUACAAGGCUUCCCUUUCAAAAUUU
GUCACCAAGAACAGUGGGUCAGUGUCCUAAAUAUGUGA
ACAGAAGAAGCUUGAUGCUUGCAACAGGAAUGAGAAAC
GUACCAGAACUAAUACAAGGGAGAGGUCUAUUUGGUGC
AAUAGCAGGGUUUUUAGAGAAUGGGUGGGAAGGAAUGG
UAGAUGGCUGGUAUGGUUUCAGACAUCAAAAUGCUCAG
GGCACAGGCCAGGCCGCUGAUUACAAGAGUACUCAGGCA
GCUAUUGAUCAAAUCACUGGGAAACUGAAUAGACUUGU
UGAAAAAACCAAUACUGAGUUCGAGUCAAUAGAAUCUG
AGUUCAGUGAGAUCGAACACCAAAUCGGUAACGUCAUC
AAUUGGACUAAGGAUUCAAUAACCGACAUUUGGACUUA
UCAGGCUGAGCUGUUGGUGGCAAUGGAGAACCAGCAUA
CAAUCGACAUGGCUGACUCAGAGAUGUUGAAUCUAUAU
GAAAGAGUGAGGAAACAACUAAGGCAGAAUGCAGAAGA
AGAUGGGAAAGGAUGUUUUGAGAUAUAUCAUGCUUGUG
AUGAUUCAUGCAUGGAGAGCAUAAGAAACAACACCUAU
GACCAUUCACAGUACAGAGAGGAAGCUCUUUUGAACAG
AUUGAAUAUCAACCCAGUGACACUCUCUUCUGGAUAUA
AAGACAUCAUUCUCUGGUUUAGCUUCGGGGCAUCAUGU
UUUGUUCUUCUAGCCGUUGUCAUGGGUCUUUUCUUUUU
CUGUCUGAAGAAUGGAAACAUGCGAUGCACAAUCUGUA UUUAG MRK_LZ_NP-
AUGGCCAGCCAGGGCACCAAGAGAAGCUACGAGCAGAUG 501 H3N2
GAGACCGACGGCGAGAGACAGAACGCCACCGAGAUCAGA SQ-031687
GCCAGCGUGGGCAAGAUGAUCGACGGCAUCGGCAGAUUC CX-003145
UACAUCCAGAUGUGCACCGAGCUCAAGCUGAGCGACUAC
GAGGGCAGACUGAUCCAGAACAGCCUGACCAUCGAAAGA
AUGGUUCUGAGCGCCUUCGACGAGAGAAGAAACAGAUA
CCUGGAGGAGCACCCCAGCGCCGGCAAGGACCCCAAGAA
GACCGGCGGCCCCAUCUACAAGAGAGUGGACGGCAGAUG
GAUGAGAGAGCUGGUGCUGUACGACAAGGAGGAGAUCA
GAAGAAUCUGGAGACAGGCCAACAACGGCGACGACGCCA
CCGCCGGCCUGACCCACAUGAUGAUCUGGCACAGCAACC
UGAACGACACCACCUACCAGAGAACCAGAGCCCUGGUGA
GAACCGGCAUGGACCCCAGAAUGUGCAGCUUAAUGCAGG
GCAGCACCCUGCCCAGAAGAUCCGGCGCCGCUGGUGCCG
CCGUCAAGGGCAUCGGCACCAUGGUGAUGGAGCUGAUCC
GCAUGAUCAAGCGCGGCAUCAACGACAGAAACUUCUGGA
GAGGCGAAAACGGCAGAAAGACCAGAAGCGCCUACGAG
AGAAUGUGCAACAUCCUGAAGGGCAAGUUCCAGACCGCC
GCCCAAAGAGCCAUGAUGGACCAGGUGAGAGAGAGCAG
AAACCCCGGCAACGCCGAGAUCGAAGACCUGAUCUUCAG
CGCCAGAUCGGCCCUGAUCCUGAGAGGCAGCGUGGCCCA
CAAGAGCUGCCUGCCCGCCUGCGUGUAUGGCCCCGCCGU
GAGCAGCGGCUACAACUUCGAGAAGGAGGGCUACAGCCU
GGUGGGCAUCGACCCCUUCAAGCUGCUGCAGAACUCUCA
GGUGUAUAGCCUGAUCAGACCCAACGAGAACCCCGCCCA
CAAGAGCCAGCUGGUGUGGAUGGCCUGCCACAGCGCCGC
CUUCGAGGACCUGAGACUGCUGAGCUUCAUCAGAGGUAC
CAAGGUGUCCCCCAGAGGCAAGCUGAGCACCAGAGGUGU
GCAGAUCGCCAGCAAUGAGAACAUGGACAAUAUGGAGA
GCAGCACCCUGGAGCUAAGAAGCAGGUACUGGGCCAUCC
GGACCAGAAGCGGCGGCAAUACCAACCAGCAGAGAGCCA
GCGCCGGCCAGAUCAGCGUGCAGCCCACCUUCAGCGUGC
AGAGAAACCUGCCCUUUGAGAAGAGCACCGUGAUGGCCG
CCUUCACCGGCAACACCGAGGGCAGAACCAGCGACAUGA
GAGCCGAGAUCAUCAGAAUGAUGGAGGGCGCCAAGCCCG
AGGAGGUGAGCUUUAGAGGCAGAGGCGUGUUCGAGCUG
AGCGACGAGAAGGCCACCAACCCAAUUGUGCCCAGCUUC
GACAUGUCGAACGAGGGCAGCUACUUCUUCGGCGACAAC GCCGAGGAGUACGACAAC
MRK_LZ_NIHG AUGGAGACCCCCGCCCAGCUGCUGUUCCUGCUGCUGCUG 502 en6HASS-TM2
UGGCUGCCCGACACCACCGGCGACACCAUCUGCAUCGGC SQ-034074
UACCACGCCAACAACAGCACCGACACCGUGGACACCGUG CX-000553
CUGGAGAAGAACGUGACCGUGACCCACAGCGUGAACCUG
GGCAGCGGCCUGAGGAUGGUGACCGGCCUGAGGAACAUC
CCCCAGAGGGAGACCAGGGGCCUGUUCGGCGCCAUCGCC
GGCUUCAUCGAGGGCGGCUGGACCGGCAUGGUGGACGGC
UGGUACGGCUACCACCACCAGAACGAGCAGGGCAGCGGC
UACGCCGCCGACCAGAAGAGCACCCAGAACGCCAUCAAC
GGCAUCACCAACAUGGUGAACAGCGUGAUCGAGAAGAU
GGGCAGCGGCGGCAGCGGCACCGACCUGGCCGAGCUGCU
GGUGCUGCUGCUGAACGAGAGGACCCUGGACUUCCACGA
CAGCAACGUGAAGAACCUGUACGAGAAGGUGAAGAGCC
AGCUGAAGAACAACGCCAAGGAGAUCGGCAACGGCUGCU
UCGAGUUCUACCACAAGUGCAACAACGAGUGCAUGGAG
AGCGUGAAGAACGGCACCUACGACUACCCCAAGUACAGC
GAGGAGAGCAAGCUGAACAGGGAGAAGAUCGACGGAGU
GAAAUUGGAAUCAAUGGGGGUCUAUCAGAUCCUGGCCA
UCUACAGCACCGUGGCCAGCAGCCUGGUGCUGCUGGUGA
GCCUGGGCGCCAUCAGCUUCUGGAUGUGCAGCAACGGCA GCCUGCAGUGCAGAAUCUGCAUC
MRK_LZ_NIHG AUGGAGACCCCCGCCCAGCUGCUGUUCCUGCUGCUGCUG 503
en6HASS-foldon UGGCUGCCCGACACCACCGGCGACACCAUCUGCAUCGGC SQ-032106
UACCACGCCAACAACAGCACCGACACCGUGGACACCGUG CX-000596
CUGGAGAAGAACGUGACCGUGACCCACAGCGUGAACCUG
GGCAGCGGCCUGAGGAUGGUGACCGGCCUGAGGAACAUC
CCCCAGAGGGAGACCAGGGGCCUGUUCGGCGCCAUCGCC
GGCUUCAUCGAGGGCGGCUGGACCGGCAUGGUGGACGGC
UGGUACGGCUACCACCACCAGAACGAGCAGGGCAGCGGC
UACGCCGCCGACCAGAAGAGCACCCAGAACGCCAUCAAC
GGCAUCACCAACAUGGUGAACAGCGUGAUCGAGAAGAU
GGGCAGCGGCGGCAGCGGCACCGACCUGGCCGAGCUGCU
GGUGCUGCUGCUGAACGAGAGGACCCUGGACUUCCACGA
CAGCAACGUGAAGAACCUGUACGAGAAGGUGAAGAGCC
AGCUGAAGAACAACGCCAAGGAGAUCGGCAACGGCUGCU
UCGAGUUCUACCACAAGUGCAACAACGAGUGCAUGGAG
AGCGUGAAGAACGGCACCUACGACUACCCCAAGUACAGC
GAGGAGAGCAAGCUGAACAGGGAGAAGAUCGACCCCGG
CAGCGGCUACAUCCCCGAGGCCCCCAGGGACGGCCAGGC
CUACGUGAGGAAGGACGGCGAGUGGGUGCUGCUGAGCA CCUUCCUG
[0963] It should be understood that each of the ORF sequences
provided herein may be combined with a 5' and/or 3' UTR, such as
those described herein.
TABLE-US-00030 TABLE 26 Additional Influenza mRNA Vaccine
Constructs Name of SEQ antigen Open Reading Frame (ORF) Sequences
ID NO MRK_pH1_ DNA ATGAAGGTGAAGCTGCTGGTGCTGCTGTGCACCTTCACCGCC 505
Con_RBD ACCTACGCCGGCGTGGCCCCTCTGCACCTGGGCAAGTGCAAC
ATCGCCGGCTGGATCCTGGGCAACCCTGAGTGCGAGAGCCTT
AGCACAGCCTCCTCCTGGAGCTACATCGTGGAGACGAGCAGC
AGCGATAACGGGACCTGCTACCCTGGCGACTTCATCGACTAC
GAGGAGCTGAGAGAGCAGCTGAGCAGCGTGAGCAGCTTCGA
GAGATTCGAGATCTTCCCTAAGACCAGCAGCTGGCCTAACCA
CGACAGCAACAAGGGCGTGACCGCCGCCTGCCCACACGCCG
GGGCCAAGAGCTTCTACAAGAACCTGATCTGGCTGGTGAAGA
AGGGCAACAGCTACCCTAAACTGAGCAAGTCCTACATCAACG
ACAAAGGCAAGGAGGTCCTCGTGCTCTGGGGCATCCACCACC
CTAGCACCAGCGCCGATCAGCAGAGCCTGTACCAGAACGCCG
ACGCGTACGTGTTCGTGGGCACCAGCAGATACAGCAAGAAGT
TCAAGCCTGAGATCGCCATCAGACCTAAGGTGAGGGACCAGG
AGGGCAGAATGAACTACTACTGGACCCTGGTGGAGCCCGGA
GATAAGATCACATTTGAGGCCACCGGCAACCTGGTGGTGCCT
AGATACGCCTTCGCCATGGAGAGAAACGCC mRNA
AUGAAGGUGAAGCUGCUGGUGCUGCUGUGCACCUUCACCGC 524
CACCUACGCCGGCGUGGCCCCUCUGCACCUGGGCAAGUGCA
ACAUCGCCGGCUGGAUCCUGGGCAACCCUGAGUGCGAGAGC
CUUAGCACAGCCUCCUCCUGGAGCUACAUCGUGGAGACGAG
CAGCAGCGAUAACGGGACCUGCUACCCUGGCGACUUCAUCG
ACUACGAGGAGCUGAGAGAGCAGCUGAGCAGCGUGAGCAG
CUUCGAGAGAUUCGAGAUCUUCCCUAAGACCAGCAGCUGGC
CUAACCACGACAGCAACAAGGGCGUGACCGCCGCCUGCCCA
CACGCCGGGGCCAAGAGCUUCUACAAGAACCUGAUCUGGCU
GGUGAAGAAGGGCAACAGCUACCCUAAACUGAGCAAGUCCU
ACAUCAACGACAAAGGCAAGGAGGUCCUCGUGCUCUGGGGC
AUCCACCACCCUAGCACCAGCGCCGAUCAGCAGAGCCUGUA
CCAGAACGCCGACGCGUACGUGUUCGUGGGCACCAGCAGAU
ACAGCAAGAAGUUCAAGCCUGAGAUCGCCAUCAGACCUAAG
GUGAGGGACCAGGAGGGCAGAAUGAACUACUACUGGACCC
UGGUGGAGCCCGGAGAUAAGAUCACAUUUGAGGCCACCGGC
AACCUGGUGGUGCCUAGAUACGCCUUCGCCAUGGAGAGAAA CGCC Protein
MKVKLLVLLCTFTATYAGVAPLHLGKCNIAGWILGNPECESLST 543
ASSWSYIVETSSSDNGTCYPGDFIDYEELREQLSSVSSFERFEIFPK
TSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPKLS
KSYINDKGKEVLVLWGIHHPSTSADQQSLYQNADAYVFVGTSR
YSKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGNLV VPRYAFAMERNA MRK_pH1_
DNA ATGAAGGCCATCCTCGTGGTGCTGCTGTACACCTTTGCCACCG 506 Con_ecto
CCAACGCCGATACCCTGTGTATCGGCTACCACGCCAACAACA
GCACCGACACCGTGGATACTGTCCTGGAGAAGAACGTGACCG
TGACCCACAGCGTGAACCTGCTGGAGGACAAGCACAACGGC
AAGCTGTGCAAGCTGAGAGGCGTGGCCCCTCTGCACCTGGGC
AAGTGCAACATCGCCGGCTGGATCCTGGGCAACCCTGAGTGC
GAGAGCCTTAGCACAGCCTCCTCCTGGAGCTACATCGTGGAG
ACGAGCAGCAGCGATAACGGGACCTGCTACCCTGGCGACTTC
ATCGACTACGAGGAGCTGAGAGAGCAGCTGAGCAGCGTGAG
CAGCTTCGAGAGATTCGAGATCTTCCCTAAGACCAGCAGCTG
GCCTAACCACGACAGCAACAAGGGCGTGACCGCCGCCTGCCC
ACACGCCGGGGCCAAGAGCTTCTACAAGAACCTGATCTGGCT
GGTGAAGAAGGGCAACAGCTACCCTAAACTGAGCAAGTCCT
ACATCAACGACAAAGGCAAGGAGGTCCTCGTGCTCTGGGGCA
TCCACCACCCTAGCACCAGCGCCGATCAGCAGAGCCTGTACC
AGAACGCCGACGCGTACGTGTTCGTGGGCACCAGCAGATACA
GCAAGAAGTTCAAGCCTGAGATCGCCATCAGACCTAAGGTGA
GGGACCAGGAGGGCAGAATGAACTACTACTGGACCCTGGTG
GAGCCCGGAGATAAGATCACATTTGAGGCCACCGGCAACCTG
GTGGTGCCTAGATACGCCTTCGCCATGGAGAGAAACGCCGGC
AGCGGCATCATCATCAGCGACACCCCTGTGCACGACTGCAAC
ACCACCTGCCAGACCCCTAAGGGCGCCATCAACACGAGCCTG
CCTTTCCAGAACATCCACCCTATCACCATCGGCAAGTGCCCTA
AGTACGTGAAGTCAACCAAACTGAGACTCGCCACCGGCCTCA
GAAACGTGCCTAGCATCCAGAGCAGAGGCCTCTTCGGCGCCA
TCGCGGGATTCATCGAGGGCGGCTGGACCGGCATGGTGGACG
GCTGGTACGGCTACCACCATCAGAACGAGCAGGGCAGCGGG
TACGCGGCCGACCTCAAGAGCACCCAGAACGCCATCGACAA
GATCACCAACAAGGTGAACAGCGTGATCGAGAAGATGAACA
CCCAGTTCACCGCCGTGGGCAAGGAGTTCAACCACCTGGAGA
AGAGAATCGAGAACCTGAACAAGAAGGTGGACGACGGCTTC
CTGGACATCTGGACCTACAACGCAGAACTGCTCGTGCTTCTG
GAGAACGAGAGAACCCTGGACTACCACGACTCCAACGTGAA
GAACCTGTACGAGAAGGTGAGAAGCCAGCTGAAGAACAACG
CCAAGGAGATCGGCAACGGCTGCTTCGAGTTCTACCACAAGT
GCGACAACACCTGCATGGAGAGCGTGAAGAACGGCACCTAC
GACTACCCTAAGTACAGCGAGGAGGCCAAGCTGAACAGAGA
GGAGATCGACGGCGTGAAGCTGGAGAGCACCAGAATCGGCT
CAGCCGGGAGCGCCGGCTACATCCCTGAGGCCCCTAGAGACG
GCCAGGCCTACGTGAGAAAGGACGGCGAGTGGGTGCTGCTG AGCACCTTCCTG mRNA
AUGAAGGCCAUCCUCGUGGUGCUGCUGUACACCUUUGCCAC 525
CGCCAACGCCGAUACCCUGUGUAUCGGCUACCACGCCAACA
ACAGCACCGACACCGUGGAUACUGUCCUGGAGAAGAACGUG
ACCGUGACCCACAGCGUGAACCUGCUGGAGGACAAGCACAA
CGGCAAGCUGUGCAAGCUGAGAGGCGUGGCCCCUCUGCACC
UGGGCAAGUGCAACAUCGCCGGCUGGAUCCUGGGCAACCCU
GAGUGCGAGAGCCUUAGCACAGCCUCCUCCUGGAGCUACAU
CGUGGAGACGAGCAGCAGCGAUAACGGGACCUGCUACCCUG
GCGACUUCAUCGACUACGAGGAGCUGAGAGAGCAGCUGAGC
AGCGUGAGCAGCUUCGAGAGAUUCGAGAUCUUCCCUAAGAC
CAGCAGCUGGCCUAACCACGACAGCAACAAGGGCGUGACCG
CCGCCUGCCCACACGCCGGGGCCAAGAGCUUCUACAAGAAC
CUGAUCUGGCUGGUGAAGAAGGGCAACAGCUACCCUAAACU
GAGCAAGUCCUACAUCAACGACAAAGGCAAGGAGGUCCUCG
UGCUCUGGGGCAUCCACCACCCUAGCACCAGCGCCGAUCAG
CAGAGCCUGUACCAGAACGCCGACGCGUACGUGUUCGUGGG
CACCAGCAGAUACAGCAAGAAGUUCAAGCCUGAGAUCGCCA
UCAGACCUAAGGUGAGGGACCAGGAGGGCAGAAUGAACUA
CUACUGGACCCUGGUGGAGCCCGGAGAUAAGAUCACAUUUG
AGGCCACCGGCAACCUGGUGGUGCCUAGAUACGCCUUCGCC
AUGGAGAGAAACGCCGGCAGCGGCAUCAUCAUCAGCGACAC
CCCUGUGCACGACUGCAACACCACCUGCCAGACCCCUAAGG
GCGCCAUCAACACGAGCCUGCCUUUCCAGAACAUCCACCCU
AUCACCAUCGGCAAGUGCCCUAAGUACGUGAAGUCAACCAA
ACUGAGACUCGCCACCGGCCUCAGAAACGUGCCUAGCAUCC
AGAGCAGAGGCCUCUUCGGCGCCAUCGCGGGAUUCAUCGAG
GGCGGCUGGACCGGCAUGGUGGACGGCUGGUACGGCUACCA
CCAUCAGAACGAGCAGGGCAGCGGGUACGCGGCCGACCUCA
AGAGCACCCAGAACGCCAUCGACAAGAUCACCAACAAGGUG
AACAGCGUGAUCGAGAAGAUGAACACCCAGUUCACCGCCGU
GGGCAAGGAGUUCAACCACCUGGAGAAGAGAAUCGAGAAC
CUGAACAAGAAGGUGGACGACGGCUUCCUGGACAUCUGGAC
CUACAACGCAGAACUGCUCGUGCUUCUGGAGAACGAGAGAA
CCCUGGACUACCACGACUCCAACGUGAAGAACCUGUACGAG
AAGGUGAGAAGCCAGCUGAAGAACAACGCCAAGGAGAUCG
GCAACGGCUGCUUCGAGUUCUACCACAAGUGCGACAACACC
UGCAUGGAGAGCGUGAAGAACGGCACCUACGACUACCCUAA
GUACAGCGAGGAGGCCAAGCUGAACAGAGAGGAGAUCGAC
GGCGUGAAGCUGGAGAGCACCAGAAUCGGCUCAGCCGGGAG
CGCCGGCUACAUCCCUGAGGCCCCUAGAGACGGCCAGGCCU
ACGUGAGAAAGGACGGCGAGUGGGUGCUGCUGAGCACCUU CCUG Protein
MKAILVVLLYTFATANADTLCIGYHANNSTDTVDTVLEKNVTV 544
THSVNLLEDKHNGKLCKLRGVAPLHLGKCNIAGWILGNPECESL
STASSWSYIVETSSSDNGTCYPGDFIDYEELREQLSSVSSFERFEIF
PKTSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPK
LSKSYINDKGKEVLVLWGIHHPSTSADQQSLYQNADAYVFVGT
SRYSKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGN
LVVPRYAFAMERNAGSGIIISDTPVHDCNTTCQTPKGAINTSLPF
QNIHPITIGKCPKYVKSTKLRLATGLRNVPSIQSRGLFGAIAGFIE
GGWTGMVDGWYGYHHQNEQGSGYAADLKSTQNAIDKITNKV
