U.S. patent application number 13/878835 was filed with the patent office on 2014-01-30 for antigen delivery platforms.
This patent application is currently assigned to Novartis AG. The applicant listed for this patent is Michael Franti, Anders Lilja, Rebecca Loomis, Peter Mason. Invention is credited to Michael Franti, Anders Lilja, Rebecca Loomis, Peter Mason.
Application Number | 20140030292 13/878835 |
Document ID | / |
Family ID | 45002110 |
Filed Date | 2014-01-30 |
United States Patent
Application |
20140030292 |
Kind Code |
A1 |
Franti; Michael ; et
al. |
January 30, 2014 |
ANTIGEN DELIVERY PLATFORMS
Abstract
This disclosure provides platforms for delivery of herpes virus
proteins to cells, particularly proteins that form complexes in
vivo. In some embodiments these proteins and the complexes they
form elicit potent neutralizing antibodies. Thus, presentation of
herpes virus proteins using the disclosed platforms permits the
generation of broad and potent immune responses useful for vaccine
development.
Inventors: |
Franti; Michael; (Redding,
CT) ; Lilja; Anders; (Somerville, MA) ;
Loomis; Rebecca; (Philadelphia, PA) ; Mason;
Peter; (Somerville, MA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Franti; Michael
Lilja; Anders
Loomis; Rebecca
Mason; Peter |
Redding
Somerville
Philadelphia
Somerville |
CT
MA
PA
MA |
US
US
US
US |
|
|
Assignee: |
Novartis AG
Basel
CH
|
Family ID: |
45002110 |
Appl. No.: |
13/878835 |
Filed: |
October 11, 2011 |
PCT Filed: |
October 11, 2011 |
PCT NO: |
PCT/US11/55834 |
371 Date: |
October 10, 2013 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
61391960 |
Oct 11, 2010 |
|
|
|
Current U.S.
Class: |
424/229.1 ;
435/320.1; 435/375; 435/70.4; 536/23.1; 536/23.72 |
Current CPC
Class: |
A61K 2039/5256 20130101;
A61K 39/12 20130101; C12N 15/86 20130101; C12N 2710/16122 20130101;
C12N 2770/36143 20130101; C12N 2710/16722 20130101; C07K 2319/92
20130101; A61K 2039/55555 20130101; A61P 31/22 20180101; C12N
2710/16134 20130101; C12N 2830/20 20130101; C12N 2840/203 20130101;
C12N 2710/16734 20130101; A61P 37/04 20180101; C07K 14/005
20130101; A61K 2039/53 20130101 |
Class at
Publication: |
424/229.1 ;
536/23.72; 435/70.4; 435/375; 536/23.1; 435/320.1 |
International
Class: |
C07K 14/005 20060101
C07K014/005; C12N 15/86 20060101 C12N015/86 |
Claims
1. A self-replicating RNA molecule comprising a polynucleotide
which comprises: a. a first nucleotide sequence encoding a first
protein or fragment thereof from a herpes virus or fragment
thereof; and b. a second nucleotide sequence encoding a second
protein or fragment thereof from said herpes virus or fragment
thereof; wherein the first nucleotide sequence and second
nucleotide sequence are operably linked to one or more control
elements so that when the self-replicating RNA molecule is
introduced into a suitable cell, the first and second herpes virus
proteins or fragments thereof are produced in an amount sufficient
for the formation of a complex in the cell that contains the first
and second proteins or fragments.
2. The self-replicating RNA molecule of claim 1 with the proviso
that the first protein and the second protein are not the same
protein or fragments of the same protein, the first protein is not
a fragment of the second protein, and the second protein is not a
fragment of the first protein.
3. The self-replicating RNA molecule of claim 2, wherein the first
nucleotide sequence is operably linked to a first control element
and the second nucleotide sequence is operably linked to a second
control element.
4. The self-replicating RNA molecule of claim 1, further comprising
a third nucleotide sequence encoding a third protein or fragment
thereof from said herpes virus, wherein the third nucleotide
sequences is operably linked to a control element.
5. The self-replicating RNA molecule of claim 4, wherein the third
nucleotide sequence is operably linked to a third control
element.
6. The self-replicating RNA molecule of claim 4, further comprising
a fourth nucleotide sequence encoding a fourth protein or fragment
thereof from said herpes virus, wherein the fourth nucleotide
sequences is operably linked to a control element.
7. The self-replicating RNA molecule of claim 6, wherein the fourth
nucleotide sequence is operably linked to a fourth control
element.
8. The self-replicating RNA molecule of claim 6, further comprising
a fifth nucleotide sequence encoding a fifth protein or fragment
thereof from said herpes virus, wherein the fifth nucleotide
sequences is operably linked to a control element.
9. The self-replicating RNA molecule of claim 8, wherein the fifth
nucleotide sequence is operably linked to a fifth control
element.
10. The self-replicating RNA molecule of claim 1 wherein the
control elements are independently selected from the group
consisting of a subgenomic promoter, an IRES, and a viral 2A
site.
11. The self-replicating RNA molecule of claim 1, wherein the
herpes virus is cytomegalovirus (CMV).
12. The self-replicating RNA molecule of claim 8 wherein the first
protein or fragment, the second protein or fragment, the third
protein or fragment, the fourth protein or fragment, and the fifth
protein or fragment are independently selected from the group
consisting of gB, gH, gL; gO; gM, gN; UL128, UL130, UL131, and a
fragment of any one of the foregoing.
13. The self-replicating RNA molecule of claim 11, wherein the
first protein or fragment is gH or a fragment thereof, and the
second protein or fragment is gL or a fragment thereof.
14. The self-replicating RNA molecule of claim 11, wherein the
first protein or fragment is gH or a fragment thereof, and the
second protein or fragment is gL or a fragment thereof, and the
third protein or fragment is gO or a fragment thereof.
15. The self-replicating RNA molecule of claim 11, wherein the
first protein or fragment is gH or a fragment thereof, and the
second protein or fragment is gL or a fragment thereof, the third
protein or fragment is UL128 or a fragment thereof, the fourth
protein or fragment is UL130 or a fragment thereof, and the fifth
protein or fragment is UL131 or a fragment thereof.
16. The self-replicating RNA molecule of claim 1, wherein the
herpes virus is varicella zoster virus (VZV).
17. The self-replicating RNA molecule of claim 16, wherein the
first protein or fragment, the second protein or fragment, the
third protein or fragment, the fourth protein or fragment, and the
fifth protein or fragment are independently selected from the group
consisting of gB, gE, gH, gI, gL, and a fragment of any one of the
foregoing.
18. The self-replicating RNA molecule of claim 16, wherein the
first protein or fragment is gH or a fragment thereof, and the
second protein or fragment is gL or a fragment thereof.
19. The self-replicating RNA molecule of claim 8, wherein the
self-replicating RNA molecule is an alphavirus replicon.
20. (canceled)
21. (canceled)
22. (canceled)
23. (canceled)
24. A composition comprising the self-replicating RNA of claim 1
and a pharmaceutically acceptable vehicle.
25. The composition of claim 24, further comprising a second
self-replicating RNA molecule that encodes a protein or fragment
thereof from the herpes virus.
26. The composition of claim 24, further comprising an RNA delivery
system.
27. The composition of claim 26, wherein the RNA delivery system is
a liposome, a polymeric nanoparticle, an oil-in-water cationic
nanoemulsion or combinations thereof.
28. (canceled)
29. A method of forming a protein complex, comprising delivering an
alphavirus replicon particle (VRP) comprising a self-replicating
RNA molecule of claim 8 to a cell, and maintaining the cell under
conditions suitable for expression of the alphavirus replicon,
wherein a protein complex is formed.
30. The method of claim 29 wherein the cell is in vivo.
31. A method of forming a protein complex, comprising delivering
the self-replicating RNA of claim 1 to a cell, and maintaining the
cell under conditions suitable for expression of said
self-replicating RNA, wherein a protein complex is formed.
32. (canceled)
33. A method of inhibiting herpes virus entry into a cell
comprising contacting the cell with the self-replicating RNA of
claim 1.
34. A method of inhibiting herpes virus entry into a cell
comprising contacting the cell with an alphavirus replicon particle
(VRP) comprising a self-replicating RNA molecule of claim 8.
35. The method of claim 33 wherein the cell is selected from the
group consisting of an epithelial cell, an endothelial cell, and a
fibroblast.
36. (canceled)
37. (canceled)
38. (canceled)
39. A method of inducing an immune response in an individual,
comprising administering to the individual a self-replicating RNA
molecule of claim 1.
40. The method of claim 39, wherein the immune response comprises
the production of neutralizing antibodies.
41. The method of claim 40 wherein the neutralizing antibodies are
complement-independent.
42. A recombinant DNA molecule that encodes the self-replicating
RNA molecule of claim 1.
43. The recombinant DNA molecule of claim 42, wherein the
recombinant DNA molecule is a plasmid.
44. (canceled)
45. (canceled)
46. (canceled)
Description
RELATED APPLICATION
[0001] This application claims the benefit of U.S. Provisional
Patent Application No. 61/391,960, filed on Oct. 11, 2010, the
entire teachings of which are incorporated herein by reference.
BACKGROUND
[0002] Herpes viruses are widespread and cause a wide range of
diseases in humans that in the worst cases can lead to substantial
morbidity and mortality, primarily in immunocompromised individuals
(e.g., transplant recipients and HIV-infected individuals). Humans
are susceptible to infection by at least eight herpes viruses.
Herpes simplex virus-1 (HSV-1, HHV-1), Herpes simplex virus-2
(HSV-2, HHV-2) and Varicella zoster virus (VZV, HHV-3) are
alpha-subfamily viruses, cytomegalovirus (CMV, HHV-5) and
Roseoloviruses (HHV-6 and HHV-7) are beta-subfamily viruses,
Epstein-Barr virus (EBV, HHV-4) and Kaposi's sarcoma-associated
herpesvirus (KSHV, HHV-8) are gamma-subfamily viruses that infect
humans.
[0003] CMV infection leads to substantial morbidity and mortality
in immunocompromised individuals (e.g., transplant recipients and
HIV-infected individuals) and congenital infection can result in
devastating defects in neurological development in neonates. CMV
envelope glycoproteins gB, gH, gL, gM and gN represent attractive
vaccine candidates as they are expressed on the viral surface and
can elicit protective virus-neutralizing humoral immune responses.
Some CMV vaccine strategies have targeted the major surface
glycoprotein B (gB), which can induce a dominant antibody response.
(Go and Pollard, JID 197:1631-1633 (2008)). CMV glycoprotein gB can
induce a neutralizing antibody response, and a large fraction of
the antibodies that neutralize infection of fibroblasts in sera
from CMV-positive patients is directed against gB (Britt 1990).
Similarly, it has been reported that gH and gM/gN are targets of
the immune response to natural infection (Urban et al (1996) J.
Gen. Virol. 77(Pt. 7):1537-47; Mach et al (2000) J. Virol.
74(24):11881-92).
[0004] Complexes of CMV proteins are also attractive vaccine
candidates because they appear to be involved in important
processes in the viral life cycle. For example, the gH/gL/gO
complex seems to have important roles in both fibroblast and
epithelial/endothelial cell entry. The prevailing model suggests
that the gH/gL/gO complex mediates infection of fibroblasts. hCMV
gO-null mutants produce small plaques on fibroblasts and very low
titer virus indicating a role in entry (Dunn (2003), Proc. Natl.
Acad. Sci. USA 100:14223-28; Hobom (2000) J. Virol. 74:7720-29).
Recent studies suggest that gO is not incorporated into virions
with gH/gL, but may act as a molecular chaperone, increasing gH/gL
export from the ER to the Golgi apparatus and incorporation into
virions (Ryckman (2009) J. Virol 82:60-70). Through pulse-chase
experiments, it was shown that small amounts of gO remain bound to
gH/gL for long periods of time but most gO dissociates and or is
degraded from the gH/gL/gO complex, as it is not found in
extracellular virions or secreted from cells. When gO was deleted
from a clinical strain of CMV (TR) those viral particles had
significantly reduced amounts of gH/gL incorporated into the
virion. Additionally, gO deleted from TR virus also inhibited entry
into epithelial and endothelial cells, suggesting that gH/gL is
also required for epithelial/endothelial cell entry (Wille (2010)
J. Virol. 84(5):2585-96).
[0005] CMV gH/gL can also associate with UL128, UL130, and UL131A
(referred to here as UL131) and form a pentameric complex that is
required for entry into several cell types, including epithelial
cells, endothelial cells, and dendritic cells (Hahn et al (2004) J.
Virol. 78(18):10023-33; Wang and Shenk (2005) Proc. Natl. Acad.
Sci. USA 102(50):18153-8; Gerna et al (2005). J. Gen. Virol. 84(Pt
6):1431-6; Ryckman et al (2008) J. Virol. 82:60-70). In contrast,
this complex is not required for infection of fibroblasts.
Laboratory hCMV isolates carry mutations in the UL128-UL131 locus,
and mutations arise in clinical isolates after only a few passages
in cultured fibroblasts (Akter et al (2003) J. Gen. Virol. 84(Pt
5):1117-22). During natural infection, the pentameric complex
elicits antibodies that neutralize infection of epithelial cells,
endothelial cells (and likely any other cell type where the
pentameric complex mediates viral entry) with very high potency
(Macagno et al (2010) J. Virol. 84(2):1005-13). It also appears
that antibodies to this complex contribute significantly to the
ability of human sera to neutralize infection of epithelial cells
(Genini et al (2011) J. Clin. Virol. 52(2):113-8).
[0006] U.S. Pat. No. 5,767,250 discloses methods for making certain
CMV protein complexes that contain gH and gL. The complexes are
produced by introducing a DNA construct that encodes gH and a DNA
construct that encodes gL into a cell so that the gH and gL are
co-expressed.
[0007] WO 2004/076645 describes recombinant DNA molecules that
encode CMV proteins. According to this document, combinations of
distinct DNA molecules that encode different CMV proteins, can be
introduced into cells to cause co-expression of the encoded CMV
proteins. When gM and gN were co-expressed in this way, they formed
a disulfide-linked complex. Rabbits immunized with DNA constructs
that produced the gM/gN complex or with a DNA construct encoding gB
produced equivalent neutralizing antibody responses.
[0008] A need exists for nucleic acids that encode two or more
herpes virus proteins, for methods of expressing two or more herpes
virus proteins in the same cell, and for immunization methods that
produce better immune responses.
SUMMARY OF THE INVENTION
[0009] The invention relates to platforms for co-delivery of two or
more herpesvirus proteins, such as cytomegalovirus (CMV) proteins,
to cells, particularly proteins that form complexes in vivo. In one
aspect, the invention is a recombinant polycistronic nucleic acid
molecules that contain a first sequence encoding a first
herpesvirus (e.g., CMV) protein or fragment thereof, and a second
sequence encoding a second herpesvirus (e.g., CMV) protein or
fragment thereof.
[0010] For example, the invention provides a self-replicating RNA
molecule comprising a polynucleotide which comprises a) a first
nucleotide sequence encoding a first protein or fragment thereof
from a herpes virus; and b) a second nucleotide sequence encoding a
second protein or fragment thereof from the herpes virus. The first
nucleotide sequence and second nucleotide sequence are operably
linked to one or more control elements so that when the
self-replicating RNA molecule is introduced into a suitable cell,
the first and second herpes virus proteins or fragments thereof are
produced in an amount sufficient for the formation of a complex in
the cell that contains the first and second proteins or fragments.
Preferably, the first protein and the second protein are not the
same protein or fragments of the same protein, the first protein is
not a fragment of the second protein, and the second protein is not
a fragment of the first protein. The first nucleotide sequence can
be operably linked to a first control element and the second
nucleotide sequence can be operably linked to a second control
element.
[0011] The self-replicating RNA molecule can further comprise a
third nucleotide sequence encoding a third protein or fragment
thereof from said herpes virus, optionally a fourth nucleotide
sequence encoding a fourth protein or fragment thereof from said
herpes virus; and optionally a fifth nucleotide sequence encoding a
fifth protein or fragment thereof from said herpes virus. When
sequences encoding additional proteins or fragments from a herpes
virus are present (i.e., the third, fourth and fifth nucleotide
sequences) they are operably linked to one or more control
elements. In one example of a pentacistronic construct, the first
nucleotide sequence is operably linked to a first control element,
the second nucleotide sequence is operably linked to a second
control element, the third nucleotide sequence is operably linked
to a third control element, the fourth nucleotide sequence is
operably linked to a fourth control element, and the fifth
nucleotide sequence is operably linked to a fifth control element.
The control elements present in the construct (e.g., first, second,
third, fourth and fifth control elements) can be independently
selected from the group consisting of a subgenomic promoter, an
IRES, and a viral (e.g., FMDV) 2A site.
[0012] The herpes virus can be HSV-1, 1, HSV-2, VZV, EBV type 1,
EBV type 2, CMV, HHV-6 type A, HHV-6 type B, HHV-7 and HHV-8. In
some embodiments, the recombinant polycistronic nucleic acid
molecule (e.g., self replicating RNA) encodes gH or a fragment
thereof and gL or a fragment thereof of any one of these herpes
viruses. In more particular embodiments, the herpes virus is CMV or
VZV.
[0013] When the recombinant polycistronic nucleic acid molecule
(e.g., self replicating RNA) encodes two or more VZV proteins, the
proteins can be selected from the group consisting of gB, gE, gH,
gI, gL and a fragment (e.g., of at least 10 amino acids) thereof.
In some embodiments, the recombinant polycistronic nucleic acid
molecule (e.g., self replicating RNA) encodes VZV gH or a fragment
thereof and VZV gL or a fragment thereof.
[0014] In a particular example, the invention provides a
self-replicating RNA molecule comprising a polynucleotide which
comprises a) a first sequence encoding a first cytomegalovirus
(CMV) protein or fragment thereof; and b) a second sequence
encoding a second CMV protein or fragment thereof. The first
sequence and second sequence are operably linked to one or more
control elements so that when the self-replicating RNA molecule is
introduced into a suitable cell, the first and second CMV proteins
are produced in an amount sufficient for the formation of a complex
in the cell that contains the first and second CMV proteins or
fragments.
[0015] The first CMV protein and the second CMV protein are
independently selected from the group consisting of gB, gH, gL; gO;
gM, gN; UL128, UL130, UL131, and a fragment of any one of the
foregoing. Preferably, the first CMV protein and the second CMV
protein are not the same protein or fragments of the same protein,
the first CMV protein is not a fragment of the second CMV protein,
and the second CMV protein is not a fragment of the first CMV
protein. If desired, the self-replicating RNA molecule can further
comprise a third sequence encoding a third CMV protein, wherein the
third sequences is operably linked to a control element. Similarly,
additional sequences encoding additional CMV proteins (e.g., a
fourth sequence encoding a fourth CMV protein, a fifth sequence
encoding a fifth CMV protein) can be included. The control elements
can be independently selected from the group consisting of a
subgenomic promoter, and IRES, and a viral 2A site.
[0016] In some embodiments, the self replicating nucleic acid
molecule encodes the CMV proteins gH and gL. In other embodiments,
the self-replicating RNA molecule encodes the CMV proteins gH, gL,
and gO. In other embodiments, the self-replicating RNA molecule
encodes the CMV proteins gH, gL, UL128, UL130 and UL131.
[0017] The self replicating RNA molecules can be an alphavirus
replicon. In such instances, the alphavirus replicon can be
delivered in the form of an alphavirus replicon particle (VRP). The
self replicating RNA molecule can also be in the form of a "naked"
RNA molecule.
[0018] The invention also relates to a recombinant DNA molecule
that encodes a self replicating RNA molecule as described herein.