NSVIEKMNTQFTAVGKEFNHLEKRIENLNKKVDDGFLDIWTYN
AELLVLLENERTLDYHDSNVKNLYEKVRSQLKNNAKEIGNGCF
EFYHKCDNTCMESVKNGTYDYPKYSEEAKLNREEIDGVKLEST
RIGSAGSAGYIPEAPRDGQAYVRKDGEWVLLSTFL MRK_sH1_ DNA
ATGAAGGTGAAGCTGCTGGTGCTGCTGTGCACCTTCACCGCC 507 Con_RBD
ACCTACGCCGGAATCGCTCCCCTGCAGCTCGGCAACTGCAGC
GTGGCCGGCTGGATTCTGGGCAACCCCGAGTGCGAACTGCTG
ATTAGCAAAGAGTCCTGGAGCTACATCGTGGAAACCCCGAAT
CCCGAGAACGGCACCTGCTACCCCGGCTACTTCGCCGACTAC
GAGGAGCTAAGAGAGCAGCTGAGTAGCGTGAGCTCATTCGA
GAGATTCGAGATCTTTCCCAAGGAGTCTAGCTGGCCCAATCA
CACCGTCACCGGCGTGTCCGCCAGCTGTAGCCACAACGGCAA
GAGCAGCTTCTACAGAAACCTGCTGTGGCTGACCGGCAAGAA
CGGACTGTACCCTAACCTGAGCAAGAGCTACGCGAACAATAA
GGAGAAGGAGGTGCTAGTGCTGTGGGGCGTGCACCATCCGCC
CAACATCGGCGACCAGAGAGCCCTGTACCACACCGAGAACG
CCTACGTGAGCGTGGTGAGCAGCCACTATAGCAGAAGATTCA
CCCCTGAGATCGCCAAGAGGCCAAAGGTGAGAGATCAGGAA
GGAAGAATAAACTACTACTGGACCCTCCTGGAGCCCGGCGAC
ACCATCATCTTCGAGGCTAACGGCAACCTGATCGCCCCTAGA TACGCCTTCGCCCTGAGCAGAGGC
mRNA AUGAAGGUGAAGCUGCUGGUGCUGCUGUGCACCUUCACCGC 526
CACCUACGCCGGAAUCGCUCCCCUGCAGCUCGGCAACUGCA
GCGUGGCCGGCUGGAUUCUGGGCAACCCCGAGUGCGAACUG
CUGAUUAGCAAAGAGUCCUGGAGCUACAUCGUGGAAACCCC
GAAUCCCGAGAACGGCACCUGCUACCCCGGCUACUUCGCCG
ACUACGAGGAGCUAAGAGAGCAGCUGAGUAGCGUGAGCUC
AUUCGAGAGAUUCGAGAUCUUUCCCAAGGAGUCUAGCUGG
CCCAAUCACACCGUCACCGGCGUGUCCGCCAGCUGUAGCCA
CAACGGCAAGAGCAGCUUCUACAGAAACCUGCUGUGGCUGA
CCGGCAAGAACGGACUGUACCCUAACCUGAGCAAGAGCUAC
GCGAACAAUAAGGAGAAGGAGGUGCUAGUGCUGUGGGGCG
UGCACCAUCCGCCCAACAUCGGCGACCAGAGAGCCCUGUAC
CACACCGAGAACGCCUACGUGAGCGUGGUGAGCAGCCACUA
UAGCAGAAGAUUCACCCCUGAGAUCGCCAAGAGGCCAAAGG
UGAGAGAUCAGGAAGGAAGAAUAAACUACUACUGGACCCU
CCUGGAGCCCGGCGACACCAUCAUCUUCGAGGCUAACGGCA
ACCUGAUCGCCCCUAGAUACGCCUUCGCCCUGAGCAGAGGC Protein
MKVKLLVLLCTFTATYAGIAPLQLGNCSVAGWILGNPECELLIS 545
KESWSYIVETPNPENGTCYPGYFADYEELREQLSSVSSFERFEIFP
KESSWPNHTVTGVSASCSHNGKSSFYRNLLWLTGKNGLYPNLS
KSYANNKEKEVLVLWGVHHPPNIGDQRALYHTENAYVSVVSSH
YSRRFTPEIAKRPKVRDQEGRINYYWTLLEPGDTIIFEANGNLIAP RYAFALSRG MRK_sH1_
DNA ATGAAGGTGAAGCTGCTGGTGCTGCTGTGTACCTTCACTGCC 508 Con_ecto
ACTTACGCCGACACCATTTGCATCGGCTACCACGCCAACAAC
AGCACCGATACCGTGGACACCGTGCTGGAGAAGAACGTCACC
GTGACCCACAGCGTGAACCTGCTGGAGGATAGCCATAACGGC
AAGCTGTGCCTGCTGAAGGGAATCGCTCCCCTGCAGCTCGGC
AACTGCAGCGTGGCCGGCTGGATTCTGGGCAACCCCGAGTGC
GAACTGCTGATTAGCAAAGAGTCCTGGAGCTACATCGTGGAA
ACCCCGAATCCCGAGAACGGCACCTGCTACCCCGGCTACTTC
GCCGACTACGAGGAGCTAAGAGAGCAGCTGAGTAGCGTGAG
CTCATTCGAGAGATTCGAGATCTTTCCCAAGGAGTCTAGCTG
GCCCAATCACACCGTCACCGGCGTGTCCGCCAGCTGTAGCCA
CAACGGCAAGAGCAGCTTCTACAGAAACCTGCTGTGGCTGAC
CGGCAAGAACGGACTGTACCCTAACCTGAGCAAGAGCTACGC
GAACAATAAGGAGAAGGAGGTGCTAGTGCTGTGGGGCGTGC
ACCATCCGCCCAACATCGGCGACCAGAGAGCCCTGTACCACA
CCGAGAACGCCTACGTGAGCGTGGTGAGCAGCCACTATAGCA
GAAGATTCACCCCTGAGATCGCCAAGAGGCCAAAGGTGAGA
GATCAGGAAGGAAGAATAAACTACTACTGGACCCTCCTGGAG
CCCGGCGACACCATCATCTTCGAGGCTAACGGCAACCTGATC
GCCCCTAGATACGCCTTCGCCCTGAGCAGAGGCTTCGGCAGC
GGCATCATCACCAGCAACGCTCCCATGGACGAGTGCGACGCC
AAGTGCCAGACCCCGCAGGGCGCCATCAACTCGAGCCTGCCC
TTCCAGAACGTGCACCCCGTGACCATCGGCGAGTGCCCCAAG
TACGTGAGAAGCGCCAAGCTGAGAATGGTGACCGGCCTGAG
AAACATCCCAAGCATCCAGAGCAGAGGGCTGTTCGGCGCCAT
CGCTGGCTTCATCGAGGGCGGCTGGACCGGCATGGTGGACGG
CTGGTACGGTTATCACCACCAGAACGAGCAGGGCAGCGGCTA
CGCCGCCGACCAGAAGTCCACCCAGAACGCCATCAACGGCAT
TACAAACAAGGTGAACAGCGTTATCGAGAAGATGAACACCC
AATTCACCGCCGTGGGCAAGGAGTTCAACAAGCTGGAGAGA
AGAATGGAGAACCTGAACAAGAAGGTGGACGACGGCTTCCT
GGACATCTGGACCTACAACGCCGAACTGCTGGTCCTGCTGGA
GAACGAGAGAACCCTGGACTTCCACGACTCCAACGTGAAGA
ACTTATACGAGAAGGTCAAATCCCAGCTGAAGAACAACGCCA
AAGAAATCGGAAACGGCTGCTTCGAATTCTACCACAAGTGCA
ACGACGAGTGCATGGAGAGCGTGAAGAACGGAACCTACGAC
TACCCCAAGTACAGCGAGGAAAGCAAACTGAACAGAGAGAA
GATCGACGGCGTGAAGTTAGAGAGCATGGGCGTGGGCAGCG
CCGGCTCTGCTGGATACATCCCTGAGGCCCCTAGAGACGGCC
AGGCCTACGTGAGAAAGGACGGCGAGTGGGTGCTGCTGAGC ACCTTCCTG mRNA
AUGAAGGUGAAGCUGCUGGUGCUGCUGUGUACCUUCACUG 527
CCACUUACGCCGACACCAUUUGCAUCGGCUACCACGCCAAC
AACAGCACCGAUACCGUGGACACCGUGCUGGAGAAGAACGU
CACCGUGACCCACAGCGUGAACCUGCUGGAGGAUAGCCAUA
ACGGCAAGCUGUGCCUGCUGAAGGGAAUCGCUCCCCUGCAG
CUCGGCAACUGCAGCGUGGCCGGCUGGAUUCUGGGCAACCC
CGAGUGCGAACUGCUGAUUAGCAAAGAGUCCUGGAGCUAC
AUCGUGGAAACCCCGAAUCCCGAGAACGGCACCUGCUACCC
CGGCUACUUCGCCGACUACGAGGAGCUAAGAGAGCAGCUGA
GUAGCGUGAGCUCAUUCGAGAGAUUCGAGAUCUUUCCCAA
GGAGUCUAGCUGGCCCAAUCACACCGUCACCGGCGUGUCCG
CCAGCUGUAGCCACAACGGCAAGAGCAGCUUCUACAGAAAC
CUGCUGUGGCUGACCGGCAAGAACGGACUGUACCCUAACCU
GAGCAAGAGCUACGCGAACAAUAAGGAGAAGGAGGUGCUA
GUGCUGUGGGGCGUGCACCAUCCGCCCAACAUCGGCGACCA
GAGAGCCCUGUACCACACCGAGAACGCCUACGUGAGCGUGG
UGAGCAGCCACUAUAGCAGAAGAUUCACCCCUGAGAUCGCC
AAGAGGCCAAAGGUGAGAGAUCAGGAAGGAAGAAUAAACU
ACUACUGGACCCUCCUGGAGCCCGGCGACACCAUCAUCUUC
GAGGCUAACGGCAACCUGAUCGCCCCUAGAUACGCCUUCGC
CCUGAGCAGAGGCUUCGGCAGCGGCAUCAUCACCAGCAACG
CUCCCAUGGACGAGUGCGACGCCAAGUGCCAGACCCCGCAG
GGCGCCAUCAACUCGAGCCUGCCCUUCCAGAACGUGCACCC
CGUGACCAUCGGCGAGUGCCCCAAGUACGUGAGAAGCGCCA
AGCUGAGAAUGGUGACCGGCCUGAGAAACAUCCCAAGCAUC
CAGAGCAGAGGGCUGUUCGGCGCCAUCGCUGGCUUCAUCGA
GGGCGGCUGGACCGGCAUGGUGGACGGCUGGUACGGUUAU
CACCACCAGAACGAGCAGGGCAGCGGCUACGCCGCCGACCA
GAAGUCCACCCAGAACGCCAUCAACGGCAUUACAAACAAGG
UGAACAGCGUUAUCGAGAAGAUGAACACCCAAUUCACCGCC
GUGGGCAAGGAGUUCAACAAGCUGGAGAGAAGAAUGGAGA
ACCUGAACAAGAAGGUGGACGACGGCUUCCUGGACAUCUGG
ACCUACAACGCCGAACUGCUGGUCCUGCUGGAGAACGAGAG
AACCCUGGACUUCCACGACUCCAACGUGAAGAACUUAUACG
AGAAGGUCAAAUCCCAGCUGAAGAACAACGCCAAAGAAAUC
GGAAACGGCUGCUUCGAAUUCUACCACAAGUGCAACGACGA
GUGCAUGGAGAGCGUGAAGAACGGAACCUACGACUACCCCA
AGUACAGCGAGGAAAGCAAACUGAACAGAGAGAAGAUCGA
CGGCGUGAAGUUAGAGAGCAUGGGCGUGGGCAGCGCCGGC
UCUGCUGGAUACAUCCCUGAGGCCCCUAGAGACGGCCAGGC
CUACGUGAGAAAGGACGGCGAGUGGGUGCUGCUGAGCACC UUCCUG Protein
MKVKLLVLLCTFTATYADTICIGYHANNSTDTVDTVLEKNVTVT 546
HSVNLLEDSHNGKLCLLKGIAPLQLGNCSVAGWILGNPECELLIS
KESWSYIVETPNPENGTCYPGYFADYEELREQLSSVSSFERFEIFP
KESSWPNHTVTGVSASCSHNGKSSFYRNLLWLTGKNGLYPNLS
KSYANNKEKEVLVLWGVHHPPNIGDQRALYHTENAYVSVVSSH
YSRRFTPEIAKRPKVRDQEGRINYYWTLLEPGDTIIFEANGNLIAP
RYAFALSRGFGSGIITSNAPMDECDAKCQTPQGAINSSLPFQNVH
PVTIGECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGFIEGGW
TGMVDGWYGYHHQNEQGSGYAADQKSTQNAINGITNKVNSVI
EKMNTQFTAVGKEFNKLERRMENLNKKVDDGFLDIWTYNAEL
LVLLENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGCFEFY
HKCNDECMESVKNGTYDYPKYSEESKLNREKIDGVKLESMGVG
SAGSAGYIPEAPRDGQAYVRKDGEWVLLSTFL MRK_sH1_ DNA
ATGAAGGTGAAACTCCTCGTCCTGCTGTGCACCTTCACCGCC 509 Con_v2
ACCTACGCCGATACCATCTGTATTGGCTACCACGCCAACAAC
TCCACCGACACCGTGGATACCGTGCTCGAGAAGAACGTGACC
GTGACCCACAGCGTGAACCTGCTGGAGAACAGCCACAACGG
CAAGCTGTGCCTGCTGAAGGGCATCGCGCCCCTGCAGTTGGG
TAACTGCTCCGTGGCCGGCTGGATCCTGGGCAACCCTGAGTG
CGAGCTGCTGATCAGCAAGGAGAGCTGGAGCTACATCGTGGA
GAAGCCTAACCCCGAGAACGGCACCTGCTACCCTGGCCACTT
CGCCGACTACGAGGAGCTGAGAGAGCAACTCAGCAGCGTGA
GCAGCTTCGAGAGATTCGAGATCTTCCCTAAGGAGAGCAGCT
GGCCCAATCACACTGTGACCGGCGTGTCCGCTTCTTGCAGCC
ATAACGGGGAAAGCTCCTTCTACAGAAATCTCCTTTGGCTGA
CGGGGAAGAACGGCCTGTACCCTAACCTGAGCAAGAGCTAC
GCCAACAACAAGGAGAAGGAGGTGCTGGTGCTGTGGGGCGT
GCACCACCCTCCTAACATCGGCGACCAGAAGGCCCTGTACCA
CACCGAGAACGCCTACGTCAGCGTGGTGTCCAGCCACTACAG
CAGAAAGTTCACCCCTGAGATCGCCAAGAGGCCTAAGGTGCG
GGACCAGGAGGGCAGAATCAACTACTACTGGACCCTGCTGGA
GCCTGGCGACACCATCATCTTCGAGGCCAACGGCAACCTGAT
CGCCCCTAGATACGCCTTCGCCCTGAGCAGAGGCTTCGGCAG
CGGCATCATCAACAGCAACGCCCCTATGGACAAGTGCGACGC
CAAGTGCCAGACTCCGCAGGGCGCTATCAACAGCTCCCTGCC
TTTCCAGAACGTGCACCCTGTGACCATCGGCGAGTGCCCTAA
GTACGTGAGAAGCGCCAAGCTGAGAATGGTGACCGGCCTGA
GAAACATCCCTAGCATCCAGAGCAGAGGCCTGTTCGGCGCCA
TCGCCGGGTTTATCGAGGGCGGCTGGACCGGCATGGTGGACG
GCTGGTACGGCTACCACCACCAGAACGAGCAGGGCTCCGGCT
ACGCCGCCGACCAGAAATCCACCCAGAACGCCATCAACGGC
ATCACCAACAAGGTGAACAGCGTCATCGAGAAGATGAACAC
CCAGTTCACCGCCGTGGGCAAGGAGTTCAACAAGCTGGAGAG
AAGAATGGAGAACCTGAACAAGAAGGTGGACGACGGCTTCA
TCGACATCTGGACCTACAACGCCGAGCTTCTGGTGCTCCTGG
AGAACGAGAGAACCCTGGACTTCCACGACAGCAACGTGAAG
AACCTGTACGAGAAGGTGAAGTCCCAGCTGAAGAACAACGC
CAAGGAGATCGGCAACGGCTGCTTCGAGTTCTACCACAAGTG
CAACGACGAGTGCATGGAGAGCGTGAAGAACGGCACCTACG
ATTACCCCAAGTACAGCGAGGAGAGCAAGCTGAACAGAGAG
AAGATCGACGGCGTGAAGCTGGAGAGCATGGGCGTGTACCA
GATCCTGGCCATCTACTCCACCGTGGCCAGTAGCCTGGTGCT
GCTGGTGAGCCTGGGCGCAATCAGCTTCTGGATGTGCAGCAA
CGGCAGCCTGCAGTGCAGAATCTGCATC mRNA
AUGAAGGUGAAACUCCUCGUCCUGCUGUGCACCUUCACCGC 528
CACCUACGCCGAUACCAUCUGUAUUGGCUACCACGCCAACA
ACUCCACCGACACCGUGGAUACCGUGCUCGAGAAGAACGUG
ACCGUGACCCACAGCGUGAACCUGCUGGAGAACAGCCACAA
CGGCAAGCUGUGCCUGCUGAAGGGCAUCGCGCCCCUGCAGU
UGGGUAACUGCUCCGUGGCCGGCUGGAUCCUGGGCAACCCU
GAGUGCGAGCUGCUGAUCAGCAAGGAGAGCUGGAGCUACA
UCGUGGAGAAGCCUAACCCCGAGAACGGCACCUGCUACCCU
GGCCACUUCGCCGACUACGAGGAGCUGAGAGAGCAACUCAG
CAGCGUGAGCAGCUUCGAGAGAUUCGAGAUCUUCCCUAAGG
AGAGCAGCUGGCCCAAUCACACUGUGACCGGCGUGUCCGCU
UCUUGCAGCCAUAACGGGGAAAGCUCCUUCUACAGAAAUCU
CCUUUGGCUGACGGGGAAGAACGGCCUGUACCCUAACCUGA
GCAAGAGCUACGCCAACAACAAGGAGAAGGAGGUGCUGGU
GCUGUGGGGCGUGCACCACCCUCCUAACAUCGGCGACCAGA
AGGCCCUGUACCACACCGAGAACGCCUACGUCAGCGUGGUG
UCCAGCCACUACAGCAGAAAGUUCACCCCUGAGAUCGCCAA
GAGGCCUAAGGUGCGGGACCAGGAGGGCAGAAUCAACUAC
UACUGGACCCUGCUGGAGCCUGGCGACACCAUCAUCUUCGA
GGCCAACGGCAACCUGAUCGCCCCUAGAUACGCCUUCGCCC
UGAGCAGAGGCUUCGGCAGCGGCAUCAUCAACAGCAACGCC
CCUAUGGACAAGUGCGACGCCAAGUGCCAGACUCCGCAGGG
CGCUAUCAACAGCUCCCUGCCUUUCCAGAACGUGCACCCUG
UGACCAUCGGCGAGUGCCCUAAGUACGUGAGAAGCGCCAAG
CUGAGAAUGGUGACCGGCCUGAGAAACAUCCCUAGCAUCCA
GAGCAGAGGCCUGUUCGGCGCCAUCGCCGGGUUUAUCGAGG
GCGGCUGGACCGGCAUGGUGGACGGCUGGUACGGCUACCAC
CACCAGAACGAGCAGGGCUCCGGCUACGCCGCCGACCAGAA
AUCCACCCAGAACGCCAUCAACGGCAUCACCAACAAGGUGA
ACAGCGUCAUCGAGAAGAUGAACACCCAGUUCACCGCCGUG
GGCAAGGAGUUCAACAAGCUGGAGAGAAGAAUGGAGAACC
UGAACAAGAAGGUGGACGACGGCUUCAUCGACAUCUGGACC
UACAACGCCGAGCUUCUGGUGCUCCUGGAGAACGAGAGAAC
CCUGGACUUCCACGACAGCAACGUGAAGAACCUGUACGAGA
AGGUGAAGUCCCAGCUGAAGAACAACGCCAAGGAGAUCGGC
AACGGCUGCUUCGAGUUCUACCACAAGUGCAACGACGAGUG
CAUGGAGAGCGUGAAGAACGGCACCUACGAUUACCCCAAGU
ACAGCGAGGAGAGCAAGCUGAACAGAGAGAAGAUCGACGG
CGUGAAGCUGGAGAGCAUGGGCGUGUACCAGAUCCUGGCCA
UCUACUCCACCGUGGCCAGUAGCCUGGUGCUGCUGGUGAGC
CUGGGCGCAAUCAGCUUCUGGAUGUGCAGCAACGGCAGCCU GCAGUGCAGAAUCUGCAUC
Protein MKVKLLVLLCTFTATYADTICIGYHANNSTDTVDTVLEKNVTVT 547
HSVNLLENSHNGKLCLLKGIAPLQLGNCSVAGWILGNPECELLIS
KESWSYIVEKPNPENGTCYPGHFADYEELREQLSSVSSFERFEIFP
KESSWPNHTVTGVSASCSHNGESSFYRNLLWLTGKNGLYPNLS
KSYANNKEKEVLVLWGVHHPPNIGDQKALYHTENAYVSVVSS
HYSRKFTPEIAKRPKVRDQEGRINYYWTLLEPGDTIIFEANGNLI
APRYAFALSRGFGSGIINSNAPMDKCDAKCQTPQGAINSSLPFQN
VHPVTIGECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGFIEGG
WTGMVDGWYGYHHQNEQGSGYAADQKSTQNAINGITNKVNS
VIEKMNTQFTAVGKEFNKLERRMENLNKKVDDGFIDIWTYNAE
LLVLLENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGCFEFY
HKCNDECMESVKNGTYDYPKYSEESKLNREKIDGVKLESMGVY
QILAIYSTVASSLVLLVSLGAISFWMCSNGSLQCRICI MRK_RBS- DNA
ATGAAGGTCAAACTTCTCGTGCTCCTGTGCACCTTCACCGCCA 510 HA129
CCTACGCGGGCGTGGCTCCGCTTCACCTGGGCAAGTGCAACA
TCGCCGGTTGGCTGCTGGGTAACCCAGAGTGCGAGCTACTGC
TGACCGTGAGCAGCTGGAGCTACATCGTGGAAACCAGCAACA
GCGACAACGGCACCTGCTACCCTGGCGACTTCATCAACTACG
AGGAGCTGAGAGAGCAGCTCAGCAGCGTGTCCAGCTTCGAG
AGATTCGAGATCTTCCCTAAGACTAGCAGCTGGCCCGACCAC
GAAACAAACAGAGGCGTGACCGCCGCTTGTCCATACGCCGGC
GCCAACAGCTTCTACAGAAACCTGATCTGGCTGGTGAAGAAG
GGCAACAGCTACCCTAAGCTGAGCAAGAGCTACGTGAACAA
CAAGGGCAAGGAGGTGCTTGTGCTGTGGGGCATCCACCACCC
TCCTACCAGCACCGACCAGCAGAGCCTGTACCAGAACGCCGA
CGCCTACGTGTTCGTGGGCAGCAGCAGATACAGCAAGAAGTT
CAAGCCTGAGATCGCCATCAGACCTAAGGTGAGGGACCAGG
AGGGCAGAATGAACTACTACTGGACTCTGGTGGAGCCCGGCG
ACAAGATCACCTTCGAGGCCACCGGCAACCTGGTGGTGCCTA
GATACGCCTTCGCCATGGAGAGAAACGCC mRNA
AUGAAGGUCAAACUUCUCGUGCUCCUGUGCACCUUCACCGC 529
CACCUACGCGGGCGUGGCUCCGCUUCACCUGGGCAAGUGCA
ACAUCGCCGGUUGGCUGCUGGGUAACCCAGAGUGCGAGCUA
CUGCUGACCGUGAGCAGCUGGAGCUACAUCGUGGAAACCAG
CAACAGCGACAACGGCACCUGCUACCCUGGCGACUUCAUCA
ACUACGAGGAGCUGAGAGAGCAGCUCAGCAGCGUGUCCAGC
UUCGAGAGAUUCGAGAUCUUCCCUAAGACUAGCAGCUGGCC
CGACCACGAAACAAACAGAGGCGUGACCGCCGCUUGUCCAU
ACGCCGGCGCCAACAGCUUCUACAGAAACCUGAUCUGGCUG
GUGAAGAAGGGCAACAGCUACCCUAAGCUGAGCAAGAGCU
ACGUGAACAACAAGGGCAAGGAGGUGCUUGUGCUGUGGGG
CAUCCACCACCCUCCUACCAGCACCGACCAGCAGAGCCUGU
ACCAGAACGCCGACGCCUACGUGUUCGUGGGCAGCAGCAGA
UACAGCAAGAAGUUCAAGCCUGAGAUCGCCAUCAGACCUAA
GGUGAGGGACCAGGAGGGCAGAAUGAACUACUACUGGACU
CUGGUGGAGCCCGGCGACAAGAUCACCUUCGAGGCCACCGG
CAACCUGGUGGUGCCUAGAUACGCCUUCGCCAUGGAGAGAA ACGCC Protein
MKVKLLVLLCTFTATYAGVAPLHLGKCNIAGWLLGNPECELLL 548
TVSSWSYIVETSNSDNGTCYPGDFINYEELREQLSSVSSFERFEIF
PKTSSWPDHETNRGVTAACPYAGANSFYRNLIWLVKKGNSYPK
LSKSYVNNKGKEVLVLWGIHHPPTSTDQQSLYQNADAYVFVGS
SRYSKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGN LVVPRYAFAMERNA MRK_H1_
DNA ATGAAGGCCATCCTGGTCGTGCTGCTCTACACATTCGCCACC 511 cot_all
GCCAACGCAGACACTCTGTGCATCGGCTACCACGCCAACAAC
AGCACCGACACCGTGGATACCGTGCTGGAGAAGAACGTGAC
CGTGACCCACAGCGTGAACCTGCTGGAGGACAAGCACAACG
GCAAGCTGTGCAAGCTGAGAGGCGTGGCCCCTCTGCACCTGG
GCAAGTGCAACATCGCCGGCTGGATCCTGGGAAACCCCGAGT
GCGAGAGCCTGTCAACCGCCTCGAGCTGGTCCTACATCGTGG
AAACCAGCAGCAGCGATAACGGGACGTGCTACCCGGGCGAC
TTCATCAACTACGAGGAGCTGAGAGAACAGCTGAGCAGCGTC
AGTAGCTTCGAGAGATTCGAGATCTTCCCTAAGACCAGCAGC
TGGCCTAACCACGACAGCAACAAGGGCGTGACCGCCGCTTGC
CCGCACGCAGGCGCCAAGAGCTTCTACAAGAACCTGATCTGG
CTGGTGAAGAAGGGCAACAGCTACCCTAAGCTGAGCAAGAG
CTACATCAACGACAAGGGGAAGGAGGTGCTAGTCCTGTGGG
GCATCCATCACCCTAGCACCACAGCCGACCAGCAAAGCCTGT
ACCAGAACGCGGACGCCTACGTGTTCGTCGGCACCAGCAGAT
ACAGCAAGAAGTTCAAGCCTGAGATCGCCATCAGACCTAAGG
TGCGAGATCAGGAGGGCAGAATGAACTACTACTGGACCCTGG
TGGAGCCCGGAGACAAGATTACTTTCGAAGCGACCGGCAACC
TGGTGGTGCCTAGATACGCCTTCGCCATGGAGAGAAACGCCG
GCAGCGGCATCATCATCAGCGACACCCCTGTGCACGACTGCA
ACACCACCTGCCAGACCCCTAAAGGCGCCATCAACACAAGCC
TGCCTTTTCAGAACATCCACCCTATCACCATCGGCAAGTGCCC
TAAGTACGTGAAGTCCACCAAGCTCCGCCTGGCAACCGGCCT
CAGGAACGTGCCTAGCATCCAGAGCAGAGGCCTGTTCGGGGC
CATAGCCGGCTTCATAGAGGGTGGCTGGACCGGCATGGTTGA
CGGGTGGTACGGATACCATCACCAGAACGAGCAAGGCAGCG
GCTACGCCGCAGACCTGAAGTCAACCCAGAACGCCATCGACA
AGATCACCAACAAGGTGAACAGCGTGATCGAGAAGATGAAC
ACCCAGTTCACCGCCGTGGGCAAGGAGTTCAACCACCTAGAG
AAGAGGATCGAGAACCTGAATAAGAAGGTGGACGACGGCTT
CCTGGACATCTGGACCTACAACGCCGAGCTGCTCGTCCTCCT
GGAGAACGAGAGAACCCTGGACTACCACGATAGCAACGTGA
AGAACCTGTACGAGAAGGTGAGAAACCAGCTGAAGAATAAC
GCCAAGGAGATCGGCAACGGCTGCTTCGAGTTCTACCACAAG
TGCGACAACACCTGCATGGAGAGCGTGAAGAACGGCACCTA
CGACTACCCTAAGTACAGCGAGGAGGCCAAGCTGAACAGAG
AGAAGATCGACGGCGTGAAGCTGGAGAGCACCAGAATCTAC
CAGATCCTGGCCATCTACAGCACCGTGGCCAGCAGCCTCGTG
CTCGTGGTGAGCCTGGGCGCCATCTCCTTCTGGATGTGCAGC
AACGGCAGCCTGCAGTGCAGAATCTGCATC mRNA
AUGAAGGCCAUCCUGGUCGUGCUGCUCUACACAUUCGCCAC 530
CGCCAACGCAGACACUCUGUGCAUCGGCUACCACGCCAACA
ACAGCACCGACACCGUGGAUACCGUGCUGGAGAAGAACGUG
ACCGUGACCCACAGCGUGAACCUGCUGGAGGACAAGCACAA
CGGCAAGCUGUGCAAGCUGAGAGGCGUGGCCCCUCUGCACC
UGGGCAAGUGCAACAUCGCCGGCUGGAUCCUGGGAAACCCC
GAGUGCGAGAGCCUGUCAACCGCCUCGAGCUGGUCCUACAU
CGUGGAAACCAGCAGCAGCGAUAACGGGACGUGCUACCCGG
GCGACUUCAUCAACUACGAGGAGCUGAGAGAACAGCUGAGC
AGCGUCAGUAGCUUCGAGAGAUUCGAGAUCUUCCCUAAGAC
CAGCAGCUGGCCUAACCACGACAGCAACAAGGGCGUGACCG
CCGCUUGCCCGCACGCAGGCGCCAAGAGCUUCUACAAGAAC
CUGAUCUGGCUGGUGAAGAAGGGCAACAGCUACCCUAAGCU
GAGCAAGAGCUACAUCAACGACAAGGGGAAGGAGGUGCUA
GUCCUGUGGGGCAUCCAUCACCCUAGCACCACAGCCGACCA
GCAAAGCCUGUACCAGAACGCGGACGCCUACGUGUUCGUCG
GCACCAGCAGAUACAGCAAGAAGUUCAAGCCUGAGAUCGCC
AUCAGACCUAAGGUGCGAGAUCAGGAGGGCAGAAUGAACU
ACUACUGGACCCUGGUGGAGCCCGGAGACAAGAUUACUUUC
GAAGCGACCGGCAACCUGGUGGUGCCUAGAUACGCCUUCGC
CAUGGAGAGAAACGCCGGCAGCGGCAUCAUCAUCAGCGACA
CCCCUGUGCACGACUGCAACACCACCUGCCAGACCCCUAAA
GGCGCCAUCAACACAAGCCUGCCUUUUCAGAACAUCCACCC
UAUCACCAUCGGCAAGUGCCCUAAGUACGUGAAGUCCACCA
AGCUCCGCCUGGCAACCGGCCUCAGGAACGUGCCUAGCAUC
CAGAGCAGAGGCCUGUUCGGGGCCAUAGCCGGCUUCAUAGA
GGGUGGCUGGACCGGCAUGGUUGACGGGUGGUACGGAUAC
CAUCACCAGAACGAGCAAGGCAGCGGCUACGCCGCAGACCU
GAAGUCAACCCAGAACGCCAUCGACAAGAUCACCAACAAGG
UGAACAGCGUGAUCGAGAAGAUGAACACCCAGUUCACCGCC
GUGGGCAAGGAGUUCAACCACCUAGAGAAGAGGAUCGAGA
ACCUGAAUAAGAAGGUGGACGACGGCUUCCUGGACAUCUG
GACCUACAACGCCGAGCUGCUCGUCCUCCUGGAGAACGAGA
GAACCCUGGACUACCACGAUAGCAACGUGAAGAACCUGUAC
GAGAAGGUGAGAAACCAGCUGAAGAAUAACGCCAAGGAGA
UCGGCAACGGCUGCUUCGAGUUCUACCACAAGUGCGACAAC
ACCUGCAUGGAGAGCGUGAAGAACGGCACCUACGACUACCC
UAAGUACAGCGAGGAGGCCAAGCUGAACAGAGAGAAGAUC
GACGGCGUGAAGCUGGAGAGCACCAGAAUCUACCAGAUCCU
GGCCAUCUACAGCACCGUGGCCAGCAGCCUCGUGCUCGUGG
UGAGCCUGGGCGCCAUCUCCUUCUGGAUGUGCAGCAACGGC AGCCUGCAGUGCAGAAUCUGCAUC
Protein MKAILVVLLYTFATANADTLCIGYHANNSTDTVDTVLEKNVTV 549
THSVNLLEDKHNGKLCKLRGVAPLHLGKCNIAGWILGNPECESL
STASSWSYIVETSSSDNGTCYPGDFINYEELREQLSSVSSFERFEIF
PKTSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPK
LSKSYINDKGKEVLVLWGIHHPSTTADQQSLYQNADAYVFVGT
SRYSKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGN
LVVPRYAFAMERNAGSGIIISDTPVHDCNTTCQTPKGAINTSLPF
QNIHPITIGKCPKYVKSTKLRLATGLRNVPSIQSRGLFGAIAGFIE
GGWTGMVDGWYGYHHQNEQGSGYAADLKSTQNAIDKITNKV
NSVIEKMNTQFTAVGKEFNHLEKRIENLNKKVDDGFLDIWTYN
AELLVLLENERTLDYHDSNVKNLYEKVRNQLKNNAKEIGNGCF
EFYHKCDNTCMESVKNGTYDYPKYSEEAKLNREKIDGVKLEST
RIYQILAIYSTVASSLVLVVSLGAISFWMCSNGSLQCRICI MRK_H3_ DNA
ATGAAGACCATCATCGCCCTGAGCTACATCCTGTGCCTGGTG 512 ConA
TTCGCGCAGAAACTCCCCGGCAACGACAATAGCACTGCCACC
CTGTGTCTGGGCCATCACGCCGTGCCTAACGGAACCCTCGTG
AAGACGATCACCAACGACCAGATCGAGGTGACCAACGCCAC
CGAGCTGGTCCAGAGTTCGAGCACCGGCAGAATCTGCGACAG
CCCTCACCGGATCCTGGACGGCGAGAACTGCACCCTGATTGA
CGCACTGCTAGGCGACCCACACTGTGACGGCTTCCAGAACAA
GGAGTGGGACCTGTTCGTGGAGAGAAGCAAGGCCTACAGCA
ACTGCTACCCTTACGACGTGCCTGACTACGCCAGCCTGAGAT
CCCTCGTGGCCTCCAGCGGCACCCTCGAGTTCAATAACGAGA
GCTTCAACTGGACCGGAGTCGCCCAGAACGGGACATCCTACG
CCTGCAAGAGAGGAAGCGTCAAGAGCTTCTTCAGCAGACTGA
ACTGGCTGCACCAGCTGAAGTACAAGTACCCTGCCCTGAACG
TGACCATGCCTAACAACGACAAGTTCGACAAGCTGTACATCT
GGGGCGTGCACCATCCCAGCACCGACAGCGACCAGACCTCCC
TGTACGTCCAGGCATCCGGCAGGGTCACCGTGAGCACCAAGA
GAAGCCAGCAGACCGTGATCCCTAACATCGGCAGCAGACCTT
GGGTCAGAGGCGTCTCTAGCAGAATCAGCATCTACTGGACCA
TAGTGAAGCCCGGCGACATCCTGCTGATCAACTCGACCGGCA
ACCTGATCGCTCCTAGGGGCTACTTCAAGATCAGAAGCGGCA
AGAGCAGCATCATGAGAAGCGACGCGCCCATCGGGAAGTGC
AACTCCGAGTGCATCACCCCTAACGGCAGCATCCCCAACGAC
AAGCCTTTCCAGAACGTGAACAGAATCACCTACGGCGCCTGC
CCTAGATACGTGAAGCAGAACACACTGAAGCTGGCCACCGGC
ATGAGGAACGTGCCTGAGAAGCAGACCAGAGGCATCTTCGG
GGCTATTGCCGGCTTCATCGAGAACGGTTGGGAGGGAATGGT
CGACGGGTGGTACGGCTTCAGACACCAGAACAGCGAAGGCA
CGGGACAGGCCGCCGACCTCAAGTCCACCCAGGCTGCCATCA
ATCAGATCAACGGGAAGCTGAACAGACTGATCGAGAAGACC
AACGAGAAGTTCCACCAGATCGAGAAGGAGTTCAGCGAGGT
GGAGGGCAGAATCCAGGACCTGGAGAAGTACGTGGAGGACA
CGAAGATCGACCTGTGGAGCTACAACGCAGAGCTGTTGGTGG
CACTGGAGAACCAGCACACCATCGACCTGACCGACAGCGAG
ATGAACAAGCTGTTCGAGAGGACCAGGAAGCAGTTACGAGA
GAACGCCGAGGACATGGGAAACGGCTGTTTTAAGATCTACCA
CAAGTGCGACAACGCCTGCATCGGGAGCATCAGGAACGGGA
CCTACGACCACGACGTGTACAGAGACGAGGCCCTGAACAAC
AGATTCCAGATCAAGGGCGTGGAGCTGAAGTCCGGCTACAAG
GACTGGATCCTGTGGATCAGCTTCGCCATCAGCTGCTTCCTGC
TGTGCGTGGTCCTCCTGGGCTTTATAATGTGGGCCTGCCAGAA
GGGCAACATCAGGTGCAACATCTGCATC mRNA
AUGAAGACCAUCAUCGCCCUGAGCUACAUCCUGUGCCUGGU 531
GUUCGCGCAGAAACUCCCCGGCAACGACAAUAGCACUGCCA
CCCUGUGUCUGGGCCAUCACGCCGUGCCUAACGGAACCCUC
GUGAAGACGAUCACCAACGACCAGAUCGAGGUGACCAACGC
CACCGAGCUGGUCCAGAGUUCGAGCACCGGCAGAAUCUGCG
ACAGCCCUCACCGGAUCCUGGACGGCGAGAACUGCACCCUG
AUUGACGCACUGCUAGGCGACCCACACUGUGACGGCUUCCA
GAACAAGGAGUGGGACCUGUUCGUGGAGAGAAGCAAGGCC
UACAGCAACUGCUACCCUUACGACGUGCCUGACUACGCCAG
CCUGAGAUCCCUCGUGGCCUCCAGCGGCACCCUCGAGUUCA
AUAACGAGAGCUUCAACUGGACCGGAGUCGCCCAGAACGGG
ACAUCCUACGCCUGCAAGAGAGGAAGCGUCAAGAGCUUCUU
CAGCAGACUGAACUGGCUGCACCAGCUGAAGUACAAGUACC
CUGCCCUGAACGUGACCAUGCCUAACAACGACAAGUUCGAC
AAGCUGUACAUCUGGGGCGUGCACCAUCCCAGCACCGACAG
CGACCAGACCUCCCUGUACGUCCAGGCAUCCGGCAGGGUCA
CCGUGAGCACCAAGAGAAGCCAGCAGACCGUGAUCCCUAAC
AUCGGCAGCAGACCUUGGGUCAGAGGCGUCUCUAGCAGAAU
CAGCAUCUACUGGACCAUAGUGAAGCCCGGCGACAUCCUGC
UGAUCAACUCGACCGGCAACCUGAUCGCUCCUAGGGGCUAC
UUCAAGAUCAGAAGCGGCAAGAGCAGCAUCAUGAGAAGCG
ACGCGCCCAUCGGGAAGUGCAACUCCGAGUGCAUCACCCCU
AACGGCAGCAUCCCCAACGACAAGCCUUUCCAGAACGUGAA
CAGAAUCACCUACGGCGCCUGCCCUAGAUACGUGAAGCAGA
ACACACUGAAGCUGGCCACCGGCAUGAGGAACGUGCCUGAG
AAGCAGACCAGAGGCAUCUUCGGGGCUAUUGCCGGCUUCAU
CGAGAACGGUUGGGAGGGAAUGGUCGACGGGUGGUACGGC
UUCAGACACCAGAACAGCGAAGGCACGGGACAGGCCGCCGA
CCUCAAGUCCACCCAGGCUGCCAUCAAUCAGAUCAACGGGA
AGCUGAACAGACUGAUCGAGAAGACCAACGAGAAGUUCCAC
CAGAUCGAGAAGGAGUUCAGCGAGGUGGAGGGCAGAAUCC
AGGACCUGGAGAAGUACGUGGAGGACACGAAGAUCGACCU
GUGGAGCUACAACGCAGAGCUGUUGGUGGCACUGGAGAAC
CAGCACACCAUCGACCUGACCGACAGCGAGAUGAACAAGCU
GUUCGAGAGGACCAGGAAGCAGUUACGAGAGAACGCCGAG
GACAUGGGAAACGGCUGUUUUAAGAUCUACCACAAGUGCG
ACAACGCCUGCAUCGGGAGCAUCAGGAACGGGACCUACGAC
CACGACGUGUACAGAGACGAGGCCCUGAACAACAGAUUCCA
GAUCAAGGGCGUGGAGCUGAAGUCCGGCUACAAGGACUGG
AUCCUGUGGAUCAGCUUCGCCAUCAGCUGCUUCCUGCUGUG
CGUGGUCCUCCUGGGCUUUAUAAUGUGGGCCUGCCAGAAGG
GCAACAUCAGGUGCAACAUCUGCAUC Protein
MKTIIALSYILCLVFAQKLPGNDNSTATLCLGHHAVPNGTLVKTI 550
TNDQIEVTNATELVQSSSTGRICDSPHRILDGENCTLIDALLGDPH
CDGFQNKEWDLFVERSKAYSNCYPYDVPDYASLRSLVASSGTL
EFNNESFNWTGVAQNGTSYACKRGSVKSFFSRLNWLHQLKYKY
PALNVTMPNNDKFDKLYIWGVHHPSTDSDQTSLYVQASGRVTV
STKRSQQTVIPNIGSRPWVRGVSSRISIYWTIVKPGDILLINSTGNL
IAPRGYFKIRSGKSSIMRSDAPIGKCNSECITPNGSIPNDKPFQNV
NRITYGACPRYVKQNTLKLATGMRNVPEKQTRGIFGAIAGFIEN
GWEGMVDGWYGFRHQNSEGTGQAADLKSTQAAINQINGKLNR
LIEKTNEKFHQIEKEFSEVEGRIQDLEKYVEDTKIDLWSYNAELL
VALENQHTIDLTDSEMNKLFERTRKQLRENAEDMGNGCFKIYH
KCDNACIGSIRNGTYDHDVYRDEALNNRFQIKGVELKSGYKDW