In some embodiments, the recombinant DNA molecule is a plasmid. In
some embodiments, the recombinant DNA molecule includes a mammalian
promoter that drive transcription of the encoded self replicating
RNA molecule.
[0019] The invention also relates to compositions that comprise a
self-replicating RNA molecule as described herein and a
pharmaceutically acceptable vehicle. The self-replicating RNA
molecule can be "naked." In some embodiments, the composition
comprises a self-replicating RNA molecule that encodes the CMV
proteins gH and gL. In other embodiments, the composition further
comprises a self-replicating RNA molecule that encodes the CMV
protein gB. The composition can also contain an RNA delivery system
such as a liposome, a polymeric nanoparticle, an oil-in-water
cationic nanoemulsion or combinations thereof. For example, the
self-replicating RNA molecule can be encapsulated in a
liposome.
[0020] In certain embodiments, the composition comprises a VRP that
contains a alphavirus replicon that encodes two or more CMV
proteins. In some embodiments, the VRP comprises a replicon that
encodes CMV gH and gL. If desired, the composition can further
comprising a second VRP containing a replicon that encodes CMV gB.
The composition can also comprise an adjuvant.
[0021] The invention also relates to methods of forming a CMV
protein complex. In some embodiments a self-replicating RNA
encoding two or more CMV proteins is delivered to a cell, the cell
is maintained under conditions suitable for expression of the CMV
proteins, wherein a CMV protein complex is formed. In other
embodiments, a VRP that contains a self-replicating RNA encoding
two or more CMV proteins is delivered to a cell, the cell is
maintained under conditions suitable for expression of the CMV
proteins, wherein a CMV protein complex is formed. The method can
be used to form a CMV protein complex in a cell in vivo.
[0022] The invention also relates to a method for inducing an
immune response in an individual. In some embodiments, a
self-replicating RNA encoding two or more CMV proteins is
administered to the individual. The self-replicating RNA molecule
can be administered as a composition that contains an RNA delivery
system, such as a liposome. In other embodiments, a VRP that
contains a self-replicating RNA encoding two or more CMV proteins
is administered to the individual. In preferred embodiments, the
self-replicating RNA molecule encodes CMV proteins gH and gL.
Preferably, the induced immune response comprises the production of
neutralizing anti-CMV antibodies. More preferably, the neutralizing
antibodies are complement-independent.
[0023] The invention also relates to a method of inhibiting CMV
entry into a cell comprising contacting the cell with a
self-replicating RNA molecule that encodes two or more CMV
proteins, such as gH and gL. The cell can be selected from the
group consisting of an epithelial cell, an endothelial cell, a
fibroblast and combinations thereof. In some embodiments, the cell
is contacted with a VRP that contains a self-replicating RNA
encoding two or more CMV proteins.
[0024] The invention also relates to the use of a self-replicating
RNA molecule that encodes two or more CMV proteins (e.g., a VRP, a
composition comprising the self-replicating RNA molecule and a
liposome) form a CMV protein complex in a cell, to induce an immune
response or to inhibit CMV entry into a cell.
BRIEF DESCRIPTION OF THE DRAWINGS
[0025] FIG. 1 is a schematic of CMV identifying known glycoprotein
complexes involved in CMV entry into target cells. Envelope
glycoproteins represent attractive vaccine candidates as they are
expressed on the viral surface and can elicit protective and long
lasting virus-neutralizing humoral immune responses. The structural
glycoproteins mediating these processes can be divided into two
classes; those that are conserved throughout the herpes virus
family and those that are not. Among those that are conserved are
gB, gH, gL, gM and gN. Many of these glycoproteins form complexes
with one another (gH/gL/.+-.gO; gH/gL/UL 128/UL 130/UL131; gM/gN)
to facilitate localization to the viral surface and to carry out
their functions in viral attachment, entry and cell fusion.
[0026] FIGS. 2A-2F are schematics of CMV constructs. FIG. 2A,
Schematic of the gB constructs ("gB FL", full-length gB; soluble
gBs "gB sol 750" and "gB sol 692") described in Example 1. Two
different soluble versions of gB were constructed; gB sol 750 lacks
the transmembrane spanning domain and cytoplasmic domain, gB sol
692 also lacks a hydrophobic region and is similar to the gB sol
described in Reap et al. (2007) Clin. Vacc. Immunol. 14:748-55.
FIG. 2B, Schematic of the gB replicon vectors used to produce viral
replicaton particles (VRPs). FIG. 2C, Schematic of the gH
constructs ("gH FL", full-length gH; soluble gH "gH sol") described
in Example 1. A single soluble version of gH was constructed which
lacked the transmembrane spanning domain. FIG. 2D, Schematic of the
gH replicon vectors used to produce VRPs. FIG. 2E, Schematic of gL
construct described in Example 1. FIG. 2F, Schematic of the gL
replicon vector used to produce VRPs. In FIGS. 2B, 2D and 2F,
"NSP1," "NSP2," "NSP3," and "NSP4," are alphavirus nonstructural
proteins 1-4, respectively, required for replication of the
virus.
[0027] FIGS. 3A and 3B show that mice immunized with gB (FL, sol
750, sol 692) or gH (FL, sol) VRPs induced antibody responses that
were neutralizing in the presence of guinea pig complement. The
neutralization assay was done by pre-incubating the CMV virus
strain TB40UL32E-GFP (which encodes the enhanced green fluorescent
protein-GFP, Sampaio et al (2005) J. Virol. 79(5):2754-67), with
mouse sera and guinea pig complement before infection of ARPE-19
epithelial cells. Five days post-infection, the number of GFP
positive cells was determined. FIG. 3A, Serum dilution curves for
all sera analyzed in ARPE-19 cells in the presence of complement.
FIG. 3B, 50% neutralization titers for the sera samples. Virus
incubated with pre-immune sera yielded low neutralization at low
dilutions (1:40-1:80). gB (FL, sol 750, sol 692) sera had very
strong neutralizing activity with 50% neutralization titers between
1:1800-1:2100. All gB immunized mice yielded a similar
neutralization profile. gH (FL, sol) sera had neutralizing activity
with 50% neutralization titers around 1:160. See Example 1.
[0028] FIG. 4A is a schematic illustration of monocistronic
replicons encoding green fluorescent protein (GFP) or red
fluorescent protein (mCherry) and a bicistronic replicon encoding
GFP and mCherry. "NSP1," "NSP2," "NSP3," and "NSP4," are alphavirus
nonstructural proteins 1-4, respectively. The polycistronic
alphavirus replicon system was designed by making modifications to
the existing alphavirus replicon system to accommodate multiple
subgenomic promoters driving genes of interest.
[0029] FIG. 4B are fluorescence plots showing FACS analysis of BHKV
cells infected with VRPs containing mono- and bicistronic RNAs.
Polycistronic alphavirus VRPs yield more cells expressing both
genes of interest at approximately equal amounts (GFP and mCherry;
72.48%) than co-infection of GFP VRP+mCherry VRP (26.30%). See
Example 2.
[0030] FIG. 5A is a schematic illustration of construction of
polycistronic alphavirus replicon constructs encoding gH/gL and
gH/gL/gO.
[0031] FIG. 5B show that gH/gL form a complex in vitro. VRPs
containing replicons encoding gH, gL, gO, gH/gL or gH/gL/gO were
produced in BHKV cells. The resulting VRPs were used to infect
ARPE-19 cells to demonstrate complex formation in vitro. The
alphavirus infected ARPE-19 cells were harvested and analyzed for
the presence of gH and gL. ARPE-19 cells infected with VRPs
encoding gH/gL produced disulfide linked complexes of gH/gL (see in
the absence of DTT, heat). gO did not detectably alter the gH/gL
association. The left hand blot shows expression of gH protein. The
right hand blot shows expression of gL protein. Molecular weight
markers are indicated between the blots. =monomeric gH, =monomeric
gL, <=herodimer (gH+gL), *=dimer of heterodimers.
[0032] FIG. 5C shows immunoprecipitation of gH and gH/gL complexes
from BHKV cells infected with VRPs. Immunoprecipitation was
performed using mouse IgG antibodies as a control (Lanes 2, 4, 7,
and 10) or mouse anti-gH antibodies (Genway) to immunoprecipitate
gH (Lanes 3, 5, 8, and 11). Western blots were performed using
pooled rabbit anti-gL antibody and rabbit anti-gH antibody. Lanes
1, 6, and 9 show gH protein (upper band .about.75 kDa) and gL
protein (lower band .about.30 kDa) for reference. Lanes 2 and 3 are
lysates infected with gH-VRP. Lane 2 shows that the control
antibody did not immunoprecipitate gH. Lane 3 shows the anti-gH
antibody immunoprecipitated gH. Lanes 4 and 5 are from lysates
infected with gL-VRP only. No gH protein was immunoprecipitated.
Lanes 7 and 8 are from lysates infected with bicistronic gH/gL-VRP.
Lane 8 shows that gL was immunoprecipitated using the gH antibody.
(See asterisk). Lanes 10 and 11 are from lysates infected with
tricistronic gH/gL/gO-VRP. Lane 11 shows that gL was
immunoprecipitated using the gH antibody. (See asterisk). Molecular
Weight markers are also shown (MW). See Example 3.
[0033] FIG. 6 shows that VRPs that affect gH/gL complex formation
in vitro induce potent immune response to CMV which is
qualitatively and quantitatively superior to the response to gB
VRPs. FIG. 6A and FIG. 6B show serum dilution curves for gH, gL,
gO, gH+gL, gH+gL+gO, gH/gL and gH/gL/gO VRP-immunized mice in
neutralization of TB40-UL32-EGFP infection of ARPE-19 cells in the
presence (FIG. 6A) or absence (FIG. 6B) of complement. Various
dilutions of sera were pre-incubated with TB40UL32E-GFP in the
presence or absence of guinea pig complement and then added to
ARPE-19 epithelial cells. After 5 day infection with the virus,
GFP-positive cells were counted. FIG. 6C is a graph showing 50%
neutralization titers obtained in the presence and absence of
complement. "3wp3," three weeks post-third immunization. VRPs
expressing single CMV proteins (gH, gL, gO VRPs or co-administered
gH, gL and gO VRPs) did not enhance neutralizing activity beyond
that of gH alone. In contrast, sera from mice immunized with
bicistronic gH/gL or tricistronic gH/gL/gO VRPs demonstrated potent
neutralizing responses. Moreover, the potent neutralizing responses
were similar in the presence and absence of guinea pig complement,
showing that polycistronic VRPs successfully induced a
complement-independent immune response. See Example 4.
[0034] FIG. 7 shows that VRPs that affect gH/gL complex formation
in vitro induced antibodies that potently neutralized infection of
MRC-5 fibroblast cells. FIG. 7A shows serum dilution curves for gH,
gL, gO, gH+gL, gH+gL+gO, gH/gL and gH/gL/gO VRP-immunized mice in
MRC-5 cells in the absence of complement. Various dilutions of sera
were pre-incubated with TB40GFP in the presence or absence of
guinea pig complement and then added to MRC-5 fibroblast cells.
After 5 day infection with the virus, GFP-positive cells were
counted. FIG. 7B is a graph showing 50% neutralization titers
obtained in a MRC-5 fibroblast cell model in the absence of
complement. "3wp3," three weeks post-third immunization. VRPs
expressing single CMV proteins (gH, gL, gO VRPs or co-administered
gH, gL and gO VRPs) did not enhance neutralizing activity beyond
that of gH alone. In contrast, sera from mice immunized with
bicistronic gH/gL or tricistronic gH/gL/gO VRPs demonstrated
extremely potent neutralizing responses. See Example 4.
[0035] FIGS. 8A and 8B are graphs showing that the neutralizing
antibodies induced by delivery of the polycistronic VRPs were
cross-neutralizing antibodies. The sera from mice immunized with
gH/gL and gH/gL/gO VRPs were able to neutralize TB40UL32E-GFP and
VR1814 clinical strains of CMV in both ARPE-19 epithelial cells
(FIG. 8A) and MRC-5 fibroblast cells (FIG. 8B) in the absence of
guinea pig complement in an IE-1 neutralization assay.
[0036] FIG. 9 is a graph showing that the neutralizing antibodies
elicited against gH FL/gL are complement-independent and similar to
natural immunity in titer. Mice were immunized with gB FL or gH
FL/gL VRPs at 1.times.10.sup.6 IU, 3 times, 3 weeks apart before
the terminal bleed. Sera was analyzed for ability to neutralize
TB40UL32E-EGFP CMV infection of ARPE-19 cells in the presence and
absence of guinea pig complement in a neutralization assay. Unlike
antibodies elicited by gB, antibodies elicited by gH FL/gL are
complement-independent. Furthermore, gH FL/gL antibodies in these
vaccinated mice were similar in titer to those found in naturally
infected human subjects.
[0037] FIG. 10 shows a plasmid map for pVCR modified
gH-SGPgL-SGPgO.
[0038] FIG. 11 show a plasmid map for pVCR modified gH-SGPgL.
[0039] FIG. 12 show a plasmid map for pVCR modified gH
sol-SGPgL.
[0040] FIG. 13 show a plasmid map for pVCR modified gH
sol-SGPgL-SGPgO.
[0041] FIG. 14A-14G show the nucleotide sequence (SEQ ID NO:______)
of the plasmid encoding the A160 self-replicating RNA molecule
which encodes CMV surface glycoprotein H (gH) and CMV surface
glycoprotein L (gL). The nucleotide sequences encoding gH and gL
are underlined.
[0042] FIG. 15A-15H show the nucleotide sequence (SEQ ID NO:______)
of the plasmid encoding the A322 self-replicating RNA molecule
which encodes the soluble form of CMV surface glycoprotein H
(gHsol) and CMV surface glycoprotein L (gL). The nucleotide
sequences encoding gHsol and gL are underlined.
[0043] FIG. 16A-16H show the nucleotide sequence (SEQ ID NO:______)
of the plasmid encoding the A323 self-replicating RNA molecule
which encodes CMV surface glycoprotein B (gB). The nucleotide
sequence encoding gB is underlined.
[0044] FIGS. 17A and 17B are histograms showing 50% neutralizing
titers of sera from mice that were immunized with VRP or
self-replicating RNA. FIG. 17A shows 50% neutralizing titers
against human CMV strain TB40UL32E-EGFP ("TB40) on ARPE-19 cells,
and FIG. 17B shows 50% neutralizing titers against human CMV strain
8819 on ARPE-19 cells
[0045] FIG. 18 is a schematic of petacistronic RNA replicons, A526,
A527, A554, A555 and A556, that encode five CMV proteins.
Subgenomic promoters are shown by arrows, other control elements
are labeled.
[0046] FIG. 19 is a fluorescence histogram showing that BHKV cells
transfected with the A527 RNA replicon express the
gH/gL/UL128/UL130/UL131 pentameric complex. Cell stain was
performed using antibodies that bind a conformational epitope
present on the pentameric complex (Macagno (2010) J. Virol.
84(2):1005-13).
[0047] FIG. 20 is a schematic and graph. The schematic shows
bicistronic RNA replicons, A160 and A531-A537, that encode CMV gH
and gL. The graph shows neutralizing activity of immune sera from
mice immunized with VRPs that contained the replicons.
[0048] FIG. 21 is a graph showing anti-VZV protein antibody
response in immune sera from mice immunized with monocistronic RNA
replicons that encoded VZV proteins or bicistronic RNA replicons
that encoded VZV gE and gI, or gH and gL. The mice were immunized
with 7 .mu.g RNA formulated with a CNE (see, Example 7).
[0049] FIG. 22 is a graph showing anti-VZV protein antibody
response in immune sera from mice immunized with monocistronic RNA
replicons that encoded VZV proteins or bicistronic RNA replicons
that encoded VZV gE and gI, or gH and gL. The mice were immunized
with 1 .mu.g RNA formulated with a CNE (see, Example 7).
DETAILED DESCRIPTION
[0050] The invention provides platforms for co-delivery of
herpesvirus proteins, such as cytomegalovirus (CMV) proteins, to
cells, particularly proteins that form complexes in vivo. In some
embodiments, these proteins and the complexes they form elicit
potent neutralizing antibodies. The immune response produced by
co-delivery of herpesvirus (e.g., CMV) proteins, particularly those
that form complexes in vivo (e.g., gH/gL), can be superior to the
immune response produced using other approaches. For example, an
RNA molecule (e.g., a replicon) that encodes both gH and gL of CMV
can induce better neutralizing titers and/or protective immunity in
comparison to an RNA molecule that encodes gB, an RNA molecule that
encodes gH, an RNA molecule that encodes gL, or even a mixture of
RNA molecules that individually encode gH or gL. Further, a
replicon encoding gH/gL/UL128/UL130/UL131 can provide responses
superior to those encoding only gH/gL.
[0051] In a general aspect, the invention relates to platforms for
delivery of two or more herpesvirus (e.g., CMV) proteins to cells.
The platforms comprise recombinant polycistronic nucleic acid
molecules that contain a first sequence encoding a first
herpesvirus (e.g., CMV) protein or fragment thereof, and a second
sequence encoding a second herpesvirus (e.g., CMV) protein or
fragment thereof. If desired, one or more additional sequences
encoding additional proteins, for example, a third herpesvirus
(e.g., CMV) protein or fragment thereof, a fourth herpesvirus
(e.g., CMV) protein or fragment thereof, a fifth herpesvirus (e.g.,
CMV) protein or fragment thereof etc. can be present in the
recombinant polycistronic nucleic acid molecule. The sequences
encoding herpesvirus (e.g., CMV) proteins or fragments thereof are
operably linked to one or more suitable control elements so that
the herpesvirus (e.g., CMV) proteins or fragments are produced by a
cell that contains the recombinant polycistronic nucleic acid.
[0052] In the polycistronic nucleic acids described herein, the
encoded first and second herpesvirus proteins or fragments, and the
encoded third, forth and fifth herpes virus proteins or fragments,
if present, generally and preferably are from the same herpes
virus. In certain examples, all herpes virus proteins or fragments
encoded by a polycistronic vector are CMV proteins or VZV
proteins.
[0053] The recombinant polycistronic nucleic acid molecules
described herein provide the advantage of delivering sequences that
encode two or more herpesvirus (e.g., CMV) proteins to a cell, and
driving the expression of the herpesvirus (e.g., CMV) proteins at
sufficient levels to result in the formation of a protein complex
containing the two or more herpesvirus (e.g., CMV) proteins in
vivo. Using this approach, the two or more encoded herpesvirus
(e.g., CMV) proteins can be expressed at sufficient intracellular
levels for the formation of herpesvirus (e.g., CMV) protein
complexes (e.g., gH/gL). For example, the encoded herpesvirus
(e.g., CMV) proteins or fragments thereof can be expressed at
substantially the same level, or if desired, at different levels by
selecting appropriate expression control sequences (e.g.,
promoters, IRES, 2A site etc.). This is significantly more
efficient way to produce protein complexes in vivo than by
co-delivering two or more individual DNA molecules that encode
different herpesvirus (e.g., CMV) to the same cell, which can be
inefficient and highly variable. See, e.g., WO 2004/076645.
[0054] The recombinant polycistronic nucleic acid molecule can be
based on any desired nucleic acid such as DNA (e.g., plasmid or
viral DNA) or RNA. Any suitable DNA or RNA can be used as the
nucleic acid vector that carries the open reading frames that
encode herpesvirus (e.g., CMV) proteins or fragments thereof.