ILWISFAISCFLLCVVLLGFIMWACQKGNIRCNICI MRK_H3_ DNA
ATGAAGACCATCATCGCCCTGAGCTACATCCTGTGCCTGGTG 513 ConB
TTCGCGCAGAAACTCCCCGGCAACGACAATAGCACTGCCACC
CTGTGTCTGGGCCATCACGCCGTGCCTAACGGAACCATCGTG
AAGACGATCACCAACGACCAGATCGAGGTGACCAACGCCAC
CGAGCTGGTCCAGAATTCGAGCACCGGCGAAATCTGCGACAG
CCCTCACCAGATCCTGGACGGCGAGAACTGCACCCTGATTGA
CGCACTGCTAGGCGACCCACAGTGTGACGGCTTCCAGAACAA
GAAGTGGGACCTGTTCGTGGAGAGAAGCAAGGCCTACAGCA
ACTGCTACCCTTACGACGTGCCTGACTACGCCAGCCTGAGAT
CCCTCGTGGCCTCCAGCGGCACCCTCGAGTTCAATAACGAGA
GCTTCAACTGGACCGGAGTCACCCAGAACGGGACATCCAGCG
CCTGCATCAGAAGAAGCAACAGCAGCTTCTTCAGCAGACTGA
ACTGGCTGACCCACCTGAACTTCAAGTACCCTGCCCTGAACG
TGACCATGCCTAACAACGAGCAGTTCGACAAGCTGTACATCT
GGGGCGTGCACCATCCCGGCACCGACAAGGACCAGATCTTCC
TGTACGCCCAGAGCTCCGGCAGGATCACCGTGAGCACCAAGA
GAAGCCAGCAGGCCGTGATCCCTAACATCGGCAGCAGACCTA
GAATCAGAAACATCCCTAGCAGAATCAGCATCTACTGGACCA
TAGTGAAGCCCGGCGACATCCTGCTGATCAACTCGACCGGCA
ACCTGATCGCTCCTAGGGGCTACTTCAAGATCAGAAGCGGCA
AGAGCAGCATCATGAGAAGCGACGCGCCCATCGGGAAGTGC
AACTCCGAGTGCATCACCCCTAACGGCAGCATCCCCAACGAC
AAGCCTTTCCAGAACGTGAACAGAATCACCTACGGCGCCTGC
CCTAGATACGTGAAGCAGAGCACACTGAAGCTGGCCACCGGC
ATGAGGAACGTGCCTGAGAAGCAGACCAGAGGCATCTTCGG
GGCTATTGCCGGCTTCATCGAGAACGGTTGGGAGGGAATGGT
CGACGGGTGGTACGGCTTCAGACACCAGAACAGCGAAGGCA
GGGGACAGGCCGCCGACCTCAAGTCCACCCAGGCTGCCATCG
ATCAGATCAACGGGAAGCTGAACAGACTGATCGGCAAGACC
AACGAGAAGTTCCACCAGATCGAGAAGGAGTTCAGCGAGGT
GGAGGGCAGAATCCAGGACCTGGAGAAGTACGTGGAGGACA
CGAAGATCGACCTGTGGAGCTACAACGCAGAGCTGTTGGTGG
CACTGGAGAACCAGCACACCATCGACCTGACCGACAGCGAG
ATGAACAAGCTGTTCGAGAAGACCAAGAAGCAGTTACGAGA
GAACGCCGAGGACATGGGAAACGGCTGTTTTAAGATCTACCA
CAAGTGCGACAACGCCTGCATCGGGAGCATCAGGAACGGGA
CCTACGACCACGACGTGTACAGAGACGAGGCCCTGAACAAC
AGATTCCAGATCAAGGGCGTGGAGCTGAAGTCCGGCTACAAG
GACTGGATCCTGTGGATCAGCTTCGCCATCAGCTGCTTCCTGC
TGTGCGTGGCCCTCCTGGGCTTTATAATGTGGGCCTGCCAGA
AGGGCAACATCAGGTGCAACATCTGCATC mRNA
AUGAAGACCAUCAUCGCCCUGAGCUACAUCCUGUGCCUGGU 532
GUUCGCGCAGAAACUCCCCGGCAACGACAAUAGCACUGCCA
CCCUGUGUCUGGGCCAUCACGCCGUGCCUAACGGAACCAUC
GUGAAGACGAUCACCAACGACCAGAUCGAGGUGACCAACGC
CACCGAGCUGGUCCAGAAUUCGAGCACCGGCGAAAUCUGCG
ACAGCCCUCACCAGAUCCUGGACGGCGAGAACUGCACCCUG
AUUGACGCACUGCUAGGCGACCCACAGUGUGACGGCUUCCA
GAACAAGAAGUGGGACCUGUUCGUGGAGAGAAGCAAGGCC
UACAGCAACUGCUACCCUUACGACGUGCCUGACUACGCCAG
CCUGAGAUCCCUCGUGGCCUCCAGCGGCACCCUCGAGUUCA
AUAACGAGAGCUUCAACUGGACCGGAGUCACCCAGAACGGG
ACAUCCAGCGCCUGCAUCAGAAGAAGCAACAGCAGCUUCUU
CAGCAGACUGAACUGGCUGACCCACCUGAACUUCAAGUACC
CUGCCCUGAACGUGACCAUGCCUAACAACGAGCAGUUCGAC
AAGCUGUACAUCUGGGGCGUGCACCAUCCCGGCACCGACAA
GGACCAGAUCUUCCUGUACGCCCAGAGCUCCGGCAGGAUCA
CCGUGAGCACCAAGAGAAGCCAGCAGGCCGUGAUCCCUAAC
AUCGGCAGCAGACCUAGAAUCAGAAACAUCCCUAGCAGAAU
CAGCAUCUACUGGACCAUAGUGAAGCCCGGCGACAUCCUGC
UGAUCAACUCGACCGGCAACCUGAUCGCUCCUAGGGGCUAC
UUCAAGAUCAGAAGCGGCAAGAGCAGCAUCAUGAGAAGCG
ACGCGCCCAUCGGGAAGUGCAACUCCGAGUGCAUCACCCCU
AACGGCAGCAUCCCCAACGACAAGCCUUUCCAGAACGUGAA
CAGAAUCACCUACGGCGCCUGCCCUAGAUACGUGAAGCAGA
GCACACUGAAGCUGGCCACCGGCAUGAGGAACGUGCCUGAG
AAGCAGACCAGAGGCAUCUUCGGGGCUAUUGCCGGCUUCAU
CGAGAACGGUUGGGAGGGAAUGGUCGACGGGUGGUACGGC
UUCAGACACCAGAACAGCGAAGGCAGGGGACAGGCCGCCGA
CCUCAAGUCCACCCAGGCUGCCAUCGAUCAGAUCAACGGGA
AGCUGAACAGACUGAUCGGCAAGACCAACGAGAAGUUCCAC
CAGAUCGAGAAGGAGUUCAGCGAGGUGGAGGGCAGAAUCC
AGGACCUGGAGAAGUACGUGGAGGACACGAAGAUCGACCU
GUGGAGCUACAACGCAGAGCUGUUGGUGGCACUGGAGAAC
CAGCACACCAUCGACCUGACCGACAGCGAGAUGAACAAGCU
GUUCGAGAAGACCAAGAAGCAGUUACGAGAGAACGCCGAG
GACAUGGGAAACGGCUGUUUUAAGAUCUACCACAAGUGCG
ACAACGCCUGCAUCGGGAGCAUCAGGAACGGGACCUACGAC
CACGACGUGUACAGAGACGAGGCCCUGAACAACAGAUUCCA
GAUCAAGGGCGUGGAGCUGAAGUCCGGCUACAAGGACUGG
AUCCUGUGGAUCAGCUUCGCCAUCAGCUGCUUCCUGCUGUG
CGUGGCCCUCCUGGGCUUUAUAAUGUGGGCCUGCCAGAAGG
GCAACAUCAGGUGCAACAUCUGCAUC Protein
MKTIIALSYILCLVFAQKLPGNDNSTATLCLGHHAVPNGTIVKTI 551
TNDQIEVTNATELVQNSSTGEICDSPHQILDGENCTLIDALLGDP
QCDGFQNKKWDLFVERSKAYSNCYPYDVPDYASLRSLVASSGT
LEFNNESFNWTGVTQNGTSSACIRRSNSSFFSRLNWLTHLNFKYP
ALNVTMPNNEQFDKLYIWGVHHPGTDKDQIFLYAQSSGRITVST
KRSQQAVIPNIGSRPRIRNIPSRISIYWTIVKPGDILLINSTGNLIAP
RGYFKIRSGKSSIMRSDAPIGKCNSECITPNGSIPNDKPFQNVNRI
TYGACPRYVKQSTLKLATGMRNVPEKQTRGIFGAIAGFIENGWE
GMVDGWYGFRHQNSEGRGQAADLKSTQAAIDQINGKLNRLIGK
TNEKFHQIEKEFSEVEGRIQDLEKYVEDTKIDLWSYNAELLVALE
NQHTIDLTDSEMNKLFEKTKKQLRENAEDMGNGCFKIYHKCDN
ACIGSIRNGTYDHDVYRDEALNNRFQIKGVELKSGYKDWILWIS
FAISCFLLCVALLGFIMWACQKGNIRCNICI MRK_H3_ DNA
ATGAAGACCATCATCGCCCTGAGCTACATCCTGTGCCTGGTG 514 con_all
TTCGCGCAGAAACTCCCCGGCAACGACAATAGCACTGCCACC
CTGTGTCTGGGCCATCACGCCGTGCCTAACGGAACCATCGTG
AAGACGATCACCAACGACCAGATCGAGGTGACCAACGCCAC
CGAGCTGGTCCAGAGTTCGAGCACCGGCGAAATCTGCGACAG
CCCTCACCAGATCCTGGACGGCGAGAACTGCACCCTGATTGA
CGCACTGCTAGGCGACCCACAGTGTGACGGCTTCCAGAACAA
GAAGTGGGACCTGTTCGTGGAGAGAAGCAAGGCCTACAGCA
ACTGCTACCCTTACGACGTGCCTGACTACGCCAGCCTGAGAT
CCCTCGTGGCCTCCAGCGGCACCCTCGAGTTCAATAACGAGA
GCTTCAACTGGACCGGAGTCACCCAGAACGGGACATCCAGCG
CCTGCATCAGAAGAAGCAACAGCAGCTTCTTCAGCAGACTGA
ACTGGCTGACCCACCTGAACTTCAAGTACCCTGCCCTGAACG
TGACCATGCCTAACAACGAGCAGTTCGACAAGCTGTACATCT
GGGGCGTGCACCATCCCGGCACCGACAAGGACCAGATCTTCC
TGTACGCCCAGGCATCCGGCAGGATCACCGTGAGCACCAAGA
GAAGCCAGCAGGCCGTGATCCCTAACATCGGCAGCAGACCTA
GAGTCAGAAACATCCCTAGCAGAATCAGCATCTACTGGACCA
TAGTGAAGCCCGGCGACATCCTGCTGATCAACTCGACCGGCA
ACCTGATCGCTCCTAGGGGCTACTTCAAGATCAGAAGCGGCA
AGAGCAGCATCATGAGAAGCGACGCGCCCATCGGGAAGTGC
AACTCCGAGTGCATCACCCCTAACGGCAGCATCCCCAACGAC
AAGCCTTTCCAGAACGTGAACAGAATCACCTACGGCGCCTGC
CCTAGATACGTGAAGCAGAACACACTGAAGCTGGCCACCGGC
ATGAGGAACGTGCCTGAGAAGCAGACCAGAGGCATCTTCGG
GGCTATTGCCGGCTTCATCGAGAACGGTTGGGAGGGAATGGT
CGACGGGTGGTACGGCTTCAGACACCAGAACAGCGAAGGCA
GGGGACAGGCCGCCGACCTCAAGTCCACCCAGGCTGCCATCG
ATCAGATCAACGGGAAGCTGAACAGACTGATCGGCAAGACC
AACGAGAAGTTCCACCAGATCGAGAAGGAGTTCAGCGAGGT
GGAGGGCAGAATCCAGGACCTGGAGAAGTACGTGGAGGACA
CGAAGATCGACCTGTGGAGCTACAACGCAGAGCTGTTGGTGG
CACTGGAGAACCAGCACACCATCGACCTGACCGACAGCGAG
ATGAACAAGCTGTTCGAGAAGACCAAGAAGCAGTTACGAGA
GAACGCCGAGGACATGGGAAACGGCTGTTTTAAGATCTACCA
CAAGTGCGACAACGCCTGCATCGGGAGCATCAGGAACGGGA
CCTACGACCACGACGTGTACAGAGACGAGGCCCTGAACAAC
AGATTCCAGATCAAGGGCGTGGAGCTGAAGTCCGGCTACAAG
GACTGGATCCTGTGGATCAGCTTCGCCATCAGCTGCTTCCTGC
TGTGCGTGGCCCTCCTGGGCTTTATAATGTGGGCCTGCCAGA
AGGGCAACATCAGGTGCAACATCTGCATC mRNA
AUGAAGACCAUCAUCGCCCUGAGCUACAUCCUGUGCCUGGU 533
GUUCGCGCAGAAACUCCCCGGCAACGACAAUAGCACUGCCA
CCCUGUGUCUGGGCCAUCACGCCGUGCCUAACGGAACCAUC
GUGAAGACGAUCACCAACGACCAGAUCGAGGUGACCAACGC
CACCGAGCUGGUCCAGAGUUCGAGCACCGGCGAAAUCUGCG
ACAGCCCUCACCAGAUCCUGGACGGCGAGAACUGCACCCUG
AUUGACGCACUGCUAGGCGACCCACAGUGUGACGGCUUCCA
GAACAAGAAGUGGGACCUGUUCGUGGAGAGAAGCAAGGCC
UACAGCAACUGCUACCCUUACGACGUGCCUGACUACGCCAG
CCUGAGAUCCCUCGUGGCCUCCAGCGGCACCCUCGAGUUCA
AUAACGAGAGCUUCAACUGGACCGGAGUCACCCAGAACGGG
ACAUCCAGCGCCUGCAUCAGAAGAAGCAACAGCAGCUUCUU
CAGCAGACUGAACUGGCUGACCCACCUGAACUUCAAGUACC
CUGCCCUGAACGUGACCAUGCCUAACAACGAGCAGUUCGAC
AAGCUGUACAUCUGGGGCGUGCACCAUCCCGGCACCGACAA
GGACCAGAUCUUCCUGUACGCCCAGGCAUCCGGCAGGAUCA
CCGUGAGCACCAAGAGAAGCCAGCAGGCCGUGAUCCCUAAC
AUCGGCAGCAGACCUAGAGUCAGAAACAUCCCUAGCAGAAU
CAGCAUCUACUGGACCAUAGUGAAGCCCGGCGACAUCCUGC
UGAUCAACUCGACCGGCAACCUGAUCGCUCCUAGGGGCUAC
UUCAAGAUCAGAAGCGGCAAGAGCAGCAUCAUGAGAAGCG
ACGCGCCCAUCGGGAAGUGCAACUCCGAGUGCAUCACCCCU
AACGGCAGCAUCCCCAACGACAAGCCUUUCCAGAACGUGAA
CAGAAUCACCUACGGCGCCUGCCCUAGAUACGUGAAGCAGA
ACACACUGAAGCUGGCCACCGGCAUGAGGAACGUGCCUGAG
AAGCAGACCAGAGGCAUCUUCGGGGCUAUUGCCGGCUUCAU
CGAGAACGGUUGGGAGGGAAUGGUCGACGGGUGGUACGGC
UUCAGACACCAGAACAGCGAAGGCAGGGGACAGGCCGCCGA
CCUCAAGUCCACCCAGGCUGCCAUCGAUCAGAUCAACGGGA
AGCUGAACAGACUGAUCGGCAAGACCAACGAGAAGUUCCAC
CAGAUCGAGAAGGAGUUCAGCGAGGUGGAGGGCAGAAUCC
AGGACCUGGAGAAGUACGUGGAGGACACGAAGAUCGACCU
GUGGAGCUACAACGCAGAGCUGUUGGUGGCACUGGAGAAC
CAGCACACCAUCGACCUGACCGACAGCGAGAUGAACAAGCU
GUUCGAGAAGACCAAGAAGCAGUUACGAGAGAACGCCGAG
GACAUGGGAAACGGCUGUUUUAAGAUCUACCACAAGUGCG
ACAACGCCUGCAUCGGGAGCAUCAGGAACGGGACCUACGAC
CACGACGUGUACAGAGACGAGGCCCUGAACAACAGAUUCCA
GAUCAAGGGCGUGGAGCUGAAGUCCGGCUACAAGGACUGG
AUCCUGUGGAUCAGCUUCGCCAUCAGCUGCUUCCUGCUGUG
CGUGGCCCUCCUGGGCUUUAUAAUGUGGGCCUGCCAGAAGG
GCAACAUCAGGUGCAACAUCUGCAUC Protein
MKTIIALSYILCLVFAQKLPGNDNSTATLCLGHHAVPNGTIVKTI 552
TNDQIEVTNATELVQSSSTGEICDSPHQILDGENCTLIDALLGDPQ
CDGFQNKKWDLFVERSKAYSNCYPYDVPDYASLRSLVASSGTL
EFNNESFNWTGVTQNGTSSACIRRSNSSFFSRLNWLTHLNFKYP
ALNVTMPNNEQFDKLYIWGVHHPGTDKDQIFLYAQASGRITVST
KRSQQAVIPNIGSRPRVRNIPSRISIYWTIVKPGDILLINSTGNLIAP
RGYFKIRSGKSSIMRSDAPIGKCNSECITPNGSIPNDKPFQNVNRI
TYGACPRYVKQNTLKLATGMRNVPEKQTRGIFGAIAGFIENGW
EGMVDGWYGFRHQNSEGRGQAADLKSTQAAIDQINGKLNRLIG
KTNEKFHQIEKEFSEVEGRIQDLEKYVEDTKIDLWSYNAELLVA
LENQHTIDLTDSEMNKLFEKTKKQLRENAEDMGNGCFKIYHKC
DNACIGSIRNGTYDHDVYRDEALNNRFQIKGVELKSGYKDWIL
WISFAISCFLLCVALLGFIMWACQKGNIRCNICI MRK_H3_ DNA
ATGAAGACCATCATCGCCCTGAGCTACATCCTGTGCCTGGTG 515 cot_all
TTCGCGCAGAAACTCCCCGGCAACGACAATAGCACTGCCACC
CTGTGTCTGGGCCATCACGCCGTGCCTAACGGAACCATCGTG
AAGACGATCACCAACGACAGAATCGAGGTGACCAACGCCAC
CGAGCTGGTCCAGAATTCGAGCATCGGCGAAATCTGCGACAG
CCCTCACCAGATCCTGGACGGCGAGAACTGCACCCTGATTGA
CGCACTGCTAGGCGACCCACAGTGTGACGGCTTCCAGAACAA
GAAGTGGGACCTGTTCGTGGAGAGAAGCAAGGCCTACAGCA
ACTGCTACCCTTACGACGTGCCTGACTACGCCAGCCTGAGAT
CCCTCGTGGCCTCCAGCGGCACCCTCGAGTTCAATAACGAGA
GCTTCAACTGGACCGGAGTCACCCAGAACGGGACATCCAGCG
CCTGCATCAGAAGAAGCAACAGCAGCTTCTTCAGCAGACTGA
ACTGGCTGACCCACCTGAACTTCAAGTACCCTGCCCTGAACG
TGACCATGCCTAACAACGAGCAGTTCGACAAGCTGTACATCT
GGGGCGTGCACCATCCCGGCACCGACAAGGACCAGATCTTCC
TGTACGCCCAGAGCTCCGGCAGGATCACCGTGAGCACCAAGA
GAAGCCAGCAGGCCGTGATCCCTAACATCGGCAGCAGACCTA
GAATCAGAAACATCCCTAGCAGAATCAGCATCTACTGGACCA
TAGTGAAGCCCGGCGACATCCTGCTGATCAACTCGACCGGCA
ACCTGATCGCTCCTAGGGGCTACTTCAAGATCAGAAGCGGCA
AGAGCAGCATCATGAGAAGCGACGCGCCCATCGGGAAGTGC
AAGTCCGAGTGCATCACCCCTAACGGCAGCATCCCCAACGAC
AAGCCTTTCCAGAACGTGAACAGAATCACCTACGGCGCCTGC
CCTAGATACGTGAAGCAGAGCACACTGAAGCTGGCCACCGGC
ATGAGGAACGTGCCTGAGAAGCAGACCAGAGGCATCTTCGG
GGCTATTGCCGGCTTCATCGAGAACGGTTGGGAGGGAATGGT
CGACGGGTGGTACGGCTTCAGACACCAGAACAGCGAAGGCA
GGGGACAGGCCGCCGACCTCAAGTCCACCCAGGCTGCCATCG
ATCAGATCAACGGGAAGCTGAACAGACTGATCGGCAAGACC
AACGAGAAGTTCCACCAGATCGAGAAGGAGTTCAGCGAGGT
GGAGGGCAGAATCCAGGACCTGGAGAAGTACGTGGAGGACA
CGAAGATCGACCTGTGGAGCTACAACGCAGAGCTGTTGGTGG
CACTGGAGAACCAGCACACCATCGACCTGACCGACAGCGAG
ATGAACAAGCTGTTCGAGAAGACCAAGAAGCAGTTACGAGA
GAACGCCGAGGACATGGGAAACGGCTGTTTTAAGATCTACCA
CAAGTGCGACAACGCCTGCATCGGGAGCATCAGGAACGGGA
CCTACGACCACGACGTGTACAGAGACGAGGCCCTGAACAAC
AGATTCCAGATCAAGGGCGTGGAGCTGAAGTCCGGCTACAAG
GACTGGATCCTGTGGATCAGCTTCGCCATCAGCTGCTTCCTGC
TGTGCGTGGCCCTCCTGGGCTTTATAATGTGGGCCTGCCAGA
AGGGCAACATCAGGTGCAACATCTGCATC mRNA