Suitable nucleic acid vectors have the capacity to carry and drive
expression of more than one protein gene. Such nucleic acid vectors
are known in the art and include, for example, plasmids, DNA
obtained from DNA viruses such as vaccinia virus vectors (e.g.,
NYVAC, see U.S. Pat. No. 5,494,807), and poxvirus vectors (e.g.,
ALVAC canarypox vector, Sanofi Pasteur), and RNA obtained from
suitable RNA viruses such as an alphavirus. If desired, the
recombinant polycistronic nucleic acid molecule can be modified,
e.g., contain modified nucleobases and or linkages as described
further herein. Preferably, the polycistronic nucleic acid molecule
is an RNA molecule.
[0055] In some aspects, the recombinant polycistronic nucleic acid
molecule is a DNA molecule such as plasmid DNA. Such DNA molecules
can, for example, encode a polycistronic replicon and contain a
mammalian promoter that drives transcription of the replicon.
Recombinant polycistronic nucleic acid molecules or this type can
be administered to a mammal and then be transcribed in situ to
produce a polycistronic replicon that expresses herpesvirus
proteins.
[0056] In some aspects, the invention is a polycistronic nucleic
acid molecule that contains a sequence encoding a herpesvirus gH or
fragment thereof, and a herpesvirus gL or a fragment thereof. The
gH and gL proteins, or fragments thereof, can be from any desired
herpes virus such as HSV-1, HSV-2, VZV, EBV type 1, EBV type 2,
CMV, HHV-6 type A, HHV-6 type B, HHV-7, KSHV, and the like.
Preferably, the herpesvirus is VZV, HSV-2, HSV-1, EBV (type 1 or
type 2) or CMV. More preferably, the herpesvirus is VZV, HSV-2 or
CMV. Even more preferably, the herpesvirus is CMV. The sequences of
gH and gL proteins and of nucleic acids that encode the proteins
from these viruses are well known in the art. Exemplary sequences
are identified in Table 1. The polycistronic nucleic acid molecule
can contain a first sequence encoding a gH protein disclosed in
Table 1, or a fragment thereof, or a sequence that is at least
about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical
thereto. The polycistronic nucleic acid molecule can also contain a
second sequence encoding a gL protein disclosed in Table 1, or a
fragment thereof, or a sequence that is at least about 90%, 91%,
92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto.
TABLE-US-00001 TABLE 1 Virus gH accession number gL accession
number HSV-1 (HHV-1) NP_044623.1 NP_044602.1 HSV-2 (HHV-2)
NP_044491.1 NP_044470.1 VZV (HHV-3) NP_040160.1 NP_040182.1 EBV
type 1 (HHV-4) YP_401700.1 YP_401678.1 EBV type 2 (HHV-4)
YP_001129496.1 YP_001129472.1 CMV (HHV-5) YP_081523.1 YP_081555.1
HHV-6 type A NP_042941.1 NP_042975.1 HHV-6 type B NP_050229.1
NP_050261.1 HHV-7 YP_073788.1 YP_073820.1 KSHV (HHV-8)
YP_001129375.1 YP_001129399.1
[0057] In this description of the invention, to facilitate a clear
description of the nucleic acids, particular sequence components
are referred to as a "first sequence," a "second sequence," etc. It
is to be understood that the first and second sequences can appear
in any desired order or orientation, and that no particular order
or orientation is intended by the words "first", "second" etc.
Similarly, protein complexes are referred to by listing the
proteins that are present in the complex, e.g., gH/gL. This is
intended to describe the complex by the proteins that are present
in the complex and does not indicate relative amounts of the
proteins or the order or orientation of sequences that encode the
proteins on a recombinant nucleic acid.
[0058] Certain preferred embodiments, such as alphavirus VRP and
self-replicating RNA that contain sequences encoding CMV proteins,
are further described herein. It is intended that the sequences
encoding CMV proteins in such preferred embodiments, can be
replaced with sequences encoding proteins, such as gH and gL from
other herpesviruses.
Alphavirus VRP Platforms
[0059] In some embodiments, CMV proteins are delivered to a cell
using alphavirus replicon particles (VRP) which employ
polycistronic replicons (or vectors) as described below. As used
herein, "polycistronic" includes bicistronic vectors as well as
vectors comprising three or more cistrons. Cistrons in a
polycistronic vector can encode CMV proteins from the same CMV
strains or from different CMV strains. The cistrons can be oriented
in any 5'-3' order. Any nucleotide sequence encoding a CMV protein
can be used to produce the protein. Exemplary sequences useful for
preparing the polycistronic nucleic acids that encode two or more
CMV proteins or fragments thereof are described herein.
[0060] As used herein, the term "alphavirus" has its conventional
meaning in the art and includes various species such as Venezuelan
equine encephalitis virus (VEE; e.g., Trinidad donkey, TC83CR,
etc.), Semliki Forest virus (SFV), Sindbis virus, Ross River virus,
Western equine encephalitis virus, Eastern equine encephalitis
virus, Chikungunya virus, S.A. AR86 virus, Everglades virus,
Mucambo virus, Barmah Forest virus, Middelburg virus, Pixuna virus,
O' nyong-nyong virus, Getah virus, Sagiyama virus, Bebaru virus,
Mayaro virus, Una virus, Aura virus, Whataroa virus, Banbanki
virus, Kyzylagach virus, Highlands J virus, Fort Morgan virus,
Ndumu virus, and Buggy Creek virus. The term alphavirus may also
include chimeric alphaviruses (e.g., as described by Perri et al.,
(2003) J. Virol. 77(19):10394-403) that contain genome sequences
from more than one alphavirus.
[0061] An "alphavirus replicon particle" (VRP) or "replicon
particle" is an alphavirus replicon packaged with alphavirus
structural proteins.
[0062] An "alphavirus replicon" (or "replicon") is an RNA molecule
which can direct its own amplification in vivo in a target cell.
The replicon encodes the polymerase(s) which catalyze RNA
amplification (nsP1, nsP2, nsP3, nsP4) and contains cis RNA
sequences required for replication which are recognized and
utilized by the encoded polymerase(s). An alphavirus replicon
typically contains the following ordered elements: 5' viral
sequences required in cis for replication, sequences which encode
biologically active alphavirus nonstructural proteins (nsP1, nsP2,
nsP3, nsP4), 3' viral sequences required in cis for replication,
and a polyadenylate tract. An alphavirus replicon also may contain
one or more viral subgenomic "junction region" promoters directing
the expression of heterologous nucleotide sequences, which may, in
certain embodiments, be modified in order to increase or reduce
viral transcription of the subgenomic fragment and heterologous
sequence(s) to be expressed. Other control elements can be used, as
described below.
[0063] Alphavirus replicons encoding CMV proteins are used to
produce VRPs. Such alphavirus replicons comprise sequences encoding
at least two CMV proteins or fragments thereof. These sequences are
operably linked to one or more suitable control elements, such as a
subgenomic promoter, an IRES (e.g., EMCV, EV71), and a viral 2A
site, which can be the same or different. Delivery of components of
these complexes using the polycistronic vectors disclosed herein is
an efficient way of providing nucleic acid sequences that encode
two or more CMV proteins in desired relative amounts; whereas if
multiple alphavirus constructs were used to deliver individual CMV
proteins for complex formation, efficient co-delivery of VRPs would
be required.
[0064] Any combination of suitable control elements can be used in
any order. In one example, a single subgenomic promoter is operable
linked to two sequences encoding two different CMV proteins, and an
IRES is positioned between the two coding sequences. In another
example, two sequences that encode two different CMV proteins are
operably linked to separate promoters. In still another example,
the two sequences that encode two different CMV proteins are
operably linked to a single promoter. The two sequences that encode
two different CMV proteins are linked to each other through a
nucleotide sequence encoding a viral 2A site, and thus encode a
single amino acid chain that contain the amino acid sequences of
both CMV proteins. The viral 2A site in this context is used to
generate two CMV proteins from encoded polyprotein.
[0065] Subgenomic Promoters
[0066] Subgenomic promoters, also known as junction region
promoters can be used to regulate protein expression. Alphaviral
subgenomic promoters regulate expression of alphaviral structural
proteins. See Strauss and Strauss, "The alphaviruses: gene
expression, replication, and evolution," Microbiol Rev. 1994
September; 58(3):491-562. A polycistronic polynucleotide can
comprise a subgenomic promoter from any alphavirus. When two or
more subgenomic promoters are present in a polycistronic
polynucleotide, the promoters can be the same or different. For
example, the subgenomic promoter can have the sequence
CTCTCTACGGCTAACCTGAATGGA (SEQ ID NO:______). In certain
embodiments, subgenomic promoters can be modified in order to
increase or reduce viral transcription of the proteins. See U.S.
Pat. No. 6,592,874.
[0067] Internal Ribosomal Entry Site (IRES)
[0068] In some embodiments, one or more control elements is an
internal ribosomal entry site (IRES). An IRES allows multiple
proteins to be made from a single mRNA transcript as ribosomes bind
to each IRES and initiate translation in the absence of a 5''-cap,
which is normally required to initiate translation of protein in
eukaryotic cells. For example, the IRES can be EV71 or EMCV.
[0069] Viral 2A Site
[0070] The FMDV 2A protein is a short peptide that serves to
separate the structural proteins of FMDV from a nonstructural
protein (FMDV 2B). Early work on this peptide suggested that it
acts as an autocatalytic protease, but other work (e.g., Donnelly
et al., (2001), J. Gen. Virol. 82, 1013-1025) suggest that this
short sequence and the following single amino acid of FMDV 2B (Gly)
acts as a translational stop-start. Regardless of the precise mode
of action, the sequence can be inserted between two polypeptides,
and effect the production of multiple individual polypeptides from
a single open reading frame. In the context of this invention, FMDV
2A sequences can be inserted between the sequences encoding at
least two CMV proteins, allowing for their synthesis as part of a
single open reading frame. For example, the open reading frame may
encode a gH protein and a gL protein separated by a sequence
encoding a viral 2A site. A single mRNA is transcribed then, during
the translation step, the gH and gL peptides are produced
separately due to the activity of the viral 2A site. Any suitable
viral 2A sequence may be used. Often, a viral 2A site comprises the
consensus sequence Asp-Val/Ile-Glu-X-Asn-Pro-Gly-Pro, where X is
any amino acid (SEQ ID NO:______). For example, the Foot and Mouth
Disease Virus 2A peptide sequence is DVESNPGP (SEQ ID NO:______).
See Trichas et al., "Use of the viral 2A peptide for bicistronic
expression in transgenic mice," BMC Biol. 2008 Sep. 15; 6:40, and
Halpin et al., "Self-processing 2A-polyproteins--a system for
co-ordinate expression of multiple proteins in transgenic plants,"
Plant J. 1999 February; 17(4):453-9.
[0071] In some embodiments an alphavirus replicon is a chimeric
replicon, such as a VEE-Sindbis chimeric replicon (VCR) or a VEE
strain TC83 replicon (TC83R) or a TC83-Sindbis chimeric replicon
(TC83CR). In some embodiments a VCR contains the packaging signal
and 3' UTR from a Sindbis replicon in place of sequences in nsP3
and at the 3' end of the VEE replicon; see Perri et al., J. Virol.
77, 10394-403, 2003. In some embodiments, a TC83CR contains the
packaging signal and 3' UTR from a Sindbis replicon in place of
sequences in nsP3 and at the 3' end of aVEE strain
TC83replicon.
Producing VRPs
[0072] Methods of preparing VRPs are well known in the art. In some
embodiments an alphavirus is assembled into a VRP using a packaging
cell. An "alphavirus packaging cell" (or "packaging cell") is a
cell that contains one or more alphavirus structural protein
expression cassettes and that produces recombinant alphavirus
particles after introduction of an alphavirus replicon, eukaryotic
layered vector initiation system (e.g., U.S. Pat. No. 5,814,482),
or recombinant alphavirus particle. The one or more different
alphavirus structural protein cassettes serve as "helpers" by
providing the alphavirus structural proteins. An "alphavirus
structural protein cassette" is an expression cassette that encodes
one or more alphavirus structural proteins and comprises at least
one and up to five copies (i.e., 1, 2, 3, 4, or 5) of an alphavirus
replicase recognition sequence. Structural protein expression
cassettes typically comprise, from 5' to 3', a 5' sequence which
initiates transcription of alphavirus RNA, an optional alphavirus
subgenomic region promoter, a nucleotide sequence encoding the
alphavirus structural protein, a 3' untranslated region (which also
directs RNA transcription), and a polyA tract. See, e.g., WO
2010/019437.
[0073] In preferred embodiments two different alphavirus structural
protein cassettes ("split" defective helpers) are used in a
packaging cell to minimize recombination events which could produce
a replication-competent virus. In some embodiments an alphavirus
structural protein cassette encodes the capsid protein (C) but not
either of the glycoproteins (E2 and E1). In some embodiments an
alphavirus structural protein cassette encodes the capsid protein
and either the E1 or E2 glycoproteins (but not both). In some
embodiments an alphavirus structural protein cassette encodes the
E2 and E1 glycoproteins but not the capsid protein. In some
embodiments an alphavirus structural protein cassette encodes the
E1 or E2 glycoprotein (but not both) and not the capsid
protein.
[0074] In some embodiments, VRPs are produced by the simultaneous
introduction of replicons and helper RNAs into cells of various
sources. Under these conditions, for example, BHKV cells
(1.times.10.sup.7) are electroporated at, for example, 220 volts,
1000 .mu.F, 2 manually pulses with 10 .mu.g replicon RNA:6 .mu.g
defective helper Cap RNA:10 .mu.g defective helper Gly RNA,
alphavirus containing supernatant is collected .about.24 hours
later. Replicons and/or helpers can also be introduced in DNA forms
which launch suitable RNAs within the transfected cells.
[0075] A packaging cell may be a mammalian cell or a non-mammalian
cell, such as an insect (e.g., SF9) or avian cell (e.g., a primary
chick or duck fibroblast or fibroblast cell line). See U.S. Pat.
No. 7,445,924. Avian sources of cells include, but are not limited
to, avian embryonic stem cells such as EB66.RTM. (VIVALIS); chicken
cells, including chicken embryonic stem cells such as EBx.RTM.
cells, chicken embryonic fibroblasts, and chicken embryonic germ
cells; duck cells such as the AGE1.CR and AGE1.CR.pIX cell lines
(ProBioGen) which are described, for example, in Vaccine
27:4975-4982 (2009) and WO2005/042728); and geese cells. In some
embodiments, a packaging cell is a primary duck fibroblast or duck
retinal cell line, such as AGE.CR (PROBIOGEN).
[0076] Mammalian sources of cells for simultaneous nucleic acid
introduction and/or packaging cells include, but are not limited
to, human or non-human primate cells, including PerC6 (PER.C6)
cells (CRUCELL N.V.), which are described, for example, in WO
01/38362 and WO 02/40665, as well as deposited under ECACC deposit
number 96022940); MRC-5 (ATCC CCL-171); WI-38 (ATCC CCL-75); fetal
rhesus lung cells (ATCC CL-160); human embryonic kidney cells
(e.g., 293 cells, typically transformed by sheared adenovirus type
5 DNA); VERO cells from monkey kidneys); cells of horse, cow (e.g.,
MDBK cells), sheep, dog (e.g., MDCK cells from dog kidneys, ATCC
CCL34 MDCK (NBL2) or MDCK 33016, deposit number DSM ACC 2219 as
described in WO 97/37001); cat, and rodent (e.g., hamster cells
such as BHK21-F, HKCC cells, or Chinese hamster ovary (CHO) cells),
and may be obtained from a wide variety of developmental stages,
including for example, adult, neonatal, fetal, and embryo.
[0077] In some embodiments a packaging cell is stably transformed
with one or more structural protein expression cassette(s).
Structural protein expression cassettes can be introduced into
cells using standard recombinant DNA techniques, including
transferrin-polycation-mediated DNA transfer, transfection with
naked or encapsulated nucleic acids, liposome-mediated cellular
fusion, intracellular transportation of DNA-coated latex beads,
protoplast fusion, viral infection, electroporation, "gene gun"
methods, and DEAE- or calcium phosphate-mediated transfection.
Structural protein expression cassettes typically are introduced
into a host cell as DNA molecules, but can also be introduced as in
vitro-transcribed RNA. Each expression cassette can be introduced
separately or substantially simultaneously.
[0078] In some embodiments, stable alphavirus packaging cell lines
are used to produce recombinant alphavirus particles. These are
alphavirus-permissive cells comprising DNA cassettes expressing the
defective helper RNA stably integrated into their genomes. See Polo
et al., Proc. Natl. Acad. Sci. USA 96, 4598-603, 1999. The helper
RNAs are constitutively expressed but the alphavirus structural
proteins are not, because the genes are under the control of an
alphavirus subgenomic promoter (Polo et al., 1999). Upon
introduction of an alphavirus replicon into the genome of a
packaging cell by transfection or VRP infection, replicase enzymes
are produced and trigger expression of the capsid and glycoprotein
genes on the helper RNAs, and output VRPs are produced.
Introduction of the replicon can be accomplished by a variety of
methods, including both transfection and infection with a seed
stock of alphavirus replicon particles. The packaging cell is then
incubated under conditions and for a time sufficient to produce
packaged alphavirus replicon particles in the culture
supernatant.
[0079] Thus, packaging cells allow VRPs to act as self-propagating
viruses. This technology allows VRPs to be produced in much the
same manner, and using the same equipment, as that used for live
attenuated vaccines or other viral vectors that have producer cell
lines available, such as replication-incompetent adenovirus vectors
grown in cells expressing the adenovirus E1A and E1B genes.
[0080] In some embodiments, a two-step process is used: the first
step comprises producing a seed stock of alphavirus replicon
particles by transfecting a packaging cell with a replicon RNA or
plasmid DNA-based replicon. A much larger stock of replicon
particles is then produced in a second step, by infecting a fresh
culture of packaging cells with the seed stock. This infection can
be performed using various multiplicities of infection (MOI),
including a MOI=0.00001, 0.00005, 0.0001, 0.0005, 0.001, 0.005,
0.01, 0.05, 0.1, 0.5, 1.0, 3, 5, 10 or 20. In some embodiments
infection is performed at a low MOI (e.g., less than 1). Over time,
replicon particles can be harvested from packaging cells infected
with the seed stock. In some embodiments, replicon particles can
then be passaged in yet larger cultures of naive packaging cells by
repeated low-multiplicity infection, resulting in commercial scale
preparations with the same high titer.
Self-Replicating RNA Platforms
[0081] Two or more CMV proteins can be produced by expression of
recombinant nucleic acids that encode the proteins in the cells of
a subject. Preferably, the recombinant nucleic acid molecules
encode two or more CMV proteins, e.g., are polycistronic. As
defined above, "polycistronic" includes bicistronic. Preferred
nucleic acids that can be administered to a subject to cause the
production of CMV proteins are self-replicating RNA molecules. The
self-replicating RNA molecules of the invention are based on the
genomic RNA of RNA viruses, but lack the genes encoding one or more
structural proteins. The self-replicating RNA molecules are capable
of being translated to produce non-structural proteins of the RNA
virus and CMV proteins encoded by the self-replicating RNA.
[0082] The self-replicating RNA generally contains at least one or
more genes selected from the group consisting of viral replicase,
viral proteases, viral helicases and other nonstructural viral
proteins, and also comprise 5'- and 3'-end cis-active replication
sequences, and a heterologous sequences that encodes two or more
desired CMV proteins. A subgenomic promoter that directs expression
of the heterologous sequence(s) can be included in the
self-replicating RNA. If desired, a heterologous sequence may be
fused in frame to other coding regions in the self-replicating RNA
and/or may be under the control of an internal ribosome entry site
(IRES).