AUGAAGACCAUCAUCGCCCUGAGCUACAUCCUGUGCCUGGU 534
GUUCGCGCAGAAACUCCCCGGCAACGACAAUAGCACUGCCA
CCCUGUGUCUGGGCCAUCACGCCGUGCCUAACGGAACCAUC
GUGAAGACGAUCACCAACGACAGAAUCGAGGUGACCAACGC
CACCGAGCUGGUCCAGAAUUCGAGCAUCGGCGAAAUCUGCG
ACAGCCCUCACCAGAUCCUGGACGGCGAGAACUGCACCCUG
AUUGACGCACUGCUAGGCGACCCACAGUGUGACGGCUUCCA
GAACAAGAAGUGGGACCUGUUCGUGGAGAGAAGCAAGGCC
UACAGCAACUGCUACCCUUACGACGUGCCUGACUACGCCAG
CCUGAGAUCCCUCGUGGCCUCCAGCGGCACCCUCGAGUUCA
AUAACGAGAGCUUCAACUGGACCGGAGUCACCCAGAACGGG
ACAUCCAGCGCCUGCAUCAGAAGAAGCAACAGCAGCUUCUU
CAGCAGACUGAACUGGCUGACCCACCUGAACUUCAAGUACC
CUGCCCUGAACGUGACCAUGCCUAACAACGAGCAGUUCGAC
AAGCUGUACAUCUGGGGCGUGCACCAUCCCGGCACCGACAA
GGACCAGAUCUUCCUGUACGCCCAGAGCUCCGGCAGGAUCA
CCGUGAGCACCAAGAGAAGCCAGCAGGCCGUGAUCCCUAAC
AUCGGCAGCAGACCUAGAAUCAGAAACAUCCCUAGCAGAAU
CAGCAUCUACUGGACCAUAGUGAAGCCCGGCGACAUCCUGC
UGAUCAACUCGACCGGCAACCUGAUCGCUCCUAGGGGCUAC
UUCAAGAUCAGAAGCGGCAAGAGCAGCAUCAUGAGAAGCG
ACGCGCCCAUCGGGAAGUGCAAGUCCGAGUGCAUCACCCCU
AACGGCAGCAUCCCCAACGACAAGCCUUUCCAGAACGUGAA
CAGAAUCACCUACGGCGCCUGCCCUAGAUACGUGAAGCAGA
GCACACUGAAGCUGGCCACCGGCAUGAGGAACGUGCCUGAG
AAGCAGACCAGAGGCAUCUUCGGGGCUAUUGCCGGCUUCAU
CGAGAACGGUUGGGAGGGAAUGGUCGACGGGUGGUACGGC
UUCAGACACCAGAACAGCGAAGGCAGGGGACAGGCCGCCGA
CCUCAAGUCCACCCAGGCUGCCAUCGAUCAGAUCAACGGGA
AGCUGAACAGACUGAUCGGCAAGACCAACGAGAAGUUCCAC
CAGAUCGAGAAGGAGUUCAGCGAGGUGGAGGGCAGAAUCC
AGGACCUGGAGAAGUACGUGGAGGACACGAAGAUCGACCU
GUGGAGCUACAACGCAGAGCUGUUGGUGGCACUGGAGAAC
CAGCACACCAUCGACCUGACCGACAGCGAGAUGAACAAGCU
GUUCGAGAAGACCAAGAAGCAGUUACGAGAGAACGCCGAG
GACAUGGGAAACGGCUGUUUUAAGAUCUACCACAAGUGCG
ACAACGCCUGCAUCGGGAGCAUCAGGAACGGGACCUACGAC
CACGACGUGUACAGAGACGAGGCCCUGAACAACAGAUUCCA
GAUCAAGGGCGUGGAGCUGAAGUCCGGCUACAAGGACUGG
AUCCUGUGGAUCAGCUUCGCCAUCAGCUGCUUCCUGCUGUG
CGUGGCCCUCCUGGGCUUUAUAAUGUGGGCCUGCCAGAAGG
GCAACAUCAGGUGCAACAUCUGCAUC Protein
MKTIIALSYILCLVFAQKLPGNDNSTATLCLGHHAVPNGTIVKTI 553
TNDRIEVTNATELVQNSSIGEICDSPHQILDGENCTLIDALLGDPQ
CDGFQNKKWDLFVERSKAYSNCYPYDVPDYASLRSLVASSGTL
EFNNESFNWTGVTQNGTSSACIRRSNSSFFSRLNWLTHLNFKYP
ALNVTMPNNEQFDKLYIWGVHHPGTDKDQIFLYAQSSGRITVST
KRSQQAVIPNIGSRPRIRNIPSRISIYWTIVKPGDILLINSTGNLIAP
RGYFKIRSGKSSIMRSDAPIGKCKSECITPNGSIPNDKPFQNVNRI
TYGACPRYVKQSTLKLATGMRNVPEKQTRGIFGAIAGFIENGWE
GMVDGWYGFRHQNSEGRGQAADLKSTQAAIDQINGKLNRLIGK
TNEKFHQIEKEFSEVEGRIQDLEKYVEDTKIDLWSYNAELLVALE
NQHTIDLTDSEMNKLFEKTKKQLRENAEDMGNGCFKIYHKCDN
ACIGSIRNGTYDHDVYRDEALNNRFQIKGVELKSGYKDWILWIS
FAISCFLLCVALLGFIMWACQKGNIRCNICI RBD1- DNA
ATGAAGGTGAAGCTTCTCGTGCTCTTATGCACCTTCACCGCCA 516 Cal09-PC-
CCTACGCCGGCGTGGCTCCGCTTCACCTTGGCAAGTGCAACA Cb
TCGCCGGCTGGATCTTGGGAAACCCCGAGTGCGAGAGCTTGA
GCACCGCCAGCAGCTGGAGCAACATCACGGAAACCCCTAGC
AGCGACAACGGCACCTGCTACCCCGGCGACTTCATCGACTAC
GAGGAGCTGCGGGAGCAGCTGAGCAGCGTGAGCAGCTTCGA
GCGGTTCGAGATCTTCCCCAAGACCAGCTCTTGGCCCAACCA
CAGCAGCAACAAGGGCGTGACCGCCGCCTGCCCTCACGCTGG
CGCCAAGAGCTTCTACAAGAACCTGATCTGGCTGGTGAAGAA
GAACGGCAGCTACCCCAAGCTGAACAAGTCTTACATTAACGA
CTCAGGCAAGGAGGTGCTGGTCCTGTGGGGCATCCACCACCC
CAGCAACAGCACCGACCAACAGAGCCTGTACCAGAACGCCG
ACACCTACGTGTTCGTGGGCAGCAGCAACTACAGCAAGAAGT
TCAAGCCCGAGATCGCCATCCGGCCCAAGGTGCGGGACCAGG
AGGGCCGGATGAACTACTACTGGACCCTGGTGGAGCCTGGCG
ACAAGATCACCTTCGAGGCCACCGGCAACCTGGTGGTGCCCC
GGTACGCCTTCGCCATGGAGCGGAACGCC mRNA
AUGAAGGUGAAGCUUCUCGUGCUCUUAUGCACCUUCACCGC 535
CACCUACGCCGGCGUGGCUCCGCUUCACCUUGGCAAGUGCA
ACAUCGCCGGCUGGAUCUUGGGAAACCCCGAGUGCGAGAGC
UUGAGCACCGCCAGCAGCUGGAGCAACAUCACGGAAACCCC
UAGCAGCGACAACGGCACCUGCUACCCCGGCGACUUCAUCG
ACUACGAGGAGCUGCGGGAGCAGCUGAGCAGCGUGAGCAGC
UUCGAGCGGUUCGAGAUCUUCCCCAAGACCAGCUCUUGGCC
CAACCACAGCAGCAACAAGGGCGUGACCGCCGCCUGCCCUC
ACGCUGGCGCCAAGAGCUUCUACAAGAACCUGAUCUGGCUG
GUGAAGAAGAACGGCAGCUACCCCAAGCUGAACAAGUCUUA
CAUUAACGACUCAGGCAAGGAGGUGCUGGUCCUGUGGGGC
AUCCACCACCCCAGCAACAGCACCGACCAACAGAGCCUGUA
CCAGAACGCCGACACCUACGUGUUCGUGGGCAGCAGCAACU
ACAGCAAGAAGUUCAAGCCCGAGAUCGCCAUCCGGCCCAAG
GUGCGGGACCAGGAGGGCCGGAUGAACUACUACUGGACCCU
GGUGGAGCCUGGCGACAAGAUCACCUUCGAGGCCACCGGCA
ACCUGGUGGUGCCCCGGUACGCCUUCGCCAUGGAGCGGAAC GCC Protein
MKVKLLVLLCTFTATYAGVAPLHLGKCNIAGWILGNPECESLST 554
ASSWSNITETPSSDNGTCYPGDFIDYEELREQLSSVSSFERFEIFPK
TSSWPNHSSNKGVTAACPHAGAKSFYKNLIWLVKKNGSYPKLN
KSYINDSGKEVLVLWGIHHPSNSTDQQSLYQNADTYVFVGSSNY
SKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGNLVV PRYAFAMERNA RBD1- DNA
ATGAAGGTGAAGCTTCTCGTGCTCTTATGCACCTTCACCGCCA 517 Cal09-PC
CCTACGCCGGCGTGGCTCCGCTTCACCTTGGCAAGTGCAACA
TCGCCGGCTGGATCTTGGGAAACCCCGAGTGCGAGAGCAACA
GCACCGCCAGCAGCTGGAGCAACATCACGGAAACCCCTAGC
AGCGACAACGGCACCTGCTACCCCGGCGACTTCATCGACTAC
GAGGAGCTGCGGGAGCAGCTGAGCAGCGTGAGCAGCTTCGA
GCGGTTCGAGATCTTCCCCAAGACCAGCTCTTGGCCCAACCA
CAGCAGCAACAAGGGCGTGACCGCCGCCTGCCCTCACGCTGG
CGCCAAGAGCTTCTACAAGAACCTGATCTGGCTGGTGAAGAA
GAACGGCAGCTACCCCAAGCTGAACAAGTCTTACATTAACGA
CTCAGGCAAGGAGGTGCTGGTCCTGTGGGGCATCCACCACCC
CAGCAACAGCACCGACCAACAGAGCCTGTACCAGAACGCCG
ACACCTACGTGTTCGTGGGCAGCAGCAACTACAGCAAGAAGT
TCAAGCCCGAGATCGCCATCCGGCCCAAGGTGCGGGACCAGG
AGGGCCGGATGAACTACTACTGGACCCTGGTGGAGCCTGGCG
ACAAGATCACCTTCGAGGCCACCGGCAACCTGGTGGTGCCCC
GGTACGCCTTCGCCATGGAGCGGAACGCC mRNA
AUGAAGGUGAAGCUUCUCGUGCUCUUAUGCACCUUCACCGC 536
CACCUACGCCGGCGUGGCUCCGCUUCACCUUGGCAAGUGCA
ACAUCGCCGGCUGGAUCUUGGGAAACCCCGAGUGCGAGAGC
AACAGCACCGCCAGCAGCUGGAGCAACAUCACGGAAACCCC
UAGCAGCGACAACGGCACCUGCUACCCCGGCGACUUCAUCG
ACUACGAGGAGCUGCGGGAGCAGCUGAGCAGCGUGAGCAGC
UUCGAGCGGUUCGAGAUCUUCCCCAAGACCAGCUCUUGGCC
CAACCACAGCAGCAACAAGGGCGUGACCGCCGCCUGCCCUC
ACGCUGGCGCCAAGAGCUUCUACAAGAACCUGAUCUGGCUG
GUGAAGAAGAACGGCAGCUACCCCAAGCUGAACAAGUCUUA
CAUUAACGACUCAGGCAAGGAGGUGCUGGUCCUGUGGGGC
AUCCACCACCCCAGCAACAGCACCGACCAACAGAGCCUGUA
CCAGAACGCCGACACCUACGUGUUCGUGGGCAGCAGCAACU
ACAGCAAGAAGUUCAAGCCCGAGAUCGCCAUCCGGCCCAAG
GUGCGGGACCAGGAGGGCCGGAUGAACUACUACUGGACCCU
GGUGGAGCCUGGCGACAAGAUCACCUUCGAGGCCACCGGCA
ACCUGGUGGUGCCCCGGUACGCCUUCGCCAUGGAGCGGAAC GCC Protein
MKVKLLVLLCTFTATYAGVAPLHLGKCNIAGWILGNPECESNST 555
ASSWSNITETPSSDNGTCYPGDFIDYEELREQLSSVSSFERFEIFPK
TSSWPNHSSNKGVTAACPHAGAKSFYKNLIWLVKKNGSYPKLN
KSYINDSGKEVLVLWGIHHPSNSTDQQSLYQNADTYVFVGSSNY
SKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGNLVV PRYAFAMERNA RBD1- DNA
ATGAAGGTGAAGCTTCTCGTGCTCTTATGCACCTTCACCGCCA 518 Cal09
CCTACGCCGGCGTGGCTCCGCTTCACCTTGGCAAGTGCAACA
TCGCCGGCTGGATCTTGGGAAACCCCGAGTGCGAGAGCTTGA
GCACCGCCAGCAGCTGGAGCAACATCACGGAAACCCCTAGC
AGCGACAACGGCACCTGCTACCCCGGCGACTTCATCGACTAC
GAGGAGCTGCGGGAGCAGCTGAGCAGCGTGAGCAGCTTCGA
GCGGTTCGAGATCTTCCCCAAGACCAGCTCTTGGCCCAACCA
CGACAGCAACAAGGGCGTGACCGCCGCCTGCCCTCACGCTGG
CGCCAAGAGCTTCTACAAGAACCTGATCTGGCTGGTGAAGAA
GGGCAACAGCTACCCCAAGCTGTCCAAGTCTTACATTAACGA
CAAGGGCAAGGAGGTGCTGGTCCTGTGGGGCATCCACCACCC
CAGCACCAGCGCCGACCAACAGAGCCTGTACCAGAACGCCG
ACACCTACGTGTTCGTGGGCAGCAGCCGGTACAGCAAGAAGT
TCAAGCCCGAGATCGCCATCCGGCCCAAGGTGCGGGACCAGG
AGGGCCGGATGAACTACTACTGGACCCTGGTGGAGCCTGGCG
ACAAGATCACCTTCGAGGCCACCGGCAACCTGGTGGTGCCCC
GGTACGCCTTCGCCATGGAGCGGAACGCC mRNA
AUGAAGGUGAAGCUUCUCGUGCUCUUAUGCACCUUCACCGC 537
CACCUACGCCGGCGUGGCUCCGCUUCACCUUGGCAAGUGCA
ACAUCGCCGGCUGGAUCUUGGGAAACCCCGAGUGCGAGAGC
UUGAGCACCGCCAGCAGCUGGAGCAACAUCACGGAAACCCC
UAGCAGCGACAACGGCACCUGCUACCCCGGCGACUUCAUCG
ACUACGAGGAGCUGCGGGAGCAGCUGAGCAGCGUGAGCAGC
UUCGAGCGGUUCGAGAUCUUCCCCAAGACCAGCUCUUGGCC
CAACCACGACAGCAACAAGGGCGUGACCGCCGCCUGCCCUC
ACGCUGGCGCCAAGAGCUUCUACAAGAACCUGAUCUGGCUG
GUGAAGAAGGGCAACAGCUACCCCAAGCUGUCCAAGUCUUA
CAUUAACGACAAGGGCAAGGAGGUGCUGGUCCUGUGGGGC
AUCCACCACCCCAGCACCAGCGCCGACCAACAGAGCCUGUA
CCAGAACGCCGACACCUACGUGUUCGUGGGCAGCAGCCGGU
ACAGCAAGAAGUUCAAGCCCGAGAUCGCCAUCCGGCCCAAG
GUGCGGGACCAGGAGGGCCGGAUGAACUACUACUGGACCCU
GGUGGAGCCUGGCGACAAGAUCACCUUCGAGGCCACCGGCA
ACCUGGUGGUGCCCCGGUACGCCUUCGCCAUGGAGCGGAAC GCC Protein
MKVKLLVLLCTFTATYAGVAPLHLGKCNIAGWILGNPECESLST 556
ASSWSNITETPSSDNGTCYPGDFIDYEELREQLSSVSSFERFEIFPK
TSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPKLS
KSYINDKGKEVLVLWGIHHPSTSADQQSLYQNADTYVFVGSSR
YSKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGNLV VPRYAFAMERNA MRK_RBD-
DNA ATGAAGGTGAAGCTTCTCGTGCTCTTATGCACCTTCACCGCCA 519 Cal09-PC-
CCTACGCCGGCGTGGCTCCGCTTCACCTTGGCAAGTGCAACA Cb
TCGCCGGCTGGATCTTGGGAAACCCCGAGTGCGAGAGCTTGA
GCACCGCCAGCAGCTGGAGCTACATCGTGGAAACCCCTAGCA
GCGACAACGGCACCTGCTACCCCGGCGACTTCATCGACTACG
AGGAGCTGCGGGAGCAGCTGAGCAGCGTGAGCAGCTTCGAG
CGGTTCGAGATCTTCCCCAAGACCAGCTCTTGGCCCAACCAC
AGCAGCAACAAGGGCGTGACCGCCGCCTGCCCTCACGCTGGC
GCCAAGAGCTTCTACAAGAACCTGATCTGGCTGGTGAAGAAG
AACGGCAGCTACCCCAAGCTGAACAAGTCTTACATTAACGAC
TCAGGCAAGGAGGTGCTGGTCCTGTGGGGCATCCACCACCCC
AGCAACAGCACCGACCAACAGAGCCTGTACCAGAACGCCGA
CACCTACGTGTTCGTGGGCAGCAGCAACTACAGCAAGAAGTT
CAAGCCCGAGATCGCCATCCGGCCCAAGGTGCGGGACCAGG
AGGGCCGGATGAACTACTACTGGACCCTGGTGGAGCCTGGCG
ACAAGATCACCTTCGAGGCCACCGGCAACCTGGTGGTGCCCC
GGTACGCCTTCGCCATGGAGCGGAACGCC mRNA
AUGAAGGUGAAGCUUCUCGUGCUCUUAUGCACCUUCACCGC 538
CACCUACGCCGGCGUGGCUCCGCUUCACCUUGGCAAGUGCA
ACAUCGCCGGCUGGAUCUUGGGAAACCCCGAGUGCGAGAGC
UUGAGCACCGCCAGCAGCUGGAGCUACAUCGUGGAAACCCC
UAGCAGCGACAACGGCACCUGCUACCCCGGCGACUUCAUCG
ACUACGAGGAGCUGCGGGAGCAGCUGAGCAGCGUGAGCAGC
UUCGAGCGGUUCGAGAUCUUCCCCAAGACCAGCUCUUGGCC
CAACCACAGCAGCAACAAGGGCGUGACCGCCGCCUGCCCUC
ACGCUGGCGCCAAGAGCUUCUACAAGAACCUGAUCUGGCUG
GUGAAGAAGAACGGCAGCUACCCCAAGCUGAACAAGUCUUA
CAUUAACGACUCAGGCAAGGAGGUGCUGGUCCUGUGGGGC
AUCCACCACCCCAGCAACAGCACCGACCAACAGAGCCUGUA
CCAGAACGCCGACACCUACGUGUUCGUGGGCAGCAGCAACU
ACAGCAAGAAGUUCAAGCCCGAGAUCGCCAUCCGGCCCAAG
GUGCGGGACCAGGAGGGCCGGAUGAACUACUACUGGACCCU
GGUGGAGCCUGGCGACAAGAUCACCUUCGAGGCCACCGGCA
ACCUGGUGGUGCCCCGGUACGCCUUCGCCAUGGAGCGGAAC GCC Protein
MKVKLLVLLCTFTATYAGVAPLHLGKCNIAGWILGNPECESLST 557
ASSWSYIVETPSSDNGTCYPGDFIDYEELREQLSSVSSFERFEIFPK
TSSWPNHSSNKGVTAACPHAGAKSFYKNLIWLVKKNGSYPKLN
KSYINDSGKEVLVLWGIHHPSNSTDQQSLYQNADTYVFVGSSNY
SKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGNLVV PRYAFAMERNA MRK_RBD-
DNA ATGAAGGTGAAGCTTCTCGTGCTCTTATGCACCTTCACCGCCA 520 Cal09-PC
CCTACGCCGGCGTGGCTCCGCTTCACCTTGGCAAGTGCAACA
TCGCCGGCTGGATCTTGGGAAACCCCGAGTGCGAGAGCAACA
GCACCGCCAGCAGCTGGAGCTACATCGTGGAAACCCCTAGCA
GCGACAACGGCACCTGCTACCCCGGCGACTTCATCGACTACG
AGGAGCTGCGGGAGCAGCTGAGCAGCGTGAGCAGCTTCGAG
CGGTTCGAGATCTTCCCCAAGACCAGCTCTTGGCCCAACCAC
AGCAGCAACAAGGGCGTGACCGCCGCCTGCCCTCACGCTGGC
GCCAAGAGCTTCTACAAGAACCTGATCTGGCTGGTGAAGAAG
AACGGCAGCTACCCCAAGCTGAACAAGTCTTACATTAACGAC
TCAGGCAAGGAGGTGCTGGTCCTGTGGGGCATCCACCACCCC
AGCAACAGCACCGACCAACAGAGCCTGTACCAGAACGCCGA
CACCTACGTGTTCGTGGGCAGCAGCAACTACAGCAAGAAGTT
CAAGCCCGAGATCGCCATCCGGCCCAAGGTGCGGGACCAGG
AGGGCCGGATGAACTACTACTGGACCCTGGTGGAGCCTGGCG
ACAAGATCACCTTCGAGGCCACCGGCAACCTGGTGGTGCCCC
GGTACGCCTTCGCCATGGAGCGGAACGCC mRNA
AUGAAGGUGAAGCUUCUCGUGCUCUUAUGCACCUUCACCGC 539
CACCUACGCCGGCGUGGCUCCGCUUCACCUUGGCAAGUGCA
ACAUCGCCGGCUGGAUCUUGGGAAACCCCGAGUGCGAGAGC
AACAGCACCGCCAGCAGCUGGAGCUACAUCGUGGAAACCCC
UAGCAGCGACAACGGCACCUGCUACCCCGGCGACUUCAUCG
ACUACGAGGAGCUGCGGGAGCAGCUGAGCAGCGUGAGCAGC
UUCGAGCGGUUCGAGAUCUUCCCCAAGACCAGCUCUUGGCC
CAACCACAGCAGCAACAAGGGCGUGACCGCCGCCUGCCCUC
ACGCUGGCGCCAAGAGCUUCUACAAGAACCUGAUCUGGCUG
GUGAAGAAGAACGGCAGCUACCCCAAGCUGAACAAGUCUUA
CAUUAACGACUCAGGCAAGGAGGUGCUGGUCCUGUGGGGC
AUCCACCACCCCAGCAACAGCACCGACCAACAGAGCCUGUA
CCAGAACGCCGACACCUACGUGUUCGUGGGCAGCAGCAACU
ACAGCAAGAAGUUCAAGCCCGAGAUCGCCAUCCGGCCCAAG
GUGCGGGACCAGGAGGGCCGGAUGAACUACUACUGGACCCU
GGUGGAGCCUGGCGACAAGAUCACCUUCGAGGCCACCGGCA
ACCUGGUGGUGCCCCGGUACGCCUUCGCCAUGGAGCGGAAC GCC Protein
MKVKLLVLLCTFTATYAGVAPLHLGKCNIAGWILGNPECESNST 558
ASSWSYIVETPSSDNGTCYPGDFIDYEELREQLSSVSSFERFEIFPK
TSSWPNHSSNKGVTAACPHAGAKSFYKNLIWLVKKNGSYPKLN
KSYINDSGKEVLVLWGIHHPSNSTDQQSLYQNADTYVFVGSSNY
SKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGNLVV PRYAFAMERNA MRK_RBD-
DNA ATGAAGGTGAAGCTTCTCGTGCTCTTATGCACCTTCACCGCCA 521 Cal09
CCTACGCCGGCGTGGCTCCGCTTCACCTTGGCAAGTGCAACA
TCGCCGGCTGGATCTTGGGAAACCCCGAGTGCGAGAGCTTGA
GCACCGCCAGCAGCTGGAGCTACATCGTGGAAACCCCTAGCA
GCGACAACGGCACCTGCTACCCCGGCGACTTCATCGACTACG
AGGAGCTGCGGGAGCAGCTGAGCAGCGTGAGCAGCTTCGAG
CGGTTCGAGATCTTCCCCAAGACCAGCTCTTGGCCCAACCAC
GACAGCAACAAGGGCGTGACCGCCGCCTGCCCTCACGCTGGC
GCCAAGAGCTTCTACAAGAACCTGATCTGGCTGGTGAAGAAG
GGCAACAGCTACCCCAAGCTGTCCAAGTCTTACATTAACGAC
AAGGGCAAGGAGGTGCTGGTCCTGTGGGGCATCCACCACCCC
AGCACCAGCGCCGACCAACAGAGCCTGTACCAGAACGCCGA
CACCTACGTGTTCGTGGGCAGCAGCCGGTACAGCAAGAAGTT
CAAGCCCGAGATCGCCATCCGGCCCAAGGTGCGGGACCAGG
AGGGCCGGATGAACTACTACTGGACCCTGGTGGAGCCTGGCG
ACAAGATCACCTTCGAGGCCACCGGCAACCTGGTGGTGCCCC
GGTACGCCTTCGCCATGGAGCGGAACGCC mRNA
AUGAAGGUGAAGCUUCUCGUGCUCUUAUGCACCUUCACCGC 540
CACCUACGCCGGCGUGGCUCCGCUUCACCUUGGCAAGUGCA
ACAUCGCCGGCUGGAUCUUGGGAAACCCCGAGUGCGAGAGC
UUGAGCACCGCCAGCAGCUGGAGCUACAUCGUGGAAACCCC
UAGCAGCGACAACGGCACCUGCUACCCCGGCGACUUCAUCG
ACUACGAGGAGCUGCGGGAGCAGCUGAGCAGCGUGAGCAGC
UUCGAGCGGUUCGAGAUCUUCCCCAAGACCAGCUCUUGGCC
CAACCACGACAGCAACAAGGGCGUGACCGCCGCCUGCCCUC
ACGCUGGCGCCAAGAGCUUCUACAAGAACCUGAUCUGGCUG
GUGAAGAAGGGCAACAGCUACCCCAAGCUGUCCAAGUCUUA
CAUUAACGACAAGGGCAAGGAGGUGCUGGUCCUGUGGGGC
AUCCACCACCCCAGCACCAGCGCCGACCAACAGAGCCUGUA
CCAGAACGCCGACACCUACGUGUUCGUGGGCAGCAGCCGGU
ACAGCAAGAAGUUCAAGCCCGAGAUCGCCAUCCGGCCCAAG
GUGCGGGACCAGGAGGGCCGGAUGAACUACUACUGGACCCU
GGUGGAGCCUGGCGACAAGAUCACCUUCGAGGCCACCGGCA
ACCUGGUGGUGCCCCGGUACGCCUUCGCCAUGGAGCGGAAC GCC Protein
MKVKLLVLLCTFTATYAGVAPLHLGKCNIAGWILGNPECESLST 559
ASSWSYIVETPSSDNGTCYPGDFIDYEELREQLSSVSSFERFEIFPK
TSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPKLS
KSYINDKGKEVLVLWGIHHPSTSADQQSLYQNADTYVFVGSSR
YSKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGNLV VPRYAFAMERNA FLHA_PR8
DNA ATGAAGGCCAATTTGTTGGTCCTTCTATGTGCCCTAGCCGCCG 522
CCGACGCCGACACAATCTGCATCGGATATCACGCAAACAACA
GCACCGACACCGTGGATACGGTCTTGGAGAAGAACGTGACCG
TGACCCATTCCGTGAACCTTCTCGAGGATAGCCACAATGGCA
AGCTGTGTAGACTCAAGGGCATTGCCCCGCTGCAGCTGGGAA
AGTGCAATATTGCTGGCTGGCTGTTGGGCAACCCTGAGTGTG
ACCCTCTGTTACCAGTGAGATCTTGGAGCTATATCGTCGAAA
CCCCTAACAGCGAGAACGGCATATGCTACCCAGGCGACTTCA
TCGACTACGAGGAACTGCGCGAGCAGCTGAGCTCTGTGTCGA
GCTTCGAGCGGTTCGAGATCTTCCCTAAGGAATCTAGCTGGC
CTAATCATAACACAAATGGCGTTACTGCTGCCTGTAGCCACG
AGGGAAAGAGCAGTTTCTACCGGAATCTGCTGTGGCTGACAG
AGAAGGAGGGCTCCTACCCTAAGCTGAAGAATAGCTATGTGA
ACAAGAAGGGCAAGGAGGTGCTGGTGCTGTGGGGAATACAC
CACCCACCTAACTCGAAGGAGCAGCAGAATCTGTACCAGAAT
GAGAATGCCTACGTGTCCGTCGTGACCTCCAACTACAACCGG
CGGTTCACGCCTGAGATCGCCGAGAGGCCTAAGGTGAGGGAC
CAGGCCGGACGCATGAACTACTACTGGACCCTGCTGAAGCCT
GGCGATACAATCATCTTCGAGGCTAATGGAAACCTGATCGCG
CCAATGTACGCCTTCGCCCTGTCCAGAGGATTCGGCAGCGGC
ATCATCACATCCAACGCCTCCATGCACGAATGCAACACCAAG
TGCCAGACGCCTCTGGGAGCTATCAATAGCAGCTTGCCTTAC
CAGAATATCCACCCTGTGACCATTGGAGAGTGTCCAAAGTAC
GTGCGCAGCGCAAAGCTGCGGATGGTCACAGGCCTGCGGAAT
ATACCTTCTATCCAGAGCCGAGGCCTGTTCGGTGCCATTGCCG
GCTTCATCGAGGGTGGCTGGACCGGAATGATCGACGGCTGGT
ATGGATACCACCACCAGAATGAACAGGGCAGCGGCTACGCC
GCCGATCAGAAGTCCACCCAGAACGCAATCAATGGTATCACA
AACAAGGTGAACACTGTAATCGAGAAGATGAACATCCAATTC
ACAGCCGTGGGCAAGGAGTTCAATAAGCTGGAGAAGCGGAT
GGAGAACCTCAACAAGAAGGTGGACGACGGCTTCCTGGATAT
CTGGACCTACAACGCAGAGCTGCTGGTGTTGCTGGAGAACGA
GAGAACCCTCGACTTCCATGATAGCAACGTTAAGAACCTATA
CGAGAAGGTGAAGTCACAGCTGAAGAATAACGCCAAGGAGA
TTGGCAACGGCTGCTTCGAATTCTACCACAAGTGCGACAACG
AGTGTATGGAGAGCGTCCGGAATGGCACCTACGACTATCCTA
AGTATAGCGAGGAGAGCAAGCTTAATAGAGAGAAGGTCGAT
GGCGTGAAGCTGGAGTCAATGGGAATCTACCAGATCCTGGCT
ATTTATTCAACCGTGGCATCAAGTCTGGTGCTTCTGGTCAGCC
TGGGCGCCATCAGCTTCTGGATGTGCTCCAATGGCAGCCTGC AATGCCGCATCTGCATA mRNA
AUGAAGGCCAAUUUGUUGGUCCUUCUAUGUGCCCUAGCCGC 541
CGCCGACGCCGACACAAUCUGCAUCGGAUAUCACGCAAACA
ACAGCACCGACACCGUGGAUACGGUCUUGGAGAAGAACGUG
ACCGUGACCCAUUCCGUGAACCUUCUCGAGGAUAGCCACAA
UGGCAAGCUGUGUAGACUCAAGGGCAUUGCCCCGCUGCAGC
UGGGAAAGUGCAAUAUUGCUGGCUGGCUGUUGGGCAACCC
UGAGUGUGACCCUCUGUUACCAGUGAGAUCUUGGAGCUAU
AUCGUCGAAACCCCUAACAGCGAGAACGGCAUAUGCUACCC
AGGCGACUUCAUCGACUACGAGGAACUGCGCGAGCAGCUGA
GCUCUGUGUCGAGCUUCGAGCGGUUCGAGAUCUUCCCUAAG
GAAUCUAGCUGGCCUAAUCAUAACACAAAUGGCGUUACUGC
UGCCUGUAGCCACGAGGGAAAGAGCAGUUUCUACCGGAAUC
UGCUGUGGCUGACAGAGAAGGAGGGCUCCUACCCUAAGCUG
AAGAAUAGCUAUGUGAACAAGAAGGGCAAGGAGGUGCUGG
UGCUGUGGGGAAUACACCACCCACCUAACUCGAAGGAGCAG
CAGAAUCUGUACCAGAAUGAGAAUGCCUACGUGUCCGUCGU
GACCUCCAACUACAACCGGCGGUUCACGCCUGAGAUCGCCG
AGAGGCCUAAGGUGAGGGACCAGGCCGGACGCAUGAACUAC
UACUGGACCCUGCUGAAGCCUGGCGAUACAAUCAUCUUCGA
GGCUAAUGGAAACCUGAUCGCGCCAAUGUACGCCUUCGCCC
UGUCCAGAGGAUUCGGCAGCGGCAUCAUCACAUCCAACGCC
UCCAUGCACGAAUGCAACACCAAGUGCCAGACGCCUCUGGG
AGCUAUCAAUAGCAGCUUGCCUUACCAGAAUAUCCACCCUG
UGACCAUUGGAGAGUGUCCAAAGUACGUGCGCAGCGCAAA
GCUGCGGAUGGUCACAGGCCUGCGGAAUAUACCUUCUAUCC
AGAGCCGAGGCCUGUUCGGUGCCAUUGCCGGCUUCAUCGAG
GGUGGCUGGACCGGAAUGAUCGACGGCUGGUAUGGAUACC
ACCACCAGAAUGAACAGGGCAGCGGCUACGCCGCCGAUCAG
AAGUCCACCCAGAACGCAAUCAAUGGUAUCACAAACAAGGU
GAACACUGUAAUCGAGAAGAUGAACAUCCAAUUCACAGCCG
UGGGCAAGGAGUUCAAUAAGCUGGAGAAGCGGAUGGAGAA
CCUCAACAAGAAGGUGGACGACGGCUUCCUGGAUAUCUGGA
CCUACAACGCAGAGCUGCUGGUGUUGCUGGAGAACGAGAG
AACCCUCGACUUCCAUGAUAGCAACGUUAAGAACCUAUACG
AGAAGGUGAAGUCACAGCUGAAGAAUAACGCCAAGGAGAU
UGGCAACGGCUGCUUCGAAUUCUACCACAAGUGCGACAACG
AGUGUAUGGAGAGCGUCCGGAAUGGCACCUACGACUAUCCU
AAGUAUAGCGAGGAGAGCAAGCUUAAUAGAGAGAAGGUCG
AUGGCGUGAAGCUGGAGUCAAUGGGAAUCUACCAGAUCCU
GGCUAUUUAUUCAACCGUGGCAUCAAGUCUGGUGCUUCUG
GUCAGCCUGGGCGCCAUCAGCUUCUGGAUGUGCUCCAAUGG CAGCCUGCAAUGCCGCAUCUGCAUA
Protein MKANLLVLLCALAAADADTICIGYHANNSTDTVDTVLEKNVTV 560
THSVNLLEDSHNGKLCRLKGIAPLQLGKCNIAGWLLGNPECDPL
LPVRSWSYIVETPNSENGICYPGDFIDYEELREQLSSVSSFERFEIF
PKESSWPNHNTNGVTAACSHEGKSSFYRNLLWLTEKEGSYPKL
KNSYVNKKGKEVLVLWGIHHPPNSKEQQNLYQNENAYVSVVT
SNYNRRFTPEIAERPKVRDQAGRMNYYWTLLKPGDTIIFEANGN
LIAPMYAFALSRGFGSGIITSNASMHECNTKCQTPLGAINSSLPY
QNIHPVTIGECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGFIE
GGWTGMIDGWYGYHHQNEQGSGYAADQKSTQNAINGITNKVN
TVIEKMNIQFTAVGKEFNKLEKRMENLNKKVDDGFLDIWTYNA
ELLVLLENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGCFEF
YHKCDNECMESVRNGTYDYPKYSEESKLNREKVDGVKLESMGI
YQILAIYSTVASSLVLLVSLGAISFWMCSNGSLQCRICI FLHA_Cal09 DNA
ATGAAGGCTATCTTGGTGGTGTTGTTGTACACATTCGCCACCG 523
CCAACGCCGACACCCTCTGCATCGGCTACCACGCGAACAATT
CAACCGACACCGTTGACACCGTCCTCGAGAAGAACGTGACCG
TGACTCATAGCGTCAACCTCCTCGAGGACAAGCATAACGGCA
AGCTCTGTAAGCTTAGAGGAGTGGCCCCTCTCCACCTGGGCA
AGTGTAACATTGCAGGCTGGATCCTGGGCAACCCTGAGTGCG
AGAGCCTGTCAACCGCTAGCAGCTGGAGCTACATCGTGGAAA
CCCCATCCAGCGATAACGGCACCTGCTACCCTGGCGATTTCA
TCGACTACGAGGAGCTGCGCGAGCAGTTGAGCAGCGTCTCCA
GCTTCGAGAGATTCGAGATCTTCCCTAAGACTAGCAGCTGGC
CTAATCATGACTCCAATAAGGGCGTGACGGCCGCCTGTCCTC
ACGCTGGAGCCAAGTCGTTCTACAAGAACCTGATCTGGCTGG
TAAAGAAGGGCAACAGCTACCCAAAGCTGAGCAAGTCCTAC
ATCAACGACAAGGGCAAGGAAGTGCTGGTGCTGTGGGGAAT
CCATCACCCAAGCACCTCTGCGGACCAGCAGTCTCTGTATCA
GAACGCCGACACCTATGTGTTCGTAGGCTCCTCCAGATACTC
CAAGAAGTTCAAGCCAGAGATTGCTATCCGCCCAAAGGTGCG
GGATCAAGAGGGTCGCATGAATTATTACTGGACCCTGGTCGA
GCCAGGCGATAAGATCACATTCGAAGCCACGGGAAATCTGGT
GGTGCCTAGATACGCTTTCGCCATGGAGAGAAACGCCGGCAG
CGGCATCATCATATCCGACACACCTGTGCACGACTGCAACAC
AACATGCCAGACGCCAAAGGGAGCCATCAACACATCTCTTCC
ATTCCAGAACATTCACCCAATCACAATCGGCAAGTGTCCAAA
GTACGTGAAGTCCACCAAGCTTAGACTGGCCACCGGCCTGCG
TAACATCCCTAGCATCCAGTCGAGAGGCCTCTTCGGCGCCAT
CGCCGGATTCATTGAAGGTGGCTGGACCGGCATGGTGGACGG
TTGGTATGGCTACCACCACCAGAACGAGCAGGGCAGCGGCTA
CGCCGCGGACCTGAAGTCCACCCAGAACGCTATTGACGAGAT
CACCAACAAGGTGAACAGCGTGATCGAGAAGATGAATACCC
AGTTCACCGCCGTCGGCAAGGAGTTCAACCATCTGGAGAAGA
GAATCGAGAACCTCAACAAGAAGGTCGACGACGGCTTCCTGG
ACATTTGGACTTACAACGCTGAGTTGTTGGTGCTTCTTGAGAA
TGAGCGGACCCTGGACTATCACGACTCAAATGTGAAGAACCT
GTACGAGAAGGTGAGATCCCAGCTGAAGAACAATGCTAAGG
AAATCGGCAACGGCTGCTTCGAGTTCTATCATAAGTGTGACA
ACACCTGCATGGAGTCTGTTAAGAACGGCACATACGACTACC
CGAAGTACTCTGAGGAGGCCAAGCTGAACCGAGAGGAGATA
GACGGCGTTAAGCTAGAAAGTACAAGGATCTACCAGATCCTT
GCCATCTACTCCACCGTGGCCTCCAGCCTGGTGTTGGTGGTGA
GCCTGGGCGCCATCAGCTTCTGGATGTGCAGTAACGGAAGCC TACAGTGCCGAATCTGCATC
mRNA AUGAAGGCUAUCUUGGUGGUGUUGUUGUACACAUUCGCCA 542
CCGCCAACGCCGACACCCUCUGCAUCGGCUACCACGCGAAC
AAUUCAACCGACACCGUUGACACCGUCCUCGAGAAGAACGU
GACCGUGACUCAUAGCGUCAACCUCCUCGAGGACAAGCAUA
ACGGCAAGCUCUGUAAGCUUAGAGGAGUGGCCCCUCUCCAC
CUGGGCAAGUGUAACAUUGCAGGCUGGAUCCUGGGCAACCC
UGAGUGCGAGAGCCUGUCAACCGCUAGCAGCUGGAGCUACA
UCGUGGAAACCCCAUCCAGCGAUAACGGCACCUGCUACCCU
GGCGAUUUCAUCGACUACGAGGAGCUGCGCGAGCAGUUGA
GCAGCGUCUCCAGCUUCGAGAGAUUCGAGAUCUUCCCUAAG
ACUAGCAGCUGGCCUAAUCAUGACUCCAAUAAGGGCGUGAC
GGCCGCCUGUCCUCACGCUGGAGCCAAGUCGUUCUACAAGA
ACCUGAUCUGGCUGGUAAAGAAGGGCAACAGCUACCCAAAG
CUGAGCAAGUCCUACAUCAACGACAAGGGCAAGGAAGUGCU
GGUGCUGUGGGGAAUCCAUCACCCAAGCACCUCUGCGGACC
AGCAGUCUCUGUAUCAGAACGCCGACACCUAUGUGUUCGUA
GGCUCCUCCAGAUACUCCAAGAAGUUCAAGCCAGAGAUUGC
UAUCCGCCCAAAGGUGCGGGAUCAAGAGGGUCGCAUGAAU
UAUUACUGGACCCUGGUCGAGCCAGGCGAUAAGAUCACAUU
CGAAGCCACGGGAAAUCUGGUGGUGCCUAGAUACGCUUUCG
CCAUGGAGAGAAACGCCGGCAGCGGCAUCAUCAUAUCCGAC
ACACCUGUGCACGACUGCAACACAACAUGCCAGACGCCAAA
GGGAGCCAUCAACACAUCUCUUCCAUUCCAGAACAUUCACC
CAAUCACAAUCGGCAAGUGUCCAAAGUACGUGAAGUCCACC
AAGCUUAGACUGGCCACCGGCCUGCGUAACAUCCCUAGCAU
CCAGUCGAGAGGCCUCUUCGGCGCCAUCGCCGGAUUCAUUG
AAGGUGGCUGGACCGGCAUGGUGGACGGUUGGUAUGGCUA
CCACCACCAGAACGAGCAGGGCAGCGGCUACGCCGCGGACC
UGAAGUCCACCCAGAACGCUAUUGACGAGAUCACCAACAAG
GUGAACAGCGUGAUCGAGAAGAUGAAUACCCAGUUCACCGC
CGUCGGCAAGGAGUUCAACCAUCUGGAGAAGAGAAUCGAG
AACCUCAACAAGAAGGUCGACGACGGCUUCCUGGACAUUUG
GACUUACAACGCUGAGUUGUUGGUGCUUCUUGAGAAUGAG