[0083] Self-replicating RNA molecules of the invention can be
designed so that the self-replicating RNA molecule cannot induce
production of infectious viral particles. This can be achieved, for
example, by omitting one or more viral genes encoding structural
proteins that are necessary for the production of viral particles
in the self-replicating RNA. For example, when the self-replicating
RNA molecule is based on an alpha virus, such as Sindbis virus
(SIN), Semliki forest virus and Venezuelan equine encephalitis
virus (VEE), one or more genes encoding viral structural proteins,
such as capsid and/or envelope glycoproteins, can be omitted. If
desired, self-replicating RNA molecules of the invention can be
designed to induce production of infectious viral particles that
are attenuated or virulent, or to produce viral particles that are
capable of a single round of subsequent infection.
[0084] A self-replicating RNA molecule can, when delivered to a
vertebrate cell even without any proteins, lead to the production
of multiple daughter RNAs by transcription from itself (or from an
antisense copy of itself). The self-replicating RNA can be directly
translated after delivery to a cell, and this translation provides
a RNA-dependent RNA polymerase which then produces transcripts from
the delivered RNA. Thus the delivered RNA leads to the production
of multiple daughter RNAs. These transcripts are antisense relative
to the delivered RNA and may be translated themselves to provide in
situ expression of encoded CMV protein, or may be transcribed to
provide further transcripts with the same sense as the delivered
RNA which are translated to provide in situ expression of the
encoded CMV protein(s).
[0085] One suitable system for achieving self-replication is to use
an alphavirus-based RNA replicon, such as an alphavirus replicon as
described herein. These + stranded replicons are translated after
delivery to a cell to produce a replicase (or
replicase-transcriptase). The replicase is translated as a
polyprotein which auto cleaves to provide a replication complex
which creates genomic - strand copies of the + strand delivered
RNA. These - strand transcripts can themselves be transcribed to
give further copies of the + stranded parent RNA and also to give
rise to one or more subgenomic transcript which encodes two or more
CMV proteins. Translation of the subgenomic transcript thus leads
to in situ expression of the CMV protein(s) by the infected cell.
Suitable alphavirus replicons can use a replicase from a Sindbis
virus, a Semliki forest virus, an eastern equine encephalitis
virus, a Venezuelan equine encephalitis virus, etc.
[0086] A preferred self-replicating RNA molecule thus encodes (i) a
RNA-dependent RNA polymerase which can transcribe RNA from the
self-replicating RNA molecule and (ii) two or more CMV proteins or
fragments thereof. The polymerase can be an alphavirus replicase
e.g. comprising alphavirus protein nsP4. Protein nsP4 is the key
catalytic component of the replicase.
[0087] Whereas natural alphavirus genomes encode structural virion
proteins in addition to the non-structural replicase polyprotein,
it is preferred that an alphavirus based self-replicating RNA
molecule of the invention does not encode all alphavirus structural
proteins. Thus the self replicating RNA can lead to the production
of genomic RNA copies of itself in a cell, but not to the
production of RNA-containing alphavirus virions. The inability to
produce these virions means that, unlike a wild-type alphavirus,
the self-replicating RNA molecule cannot perpetuate itself in
infectious form. The alphavirus structural proteins which are
necessary for perpetuation in wild-type viruses are absent from
self replicating RNAs of the invention and their place is taken by
gene(s) encoding the desired gene product (CMV protein or fragment
thereof), such that the subgenomic transcript encodes the desired
gene product rather than the structural alphavirus virion
proteins.
[0088] Thus a self-replicating RNA molecule useful with the
invention have two sequences that encode different CMV proteins or
fragments thereof. The sequences encoding the CMV proteins or
fragments can be in any desired orientation, and can be operably
linked to the same or separate promoters. If desired, the sequences
encoding the CMV proteins or fragments can be part of a single open
reading frame. In some embodiments the RNA may have one or more
additional (downstream) sequences or open reading frames e.g. that
encode other additional CMV proteins or fragments thereof. A
self-replicating RNA molecule can have a 5' sequence which is
compatible with the encoded replicase.
[0089] In one aspect, the self-replicating RNA molecule is derived
from or based on an alphavirus, such as an alphavirus replicon as
defined herein. In other aspects, the self-replicating RNA molecule
is derived from or based on a virus other than an alphavirus,
preferably, a positive-stranded RNA viruses, and more preferably a
picornavirus, flavivirus, rubivirus, pestivirus, hepacivirus,
calicivirus, or coronavirus. Suitable wild-type alphavirus
sequences are well-known and are available from sequence
depositories, such as the American Type Culture Collection,
Rockville, Md. Representative examples of suitable alphaviruses
include Aura (ATCC VR-368), Bebaru virus (ATCC VR-600, ATCC
VR-1240), Cabassou (ATCC VR-922), Chikungunya virus (ATCC VR-64,
ATCC VR-1241), Eastern equine encephalomyelitis virus (ATCC VR-65,
ATCC VR-1242), Fort Morgan (ATCC VR-924), Getah virus (ATCC VR-369,
ATCC VR-1243), Kyzylagach (ATCC VR-927), Mayaro virus (ATCC VR-66;
ATCC VR-1277), Middleburg (ATCC VR-370), Mucambo virus (ATCC
VR-580, ATCC VR-1244), Ndumu (ATCC VR-371), Pixuna virus (ATCC
VR-372, ATCC VR-1245), Ross River virus (ATCC VR-373, ATCC
VR-1246), Semliki Forest (ATCC VR-67, ATCC VR-1247), Sindbis virus
(ATCC VR-68, ATCC VR-1248), Tonate (ATCC VR-925), Triniti (ATCC
VR-469), Una (ATCC VR-374), Venezuelan equine encephalomyelitis
(ATCC VR-69, ATCC VR-923, ATCC VR-1250 ATCC VR-1249, ATCC VR-532),
Western equine encephalomyelitis (ATCC VR-70, ATCC VR-1251, ATCC
VR-622, ATCC VR-1252), Whataroa (ATCC VR-926), and Y-62-33 (ATCC
VR-375).
[0090] The self-replicating RNA molecules of the invention can
contain one or more modified nucleotides and therefore have
improved stability and be resistant to degradation and clearance in
vivo, and other advantages. Without wishing to be bound by any
particular theory, it is believed that self-replicating RNA
molecules that contain modified nucleotides avoid or reduce
stimulation of endosomal and cytoplasmic immune receptors when the
self-replicating RNA is delivered into a cell. This permits
self-replication, amplification and expression of protein to occur.
This also reduces safety concerns relative to self-replicating RNA
that does not contain modified nucleotides, because the
self-replicating RNA that contains modified nucleotides reduce
activation of the innate immune system and subsequent undesired
consequences (e.g., inflammation at injection site, irritation at
injection site, pain, and the like). It is also believed that the
RNA molecules produced as a result of self-replication are
recognized as foreign nucleic acids by the cytoplasmic immune
receptors. Thus, self-replicating RNA molecules that contain
modified nucleotides provide for efficient amplification of the RNA
in a host cell and expression of CMV proteins, as well as adjuvant
effects.
[0091] The RNA sequence can be modified with respect to its codon
usage, for example, to increase translation efficacy and half-life
of the RNA. A poly A tail (e.g., of about 30 adenosine residues or
more) may be attached to the 3' end of the RNA to increase its
half-life. The 5' end of the RNA may be capped with a modified
ribonucleotide with the structure m7G (5') ppp (5') N (cap 0
structure) or a derivative thereof, which can be incorporated
during RNA synthesis or can be enzymatically engineered after RNA
transcription (e.g., by using Vaccinia Virus Capping Enzyme (VCE)
consisting of mRNA triphosphatase, guanylyl-transferase and
guanine-7-methylransferase, which catalyzes the construction of
N7-monomethylated cap 0 structures). Cap 0 structure can provide
stability and translational efficacy to the RNA molecule. The 5'
cap of the RNA molecule may be further modified by a
2'-O-Methyltransferase which results in the generation of a cap 1
structure (m7 Gppp [m2'-O] N), which may further increases
translation efficacy. A cap 1 structure may also increase in vivo
potency.
[0092] As used herein, "modified nucleotide" refers to a nucleotide
that contains one or more chemical modifications (e.g.,
substitutions) in or on the nitrogenous base of the nucleoside
(e.g., cytosine (C), thymine (T) or uracil (U), adenine (A) or
guanine (G)). If desired, a self replicating RNA molecule can
contain chemical modifications in or on the sugar moiety of the
nucleoside (e.g., ribose, deoxyribose, modified ribose, modified
deoxyribose, six-membered sugar analog, or open-chain sugar
analog), or the phosphate.
[0093] The self-replicating RNA molecules can contain at least one
modified nucleotide, that preferably is not part of the 5' cap
(e.g., in addition to the modification that are part of the 5''
cap). Accordingly, the self-replicating RNA molecule can contain a
modified nucleotide at a single position, can contain a particular
modified nucleotide (e.g., pseudouridine, N6-methyladenosine,
5-methylcytidine, 5-methyluridine) at two or more positions, or can
contain two, three, four, five, six, seven, eight, nine, ten or
more modified nucleotides (e.g., each at one or more positions).
Preferably, the self-replicating RNA molecules comprise modified
nucleotides that contain a modification on or in the nitrogenous
base, but do not contain modified sugar or phosphate moieties.
[0094] In some examples, between 0.001% and 99% or 100% of the
nucleotides in a self-replicating RNA molecule are modified
nucleotides. For example, 0.001%-25%, 0.01%-25%, 0.1%-25%, or
1%-25% of the nucleotides in a self-replicating RNA molecule are
modified nucleotides.
[0095] In other examples, between 0.001% and 99% or 100% of a
particular unmodified nucleotide in a self-replicating RNA molecule
is replaced with a modified nucleotide. For example, about 1% of
the nucleotides in the self-replicating RNA molecule that contain
uridine can be modified, such as by replacement of uridine with
pseudouridine. In other examples, the desired amount (percentage)
of two, three, or four particular nucleotides (nucleotides that
contain uridine, cytidine, guanosine, or adenine) in a
self-replicating RNA molecule are modified nucleotides. For
example, 0.001%-25%, 0.01%-25%, 0.1%-25, or 1%-25% of a particular
nucleotide in a self-replicating RNA molecule are modified
nucleotides. In other examples, 0.001%-20%, 0.001%-15%, 0.001%-10%,
0.01%-20%, 0.01%-15%, 0.1%-25, 0.01%-10%, 1%-20%, 1%-15%, 1%-10%,
or about 5%, about 10%, about 15%, about 20% of a particular
nucleotide in a self-replicating RNA molecule are modified
nucleotides.
[0096] It is preferred that less than 100% of the nucleotides in a
self-replicating RNA molecule are modified nucleotides. It is also
preferred that less than 100% of a particular nucleotide in a
self-replicating RNA molecule are modified nucleotides. Thus,
preferred self-replicating RNA molecules comprise at least some
unmodified nucleotides.
[0097] There are more than 96 naturally occurring nucleoside
modifications found on mammalian RNA. See, e.g., Limbach et al.,
Nucleic Acids Research, 22(12):2183-2196 (1994). The preparation of
nucleotides and modified nucleotides and nucleosides are well-known
in the art, e.g. from U.S. Pat. Nos. 4,373,071, 4,458,066,
4,500,707, 4,668,777, 4,973,679, 5,047,524, 5,132,418, 5,153,319,
5,262,530, 5,700,642 all of which are incorporated herein by
reference in their entirety, and many modified nucleosides and
modified nucleotides are commercially available.
[0098] Modified nucleobases which can be incorporated into modified
nucleosides and nucleotides and be present in the RNA molecules
include: m5C (5-methylcytidine), m5U (5-methyluridine), m6A
(N6-methyladenosine), s2U (2-thiouridine), Um (2'-O-methyluridine),
m1A (1-methyladenosine); m2A (2-methyladenosine); Am
(2-1-O-methyladenosine); ms2m6A (2-methylthio-N6-methyladenosine);
i6A (N6-isopentenyladenosine); ms2i6A (2-methylthio-N6
isopentenyladenosine); io6A (N6-(cis-hydroxyisopentenyl)adenosine);
ms2io6A (2-methylthio-N6-(cis-hydroxyisopentenyl) adenosine); g6A
(N6-glycinylcarbamoyladenosine); t6A (N6-threonyl
carbamoyladenosine); ms2t6A (2-methylthio-N6-threonyl
carbamoyladenosine); m6t6A
(N6-methyl-N6-threonylcarbamoyladenosine); hn6A
(N6-hydroxynorvalylcarbamoyl adenosine); ms2hn6A
(2-methylthio-N6-hydroxynorvalyl carbamoyladenosine); Ar(p)
(2'-O-ribosyladenosine (phosphate)); I (inosine); m1I
(1-methylinosine); m'Im (1,2'-O-dimethylinosine); m3C
(3-methylcytidine); Cm (2T-O-methylcytidine); s2C (2-thiocytidine);
ac4C(N4-acetylcytidine); f5C (5-formylcytidine); m5Cm
(5,2-O-dimethylcytidine); ac4Cm (N4acetyl2TOmethylcytidine); k2C
(lysidine); m1G (1-methylguanosine); m2G (N2-methylguanosine); m7G
(7-methylguanosine); Gm (2'-O-methylguanosine); m22G
(N2,N2-dimethylguanosine); m2Gm (N2,2'-O-dimethylguanosine); m22Gm
(N2,N2,2'-O-trimethylguanosine); Gr(p) (2'-O-ribosylguanosine
(phosphate)); yW (wybutosine); o2yW (peroxywybutosine); OHyW
(hydroxywybutosine); OHyW* (undermodified hydroxywybutosine); imG
(wyosine); mimG (methylguanosine); Q (queuosine); oQ
(epoxyqueuosine); galQ (galtactosyl-queuosine); manQ
(mannosylqueuosine); preQo (7-cyano-7-deazaguanosine); preQi
(7-aminomethyl-7-deazaguanosine); G* (archaeosine); D
(dihydrouridine); m5Um (5,2'-O-dimethyluridine); s4U
(4-thiouridine); m5s2U (5-methyl-2-thiouridine); s2Um
(2-thio-2'-O-methyluridine); acp3U
(3-(3-amino-3-carboxypropyl)uridine); ho5U (5-hydroxyuridine); mo5U
(5-methoxyuridine); cmo5U (uridine 5-oxyacetic acid); mcmo5U
(uridine 5-oxyacetic acid methyl ester); chm5U
(5-(carboxyhydroxymethyl)uridine)); mchm5U
(5-(carboxyhydroxymethyl)uridine methyl ester); mcm5U
(5-methoxycarbonyl methyluridine); mcm5Um
(S-methoxycarbonylmethyl-2-O-methyluridine); mcm5s2U
(5-methoxycarbonylmethyl-2-thiouridine); nm5s2U
(5-aminomethyl-2-thiouridine); mnm5U (5-methylaminomethyluridine);
mnm5s2U (5-methylaminomethyl-2-thiouridine); mnm5se2U
(5-methylaminomethyl-2-selenouridine); ncm5U (5-carbamoylmethyl
uridine); ncm5Um (5-carbamoylmethyl-2'-O-methyluridine); cmnm5U
(5-carboxymethylaminomethyluridine); cnmm5Um
(5-carboxymethylaminomethyl-2-L-O-methyluridine); cmnm5s2U
(5-carboxymethylaminomethyl-2-thiouridine); m62A
(N6,N6-dimethyladenosine); Tm (2'-O-methylinosine);
m4C(N4-methylcytidine); m4Cm (N4,2-O-dimethylcytidine); hm5C
(5-hydroxymethylcytidine); m3U (3-methyluridine); cm5U
(5-carboxymethyluridine); m6 Am (N6,T-O-dimethyladenosine); rn62 Am
(N6,N6,O-2-trimethyladenosine); m2'7G (N2,7-dimethylguanosine);
m2'2'7G (N2,N2,7-trimethylguanosine); m3Um
(3,2T-O-dimethyluridine); m5D (5-methyldihydrouridine); f5Cm
(5-formyl-2'-O-methylcytidine); m1Gm (1,2'-O-dimethylguanosine);
m'Am (1,2-O-dimethyl adenosine) irinomethyluridine); tm5s2U
(S-taurinomethyl-2-thiouridine)); imG-14 (4-demethyl guanosine);
imG2 (isoguanosine); ac6A (N6-acetyladenosine), hypoxanthine,
inosine, 8-oxo-adenine, 7-substituted derivatives thereof,
dihydrouracil, pseudouracil, 2-thiouracil, 4-thiouracil,
5-aminouracil, 5-(C.sub.1-C.sub.6)-alkyluracil, 5-methyluracil,
5-(C.sub.2-C.sub.6)-alkenyluracil,
5-(C.sub.2-C.sub.6)-alkynyluracil, 5-(hydroxymethyl)uracil,
5-chlorouracil, 5-fluorouracil, 5-bromouracil, 5-hydroxycytosine,
5-(C.sub.1-C.sub.6)-alkylcytosine, 5-methylcytosine,
5-(C.sub.2-C.sub.6)-alkenylcytosine,
5-(C.sub.2-C.sub.6)-alkynylcytosine, 5-chlorocytosine,
5-fluorocytosine, 5-bromocytosine, N2-dimethylguanine,
7-deazaguanine, 8-azaguanine, 7-deaza-7-substituted guanine,
7-deaza-7-(C2-C6)alkynylguanine, 7-deaza-8-substituted guanine,
8-hydroxyguanine, 6-thioguanine, 8-oxoguanine, 2-aminopurine,
2-amino-6-chloropurine, 2,4-diaminopurine, 2,6-diaminopurine,
8-azapurine, substituted 7-deazapurine, 7-deaza-7-substituted
purine, 7-deaza-8-substituted purine, hydrogen (abasic residue),
m5C, m5U, m6A, s2U, W, or 2'-O-methyl-U. Any one or any combination
of these modified nucleobases may be included in the
self-replicating RNA of the invention. Many of these modified
nucleobases and their corresponding ribonucleosides are available
from commercial suppliers.
[0099] If desired, the self-replicating RNA molecule can contain
phosphoramidate, phosphorothioate, and/or methylphosphonate
linkages.
[0100] Self-replicating RNA molecules that comprise at least one
modified nucleotide can be prepared using any suitable method.
Several suitable methods are known in the art for producing RNA
molecules that contain modified nucleotides. For example, a
self-replicating RNA molecule that contains modified nucleotides
can be prepared by transcribing (e.g., in vitro transcription) a
DNA that encodes the self-replicating RNA molecule using a suitable
DNA-dependent RNA polymerase, such as T7 phage RNA polymerase, SP6
phage RNA polymerase, T3 phage RNA polymerase, and the like, or
mutants of these polymerases which allow efficient incorporation of
modified nucleotides into RNA molecules. The transcription reaction
will contain nucleotides and modified nucleotides, and other
components that support the activity of the selected polymerase,
such as a suitable buffer, and suitable salts. The incorporation of
nucleotide analogs into a self-replicating RNA may be engineered,
for example, to alter the stability of such RNA molecules, to
increase resistance against RNases, to establish replication after
introduction into appropriate host cells ("infectivity" of the
RNA), and/or to induce or reduce innate and adaptive immune
responses.
[0101] Suitable synthetic methods can be used alone, or in
combination with one or more other methods (e.g., recombinant DNA
or RNA technology), to produce a self-replicating RNA molecule that
contain one or more modified nucleotides. Suitable methods for de
novo synthesis are well-known in the art and can be adapted for
particular applications. Exemplary methods include, for example,
chemical synthesis using suitable protecting groups such as CEM
(Masuda et al., (2007) Nucleic Acids Symposium Series 51:3-4), the
.beta.-cyanoethyl phosphoramidite method (Beaucage S L et al.