CGGACCCUGGACUAUCACGACUCAAAUGUGAAGAACCUGUA
CGAGAAGGUGAGAUCCCAGCUGAAGAACAAUGCUAAGGAA
AUCGGCAACGGCUGCUUCGAGUUCUAUCAUAAGUGUGACA
ACACCUGCAUGGAGUCUGUUAAGAACGGCACAUACGACUAC
CCGAAGUACUCUGAGGAGGCCAAGCUGAACCGAGAGGAGA
UAGACGGCGUUAAGCUAGAAAGUACAAGGAUCUACCAGAU
CCUUGCCAUCUACUCCACCGUGGCCUCCAGCCUGGUGUUGG
UGGUGAGCCUGGGCGCCAUCAGCUUCUGGAUGUGCAGUAAC
GGAAGCCUACAGUGCCGAAUCUGCAUC Protein
MKAILVVLLYTFATANADTLCIGYHANNSTDTVDTVLEKNVTV 561
THSVNLLEDKHNGKLCKLRGVAPLHLGKCNIAGWILGNPECESL
STASSWSYIVETPSSDNGTCYPGDFIDYEELREQLSSVSSFERFEIF
PKTSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPK
LSKSYINDKGKEVLVLWGIHHPSTSADQQSLYQNADTYVFVGSS
RYSKKFKPEIAIRPKVRDQEGRMNYYWTLVEPGDKITFEATGNL
VVPRYAFAMERNAGSGIIISDTPVHDCNTTCQTPKGAINTSLPFQ
NIHPITIGKCPKYVKSTKLRLATGLRNIPSIQSRGLFGAIAGFIEGG
WTGMVDGWYGYHHQNEQGSGYAADLKSTQNAIDEITNKVNSV
IEKMNTQFTAVGKEFNHLEKRIENLNKKVDDGFLDIWTYNAELL
VLLENERTLDYHDSNVKNLYEKVRSQLKNNAKEIGNGCFEFYH
KCDNTCMESVKNGTYDYPKYSEEAKLNREEIDGVKLESTRIYQI
LAIYSTVASSLVLVVSLGAISFWMCSNGSLQCRICI eH1HA_d5 Protein
METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDTVDTVLEKNV 562 v1
TVTHSVNLLEDSHNGKLCRLKGIAPLQLGKCNIAGWLLGNPECD
PLPPMKSWSYIVETPNSENGICYPGDFIDYEELREQLSSVSSFERF
EIFPKGSSWPNHNTNGVTAACSHEGKNSFYRNLLWLTKKEGLY
PNLENSYVNKKEKEVLVLWGIHHPSNNKEQQNLYQNENAYVSV
VTSNYNRRFTPEIAERPKVRDQAGRMNYYWTLLKPGDTIIFEAN
GNLIAPMYAFALSRGFGSGIITSNASMHECNTKCQTPLGAINSSL
PYQNIHPVTIGECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGF
IEGGWTGMIDGWYGYHHQNEQGSGYAADQKSTQNAINGITNK
VNTVIEKMNIQFTAVGKEFNKLEKRMENLNKKVDDGFLDIWTY
NAELLVLLENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGC
FEFYHKCDNECMESVRNGTYDYPKYSEESKLNREKVDGVKLES
MGIGSAGSAGYIPEAPRDGQAYVRKDGEWVLLSTFL eH1HA_d5 Protein
METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDTVDTVLEKNV 563 v2
TVTHSVNLLEDSHNGKLCRLKG1APLQLGKCN1AGWLLGNPECD
PLPPMKSWSYIVETPNSENGICYPGDFIDYEELREQLSSVSSFERF
EIFPKGSSWPNHTTNGVTAACSHEGKNSFYRNLLWLTKKEGSYP
NLKNSYVNKKEKEVLVLWGIHHPSNSKEQQNLYQNENAHVSV
VTSNYNRRFTPEIAERPKVRDQAGRMNYYWTLLKPGDTIIFEAD
GNLIAPMYAFALSRGFGSGIITSNASMHECNTKCQTPLGAINSSL
PYQNIHPVTIGECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGF
IEGGWTGMIDGWYGYHHQNEQGSGYAADQKSTQNAINGITNK
VNTVIEKMNIQFTAVGKEFNKLEKRMENLNKKVDDGFLDIWTY
NAELLVLLENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGC
FEFYHKCDNECMESVRNGTYDYPKYSEESKLNREKVDGVKLES
MGIGSAGSAGYIPEAPRDGQAYVRKDGEWVLLSTFL eH1HA_d5 Protein
METPAQLLFLLLLWLPDTTGDTICIGYFIANNSTDTVDTVLEKNV 564 v3
TVTHSVNLLEDSHNGKLCRLKGIAPLQLGKCNIAGWLLGNPECD
PLPPMKSWSYIVETPNSENGICYPGDFIDYEELREQLSSVSSFERF
EIFPKGSSWPDHNTNGVTAACSHEGKNSFYRNLLWLTEKKGSYP
NLKNPYVNKKEKEVLVLWGIHHPSNSKEQQNLYRNENAYVSV
VTSNYNRRFTPEIAERPKVRDQAGRMNYYWTLLKPGDTIIFEAN
GNLIAPMYAFALSRGFGSGIITSNASMHECNTKCQTPLGAINSSL
PYQNIHPVTIGECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGF
IEGGWTGMIDGWYGYHHQNEQGSGYAADQKSTQNAINGITNK
VNTVIEKMNIQFTAVGKEFNKLEKRMENLNKKVDDGFLDIWTY
NAELLVLLENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGC
FEFYHKCDNECMESVRNGTYDYPKYSEESKLNREKVDGVKLES
MGIGSAGSAGYIPEAPRDGQAYVRKDGEWVLLSTFL eH1HA_d5 Protein
METPAQLLFLLLLWLPDTTGDTICIGYHANNSTDTVDTVLEKNV 565 v4
TVTHSVNLLEDSHNGKLCKLKGIAPLQLGKCNIAGWLLGNPGC
DPLLPVGSWSYIVETPNSENGICYPGDFIDYEELREQLSSVSSFER
FKIFPKESSWPDHNTNGVTAACSHEGKNSFYRNLLWLTKKESSY
PNLENSYVNKKRKEVLVLWGIHHPSNSKEQQNLYQNENAYVSV
VTSNYNRRFTPEIAERPKVKGQAGRMNYYWTLLKPGDTIIFEAN
GNLIAPMYAFALSRGFGSGIITSNASMHECNTKCQTPLGAINSSL
PYQNIHPVTIGECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGF
IEGGWTGMIDGWYGYHHQNEQGSGYAADQKSTQNAINGITNK
VNTVIEKMNIQFTAVGKEFNKLEKRMENLNKKVDDGFLDIWTY
NAELLVLLENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGC
FEFYHKCDNECMESVRNGTYDYPKYSEESKLNREKVDGVKLES
MGIGSAGSAGYIPEAPRDGQAYVRKDGEWVLLSTFL eH1HA_d5 mRNA
AUGGAGACGCCUGCUCAGCUGCUCUUUCUGCUGCUCCUGUG 566 v1
GUUGCCCGAUACCACUGGGGACACUAUCUGUAUCGGAUACC
ACGCCAACAACUCAACCGAUACCGUGGAUACUGUCCUCGAA
AAGAAUGUGACCGUUACACAUUCAGUAAAUUUGUUAGAGG
AUUCUCACAAUGGGAAGCUGUGUCGACUGAAGGGGAUCGC
UCCCCUGCAACUGGGGAAGUGCAACAUCGCUGGAUGGUUGC
UCGGCAACCCGGAAUGCGAUCCGCUGCCACCCAUGAAGAGU
UGGAGCUAUAUUGUCGAGACCCCUAACUCAGAGAACGGUA
UAUGCUACCCUGGAGAUUUUAUCGAUUACGAAGAGCUGCG
GGAACAGCUGAGCAGCGUCUCCAGUUUCGAACGGUUUGAA
AUAUUCCCCAAGGGCAGUUCCUGGCCCAAUCACAACACUAA
UGGCGUCACCGCCGCCUGCUCACACGAGGGUAAGAACUCUU
UUUACCGCAAUCUGCUUUGGCUUACUAAGAAGGAAGGACU
GUACCCGAAUCUGGAGAACAGUUACGUCAACAAGAAAGAG
AAAGAGGUCCUGGUGCUGUGGGGAAUUCACCACCCUUCCAA
UAACAAGGAACAGCAGAAUCUGUACCAAAACGAAAAUGCU
UACGUGAGUGUGGUGACCUCGAACUAUAAUAGACGAUUCA
CACCUGAGAUUGCCGAGCGUCCCAAAGUUAGGGACCAAGCC
GGUAGGAUGAACUACUACUGGACUCUCCUGAAGCCCGGUGA
CACCAUUAUCUUCGAGGCCAAUGGUAAUCUGAUCGCCCCUA
UGUACGCUUUCGCACUGUCACGCGGGUUCGGAUCUGGGAUA
AUUACUUCGAACGCUAGCAUGCAUGAGUGUAAUACCAAGU
GCCAGACCCCACUUGGAGCAAUCAAUUCCAGCCUACCUUAU
CAGAAUAUUCAUCCCGUGACCAUCGGAGAAUGCCCAAAGUA
CGUUAGGUCCGCUAAACUGAGGAUGGUGACUGGCUUGAGG
AACAUACCAUCUAUCCAAUCUAGGGGCCUGUUUGGCGCUAU
UGCCGGGUUCAUCGAGGGUGGCUGGACAGGCAUGAUUGAC
GGGUGGUACGGUUACCACCACCAGAACGAGCAGGGAUCCGG
CUAUGCAGCUGACCAGAAGUCAACCCAGAACGCAAUCAACG
GCAUCACAAAUAAGGUCAAUACUGUGAUCGAAAAGAUGAA
CAUCCAAUUCACUGCCGUGGGCAAGGAGUUUAAUAAGCUCG
AGAAGCGCAUGGAAAAUCUGAACAAAAAAGUGGACGAUGG
CUUCCUGGAUAUAUGGACUUACAACGCCGAGCUCCUUGUGC
UUCUGGAGAACGAACGUACCUUGGACUUUCAUGAUAGUAA
CGUCAAGAAUUUGUACGAGAAGGUUAAAUCCCAGCUGAAG
AACAAUGCCAAGGAAAUCGGCAACGGCUGUUUUGAAUUUU
ACCAUAAAUGCGACAAUGAGUGCAUGGAAUCCGUACGCAA
UGGGACAUACGAUUACCCUAAAUACUCCGAGGAAAGCAAGC
UCAACCGAGAAAAAGUGGACGGCGUCAAGCUCGAAUCAAU
GGGUAUUGGCAGUGCCGGAUCCGCCGGGUAUAUCCCCGAGG
CCCCUAGAGACGGCCAAGCCUAUGUGCGGAAAGACGGCGAA UGGGUUCUGCUAUCCACCUUCUUA
eH1HA_d5 5' UTR GGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAG 574 v1
AGCCACC eH1HA_d5 3' UTR UGAUAAUAGGCUGGAGCCUCGGUGGCCAUGCUUCUUGCCCC
575 v1 UUGGGCCUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUA
CCCCCGUGGUCUUUGAAUAAAGUCUGAGUGGGCGGC eH1HA_d5 DNA
ATGGAGACGCCTGCTCAGCTGCTCTTTCTGCTGCTCCTGTGGT 570 v1
TGCCCGATACCACTGGGGACACTATCTGTATCGGATACCACG
CCAACAACTCAACCGATACCGTGGATACTGTCCTCGAAAAGA
ATGTGACCGTTACACATTCAGTAAATTTGTTAGAGGATTCTCA
CAATGGGAAGCTGTGTCGACTGAAGGGGATCGCTCCCCTGCA
ACTGGGGAAGTGCAACATCGCTGGATGGTTGCTCGGCAACCC
GGAATGCGATCCGCTGCCACCCATGAAGAGTTGGAGCTATAT
TGTCGAGACCCCTAACTCAGAGAACGGTATATGCTACCCTGG
AGATTTTATCGATTACGAAGAGCTGCGGGAACAGCTGAGCAG
CGTCTCCAGTTTCGAACGGTTTGAAATATTCCCCAAGGGCAG
TTCCTGGCCCAATCACAACACTAATGGCGTCACCGCCGCCTG
CTCACACGAGGGTAAGAACTCTTTTTACCGCAATCTGCTTTGG
CTTACTAAGAAGGAAGGACTGTACCCGAATCTGGAGAACAGT
TACGTCAACAAGAAAGAGAAAGAGGTCCTGGTGCTGTGGGG
AATTCACCACCCTTCCAATAACAAGGAACAGCAGAATCTGTA
CCAAAACGAAAATGCTTACGTGAGTGTGGTGACCTCGAACTA
TAATAGACGATTCACACCTGAGATTGCCGAGCGTCCCAAAGT
TAGGGACCAAGCCGGTAGGATGAACTACTACTGGACTCTCCT
GAAGCCCGGTGACACCATTATCTTCGAGGCCAATGGTAATCT
GATCGCCCCTATGTACGCTTTCGCACTGTCACGCGGGTTCGGA
TCTGGGATAATTACTTCGAACGCTAGCATGCATGAGTGTAAT
ACCAAGTGCCAGACCCCACTTGGAGCAATCAATTCCAGCCTA
CCTTATCAGAATATTCATCCCGTGACCATCGGAGAATGCCCA
AAGTACGTTAGGTCCGCTAAACTGAGGATGGTGACTGGCTTG
AGGAACATACCATCTATCCAATCTAGGGGCCTGTTTGGCGCT
ATTGCCGGGTTCATCGAGGGTGGCTGGACAGGCATGATTGAC
GGGTGGTACGGTTACCACCACCAGAACGAGCAGGGATCCGG
CTATGCAGCTGACCAGAAGTCAACCCAGAACGCAATCAACGG
CATCACAAATAAGGTCAATACTGTGATCGAAAAGATGAACAT
CCAATTCACTGCCGTGGGCAAGGAGTTTAATAAGCTCGAGAA
GCGCATGGAAAATCTGAACAAAAAAGTGGACGATGGCTTCCT
GGATATATGGACTTACAACGCCGAGCTCCTTGTGCTTCTGGA
GAACGAACGTACCTTGGACTTTCATGATAGTAACGTCAAGAA
TTTGTACGAGAAGGTTAAATCCCAGCTGAAGAACAATGCCAA
GGAAATCGGCAACGGCTGTTTTGAATTTTACCATAAATGCGA
CAATGAGTGCATGGAATCCGTACGCAATGGGACATACGATTA
CCCTAAATACTCCGAGGAAAGCAAGCTCAACCGAGAAAAAG
TGGACGGCGTCAAGCTCGAATCAATGGGTATTGGCAGTGCCG
GATCCGCCGGGTATATCCCCGAGGCCCCTAGAGACGGCCAAG
CCTATGTGCGGAAAGACGGCGAATGGGTTCTGCTATCCACCT TCTTA eH1HA_d5 mRNA
AUGGAGACGCCUGCUCAGCUGCUCUUUCUGCUGCUCCUGUG 567 v2
GUUGCCCGAUACCACUGGGGACACUAUCUGUAUCGGAUACC
ACGCCAACAACUCAACCGAUACCGUGGAUACUGUCCUCGAA
AAGAAUGUGACCGUUACACAUUCAGUAAAUUUGUUAGAGG
AUUCUCACAAUGGGAAGCUGUGUCGACUGAAGGGGAUCGC
UCCCCUGCAACUGGGGAAGUGCAACAUCGCUGGAUGGUUGC
UCGGCAACCCGGAAUGCGAUCCGCUGCCACCCAUGAAGAGU
UGGAGCUAUAUUGUCGAGACCCCUAACUCAGAGAACGGUA
UAUGCUACCCUGGAGAUUUUAUCGAUUACGAAGAGCUGCG
GGAACAGCUGAGCAGCGUCUCCAGUUUCGAACGGUUUGAA
AUAUUCCCCAAGGGCAGUUCCUGGCCCAAUCACACCACUAA
UGGCGUCACCGCCGCCUGCUCACACGAGGGUAAGAACUCUU
UUUACCGCAAUCUGCUUUGGCUUACUAAGAAGGAAGGAAG
UUACCCGAAUCUGAAAAACAGUUACGUCAACAAGAAAGAG
AAAGAGGUCCUGGUGCUGUGGGGAAUUCACCACCCUUCCAA
UUCGAAGGAACAGCAGAAUCUGUACCAAAACGAAAAUGCU
CACGUGAGUGUGGUGACCUCGAACUAUAAUAGACGAUUCA
CACCUGAGAUUGCCGAGCGUCCCAAAGUUAGGGACCAAGCC
GGUAGGAUGAACUACUACUGGACUCUCCUGAAGCCCGGUGA
CACCAUUAUCUUCGAGGCCGACGGUAAUCUGAUCGCCCCUA
UGUACGCUUUCGCACUGUCACGCGGGUUCGGAUCUGGGAUA
AUUACUUCGAACGCUAGCAUGCAUGAGUGUAAUACCAAGU
GCCAGACCCCACUUGGAGCAAUCAAUUCCAGCCUACCUUAU
CAGAAUAUUCAUCCCGUGACCAUCGGAGAAUGCCCAAAGUA
CGUUAGGUCCGCUAAACUGAGGAUGGUGACUGGCUUGAGG
AACAUACCAUCUAUCCAAUCUAGGGGCCUGUUUGGCGCUAU
UGCCGGGUUCAUCGAGGGUGGCUGGACAGGCAUGAUUGAC
GGGUGGUACGGUUACCACCACCAGAACGAGCAGGGAUCCGG
CUAUGCAGCUGACCAGAAGUCAACCCAGAACGCAAUCAACG
GCAUCACAAAUAAGGUCAAUACUGUGAUCGAAAAGAUGAA
CAUCCAAUUCACUGCCGUGGGCAAGGAGUUUAAUAAGCUCG
AGAAGCGCAUGGAAAAUCUGAACAAAAAAGUGGACGAUGG
CUUCCUGGAUAUAUGGACUUACAACGCCGAGCUCCUUGUGC
UUCUGGAGAACGAACGUACCUUGGACUUUCAUGAUAGUAA
CGUCAAGAAUUUGUACGAGAAGGUUAAAUCCCAGCUGAAG
AACAAUGCCAAGGAAAUCGGCAACGGCUGUUUUGAAUUUU
ACCAUAAAUGCGACAAUGAGUGCAUGGAAUCCGUACGCAA
UGGGACAUACGAUUACCCUAAAUACUCCGAGGAAAGCAAGC
UCAACCGAGAAAAAGUGGACGGCGUCAAGCUCGAAUCAAU
GGGUAUUGGCAGUGCCGGAUCCGCCGGGUAUAUCCCCGAGG
CCCCUAGAGACGGCCAAGCCUAUGUGCGGAAAGACGGCGAA UGGGUUCUGCUAUCCACCUUCUUA
eH1HA_d5 5' UTR GGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAG 574 v2
AGCCACC eH1HA_d5 3' UTR UGAUAAUAGGCUGGAGCCUCGGUGGCCAUGCUUCUUGCCCC
575 v2 UUGGGCCUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUA
CCCCCGUGGUCUUUGAAUAAAGUCUGAGUGGGCGGC eH1HA_d5 DNA
ATGGAGACGCCTGCTCAGCTGCTCTTTCTGCTGCTCCTGTGGT 571 v2
TGCCCGATACCACTGGGGACACTATCTGTATCGGATACCACG
CCAACAACTCAACCGATACCGTGGATACTGTCCTCGAAAAGA
ATGTGACCGTTACACATTCAGTAAATTTGTTAGAGGATTCTCA
CAATGGGAAGCTGTGTCGACTGAAGGGGATCGCTCCCCTGCA
ACTGGGGAAGTGCAACATCGCTGGATGGTTGCTCGGCAACCC
GGAATGCGATCCGCTGCCACCCATGAAGAGTTGGAGCTATAT
TGTCGAGACCCCTAACTCAGAGAACGGTATATGCTACCCTGG
AGATTTTATCGATTACGAAGAGCTGCGGGAACAGCTGAGCAG
CGTCTCCAGTTTCGAACGGTTTGAAATATTCCCCAAGGGCAG
TTCCTGGCCCAATCACACCACTAATGGCGTCACCGCCGCCTG
CTCACACGAGGGTAAGAACTCTTTTTACCGCAATCTGCTTTGG
CTTACTAAGAAGGAAGGAAGTTACCCGAATCTGAAAAACAGT
TACGTCAACAAGAAAGAGAAAGAGGTCCTGGTGCTGTGGGG
AATTCACCACCCTTCCAATTCGAAGGAACAGCAGAATCTGTA