(1981) Tetrahedron Lett 22:1859); nucleoside H-phosphonate method
(Garegg P et al. (1986) Tetrahedron Lett 27:4051-4; Froehler B C et
al. (1986) Nucl Acid Res 14:5399-407; Garegg P et al. (1986)
Tetrahedron Lett 27:4055-8; Gaffney B L et al. (1988) Tetrahedron
Lett 29:2619-22). These chemistries can be performed or adapted for
use with automated nucleic acid synthesizers that are commercially
available. Additional suitable synthetic methods are disclosed in
Uhlmann et al. (1990) Chem Rev 90:544-84, and Goodchild J (1990)
Bioconjugate Chem 1: 165. Nucleic acid synthesis can also be
performed using suitable recombinant methods that are well-known
and conventional in the art, including cloning, processing, and/or
expression of polynucleotides and gene products encoded by such
polynucleotides. DNA shuffling by random fragmentation and PCR
reassembly of gene fragments and synthetic polynucleotides are
examples of known techniques that can be used to design and
engineer polynucleotide sequences. Site-directed mutagenesis can be
used to alter nucleic acids and the encoded proteins, for example,
to insert new restriction sites, alter glycosylation patterns,
change codon preference, produce splice variants, introduce
mutations and the like. Suitable methods for transcription,
translation and expression of nucleic acid sequences are known and
conventional in the art. (See generally, Current Protocols in
Molecular Biology, Vol. 2, Ed. Ausubel, et al., Greene Publish.
Assoc. & Wiley Interscience, Ch. 13, 1988; Glover, DNA Cloning,
Vol. II, IRL Press, Wash., D.C., Ch. 3, 1986; Bitter, et al., in
Methods in Enzymology 153:516-544 (1987); The Molecular Biology of
the Yeast Saccharomyces, Eds. Strathern et al., Cold Spring Harbor
Press, Vols. I and II, 1982; and Sambrook et al., Molecular
Cloning: A Laboratory Manual, Cold Spring Harbor Press, 1989.)
[0102] The presence and/or quantity of one or more modified
nucleotides in a self-replicating RNA molecule can be determined
using any suitable method. For example, a self-replicating RNA can
be digested to monophosphates (e.g., using nuclease P1) and
dephosphorylated (e.g., using a suitable phosphatase such as CIAP),
and the resulting nucleosides analyzed by reversed phase HPLC
(e.g., usings a YMC Pack ODS-AQ column (5 micron, 4.6.times.250 mm)
and elute using a gradient, 30% B (0-5 min) to 100% B (5-13 min)
and at 100% B (13-40) min, flow Rate (0.7 ml/min), UV detection
(wavelength: 260 nm), column temperature (30.degree. C.). Buffer A
(20 mM acetic acid-ammonium acetate pH 3.5), buffer B (20 mM acetic
acid-ammonium acetate pH 3.5/methanol [90/10])).
[0103] The self-replicating RNA may be associated with a delivery
system. The self-replicating RNA may be administered with or
without an adjuvant.
[0104] RNA Delivery Systems
[0105] The self-replicating RNA described herein are suitable for
delivery in a variety of modalities, such as naked RNA delivery or
in combination with lipids, polymers or other compounds that
facilitate entry into the cells. Self-replicating RNA molecules can
be introduced into target cells or subjects using any suitable
technique, e.g., by direct injection, microinjection,
electroporation, lipofection, biolystics, and the like. The
self-replicating RNA molecule may also be introduced into cells by
way of receptor-mediated endocytosis. See e.g., U.S. Pat. No.
6,090,619; Wu and Wu, J. Biol. Chem., 263:14621 (1988); and Curiel
et al., Proc. Natl. Acad. Sci. USA, 88:8850 (1991). For example,
U.S. Pat. No. 6,083,741 discloses introducing an exogenous nucleic
acid into mammalian cells by associating the nucleic acid to a
polycation moiety (e.g., poly-L-lysine having 3-100 lysine
residues), which is itself coupled to an integrin receptor-binding
moiety (e.g., a cyclic peptide having the sequence Arg-Gly-Asp (SEQ
ID NO:______).
[0106] The self-replicating RNA molecules can be delivered into
cells via amphiphiles. See e.g., U.S. Pat. No. 6,071,890.
Typically, a nucleic acid molecule may form a complex with the
cationic amphiphile. Mammalian cells contacted with the complex can
readily take it up.
[0107] The self-replicating RNA can be delivered as naked RNA (e.g.
merely as an aqueous solution of RNA) but, to enhance entry into
cells and also subsequent intercellular effects, the
self-replicating RNA is preferably administered in combination with
a delivery system, such as a particulate or emulsion delivery
system. A large number of delivery systems are well known to those
of skill in the art. Such delivery systems include, for example
liposome-based delivery (Debs and Zhu (1993) WO 93/24640; Mannino
and Gould-Fogerite (1988) BioTechniques 6(7): 682-691; Rose U.S.
Pat. No. 5,279,833; Brigham (1991) WO 91/06309; and Felgner et al.
(1987) Proc. Natl. Acad. Sci. USA 84: 7413-7414), as well as use of
viral vectors (e.g., adenoviral (see, e.g., Berns et al. (1995)
Ann. NY Acad. Sci. 772: 95-104; Ali et al. (1994) Gene Ther. 1:
367-384; and Haddada et al. (1995) Curr. Top. Microbiol. Immunol.
199 (Pt 3): 297-306 for review), papillomaviral, retroviral (see,
e.g., Buchscher et al. (1992) J. Virol. 66(5) 2731-2739; Johann et
al. (1992) J. Virol. 66 (5): 1635-1640 (1992); Sommerfelt et al.,
(1990) Virol. 176:58-59; Wilson et al. (1989) J. Virol.
63:2374-2378; Miller et al., J. Virol. 65:2220-2224 (1991);
Wong-Staal et al., PCT/US94/05700, and Rosenburg and Fauci (1993)
in Fundamental Immunology, Third Edition Paul (ed) Raven Press,
Ltd., New York and the references therein, and Yu et al., Gene
Therapy (1994) supra.), and adeno-associated viral vectors (see,
West et al. (1987) Virology 160:38-47; Carter et al. (1989) U.S.
Pat. No. 4,797,368; Carter et al. WO 93/24641 (1993); Kotin (1994)
Human Gene Therapy 5:793-801; Muzyczka (1994) J. Clin. Invst.
94:1351 and Samulski (supra) for an overview of AAV vectors; see
also, Lebkowski, U.S. Pat. No. 5,173,414; Tratschin et al. (1985)
Mol. Cell. Biol. 5(11):3251-3260; Tratschin, et al. (1984) Mol.
Cell. Biol., 4:2072-2081; Hermonat and Muzyczka (1984) Proc. Natl.
Acad. Sci. USA, 81:6466-6470; McLaughlin et al. (1988) and Samulski
et al. (1989) J. Virol., 63:03822-3828), and the like.
[0108] Three particularly useful delivery systems are (i)
liposomes, (ii) non-toxic and biodegradable polymer microparticles,
and (iii) cationic submicron oil-in-water emulsions.
[0109] Liposomes
[0110] Various amphiphilic lipids can form bilayers in an aqueous
environment to encapsulate a RNA-containing aqueous core as a
liposome. These lipids can have an anionic, cationic or
zwitterionic hydrophilic head group. Formation of liposomes from
anionic phospholipids dates back to the 1960s, and cationic
liposome-forming lipids have been studied since the 1990s. Some
phospholipids are anionic whereas other are zwitterionic. Suitable
classes of phospholipid include, but are not limited to,
phosphatidylethanolamines, phosphatidylcholines,
phosphatidylserines, and phosphatidylglycerols, and some useful
phospholipids are listed in Table 2. Useful cationic lipids
include, but are not limited to, dioleoyl trimethylammonium propane
(DOTAP), 1,2-distearyloxy-N,N-dimethyl-3-aminopropane (DSDMA),
1,2-dioleyloxy-N,Ndimethyl-3-aminopropane (DODMA),
1,2-dilinoleyloxy-N,N-dimethyl-3-aminopropane (DLinDMA),
1,2-dilinolenyloxy-N,N-dimethyl-3-aminopropane (DLenDMA).
Zwitterionic lipids include, but are not limited to, acyl
zwitterionic lipids and ether zwitterionic lipids. Examples of
useful zwitterionic lipids are DPPC, DOPC and
dodecylphosphocholine. The lipids can be saturated or
unsaturated.
[0111] Liposomes can be formed from a single lipid or from a
mixture of lipids. A mixture may comprise (i) a mixture of anionic
lipids (ii) a mixture of cationic lipids (iii) a mixture of
zwitterionic lipids (iv) a mixture of anionic lipids and cationic
lipids (v) a mixture of anionic lipids and zwitterionic lipids (vi)
a mixture of zwitterionic lipids and cationic lipids or (vii) a
mixture of anionic lipids, cationic lipids and zwitterionic lipids.
Similarly, a mixture may comprise both saturated and unsaturated
lipids. For example, a mixture may comprise DSPC (zwitterionic,
saturated), DlinDMA (cationic, unsaturated), and/or DMPG (anionic,
saturated). Where a mixture of lipids is used, not all of the
component lipids in the mixture need to be amphiphilic e.g. one or
more amphiphilic lipids can be mixed with cholesterol.
[0112] The hydrophilic portion of a lipid can be PEGylated (i.e.
modified by covalent attachment of a polyethylene glycol). This
modification can increase stability and prevent non-specific
adsorption of the liposomes. For instance, lipids can be conjugated
to PEG using techniques such as those disclosed in Heyes et al.
(2005) J Controlled Release 107:276-87.
[0113] A mixture of DSPC, DlinDMA, PEG-DMPG and cholesterol can be
used to form liposomes. A separate aspect of the invention is a
liposome comprising DSPC, DlinDMA, PEG-DMG and cholesterol. This
liposome preferably encapsulates RNA, such as a self-replicating
RNA e.g. encoding an immunogen.
[0114] Liposomes are usually divided into three groups:
multilamellar vesicles (MLV); small unilamellar vesicles (SUV); and
large unilamellar vesicles (LUV). MLVs have multiple bilayers in
each vesicle, forming several separate aqueous compartments. SUVs
and LUVs have a single bilayer encapsulating an aqueous core; SUVs
typically have a diameter .ltoreq.50 nm, and LUVs have a diameter
>50 nm. Liposomes useful with of the invention are ideally LUVs
with a diameter in the range of 50-220 nm. For a composition
comprising a population of LUVs with different diameters: (i) at
least 80% by number should have diameters in the range of 20-220
nm, (ii) the average diameter (Zav, by intensity) of the population
is ideally in the range of 40-200 nm, and/or (iii) the diameters
should have a polydispersity index <0.2.
[0115] Techniques for preparing suitable liposomes are well known
in the art e.g. see Liposomes: Methods and Protocols, Volume 1:
Pharmaceutical Nanocarriers: Methods and Protocols. (ed. Weissig).
Humana Press, 2009. ISBN 160327359X; Liposome Technology, volumes
I, II & III. (ed. Gregoriadis). Informa Healthcare, 2006; and
Functional Polymer Colloids and Microparticles volume 4
(Microspheres, microcapsules & liposomes). (eds. Arshady &
Guyot). Citus Books, 2002. One useful method involves mixing (i) an
ethanolic solution of the lipids (ii) an aqueous solution of the
nucleic acid and (iii) buffer, followed by mixing, equilibration,
dilution and purification (Heyes et al. (2005) J Controlled Release
107:276-87.).
[0116] RNA is preferably encapsulated within the liposomes, and so
the liposome forms a outer layer around an aqueous RNA-containing
core. This encapsulation has been found to protect RNA from RNase
digestion. The liposomes can include some external RNA (e.g. on the
surface of the liposomes), but preferably, at least half of the RNA
(and ideally substantially all of it) is encapsulated.
[0117] Polymeric Microparticles
[0118] Various polymers can form microparticles to encapsulate or
adsorb RNA. The use of a substantially non-toxic polymer means that
a recipient can safely receive the particles, and the use of a
biodegradable polymer means that the particles can be metabolised
after delivery to avoid long-term persistence. Useful polymers are
also sterilisable, to assist in preparing pharmaceutical grade
formulations.
[0119] Suitable non-toxic and biodegradable polymers include, but
are not limited to, poly(.alpha.-hydroxy acids), polyhydroxy
butyric acids, polylactones (including polycaprolactones),
polydioxanones, polyvalerolactone, polyorthoesters, polyanhydrides,
polycyanoacrylates, tyrosine-derived polycarbonates,
polyvinyl-pyrrolidinones or polyester-amides, and combinations
thereof.
[0120] In some embodiments, the microparticles are formed from
poly(.alpha.-hydroxy acids), such as a poly(lactides) ("PLA"),
copolymers of lactide and glycolide such as a
poly(D,L-lactide-co-glycolide) ("PLG"), and copolymers of
D,L-lactide and caprolactone. Useful PLG polymers include those
having a lactide/glycolide molar ratio ranging, for example, from
20:80 to 80:20 e.g. 25:75, 40:60, 45:55, 55:45, 60:40, 75:25.
Useful PLG polymers include those having a molecular weight
between, for example, 5,000-200,000 Da e.g. between 10,000-100,000,
20,000-70,000, 40,000-50,000 Da.
[0121] The microparticles ideally have a diameter in the range of
0.02 .mu.m to 8 .mu.m. For a composition comprising a population of
microparticles with different diameters at least 80% by number
should have diameters in the range of 0.03-7 .mu.m.
[0122] Techniques for preparing suitable microparticles are well
known in the art e.g. see Functional Polymer Colloids and
Microparticles volume 4 (Microspheres, microcapsules &
liposomes). (eds. Arshady & Guyot). Citus Books, 2002; Polymers
in Drug Delivery. (eds. Uchegbu & Schatzlein). CRC Press, 2006.
(in particular chapter 7) and Microparticulate Systems for the
Delivery of Proteins and Vaccines. (eds. Cohen & Bernstein).
CRC Press, 1996. To facilitate adsorption of RNA, a microparticle
may include a cationic surfactant and/or lipid e.g. as disclosed in
O'Hagan et al. (2001) J Virology 75:9037-9043; and Singh et al.
(2003) Pharmaceutical Research 20: 247-251. An alternative way of
making polymeric microparticles is by molding and curing e.g. as
disclosed in WO2009/132206.
[0123] Microparticles of the invention can have a zeta potential of
between 40-100 mV. RNA can be adsorbed to the microparticles, and
adsorption is facilitated by including cationic materials (e.g.
cationic lipids) in the microparticle.
[0124] Oil-in-Water Cationic Emulsions
[0125] Oil-in-water emulsions are known for adjuvanting influenza
vaccines e.g. the MF59.TM. adjuvant in the FLUAD.TM. product, and
the AS03 adjuvant in the PREPANDRIX.TM. product. RNA delivery can
be accomplished with the use of an oil-in-water emulsion, provided
that the emulsion includes one or more cationic molecules. For
instance, a cationic lipid can be included in the emulsion to
provide a positively charged droplet surface to which
negatively-charged RNA can attach.
[0126] The emulsion comprises one or more oils. Suitable oil(s)
include those from, for example, an animal (such as fish) or a
vegetable source. The oil is ideally biodegradable (metabolizable)
and biocompatible. Sources for vegetable oils include nuts, seeds
and grains. Peanut oil, soybean oil, coconut oil, and olive oil,
the most commonly available, exemplify the nut oils. Jojoba oil can
be used e.g. obtained from the jojoba bean. Seed oils include
safflower oil, cottonseed oil, sunflower seed oil, sesame seed oil
and the like. In the grain group, corn oil is the most readily
available, but the oil of other cereal grains such as wheat, oats,
rye, rice, teff, triticale and the like may also be used. 6-10
carbon fatty acid esters of glycerol and 1,2-propanediol, while not
occurring naturally in seed oils, may be prepared by hydrolysis,
separation and esterification of the appropriate materials starting
from the nut and seed oils. Fats and oils from mammalian milk are
metabolizable and so may be used. The procedures for separation,
purification, saponification and other means necessary for
obtaining pure oils from animal sources are well known in the
art.
[0127] Most fish contain metabolizable oils which may be readily
recovered. For example, cod liver oil, shark liver oils, and whale
oil such as spermaceti exemplify several of the fish oils which may
be used herein. A number of branched chain oils are synthesized
biochemically in 5-carbon isoprene units and are generally referred
to as terpenoids. Squalane, the saturated analog to squalene, can
also be used. Fish oils, including squalene and squalane, are
readily available from commercial sources or may be obtained by
methods known in the art.
[0128] Other useful oils are the tocopherols, particularly in
combination with squalene. Where the oil phase of an emulsion
includes a tocopherol, any of the .alpha., .beta., .gamma.,
.delta., .epsilon. or .xi. tocopherols can be used, but
.alpha.-tocopherols are preferred. D-.alpha.-tocopherol and
DL-.alpha.-tocopherol can both be used. A preferred
.alpha.-tocopherol is DL-.alpha.-tocopherol. An oil combination
comprising squalene and a tocopherol (e.g. DL-.alpha.-tocopherol)
can be used.
[0129] Preferred emulsions comprise squalene, a shark liver oil
which is a branched, unsaturated terpenoid (C.sub.30H.sub.50;
[(CH.sub.3).sub.2C[.dbd.CHCH.sub.2CH.sub.2C(CH.sub.3)].sub.2.dbd.CHCH.sub-
.2--].sub.2;
2,6,10,15,19,23-hexamethyl-2,6,10,14,18,22-tetracosahexaene; CAS RN
7683-64-9).
[0130] The oil in the emulsion may comprise a combination of oils
e.g. squalene and at least one further oil.
[0131] The aqueous component of the emulsion can be plain water
(e.g. w.f.i.) or can include further components e.g. solutes. For
instance, it may include salts to form a buffer e.g. citrate or
phosphate salts, such as sodium salts. Typical buffers include: a
phosphate buffer; a Tris buffer; a borate buffer; a succinate
buffer; a histidine buffer; or a citrate buffer. A buffered aqueous
phase is preferred, and buffers will typically be included in the
5-20 mM range.
[0132] The emulsion also includes a cationic lipid. Preferably this
lipid is a surfactant so that it can facilitate formation and
stabilization of the emulsion. Useful cationic lipids generally
contains a nitrogen atom that is positively charged under
physiological conditions e.g. as a tertiary or quaternary amine.
This nitrogen can be in the hydrophilic head group of an
amphiphilic surfactant. Useful cationic lipids include, but are not
limited to: 1,2-dioleoyloxy-3-(trimethylammonio)propane (DOTAP),
3'-[N--(N',N'-Dimethylaminoethane)-carbamoyl]Cholesterol (DC
Cholesterol), dimethyldioctadecyl-ammonium (DDA e.g. the bromide),
1,2-Dimyristoyl-3-Trimethyl-AmmoniumPropane (DMTAP),
dipalmitoyl(C16:0)trimethyl ammonium propane (DPTAP),
distearoyltrimethylammonium propane (DSTAP). Other useful cationic
lipids are: benzalkonium chloride (BAK), benzethonium chloride,
cetramide (which contains tetradecyltrimethylammonium bromide and
possibly small amounts of dedecyltrimethylammonium bromide and
hexadecyltrimethyl ammonium bromide), cetylpyridinium chloride
(CPC), cetyl trimethylammonium chloride (CTAC),
N,N',N'-polyoxyethylene (10)-N-tallow-1,3-diaminopropane,
dodecyltrimethylammonium bromide, hexadecyltrimethyl-ammonium
bromide, mixed alkyl-trimethyl-ammonium bromide,
benzyldimethyldodecylammonium chloride,
benzyldimethylhexadecyl-ammonium chloride, benzyltrimethylammonium
methoxide, cetyldimethylethylammonium bromide, dimethyldioctadecyl
ammonium bromide (DDAB), methylbenzethonium chloride, decamethonium
chloride, methyl mixed trialkyl ammonium chloride, methyl
trioctylammonium chloride), N,N-dimethyl-N-[2
(2-methyl-4-(1,1,3,3tetramethylbutyl)-phenoxy]-ethoxy)ethyl]-benzenemetha-
-naminium chloride (DEBDA), dialkyldimethylammonium salts,
[1-(2,3-dioleyloxy)-propyl]-N,N,N,trimethylammonium chloride,
1,2-diacyl-3-(trimethylammonio) propane (acyl group=dimyristoyl,
dipalmitoyl, distearoyl, dioleoyl), 1,2-diacyl-3
(dimethylammonio)propane (acyl group=dimyristoyl, dipalmitoyl,
distearoyl, dioleoyl),
1,2-dioleoyl-3-(4'-trimethyl-ammonio)butanoyl-sn-glycerol,
1,2-dioleoyl 3-succinyl-sn-glycerol choline ester, cholesteryl
(4'-trimethylammonio) butanoate), N-alkyl pyridinium salts (e.g.
cetylpyridinium bromide and cetylpyridinium chloride),
N-alkylpiperidinium salts, dicationic bolaform electrolytes
(C12Me6; C12BU6), dialkylglycetylphosphorylcholine, lysolecithin,
L-.alpha.dioleoylphosphatidylethanolamine, cholesterol
hemisuccinate choline ester, lipopolyamines, including but not
limited to dioctadecylamidoglycylspermine (DOGS), dipalmitoyl
phosphatidylethanol-amidospermine (DPPES), lipopoly-L (or D)-lysine
(LPLL, LPDL), poly(L (or D)-lysine conjugated to
N-glutarylphosphatidylethanolamine, didodecyl glutamate ester with
pendant amino group (C GluPhCnN), ditetradecyl glutamate ester with
pendant amino group (C14GluCnN+), cationic derivatives of
cholesterol, including but not limited to
cholesteryl-3.beta.-oxysuccinamidoethylenetrimethylammonium salt,
cholesteryl-3.beta.-oxysuccinamidoethylene-dimethylamine,
cholesteryl-3.beta.-carboxyamidoethylenetrimethylammonium salt, and
cholesteryl-3.beta.-carboxyamidoethylenedimethylamine. Other useful
cationic lipids are described in US 2008/0085870 and US
2008/0057080, which are incorporated herein by reference. The
cationic lipid is preferably biodegradable (metabolizable) and
biocompatible.
[0133] In addition to the oil and cationic lipid, an emulsion can
include a non-ionic surfactant and/or a zwitterionic surfactant.
Such surfactants include, but are not limited to: the
polyoxyethylene sorbitan esters surfactants (commonly referred to
as the Tweens), especially polysorbate 20 and polysorbate 80;
copolymers of ethylene oxide (EO), propylene oxide (PO), and/or
butylene oxide (BO), sold under the DOWFAX.TM. tradename, such as
linear EO/PO block copolymers; octoxynols, which can vary in the
number of repeating ethoxy (oxy-1,2-ethanediyl) groups, with
octoxynol-9 (Triton X-100, or t-octylphenoxypolyethoxyethanol)
being of particular interest; (octylphenoxy)polyethoxyethanol
(IGEPAL CA-630/NP-40); phospholipids such as phosphatidylcholine
(lecithin); polyoxyethylene fatty ethers derived from lauryl,
cetyl, stearyl and oleyl alcohols (known as Brij surfactants), such
as triethyleneglycol monolauryl ether (Brij 30);
polyoxyethylene-9-lauryl ether; and sorbitan esters (commonly known
as the Spans), such as sorbitan trioleate (Span 85) and sorbitan
monolaurate. Preferred surfactants for including in the emulsion
are polysorbate 80 (Tween 80; polyoxyethylene sorbitan monooleate),
Span 85 (sorbitan trioleate), lecithin and Triton X-100.
[0134] Mixtures of these surfactants can be included in the
emulsion e.g. Tween 80/Span 85 mixtures, or Tween 80/Triton-X100
mixtures. A combination of a polyoxyethylene sorbitan ester such as
polyoxyethylene sorbitan monooleate (Tween 80) and an octoxynol
such as t-octylphenoxy-polyethoxyethanol (Triton X-100) is also
suitable. Another useful combination comprises laureth 9 plus a
polyoxyethylene sorbitan ester and/or an octoxynol. Useful mixtures
can comprise a surfactant with a HLB value in the range of 10-20
(e.g. polysorbate 80, with a HLB of 15.0) and a surfactant with a
HLB value in the range of 1-10 (e.g. sorbitan trioleate, with a HLB
of 1.8).
[0135] Preferred amounts of oil (% by volume) in the final emulsion
are between 2-20% e.g. 5-15%, 6-14%, 7-13%, 8-12%. A squalene
content of about 4-6% or about 9-11% is particularly useful.
[0136] Preferred amounts of surfactants (% by weight) in the final
emulsion are between 0.001% and 8%. For example: polyoxyethylene
sorbitan esters (such as polysorbate 80) 0.2 to 4%, in particular
between 0.4-0.6%, between 0.45-0.55%, about 0.5% or between 1.5-2%,
between 1.8-2.2%, between 1.9-2.1%, about 2%, or 0.85-0.95%, or
about 1%; sorbitan esters (such as sorbitan trioleate) 0.02 to 2%,
in particular about 0.5% or about 1%; octyl- or nonylphenoxy
polyoxyethanols (such as Triton X-100) 0.001 to 0.1%, in particular
0.005 to 0.02%; polyoxyethylene ethers (such as laureth 9) 0.1 to
8%, preferably 0.1 to 10% and in particular 0.1 to 1% or about
0.5%.
[0137] The absolute amounts of oil and surfactant, and their ratio,
can be varied within wide limits while still forming an emulsion. A
skilled person can easily vary the relative proportions of the
components to obtain a desired emulsion, but a weight ratio of
between 4:1 and 5:1 for oil and surfactant is typical (excess
oil).
[0138] An important parameter for ensuring immunostimulatory
activity of an emulsion, particularly in large animals, is the oil
droplet size (diameter). The most effective emulsions have a
droplet size in the submicron range. Suitably the droplet sizes
will be in the range 50-750 nm. Most usefully the average droplet
size is less than 250 nm e.g. less than 200 nm, less than 150 nm.
The average droplet size is usefully in the range of 80-180 nm.
Ideally, at least 80% (by number) of the emulsion's oil droplets
are less than 250 nm in diameter, and preferably at least 90%.
Apparatuses for determining the average droplet size in an
emulsion, and the size distribution, are commercially available.
These typically use the techniques of dynamic light scattering
and/or single-particle optical sensing e.g. the Accusizer.TM. and
Nicomp.TM. series of instruments available from Particle Sizing
Systems (Santa Barbara, USA), or the Zetasizer.TM. instruments from
Malvern Instruments (UK), or the Particle Size Distribution
Analyzer instruments from Horiba (Kyoto, Japan).
[0139] Ideally, the distribution of droplet sizes (by number) has
only one maximum i.e. there is a single population of droplets
distributed around an average (mode), rather than having two
maxima. Preferred emulsions have a polydispersity of <0.4 e.g.
0.3, 0.2, or less.
[0140] Suitable emulsions with submicron droplets and a narrow size
distribution can be obtained by the use of microfluidization. This
technique reduces average oil droplet size by propelling streams of
input components through geometrically fixed channels at high
pressure and high velocity. These streams contact channel walls,
chamber walls and each other. The results shear, impact and
cavitation forces cause a reduction in droplet size. Repeated steps
of microfluidization can be performed until an emulsion with a
desired droplet size average and distribution are achieved.
[0141] As an alternative to microfluidization, thermal methods can
be used to cause phase inversion. These methods can also provide a
submicron emulsion with a tight particle size distribution.
[0142] Preferred emulsions can be filter sterilized i.e. their
droplets can pass through a 220 nm filter. As well as providing a
sterilization, this procedure also removes any large droplets in
the emulsion.
[0143] In certain embodiments, the cationic lipid in the emulsion
is DOTAP. The cationic oil-in-water emulsion may comprise from
about 0.5 mg/ml to about 25 mg/ml DOTAP. For example, the cationic
oil-in-water emulsion may comprise DOTAP at from about 0.5 mg/ml to
about 25 mg/ml, from about 0.6 mg/ml to about 25 mg/ml, from about
0.7 mg/ml to about 25 mg/ml, from about 0.8 mg/ml to about 25
mg/ml, from about 0.9 mg/ml to about 25 mg/ml, from about 1.0 mg/ml
to about 25 mg/ml, from about 1.1 mg/ml to about 25 mg/ml, from
about 1.2 mg/ml to about 25 mg/ml, from about 1.3 mg/ml to about 25
mg/ml, from about 1.4 mg/ml to about 25 mg/ml, from about 1.5 mg/ml
to about 25 mg/ml, from about 1.6 mg/ml to about 25 mg/ml, from
about 1.7 mg/ml to about 25 mg/ml, from about 0.5 mg/ml to about 24
mg/ml, from about 0.5 mg/ml to about 22 mg/ml, from about 0.5 mg/ml
to about 20 mg/ml, from about 0.5 mg/ml to about 18 mg/ml, from
about 0.5 mg/ml to about 15 mg/ml, from about 0.5 mg/ml to about 12
mg/ml, from about 0.5 mg/ml to about 10 mg/ml, from about 0.5 mg/ml
to about 5 mg/ml, from about 0.5 mg/ml to about 2 mg/ml, from about
0.5 mg/ml to about 1.9 mg/ml, from about 0.5 mg/ml to about 1.8
mg/ml, from about 0.5 mg/ml to about 1.7 mg/ml, from about 0.5
mg/ml to about 1.6 mg/ml, from about 0.6 mg/ml to about 1.6 mg/ml,
from about 0.7 mg/ml to about 1.6 mg/ml, from about 0.8 mg/ml to
about 1.6 mg/ml, about 0.5 mg/ml, about 0.6 mg/ml, about 0.7 mg/ml,
about 0.8 mg/ml, about 0.9 mg/ml, about 1.0 mg/ml, about 1.1 mg/ml,
about 1.2 mg/ml, about 1.3 mg/ml, about 1.4 mg/ml, about 1.5 mg/ml,
about 1.6 mg/ml, about 12 mg/ml, about 18 mg/ml, about 20 mg/ml,
about 21.8 mg/ml, about 24 mg/ml, etc. In an exemplary embodiment,
the cationic oil-in-water emulsion comprises from about 0.8 mg/ml
to about 1.6 mg/ml DOTAP, such as 0.8 mg/ml, 1.2 mg/ml, 1.4 mg/ml
or 1.6 mg/ml.
[0144] In certain embodiments, the cationic lipid is DC
Cholesterol. The cationic oil-in-water emulsion may comprise DC
Cholesterol at from about 0.1 mg/ml to about 5 mg/ml DC
Cholesterol. For example, the cationic oil-in-water emulsion may
comprise DC Cholesterol from about 0.1 mg/ml to about 5 mg/ml, from
about 0.2 mg/ml to about 5 mg/ml, from about 0.3 mg/ml to about 5
mg/ml, from about 0.4 mg/ml to about 5 mg/ml, from about 0.5 mg/ml
to about 5 mg/ml, from about 0.62 mg/ml to about 5 mg/ml, from
about 1 mg/ml to about 5 mg/ml, from about 1.5 mg/ml to about 5
mg/ml, from about 2 mg/ml to about 5 mg/ml, from about 2.46 mg/ml
to about 5 mg/ml, from about 3 mg/ml to about 5 mg/ml, from about
3.5 mg/ml to about 5 mg/ml, from about 4 mg/ml to about 5 mg/ml,
from about 4.5 mg/ml to about 5 mg/ml, from about 0.1 mg/ml to
about 4.92 mg/ml, from about 0.1 mg/ml to about 4.5 mg/ml, from
about 0.1 mg/ml to about 4 mg/ml, from about 0.1 mg/ml to about 3.5
mg/ml, from about 0.1 mg/ml to about 3 mg/ml, from about 0.1 mg/ml
to about 2.46 mg/ml, from about 0.1 mg/ml to about 2 mg/ml, from
about 0.1 mg/ml to about 1.5 mg/ml, from about 0.1 mg/ml to about 1
mg/ml, from about 0.1 mg/ml to about 0.62 mg/ml, about 0.15 mg/ml,
about 0.3 mg/ml, about 0.6 mg/ml, about 0.62 mg/ml, about 0.9
mg/ml, about 1.2 mg/ml, about 2.46 mg/ml, about 4.92 mg/ml, etc. In
an exemplary embodiment, the cationic oil-in-water emulsion
comprises from about 0.62 mg/ml to about 4.92 mg/ml DC Cholesterol,
such as 2.46 mg/ml.
[0145] In certain embodiments, the cationic lipid is DDA. The
cationic oil-in-water emulsion may comprise from about 0.1 mg/ml to
about 5 mg/ml DDA. For example, the cationic oil-in-water emulsion
may comprise DDA at from about 0.1 mg/ml to about 5 mg/ml, from
about 0.1 mg/ml to about 4.5 mg/ml, from about 0.1 mg/ml to about 4
mg/ml, from about 0.1 mg/ml to about 3.5 mg/ml, from about 0.1
mg/ml to about 3 mg/ml, from about 0.1 mg/ml to about 2.5 mg/ml,
from about 0.1 mg/ml to about 2 mg/ml, from about 0.1 mg/ml to
about 1.5 mg/ml, from about 0.1 mg/ml to about 1.45 mg/ml, from
about 0.2 mg/ml to about 5 mg/ml, from about 0.3 mg/ml to about 5
mg/ml, from about 0.4 mg/ml to about 5 mg/ml, from about 0.5 mg/ml
to about 5 mg/ml, from about 0.6 mg/ml to about 5 mg/ml, from about
0.73 mg/ml to about 5 mg/ml, from about 0.8 mg/ml to about 5 mg/ml,
from about 0.9 mg/ml to about 5 mg/ml, from about 1.0 mg/ml to
about 5 mg/ml, from about 1.2 mg/ml to about 5 mg/ml, from about
1.45 mg/ml to about 5 mg/ml, from about 2 mg/ml to about 5 mg/ml,
from about 2.5 mg/ml to about 5 mg/ml, from about 3 mg/ml to about
5 mg/ml, from about 3.5 mg/ml to about 5 mg/ml, from about 4 mg/ml
to about 5 mg/ml, from about 4.5 mg/ml to about 5 mg/ml, about 1.2
mg/ml, about 1.45 mg/ml, etc. Alternatively, the cationic
oil-in-water emulsion may comprise DDA at about 20 mg/ml, about 21
mg/ml, about 21.5 mg/ml, about 21.6 mg/ml, about 25 mg/ml. In an
exemplary embodiment, the cationic oil-in-water emulsion comprises
from about 0.73 mg/ml to about 1.45 mg/ml DDA, such as 1.45
mg/ml.
[0146] Catheters or like devices may be used to deliver the
self-replicating RNA molecules of the invention, as naked RNA or in
combination with a delivery system, into a target organ or tissue.
Suitable catheters are disclosed in, e.g., U.S. Pat. Nos.
4,186,745; 5,397,307; 5,547,472; 5,674,192; and 6,129,705, all of
which are incorporated herein by reference.
[0147] The present invention includes the use of suitable delivery
systems, such as liposomes, polymer microparticles or submicron
emulsion microparticles with encapsulated or adsorbed
self-replicating RNA, to deliver a self-replicating RNA molecule
that encodes two or more CMV proteins, for example, to elicit an
immune response alone, or in combination with another
macromolecule. The invention includes liposomes, microparticles and
submicron emulsions with adsorbed and/or encapsulated
self-replicating RNA molecules, and combinations thereof.
[0148] The self-replicating RNA molecules associated with liposomes
and submicron emulsion microparticles can be effectively delivered
to a host cell, and can induce an immune response to the protein
encoded by the self-replicating RNA.
[0149] Polycistronic self replicating RNA molecules that encode CMV
proteins, and VRPs produced using polycistronic alphavirus
replicons, can be used to form CMV protein complexes in a cell.
Complexes include, but are not limited to, gB/gH/gL; gH/gL;
gH/gL/gO; gM/gN; gH/gL/UL128/UL130/UL131; and
UL128/UL130/UL131.
[0150] In some embodiments combinations of VRPs are delivered to a
cell. Combinations include, but are not limited to: [0151] 1. a
gH/gL VRP and another VRP; [0152] 2. a gH/gL VRP and a gB VRP;
[0153] 3. a gH/gL/gO VRP and a gB VRP; [0154] 4. a gB VRP and a
gH/gL/UL128/UL130/UL131 VRP; [0155] 5. a gB VRP and
UL128/UL130/UL131 VRP; [0156] 6. a gB VRP and a gM/gN VRP; [0157]
7. a gB VRP, a gH/gL VRP, and a UL128/UL130/UL131 VRP; [0158] 8. a
gB VRP, a gH/gLgO VRP, and a UL128/UL130/UL131 VRP; [0159] 9. a gB
VRP, a gM/gN VRP, a gH/gL VRP, and a UL128/UL130/UL131 VRP; [0160]
10. a gB VRP, a gM/gN VRP, a gH/gL/0 VRP, and a UL128/UL130/UL131
VRP; [0161] 11. a gH/gL VRP and a UL128/UL130/UL131 VRP; and
[0162] In some embodiments combinations of self-replicating RNA
molecules are delivered to a cell. Combinations include, but are
not limited to: [0163] 1. a self-replicating RNA molecule encoding
gH/gL and a self-replicating RNA molecule encoding another protein;
[0164] 2. a self-replicating RNA molecule encoding gH and gL and a
self-replicating RNA molecule encoding gB; [0165] 3. a
self-replicating RNA molecule encoding gH, gL and gO and a
self-replicating RNA molecule encoding gB; [0166] 4. a
self-replicating RNA molecule encoding gB and a self-replicating
RNA molecule encoding gH, gL, UL128, UL130 and UL131; [0167] 5. a
self-replicating RNA molecule encoding gB and a self-replicating
RNA molecule encoding UL128, UL130 and UL131; [0168] 6. a
self-replicating RNA molecule encoding gB and a self-replicating
RNA molecule encoding gM and gN; [0169] 7. a self-replicating RNA
molecule encoding gB, a self-replicating RNA molecule encoding gH
and gL, and a self-replicating RNA molecule encoding UL128, UL130
and UL131; [0170] 8. a self-replicating RNA molecule encoding gB, a
self-replicating RNA molecule encoding gH, gL, and gO, and a
self-replicating RNA molecule encoding UL128, UL130 and UL131;
[0171] 9. a self-replicating RNA molecule encoding gB, a
self-replicating RNA molecule encoding gM and gN, a
self-replicating RNA molecule encoding gH and gL, and a
self-replicating RNA molecule encoding UL128, UL130 and UL131;
[0172] 10. a self-replicating RNA molecule encoding gB, a
self-replicating RNA molecule encoding gM and gN, a
self-replicating RNA molecule encoding gH, gL and gO, and a
self-replicating RNA molecule encoding UL128, UL130 and UL131;
[0173] 11. a self-replicating RNA molecule encoding gH and gL, and
a self-replicating RNA molecule encoding UL128, UL130 and UL131;
and
CMV Proteins
[0174] Suitable CMV proteins include gB, gH, gL, gO, and can be
from any CMV strain. Other suitable CMV proteins include UL128,
UL130 and UL131, and can be from any CMV strain. For example, CMV
proteins can be from Merlin, AD169, VR1814, Towne, Toledo, TR, PH,
TB40, or Fix strains of CMV. Exemplary CMV proteins and fragments
are described herein. These proteins and fragments can be encoded
by any suitable nucleotide sequence, including sequences that are
codon optimized or deoptimized for expression in a desired host,
such as a human cell. Exemplary sequences of CMV proteins and
nucleic acids encoding the proteins are provided in Table 2
TABLE-US-00002 TABLE 2 Full length gH polynucleotide (CMV gH FL)
SEQ ID NO: Full length gH polypeptide (CMV gH FL) SEQ ID NO: Full
length gL polynucleotide (CMV gL FL) SEQ ID NO: Full length gL
polypeptide (CMV gL FL) SEQ ID NO: Full length gO polynucleotide
(CMV gO FL) SEQ ID NO: Full length gO polypeptide (CMV gO FL) SEQ
ID NO: gH sol polynucleotide (CMV gH sol) SEQ ID NO: gH sol
polypeptide (CMV gH sol) SEQ ID NO: Full length UL128
polynucleotide (CMV UL128 FL) SEQ ID NO: Full length UL128
polypeptide (CMV UL128 FL) SEQ ID NO: Full length UL130
polynucleotide (CMV UL130 FL) SEQ ID NO: Full length UL130
polypeptide (CMV UL130 FL) SEQ ID NO: Full length UL131
polynucleotide (CMV UL131 FL) SEQ ID NO: Full length UL131
polypeptide (CMV UL131 FL) SEQ ID NO: Full length gB polynucleotide
(CMV gB FL) SEQ ID NO: Full length gB polypeptide (CMV gB FL) SEQ
ID NO: gB sol 750 polynucleotide (CMV gB 750) SEQ ID NO: gB sol 750
polypeptide (CMV gB 750) SEQ ID NO: gB sol 692 polynucleotide (CMV
gB 692) SEQ ID NO: gB sol 692 polypeptide (CMV gB 692) SEQ ID NO:
Full length gM polynucleotide (CMV gM FL) SEQ ID NO: Full length gM
polynucleotide (CMV gM FL) SEQ ID NO: Full length gN polynucleotide
(CMV gN FL) SEQ ID NO: Full length gN polynucleotide (CMV gN FL)
SEQ ID NO: .sub.--
[0175] CMV gB Proteins
[0176] A gB protein can be full length or can omit one or more
regions of the protein. Alternatively, fragments of a gB protein
can be used. gB amino acids are numbered according to the
full-length gB amino acid sequence (CMV gB FL) shown in SEQ ID
NO:______, which is 907 amino acids long. Suitable regions of a gB
protein, which can be excluded from the full-length protein or
included as fragments include: the signal sequence (amino acids
1-24), a gB-DLD disintegrin-like domain (amino acids 57-146), a
furin cleavage site (amino acids 459-460), a heptad repeat region
(679-693), a membrane spanning domain (amino acids 751-771), and a
cytoplasmic domain from amino acids 771-906. In some embodiments a
gB protein includes amino acids 67-86 (Neutralizing Epitope AD2)
and/or amino acids 532-635 (Immunodominant Epitope AD1). Specific
examples of gB fragments, include "gB sol 692," which includes the
first 692 amino acids of gB, and "gB sol 750," which includes the
first 750 amino acids of gB. The signal sequence, amino acids 1-24,
can be present or absent from gB sol 692 and gB sol 750 as desired.