CCAAAACGAAAATGCTCACGTGAGTGTGGTGACCTCGAACTA
TAATAGACGATTCACACCTGAGATTGCCGAGCGTCCCAAAGT
TAGGGACCAAGCCGGTAGGATGAACTACTACTGGACTCTCCT
GAAGCCCGGTGACACCATTATCTTCGAGGCCGACGGTAATCT
GATCGCCCCTATGTACGCTTTCGCACTGTCACGCGGGTTCGGA
TCTGGGATAATTACTTCGAACGCTAGCATGCATGAGTGTAAT
ACCAAGTGCCAGACCCCACTTGGAGCAATCAATTCCAGCCTA
CCTTATCAGAATATTCATCCCGTGACCATCGGAGAATGCCCA
AAGTACGTTAGGTCCGCTAAACTGAGGATGGTGACTGGCTTG
AGGAACATACCATCTATCCAATCTAGGGGCCTGTTTGGCGCT
ATTGCCGGGTTCATCGAGGGTGGCTGGACAGGCATGATTGAC
GGGTGGTACGGTTACCACCACCAGAACGAGCAGGGATCCGG
CTATGCAGCTGACCAGAAGTCAACCCAGAACGCAATCAACGG
CATCACAAATAAGGTCAATACTGTGATCGAAAAGATGAACAT
CCAATTCACTGCCGTGGGCAAGGAGTTTAATAAGCTCGAGAA
GCGCATGGAAAATCTGAACAAAAAAGTGGACGATGGCTTCCT
GGATATATGGACTTACAACGCCGAGCTCCTTGTGCTTCTGGA
GAACGAACGTACCTTGGACTTTCATGATAGTAACGTCAAGAA
TTTGTACGAGAAGGTTAAATCCCAGCTGAAGAACAATGCCAA
GGAAATCGGCAACGGCTGTTTTGAATTTTACCATAAATGCGA
CAATGAGTGCATGGAATCCGTACGCAATGGGACATACGATTA
CCCTAAATACTCCGAGGAAAGCAAGCTCAACCGAGAAAAAG
TGGACGGCGTCAAGCTCGAATCAATGGGTATTGGCAGTGCCG
GATCCGCCGGGTATATCCCCGAGGCCCCTAGAGACGGCCAAG
CCTATGTGCGGAAAGACGGCGAATGGGTTCTGCTATCCACCT TCTTA eH1HA_d5 mRNA
AUGGAGACGCCUGCUCAGCUGCUCUUUCUGCUGCUCCUGUG 568 v3
GUUGCCCGAUACCACUGGGGACACUAUCUGUAUCGGAUACC
ACGCCAACAACUCAACCGAUACCGUGGAUACUGUCCUCGAA
AAGAAUGUGACCGUUACACAUUCAGUAAAUUUGUUAGAGG
AUUCUCACAAUGGGAAGCUGUGUCGACUGAAGGGGAUCGC
UCCCCUGCAACUGGGGAAGUGCAACAUCGCUGGAUGGUUGC
UCGGCAACCCGGAAUGCGAUCCGCUGCCACCCAUGAAGAGU
UGGAGCUAUAUUGUCGAGACCCCUAACUCAGAGAACGGUA
UAUGCUACCCUGGAGAUUUUAUCGAUUACGAAGAGCUGCG
GGAACAGCUGAGCAGCGUCUCCAGUUUCGAACGGUUUGAA
AUAUUCCCCAAGGGCAGUUCCUGGCCCGACCACAACACUAA
UGGCGUCACCGCCGCCUGCUCACACGAGGGUAAGAACUCUU
UUUACCGCAAUCUGCUUUGGCUUACUGAGAAGAAGGGAAG
UUACCCGAAUCUGAAAAACCCCUACGUCAACAAGAAAGAGA
AAGAGGUCCUGGUGCUGUGGGGAAUUCACCACCCUUCCAAU
UCGAAGGAACAGCAGAAUCUGUACAGAAACGAAAAUGCUU
ACGUGAGUGUGGUGACCUCGAACUAUAAUAGACGAUUCAC
ACCUGAGAUUGCCGAGCGUCCCAAAGUUAGGGACCAAGCCG
GUAGGAUGAACUACUACUGGACUCUCCUGAAGCCCGGUGAC
ACCAUUAUCUUCGAGGCCAAUGGUAAUCUGAUCGCCCCUAU
GUACGCUUUCGCACUGUCACGCGGGUUCGGAUCUGGGAUAA
UUACUUCGAACGCUAGCAUGCAUGAGUGUAAUACCAAGUG
CCAGACCCCACUUGGAGCAAUCAAUUCCAGCCUACCUUAUC
AGAAUAUUCAUCCCGUGACCAUCGGAGAAUGCCCAAAGUAC
GUUAGGUCCGCUAAACUGAGGAUGGUGACUGGCUUGAGGA
ACAUACCAUCUAUCCAAUCUAGGGGCCUGUUUGGCGCUAUU
GCCGGGUUCAUCGAGGGUGGCUGGACAGGCAUGAUUGACG
GGUGGUACGGUUACCACCACCAGAACGAGCAGGGAUCCGGC
UAUGCAGCUGACCAGAAGUCAACCCAGAACGCAAUCAACGG
CAUCACAAAUAAGGUCAAUACUGUGAUCGAAAAGAUGAAC
AUCCAAUUCACUGCCGUGGGCAAGGAGUUUAAUAAGCUCG
AGAAGCGCAUGGAAAAUCUGAACAAAAAAGUGGACGAUGG
CUUCCUGGAUAUAUGGACUUACAACGCCGAGCUCCUUGUGC
UUCUGGAGAACGAACGUACCUUGGACUUUCAUGAUAGUAA
CGUCAAGAAUUUGUACGAGAAGGUUAAAUCCCAGCUGAAG
AACAAUGCCAAGGAAAUCGGCAACGGCUGUUUUGAAUUUU
ACCAUAAAUGCGACAAUGAGUGCAUGGAAUCCGUACGCAA
UGGGACAUACGAUUACCCUAAAUACUCCGAGGAAAGCAAGC
UCAACCGAGAAAAAGUGGACGGCGUCAAGCUCGAAUCAAU
GGGUAUUGGCAGUGCCGGAUCCGCCGGGUAUAUCCCCGAGG
CCCCUAGAGACGGCCAAGCCUAUGUGCGGAAAGACGGCGAA UGGGUUCUGCUAUCCACCUUCUUA
eH1HA_d5 5' UTR GGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAG 574 v3
AGCCACC eH1HA_d5 3' UTR UGAUAAUAGGCUGGAGCCUCGGUGGCCAUGCUUCUUGCCCC
575 v3 UUGGGCCUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUA
CCCCCGUGGUCUUUGAAUAAAGUCUGAGUGGGCGGC eH1HA_d5 DNA
ATGGAGACGCCTGCTCAGCTGCTCTTTCTGCTGCTCCTGTGGT 572 v3
TGCCCGATACCACTGGGGACACTATCTGTATCGGATACCACG
CCAACAACTCAACCGATACCGTGGATACTGTCCTCGAAAAGA
ATGTGACCGTTACACATTCAGTAAATTTGTTAGAGGATTCTCA
CAATGGGAAGCTGTGTCGACTGAAGGGGATCGCTCCCCTGCA
ACTGGGGAAGTGCAACATCGCTGGATGGTTGCTCGGCAACCC
GGAATGCGATCCGCTGCCACCCATGAAGAGTTGGAGCTATAT
TGTCGAGACCCCTAACTCAGAGAACGGTATATGCTACCCTGG
AGATTTTATCGATTACGAAGAGCTGCGGGAACAGCTGAGCAG
CGTCTCCAGTTTCGAACGGTTTGAAATATTCCCCAAGGGCAG
TTCCTGGCCCGACCACAACACTAATGGCGTCACCGCCGCCTG
CTCACACGAGGGTAAGAACTCTTTTTACCGCAATCTGCTTTGG
CTTACTGAGAAGAAGGGAAGTTACCCGAATCTGAAAAACCCC
TACGTCAACAAGAAAGAGAAAGAGGTCCTGGTGCTGTGGGG
AATTCACCACCCTTCCAATTCGAAGGAACAGCAGAATCTGTA
CAGAAACGAAAATGCTTACGTGAGTGTGGTGACCTCGAACTA
TAATAGACGATTCACACCTGAGATTGCCGAGCGTCCCAAAGT
TAGGGACCAAGCCGGTAGGATGAACTACTACTGGACTCTCCT
GAAGCCCGGTGACACCATTATCTTCGAGGCCAATGGTAATCT
GATCGCCCCTATGTACGCTTTCGCACTGTCACGCGGGTTCGGA
TCTGGGATAATTACTTCGAACGCTAGCATGCATGAGTGTAAT
ACCAAGTGCCAGACCCCACTTGGAGCAATCAATTCCAGCCTA
CCTTATCAGAATATTCATCCCGTGACCATCGGAGAATGCCCA
AAGTACGTTAGGTCCGCTAAACTGAGGATGGTGACTGGCTTG
AGGAACATACCATCTATCCAATCTAGGGGCCTGTTTGGCGCT
ATTGCCGGGTTCATCGAGGGTGGCTGGACAGGCATGATTGAC
GGGTGGTACGGTTACCACCACCAGAACGAGCAGGGATCCGG
CTATGCAGCTGACCAGAAGTCAACCCAGAACGCAATCAACGG
CATCACAAATAAGGTCAATACTGTGATCGAAAAGATGAACAT
CCAATTCACTGCCGTGGGCAAGGAGTTTAATAAGCTCGAGAA
GCGCATGGAAAATCTGAACAAAAAAGTGGACGATGGCTTCCT
GGATATATGGACTTACAACGCCGAGCTCCTTGTGCTTCTGGA
GAACGAACGTACCTTGGACTTTCATGATAGTAACGTCAAGAA
TTTGTACGAGAAGGTTAAATCCCAGCTGAAGAACAATGCCAA
GGAAATCGGCAACGGCTGTTTTGAATTTTACCATAAATGCGA
CAATGAGTGCATGGAATCCGTACGCAATGGGACATACGATTA
CCCTAAATACTCCGAGGAAAGCAAGCTCAACCGAGAAAAAG
TGGACGGCGTCAAGCTCGAATCAATGGGTATTGGCAGTGCCG
GATCCGCCGGGTATATCCCCGAGGCCCCTAGAGACGGCCAAG
CCTATGTGCGGAAAGACGGCGAATGGGTTCTGCTATCCACCT TCTTA eH1HA_d5 mRNA
AUGGAGACGCCUGCUCAGCUGCUCUUUCUGCUGCUCCUGUG 569 v4
GUUGCCCGAUACCACUGGGGACACUAUCUGUAUCGGAUACC
ACGCCAACAACUCAACCGAUACCGUGGAUACUGUCCUCGAA
AAGAAUGUGACCGUUACACAUUCAGUAAAUUUGUUAGAGG
AUUCUCACAAUGGGAAGCUGUGUAAGCUGAAGGGGAUCGC
UCCCCUGCAACUGGGGAAGUGCAACAUCGCUGGAUGGUUGC
UCGGCAACCCGGGCUGCGAUCCGCUGCUGCCCGUUGGCAGU
UGGAGCUAUAUUGUCGAGACCCCUAACUCAGAGAACGGUA
UAUGCUACCCUGGAGAUUUUAUCGAUUACGAAGAGCUGCG
GGAACAGCUGAGCAGCGUCUCCAGUUUCGAACGGUUUAAG
AUAUUCCCCAAGGAGAGUUCCUGGCCCGACCACAACACUAA
UGGCGUCACCGCCGCCUGCUCACACGAGGGUAAGAACUCUU
UUUACCGCAAUCUGCUUUGGCUUACUAAGAAGGAAAGCAG
UUACCCGAAUCUGGAGAACAGUUACGUCAACAAGAAACGG
AAAGAGGUCCUGGUGCUGUGGGGAAUUCACCACCCUUCCAA
UUCGAAGGAACAGCAGAAUCUGUACCAAAACGAAAAUGCU
UACGUGAGUGUGGUGACCUCGAACUAUAAUAGACGAUUCA
CACCUGAGAUUGCCGAGCGUCCCAAAGUUAAGGGCCAAGCC
GGUAGGAUGAACUACUACUGGACUCUCCUGAAGCCCGGUGA
CACCAUUAUCUUCGAGGCCAAUGGUAAUCUGAUCGCCCCUA
UGUACGCUUUCGCACUGUCACGCGGGUUCGGAUCUGGGAUA
AUUACUUCGAACGCUAGCAUGCAUGAGUGUAAUACCAAGU
GCCAGACCCCACUUGGAGCAAUCAAUUCCAGCCUACCUUAU
CAGAAUAUUCAUCCCGUGACCAUCGGAGAAUGCCCAAAGUA
CGUUAGGUCCGCUAAACUGAGGAUGGUGACUGGCUUGAGG
AACAUACCAUCUAUCCAAUCUAGGGGCCUGUUUGGCGCUAU
UGCCGGGUUCAUCGAGGGUGGCUGGACAGGCAUGAUUGAC
GGGUGGUACGGUUACCACCACCAGAACGAGCAGGGAUCCGG
CUAUGCAGCUGACCAGAAGUCAACCCAGAACGCAAUCAACG
GCAUCACAAAUAAGGUCAAUACUGUGAUCGAAAAGAUGAA
CAUCCAAUUCACUGCCGUGGGCAAGGAGUUUAAUAAGCUCG
AGAAGCGCAUGGAAAAUCUGAACAAAAAAGUGGACGAUGG
CUUCCUGGAUAUAUGGACUUACAACGCCGAGCUCCUUGUGC
UUCUGGAGAACGAACGUACCUUGGACUUUCAUGAUAGUAA
CGUCAAGAAUUUGUACGAGAAGGUUAAAUCCCAGCUGAAG
AACAAUGCCAAGGAAAUCGGCAACGGCUGUUUUGAAUUUU
ACCAUAAAUGCGACAAUGAGUGCAUGGAAUCCGUACGCAA
UGGGACAUACGAUUACCCUAAAUACUCCGAGGAAAGCAAGC
UCAACCGAGAAAAAGUGGACGGCGUCAAGCUCGAAUCAAU
GGGUAUUGGCAGUGCCGGAUCCGCCGGGUAUAUCCCCGAGG
CCCCUAGAGACGGCCAAGCCUAUGUGCGGAAAGACGGCGAA UGGGUUCUGCUAUCCACCUUCUUA
eH1HA_d5 5' UTR GGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAG 574 v4
AGCCACC eH1HA_d5 3' UTR UGAUAAUAGGCUGGAGCCUCGGUGGCCAUGCUUCUUGCCCC
575 v4 UUGGGCCUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUA
CCCCCGUGGUCUUUGAAUAAAGUCUGAGUGGGCGGC eH1HA_d5 DNA
ATGGAGACGCCTGCTCAGCTGCTCTTTCTGCTGCTCCTGTGGT 573 v4
TGCCCGATACCACTGGGGACACTATCTGTATCGGATACCACG
CCAACAACTCAACCGATACCGTGGATACTGTCCTCGAAAAGA
ATGTGACCGTTACACATTCAGTAAATTTGTTAGAGGATTCTCA
CAATGGGAAGCTGTGTAAGCTGAAGGGGATCGCTCCCCTGCA
ACTGGGGAAGTGCAACATCGCTGGATGGTTGCTCGGCAACCC
GGGCTGCGATCCGCTGCTGCCCGTTGGCAGTTGGAGCTATAT
TGTCGAGACCCCTAACTCAGAGAACGGTATATGCTACCCTGG
AGATTTTATCGATTACGAAGAGCTGCGGGAACAGCTGAGCAG
CGTCTCCAGTTTCGAACGGTTTAAGATATTCCCCAAGGAGAG
TTCCTGGCCCGACCACAACACTAATGGCGTCACCGCCGCCTG
CTCACACGAGGGTAAGAACTCTTTTTACCGCAATCTGCTTTGG
CTTACTAAGAAGGAAAGCAGTTACCCGAATCTGGAGAACAGT
TACGTCAACAAGAAACGGAAAGAGGTCCTGGTGCTGTGGGG
AATTCACCACCCTTCCAATTCGAAGGAACAGCAGAATCTGTA
CCAAAACGAAAATGCTTACGTGAGTGTGGTGACCTCGAACTA
TAATAGACGATTCACACCTGAGATTGCCGAGCGTCCCAAAGT
TAAGGGCCAAGCCGGTAGGATGAACTACTACTGGACTCTCCT
GAAGCCCGGTGACACCATTATCTTCGAGGCCAATGGTAATCT
GATCGCCCCTATGTACGCTTTCGCACTGTCACGCGGGTTCGGA
TCTGGGATAATTACTTCGAACGCTAGCATGCATGAGTGTAAT
ACCAAGTGCCAGACCCCACTTGGAGCAATCAATTCCAGCCTA
CCTTATCAGAATATTCATCCCGTGACCATCGGAGAATGCCCA
AAGTACGTTAGGTCCGCTAAACTGAGGATGGTGACTGGCTTG
AGGAACATACCATCTATCCAATCTAGGGGCCTGTTTGGCGCT
ATTGCCGGGTTCATCGAGGGTGGCTGGACAGGCATGATTGAC
GGGTGGTACGGTTACCACCACCAGAACGAGCAGGGATCCGG
CTATGCAGCTGACCAGAAGTCAACCCAGAACGCAATCAACGG
CATCACAAATAAGGTCAATACTGTGATCGAAAAGATGAACAT
CCAATTCACTGCCGTGGGCAAGGAGTTTAATAAGCTCGAGAA
GCGCATGGAAAATCTGAACAAAAAAGTGGACGATGGCTTCCT
GGATATATGGACTTACAACGCCGAGCTCCTTGTGCTTCTGGA
GAACGAACGTACCTTGGACTTTCATGATAGTAACGTCAAGAA
TTTGTACGAGAAGGTTAAATCCCAGCTGAAGAACAATGCCAA
GGAAATCGGCAACGGCTGTTTTGAATTTTACCATAAATGCGA
CAATGAGTGCATGGAATCCGTACGCAATGGGACATACGATTA
CCCTAAATACTCCGAGGAAAGCAAGCTCAACCGAGAAAAAG
TGGACGGCGTCAAGCTCGAATCAATGGGTATTGGCAGTGCCG
GATCCGCCGGGTATATCCCCGAGGCCCCTAGAGACGGCCAAG
CCTATGTGCGGAAAGACGGCGAATGGGTTCTGCTATCCACCT TCTTA
[0964] It should be understood that the 5' and/or 3' UTR for each
construct may be omitted, modified or substituted for a different
UTR sequences in any one of the vaccines as provided herein.
Equivalents
[0965] Those skilled in the art will recognize, or be able to
ascertain using no more than routine experimentation, many
equivalents to the specific embodiments of the disclosure described
herein. Such equivalents are intended to be encompassed by the
following claims.
[0966] All references, including patent documents, disclosed herein
are incorporated by reference in their entirety.
Sequence CWU 0 SQTB SEQUENCE LISTING The patent application
contains a lengthy "Sequence Listing" section. A copy of the
"Sequence Listing" is available in electronic form from the USPTO
web site
(https://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US20220080038A9).
An electronic copy of the "Sequence Listing" will also be available
from the USPTO upon request and payment of the fee set forth in 37
CFR 1.19(b)(3).
0 SQTB SEQUENCE LISTING The patent application contains a lengthy
"Sequence Listing" section. A copy of the "Sequence Listing" is
available in electronic form from the USPTO web site
(https://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US20220080038A9).
An electronic copy of the "Sequence Listing" will also be available
from the USPTO upon request and payment of the fee set forth in 37
CFR 1.19(b)(3).
* * * * *
References