Optionally, the gB protein can be a gB fragment of 10 amino acids
or longer. For example, the number of amino acids in the fragment
can comprise 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 125, 150,
175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475,
500, 525, 550, 575, 600, 625, 650, 675, 700, 725, 750, 775, 800,
825, 850, or 875 amino acids. A gB fragment can begin at any of
residue number: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 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, 60, 61, 62, 63, 64, 65, 66,
67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83,
84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99,
100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112,
113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125,
126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138,
139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151,
152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164,
165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177,
178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190,
191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203,
204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216,
217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229,
230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242,
243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255,
256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268,
269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281,
282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294,
295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307,
308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320,
321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333,
334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346,
347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359,
360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372,
373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385,
386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398,
399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411,
412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424,
425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437,
438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450,
451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463,
464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476,
477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489,
490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502,
503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515,
516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528,
529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541,
542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554,
555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567,
568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580,
581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593,
594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606,
607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619,
620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632,
633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645,
646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658,
659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671,
672, 673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684,
685, 686, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697,
698, 699, 700, 701, 702, 703, 704, 705, 706, 707, 708, 709, 710,
711, 712, 713, 714, 715, 716, 717, 718, 719, 720, 721, 722, 723,
724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736,
737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749,
750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762,
763, 764, 765, 766, 767, 768, 769, 770, 771, 772, 773, 774, 775,
776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788,
789, 790, 791, 792, 793, 794, 795, 796, 797, 798, 799, 800, 801,
802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 812, 813, 814,
815, 816, 817, 818, 819, 820, 821, 822, 823, 824, 825, 826, 827,
828, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840,
841, 842, 843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853,
854, 855, 856, 857, 858, 859, 860, 861, 862, 863, 864, 865, 866,
867, 868, 869, 870, 871, 872, 873, 874, 875, 876, 877, 878, 879,
880, 881, 882, 883, 884, 885, 886, 887, 888, 889, 890, 891, 892,
893, 894, 895, 896, or 897.
[0177] Optionally, a gB fragment can extend further into the
N-terminus by 5, 10, 20, or 30 amino acids from the starting
residue of the fragment. Optionally, a gB fragment can extend
further into the C-terminus by 5, 10, 20, or 30 amino acids from
the last residue of the fragment.
[0178] CMV gH Proteins
[0179] In some embodiments, a gH protein is a full-length gH
protein (CMV gH FL, SEQ ID NO:______, for example, which is a 743
amino acid protein). gH has a membrane spanning domain and a
cytoplasmic domain starting at position 716 to position 743.
Removing amino acids from 717 to 743 provides a soluble gH (e.g.,
CMV gH sol, SEQ ID NO:______). In some embodiments the gH protein
can be a gH fragment of 10 amino acids or longer. For example, the
number of amino acids in the fragment can comprise 10, 15, 20, 30,
40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 225, 250, 275,
300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600,
625, 650, 675, 700, or 725 amino acids. Optionally, the gH protein
can be a gH fragment of 10 amino acids or longer. For example, the
number of amino acids in the fragment can comprise 10, 15, 20, 30,
40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 225, 250, 275,
300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600,
625, 650, 675, 700, or 725 amino acids. A gH fragment can begin at
any of residue number: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,
14, 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, 60, 61, 62, 63, 64,
65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81,
82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98,
99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111,
112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124,
125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137,
138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150,
151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163,
164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176,
177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189,
190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202,
203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215,
216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228,
229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241,
242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254,
255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267,
268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280,
281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293,
294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306,
307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319,
320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332,
333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345,
346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358,
359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371,
372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384,
385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397,
398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410,
411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423,
424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436,
437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449,
450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462,
463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475,
476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488,
489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501,
502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514,
515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527,
528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540,
541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553,
554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566,
567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579,
580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592,
593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605,
606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618,
619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631,
632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644,
645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657,
658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670,
671, 672, 673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683,
684, 685, 686, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696,
697, 698, 699, 700, 701, 702, 703, 704, 705, 706, 707, 708, 709,
710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720, 721, 722,
723, 724, 725, 726, 727, 728, 729, 730, 731, or 732.
[0180] gH residues are numbered according to the full-length gH
amino acid sequence (CMV gH FL) shown in SEQ ID NO:______.
Optionally, a gH fragment can extend further into the N-terminus by
5, 10, 20, or 30 amino acids from the starting residue of the
fragment. Optionally, a gH fragment can extend further into the
C-terminus by 5, 10, 20, or 30 amino acids from the last residue of
the fragment.
[0181] CMV gL Proteins
[0182] In some embodiments a gL protein is a full-length gL protein
(CMV gL FL, SEQ ID NO:______, for example, which is a 278 amino
acid protein). In some embodiments a gL fragment can be used. For
example, the number of amino acids in the fragment can comprise 10,
15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 225,
or 250 amino acids. A gL fragment can begin at any of residue
number: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 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, 60, 61, 62, 63, 64, 65, 66, 67, 68,
69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85,
86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101,
102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114,
115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127,
128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140,
141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153,
154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166,
167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179,
180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192,
193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205,
206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218,
219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231,
232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244,
245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257,
258, 259, 260, 261, 262, 263, 264, 265, 266, 267, or 268.
[0183] gL residues are numbered according to the full-length gL
amino acid sequence (CMV gL FL) shown in SEQ ID NO:______.
Optionally, a gL fragment can extend further into the N-terminus by
5, 10, 20, or 30 amino acids from the starting residue of the
fragment. Optionally, a gL fragment can extend further into the
C-terminus by 5, 10, 20, or 30 amino acids from the last residue of
the fragment.
[0184] CMV gO Proteins
[0185] In some embodiments, a gO protein is a full-length gO
protein (CMV gO FL, SEQ ID NO:______, for example, which is a 472
amino acid protein). In some embodiments the gO protein can be a gO
fragment of 10 amino acids or longer. For example, the number of
amino acids in the fragment can comprise 10, 15, 20, 30, 40, 50,
60, 70, 80, 90, 100, 125, 150, 175, 200, 225, 250, 275, 300, 325,
350, 375, 400, 425, or 450 amino acids. A gO fragment can begin at
any of residue number: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,
14, 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, 60, 61, 62, 63, 64,
65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81,
82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98,
99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111,
112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124,
125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137,
138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150,
151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163,
164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176,
177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189,
190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202,
203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215,
216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228,
229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241,
242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254,
255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267,
268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280,
281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293,
294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306,
307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319,
320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332,
333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345,
346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358,
359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371,
372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384,
385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397,
398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410,
411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423,
424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436,
437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449,
450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, or
462.
[0186] gO residues are numbered according to the full-length gO
amino acid sequence (CMV gO FL) shown in SEQ ID NO:______.
Optionally, a gO fragment can extend further into the N-terminus by
5, 10, 20, or 30 amino acids from the starting residue of the
fragment. Optionally, a gO fragment can extend further into the
C-terminus by 5, 10, 20, or 30 amino acids from the last residue of
the fragment.
[0187] CMV gM Proteins
[0188] In some embodiments, a gM protein is a full-length gM
protein (CMV gM FL, SEQ ID NO:______, for example, which is a 371
amino acid protein). In some embodiments the gM protein can be a gM
fragment of 10 amino acids or longer. For example, the number of
amino acids in the fragment can comprise 10, 15, 20, 30, 40, 50,
60, 70, 80, 90, 100, 125, 150, 175, 200, 225, 250, 275, 300, 325,
or 350 amino acids. A gM fragment can begin at any of residue
number: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 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, 60, 61, 62, 63, 64, 65, 66, 67, 68,
69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85,
86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101,
102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114,
115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127,
128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140,
141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153,
154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166,
167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179,
180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192,
193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205,
206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218,
219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231,
232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244,
245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257,
258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270,
271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283,
284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296,
297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309,
310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322,
323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335,
336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348,
349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, or
361.
[0189] gM residues are numbered according to the full-length gM
amino acid sequence (CMV gM FL) shown in SEQ ID NO:______.
Optionally, a gM fragment can extend further into the N-terminus by
5, 10, 20, or 30 amino acids from the starting residue of the
fragment. Optionally, a gM fragment can extend further into the
C-terminus by 5, 10, 20, or 30 amino acids from the last residue of
the fragment.
[0190] CMv gN Proteins
[0191] In some embodiments, a gN protein is a full-length gN
protein (CMV gN FL, SEQ ID NO:______, for example, which is a 135
amino acid protein). In some embodiments the gN protein can be a gN
fragment of 10 amino acids or longer. For example, the number of
amino acids in the fragment can comprise 10, 15, 20, 30, 40, 50,
60, 70, 80, 90, 100, or 125 amino acids. A gN fragment can begin at
any of residue number: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,
14, 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, 60, 61, 62, 63, 64,
65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81,
82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98,
99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111,
112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, or
125.
[0192] gN residues are numbered according to the full-length gN
amino acid sequence (CMV gN FL) shown in SEQ ID NO:______.
Optionally, a gN fragment can extend further into the N-terminus by
5, 10, 20, or 30 amino acids from the starting residue of the
fragment. Optionally, a gN fragment can extend further into the
C-terminus by 5, 10, 20, or 30 amino acids from the last residue of
the fragment.
[0193] CMV UL128 Proteins
[0194] In some embodiments, a UL128 protein is a full-length UL128
protein (CMV UL128 FL, SEQ ID NO:______, for example, which is a
171 amino acid protein). In some embodiments the UL128 protein can
be a UL128 fragment of 10 amino acids or longer. For example, the
number of amino acids in the fragment can comprise 10, 15, 20, 30,
40, 50, 60, 70, 80, 90, 100, 125, or 150 amino acids. A UL128
fragment can begin at any of residue number: 1, 2, 3, 4, 5, 6, 7,
8, 9, 10, 11, 12, 13, 14, 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, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75,
76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92,
93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107,
108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120,
121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133,
134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146,
147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159,
160, or 161.
[0195] UL128 residues are numbered according to the full-length
UL128 amino acid sequence (CMV UL128 FL) shown in SEQ ID NO:______.
Optionally, a UL128 fragment can extend further into the N-terminus
by 5, 10, 20, or 30 amino acids from the starting residue of the
fragment. Optionally, a UL128 fragment can extend further into the
C-terminus by 5, 10, 20, or 30 amino acids from the last residue of
the fragment.
[0196] CMV UL130 Proteins
[0197] In some embodiments, a UL130 protein is a full-length UL130
protein (CMV UL130 FL, SEQ ID NO:______, for example, which is a
214 amino acid protein). In some embodiments the UL130 protein can
be a UL130 fragment of 10 amino acids or longer. For example, the
number of amino acids in the fragment can comprise 10, 15, 20, 30,
40, 50, 60, 70, 80, 90, 100, 125, 150, 175, or 200 amino acids. A
UL130 fragment can begin at any of residue number: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 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, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74,
75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91,
92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106,
107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119,
120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132,
133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145,
146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158,
159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171,
172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184,
185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197,
198, 199, 200, 201, 202, 203, or 204.
[0198] UL130 residues are numbered according to the full-length
UL130 amino acid sequence (CMV UL130 FL) shown in SEQ ID NO:______.
Optionally, a UL130 fragment can extend further into the N-terminus
by 5, 10, 20, or 30 amino acids from the starting residue of the
fragment. Optionally, a UL130 fragment can extend further into the
C-terminus by 5, 10, 20, or 30 amino acids from the last residue of
the fragment.
[0199] CMV UL131 Proteins
[0200] In some embodiments, a UL131 protein is a full-length UL131
protein (CMV UL131, SEQ ID NO:______, for example, which is a 129
amino acid protein). In some embodiments the UL131 protein can be a
UL131 fragment of 10 amino acids or longer. For example, the number
of amino acids in the fragment can comprise 10, 15, 20, 30, 40, 50,
60, 70, 80, 90, 100, 125, 150, 175, or 200 amino acids. A UL131
fragment can begin at any of residue number: 1, 2, 3, 4, 5, 6, 7,
8, 9, 10, 11, 12, 13, 14, 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, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75,
76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92,
93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107,
108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119.
[0201] UL131 residues are numbered according to the full-length
UL131 amino acid sequence (CMV UL131 FL) shown in SEQ ID NO:______.
Optionally, a UL131 fragment can extend further into the N-terminus
by 5, 10, 20, or 30 amino acids from the starting residue of the
fragment. Optionally, a UL 131 fragment can extend further into the
C-terminus by 5, 10, 20, or 30 amino acids from the last residue of
the fragment.
[0202] As stated above, the invention relates to recombinant
polycistronic nucleic acid molecules that contain a first sequence
encoding a first herpesvirus protein or fragment thereof, and a
second sequence encoding a second herpesvirus protein or fragment
thereof. Accordingly, the foregoing description of certain
preferred embodiments, such as alphavirus VRPs and self-replicating
RNAs that contain sequences encoding two or more CMV proteins or
fragments thereof, is illustrative of the invention but does not
limit the scope of the invention. It will be appreciated that the
sequences encoding CMV proteins in such preferred embodiments, can
be replaced with sequences encoding proteins, such as gH and gL, or
fragments thereof that are 10 amino acids long or longer, from
other herpesviruses such as HHV-1, HHV-2, HHV-3, HHV-4, HHV-6,
HHV-7 and HHV-8. For example, suitable VZV (HHV-3) proteins include
gB, gE, gH, gI, and gL, and fragments thereof that are 10 amino
acids long or longer, and can be from any VZV strain. For example,
VZV proteins or fragments thereof can be from pOka, Dumas, HJO,
CA123, or DR strains of VZV. These exemplary VZV proteins and
fragments thereof can be encoded by any suitable nucleotide
sequence, including sequences that are codon optimized or
deoptimized for expression in a desired host, such as a human cell.
Exemplary sequences of VZV proteins are provided herein.
[0203] For example, in one embodiment, the polycistronic nucleic
acid molecule contains a first sequence encoding a VZV gH protein
or fragment thereof, and a second sequence encoding a VZV gL
protein or fragment thereof.
[0204] In some embodiments, each of the sequences encoding a herpes
virus protein or fragment that are present in the polycistronic
nucleic acid molecule is operably linked to its own control
elements. For example, each sequences encoding a herpes virus
protein or fragment is operably linked to its own subgenomic
promoter. Thus the polycistronic nucleic acid molecule, such as an
alphavirus replicon, can contain two, three, four or five
subgenomic promoters, each of which controls expression of a herpes
virus protein or fragment. When this type of polycistronic nucleic
acid molecule is a self replicating RNA, such as an alphavirus
replicon, it can be packaged as a VRP, or associate or formulated
with an RNA delivery system.
Methods and Uses
[0205] In some embodiments, self-replicating RNA molecules or VRPs
are administered to an individual to stimulate an immune response.
In such embodiments, self-replicating RNA molecules or VRPs
typically are present in a composition which may comprise a
pharmaceutically acceptable carrier and, optionally, an adjuvant.
See, e.g., U.S. Pat. No. 6,299,884; U.S. Pat. No. 7,641,911; U.S.
Pat. No. 7,306,805; and US 2007/0207090.
[0206] The immune response can comprise a humoral immune response,
a cell-mediated immune response, or both. In some embodiments an
immune response is induced against each delivered CMV protein. A
cell-mediated immune response can comprise a Helper T-cell
(T.sub.h) response, a CD8+ cytotoxic T-cell (CTL) response, or
both. In some embodiments the immune response comprises a humoral
immune response, and the antibodies are neutralizing antibodies.
Neutralizing antibodies block viral infection of cells. CMV infects
epithelial cells and also fibroblast cells. In some embodiments the
immune response reduces or prevents infection of both cell types.
Neutralizing antibody responses can be complement-dependent or
complement-independent. In some embodiments the neutralizing
antibody response is complement-independent. In some embodiments
the neutralizing antibody response is cross-neutralizing; i.e., an
antibody generated against an administered composition neutralizes
a CMV virus of a strain other than the strain used in the
composition.
[0207] A useful measure of antibody potency in the art is "50%
neutralization titer." To determine 50% neutralizing titer, serum
from immunized animals is diluted to assess how dilute serum can be
yet retain the ability to block entry of 50% of viruses into cells.
For example, a titer of 700 means that serum retained the ability
to neutralize 50% of virus after being diluted 700-fold. Thus,
higher titers indicate more potent neutralizing antibody responses.
In some embodiments, this titer is in a range having a lower limit
of about 200, about 400, about 600, about 800, about 1000, about
1500, about 2000, about 2500, about 3000, about 3500, about 4000,
about 4500, about 5000, about 5500, about 6000, about 6500, or
about 7000. The 50% neutralization titer range can have an upper
limit of about 400, about 600, about 800, about 1000, about 1500,
about 200, about 2500, about 3000, about 3500, about 4000, about
4500, about 5000, about 5500, about 6000, about 6500, about 7000,
about 8000, about 9000, about 10000, about 11000, about 12000,
about 13000, about 14000, about 15000, about 16000, about 17000,
about 18000, about 19000, about 20000, about 21000, about 22000,
about 23000, about 24000, about 25000, about 26000, about 27000,
about 28000, about 29000, or about 30000. For example, the 50%
neutralization titer can be about 3000 to about 6500. "About" means
plus or minus 10% of the recited value. Neutralization titer can be
measured as described in the specific examples, below.
[0208] An immune response can be stimulated by administering VRPs
or self-replicating RNA to an individual, typically a mammal,
including a human. In some embodiments the immune response induced
is a protective immune response, i.e., the response reduces the
risk or severity of CMV infection. Stimulating a protective immune
response is particularly desirable in some populations particularly
at risk from CMV infection and disease. For example, at-risk
populations include solid organ transplant (SOT) patients, bone
marrow transplant patients, and hematopoietic stem cell transplant
(HSCT) patients. VRPs can be administered to a transplant donor
pre-transplant, or a transplant recipient pre- and/or
post-transplant. Because vertical transmission from mother to child
is a common source of infecting infants, administering VRPs or
self-replicating RNA to a woman who can become pregnant is
particularly useful.
[0209] Any suitable route of administration can be used. For
example, a composition can be administered intra-muscularly,
intra-peritoneally, sub-cutaneously, or trans-dermally. Some
embodiments will be administered through an intra-mucosal route
such as intra-orally, intra-nasally, intra-vaginally, and
intra-rectally. Compositions can be administered according to any
suitable schedule.
[0210] All patents, patent applications, and references cited in
this disclosure, including nucleotide and amino acid sequences
referred to by accession number, are expressly incorporated herein
by reference. The above disclosure is a general description. A more
complete understanding can be obtained by reference to the
following specific examples, which are provided for purposes of
illustration only.
Example 1
Delivery of Individual CMV Antigens Using a VRP Platform
[0211] Each of CMV glycoproteins gB and gH induce neutralizing
responses, and gB is the dominant antigen among antibodies in human
sera that neutralize infection of fibroblasts (Britt et al. (1990)
J. Virol. 64(3):1079-85). The following experiments demonstrate in
mice a neutralizing response against these antigens delivered using
a VRP platform.
[0212] Each CMV antigen was cloned into a pcDNA-6H is vector
(Invitrogen) and tested for protein expression before cloning into
an alphavirus replicon vector, pVCR 2.1 SalI/XbaI derived from the
plasmid described by Perri et al. (J. Virol 77(19)10394-10403
(2003)) producing the constructs shown in FIG. 2. pVCR 2.1
SalI/XbaI is a self-replicating RNA vector that, when
electroporated with defective helper capsid and glycoprotein RNA,
forms an infectious alphavirus particle.
[0213] pVCR vectors were used to make RNA which was electroporated
into baby hamster kidney (BHKV) cells in the presence of defective
helper capsid and glycoprotein RNAs derived from Venezuelan equine
encephalitis virus (VEE). After electroporation, the supernatant
containing secreted alphavirus vector particles (VRPs) was
collected, purified, titered, and used for mouse immunization
studies. Mice were immunized with 1.times.10.sup.6 infectious units
(IU)/mouse in a series of two immunizations, three weeks apart. The
terminal bleed was three weeks after the second immunization.
[0214] Monocistronic gB, gH and gL VRPs
[0215] Two different versions of soluble gB were constructed: "gB
sol 750" lacks the transmembrane spanning domain and cytoplasmic
domain; and "gB sol 692" also lacks a hydrophobic region (FIG. 2A)
and is similar to the Reap et al. construct. A soluble gH which
lacks the transmembrane spanning domain and cytoplasmic domain ("gH
sol 716") was also constructed (FIG. 2C). Sera from immunized mice
were screened in several assays. Immunoblot (data not shown) and
immunofluorescence assays were used to confirm specific antibody
responses to the antigens. Neutralization assays were used to
demonstrate that the elicited antibody responses were able to
neutralize CMV infection.
[0216] Sera from immunized mice were examined by immunofluorescence
for recognition of gB in 293T cells transfected with constructs
expressing gB-6H is. Cells were probed with either anti-His
antibodies ("anti-6H is"), a monoclonal gB antibody ("anti-gB
27-156"), or collected pooled mouse sera. Pre-immune serum was
negative in all cases. In cells transfected with constructs
expressing gB FL-6H is, fixed, and permeabilized, anti-6H is
staining revealed an expression pattern of surface expression with
a punctate cytoplasmic pattern most likely corresponding to the
endocytic/exocytic trafficking pathway. Both anti-gB 27-156 and the
pooled mouse sera showed a similar expression pattern. Sera from
mice immunized with each of gB FL VRPs, gB sol 750 VRPs, and gB sol
692 VRPs showed the same expression pattern.
[0217] Mice immunized with gH FL VRPs and gH sol 716 VRPs produced
antibodies specific to gH. Immunofluorescence analysis of 293T
cells transfected with constructs expressing gH FL-6H is detected
strong recognition of gH by anti-6H is, anti-gH, and pooled mouse
sera. Sera collected from mice immunized with gL VRPs produced a
specific antibody response as determined by immunoblot analysis and
immunofluorescence. gL VRPs failed to elicit a neutralizing
response.
[0218] Sera from mice immunized with gB VRPs or gH VRPs were
analyzed for the presence of neutralizing antibodies using a CMV
neutralization assay. Sera at various dilutions were pre-incubated
with CMV virus TB40UL32EGFP ("TB40-GFP," a clinical isolate
engineered to express GFP and then added to ARPE-19 epithelial
cells and incubated for 5 days. At 5 days post-infection, the
GFP-positive cells were counted. In this assay, cells incubated
with serum containing neutralizing antibodies have fewer
GFP-positive cells compared to cells incubated with virus alone or
with virus incubated with pre-immune sera. Sera from mice immunized
with gB VRPs, gB FL VRPs, gB sol 750 VRPs, or gB sol 692 VRPs had
strong neutralizing activity in the presence of guinea pig
complement (50% neutralization titer at a serum dilution of
1:1280-1:2560; FIG. 3). Sera from mice immunized with gH FL VRPs or
gH sol VRPs had some neutralizing activity that was independent of
guinea pig complement (FIG. 3).
Example 2
Construction of Polycistronic Alphavirus Vectors
[0219] CMV produces several multi-protein complexes during
infection. To determine whether a single replicon expressing all
components of a desired complex can be used to produce the CMV
complex in a subject, or whether components of the complex could be
co-delivered from multiple replicon vectors, we designed a platform
that allows controlled expression of multiple CMV proteins.
[0220] An alphavirus vector (pVCR 2.1 SalI/XbaI) was modified to
allow assembly of multiple subgenomic promoters (SGP) and genes of
interest (GOI). pVCR 2.1SalI/XbaI ApaI site at 11026-31 bp was
changed from GGGCCC (SEQ ID NO:______) to GGCGCC (SEQ ID
NO:______). ClaI and PmlI restriction sites added in the region
immediately downstream of the first subgenomic promoter and
SalI-XbaI insert sites. The sequence at 7727-7754 bp was changed
from ctcgatgtacttccgaggaactgatgtg (SEQ ID NO:______) to
ATCGATGTACTTCCGAGGAACTCACGTG (SEQ ID NO:______).
[0221] A shuttling vector system was designed to allow insertion of
a GOI directly downstream of a SGP using the SalI-XbaI sites. pcDNA
3.1 (-) C was modified as follows. Three SalI sites were deleted:
positions 1046-1051 bp, 3332-3337 bp and 5519-21, 1-3 bp from
GTCGAC (SEQ ID NO:______) to GTCTAC (SEQ ID NO:______). pcDNA 3.1
(-) C was modified to mutate an XbaI site at position 916-921 bp
from TCTAGA (SEQ ID NO:______) to TCAAGA (SEQ ID NO:______). pcDNA
3.1 (-) C was modified to add a ClaI site and SacII site at
positions 942-947 (ClaI) and 950-955 (SacII) by from ctggatatctgcag
(SEQ ID NO:______) to ATCGATATCCGCGG (SEQ ID NO:______).
[0222] Once the restriction sites were added and the resulting
sequence was verified, the region from by 7611-7689
(ctataactctctacggctaacctgaatggactacgacatagtctagtcgaccaagcctctagacggc
gcgcccaccca) (SEQ ID NO:______) was amplified from the modified
pVCR 2.1 alphavirus vector using the following primers
TABLE-US-00003 Forward SGP S-X Not F: (SEQ ID NO: )
5'ATAAGAATGCGGCCGCCTATAACTCTCTACGGCTAACC3' Reverse SGP S-X Cla R:
(SEQ ID NO: ) 5'CCATCGATTGGGTGGGCGCGCCGTCTAG3' or Forward SGP S-X
Cla F: (SEQ ID NO: ) 5'CCATCGATCTATAACTCTCTACGGCTAACC3' and Reverse
SGP S-X Sac R: (S SEQ ID NO: _) 5'TCCCCGCGGTGGGTGGGCGCGCCGTCTAG
3'.
[0223] The amplified regions were added into the modified pcDNA
3.1(-)C vector to make shuttling vectors (pcDNA SV) between
appropriate sites (NotI-ClaI or ClaI-SacII). Insertion of the
NotI-SGP Sal-Xba-ClaI forms pcDNA SV cassette 2, insertion of the
ClaI-SGP Sal-Xba-SacII forms pcDNA SV cassette 3. These SV
cassettes were sequenced. The pcDNA SV cassette 2 contains an
additional 12 bp between the XbaI site and the ClaI site
(CCACTGTGATCG) (SEQ ID NO:______) because the ClaI site was not cut
in the pcDNA SV cassette 2 vector. A PmlI site was therefore added.
For pcDNA SV cassette 2, the PmlI site was inserted at by 1012
(CACGTG) (SEQ ID NO:______). For cassette 3, PmlI site was added at
by 935-940 (ACTGTG (SEQ ID NO:______) was changed to CACGTG (SEQ ID
NO:______).
[0224] For each polycistronic vector the first gene was inserted
directly into the pVCR 2.1 modified vector using the SalI-XbaI
sites. The second gene was ligated into pcDNA SV cassette 2 using
SalI-XbaI and excised using NotI-PmlI, NotI-SacII or PCRed using
primers for NotI-ClaI and digested using NotI and ClaI. The
resulting insert SGP-SalI-GOI-Xba was ligated into the modified
pVCR 2.1 vector using NotI-PmlI, NotI-SacII, or NotI-ClaI sites.
The NotI-ClaI insert was used only when a desired gene in the
construct contained a PmlI site.
[0225] In some cases a third gene was ligated into pcDNA SV
cassette 3 using SalI-XbaI and excised using PmlI-SacII or PCRed
using primers for ClaI-SacII and digested using ClaI and SacII. The
resulting insert SGP-SalI-GOI-XbaI was ligated into the modified
pVCR 2.1 using PmlI-SacII or ClaI-SacII.
[0226] SalI-XbaI digestion was used to validate construction of the
polycistronic vector DNA. After digestion with SalI-XbaI, agarose
gel electrophoresis was performed to confirm the presence of the
GOIs. The polycistronic vector DNA was then linearized with PmeI
overnight, purified using Qiagen's PCR purification kit, and used
as template to make RNA using the Ambion mMessage mMachine kit. RNA
quality was checked by running a sample aliquot on an RNA agarose
gel.
[0227] Expression from a Polycistronic Vector
[0228] Fluorescent proteins GFP (green fluorescent protein) and
mCherry (red fluorescent protein) were used as the GOIs to assess
the ability of the polycistronic vector to express two proteins. We
prepared a bicistronic vector in which GFP would be expressed using
a first subgenomic promoter and mCherry would be expressed from a
second subgenomic promoter (FIG. 4A). Polynucleotides containing
coding sequences for these proteins were inserted using SalI-XbaI
sites. The first polynucleotide (GFP) was inserted directly into
the modified alphavirus replicon vector. The second polynucleotide
(mCherry) was inserted first into a shuttling vector that contains
a subgenomic promoter directly upstream of the coding sequence. A
fragment containing both the second subgenomic promoter and the
second polynucleotide was isolated and ligated into the modified
alphavirus replicon vector containing the first polynucleotide,
providing an alphavirus replicon with multiple subgenomic
promoters.
[0229] VRPs were produced in BHKV cells by electroporating replicon
RNAs with defective helper RNAs for Cap and Gly. The VRPs were
harvested 24 hours after electroporation and used to infect BHKV
cells at a multiplicity of infection (MOI) of 20 infectious units
(IU) per cell.
[0230] The experiment tested four sets of VRPs: one VRP expressing
only GFP; one VRP expressing mCherry; one VRP expressing only GFP
and one VRP expressing only mCherry, both at MOI of 20 IU/cell; and
one VRP containing the bicistronic vector GFP(1)-SGPmCherry(2).
VRP-infected BHKV cells were examined 24 hours post-infection to
determine percent of colocalization. Nearly all the cells were
positive for GFP or mCherry when singly infected. Cells infected
with two separate VRPs appeared either green or red. Very few cells
were yellow, indicating that few cells expressed GFP and mCherry at
equal levels and that there was a low level of co-infection. These
data were confirmed using FACS analysis (FIG. 4B).
[0231] In contrast, cells infected with alphavirus containing the
bicistronic vector GFP(1)-SGPmCherry(2) were all yellow, which
indicates approximately equal expression of GFP and mCherry. This
study demonstrates that multiple proteins can be expressed
successfully from a single polycistronic alphavirus replicon
vector.
Example 3
Production of CMV Complexes
[0232] This example demonstrates that CMV protein complexes can be
formed in a cell after delivery of the complex components from a
polycistronic alphavirus replicon vector.
[0233] gH/gL and gH/gL/gO Complexes
[0234] Polycistronic gH/gL and gH/gL/gO alphavirus replicons were
constructed as described above (shown schematically in FIG. 5A).
VRPs containing gH, gL, gO, gH/gL and gH/gL/gO encoding replicons
were produced in BHKV cells as described above and used to infect
BHKV cells to demonstrate complex formation in vitro. VRP infected
ARPE-19 cells produced disulfide linked complexes of gH/gL. gO did
not detectably alter gH/gL association (FIG. 5B).
[0235] Immunofluorescence studies were conducted to evaluate the
localization of gH and gL delivered alone and when delivered using
a polycistronic alphavirus to look at relocalization of the
proteins when co-expressed. gH localization did not appear to
change in the presence or absence of gL, or gL/gO. gL localization
did change when in the presence of gH and gH/gO.
[0236] Finally, gH/gL association was examined via
immunoprecipitation. A commercial gH antibody (Genway) was used to
investigate the association of gH and gL. In all cases, the gH
antibody efficiently immunoprecipitated gH (FIG. 5C). When no gH
was present, gL was not immunoprecipitated. When gL was expressed
in the presence of gH or gH/gO, there was association of gL with gH
(FIG. 5C).
[0237] The relocalization of gL in the presence of gH and the
association of gH/gL (with or without gO) indicates that all
components of the polycistronic alphavirus replicons were expressed
and associated to form a complex.
Example 4
VRPs that Effect gH/gL Complex Formation In Vitro Induce Potent
Immune Response to CMV which is Qualitatively and Quantitatively
Superior to the Immune Response Elicited to gB VRPs
[0238] This example demonstrates the induction of robust immune
responses to complexes formed by delivering polycistronic gH/gL
VRPs or gH/gL/gO VRPs compared with immune responses obtained using
VRPs delivering single components or single-component VRPs
administered in combination or to responses elicited by gB
VRPs.
[0239] Mice were infected three times with VRPs administered 3
weeks apart (10.sup.6 IU per mouse; 5 BalbC mice/group). Sera
collected from immunizations with single and polycistronic VRPs
were screened for neutralizing antibodies using a CMV
neutralization assay as described above. Neutralization titer was
measured as follows. Various dilutions of sera were pre-incubated
with TB40-UL32-EGFP in the presence or absence of guinea pig
complement and then added to ARPE-19 epithelial cells or MRC-5
fibroblast cells and incubated for 5 days. After 5 days infection
with the virus, GFP-positive cells were counted. Results for the
ARPE-19 cells are shown in FIG. 6A, FIG. 6B, and FIG. 6C. Results
for the MRC-5 cells are shown in FIG. 7A and FIG. 7B.
[0240] Sera from mice immunized with gH FL VRPs had low
complement-independent neutralizing activity (FIG. 6A and FIG. 6B).
No neutralizing activity was observed using sera from mice
immunized with only gL or gO in the presence or absence of guinea
pig complement. (FIG. 6C) Pooled sera from immunization with
several CMV gB proteins (gB FL, gB sol 750, and gB sol 692)
demonstrated strong neutralizing activity in the presence of guinea
pig complement, with a 50% neutralization titer at 1:1280 sera
dilution. However, there was no neutralizing activity in the
absence of guinea pig complement in ARPE-19 cells for the pooled gB
sera. VRPs expressing single CMV proteins (gH- or gL-VRPs or
co-administering gH-, gL-, and gO-VRPs at 10.sup.6 IU/mouse/VRP)
did not enhance neutralizing activity beyond that of gH alone.
[0241] In contrast, sera from mice immunized with bicistronic gH/gL
or tricistronic gH/gL/gO VRPs (1.times.10.sup.6 IU/mouse)
demonstrated robust neutralizing responses. Moreover, the responses
were similar in the presence and absence of guinea pig complement,
showing that polycistronic VRPs successfully induced a
complement-independent immune response. (FIG. 6C.) The 50%
neutralization titer was 1:3500-6400+ sera dilution in ARPE-19
cells with TB40-GFP CMV virus. This titer is approximately 3-4 fold
higher titer than the 50% complement-dependent neutralization titer
for gB pooled sera.
[0242] Results in the MRC-5 fibroblast cells were similar to those
in ARPE-19 cells (FIGS. 7A and 7B). Sera from mice immunized with
bicistronic gH/gL or tricistronic gH/gL/gO VRPs demonstrated strong
neutralizing activity compared to sera from mice immunized with
VRPs encoding gH alone, gL alone, or gO alone and to sera from mice
immunized by coadministration of gH VRPs and gL VRPs, or
coadministration of gH VRPs, gL VRPs, and gO VRPs. These results
demonstrate that administration of the polycistronic VRPs induced
an immune response that provides good complement-independent
neutralization of CMV infection of fibroblast cells. To assess the
breadth and potency of the gH/gL immune sera against different
strains of CMV, we compared the ability of the sera to block
infection of fibroblasts and epithelial cells with six different
strains of CMV. FIG. 8 shows that the gH/gL sera potently
neutralize infection of both cell types with a broad range of
strains.
[0243] These data also demonstrate strong neutralizing activity for
sera from mice immunized with the polycistronic VRPs but not with
mixed pools of VRPs expressing only one protein. This shows that
polycistronic replicons that encode the components of a protein
complex on a single replicon result in efficient production of the
complex in situ. Moreover, because Merlin strain CMV proteins were
used to stimulate these responses, the in vitro data obtained using
TB40 strain CMV virus demonstrates that the neutralizing antibodies
induced by delivery of the polycistronic VRPs are
cross-neutralizing antibodies.
Example 5
RNA Synthesis
[0244] Plasmid DNA encoding alphavirus replicons (see FIGS. 14-16)
served as a template for synthesis of RNA in vitro. Alphavirus
replicons contain the genetic elements required for RNA replication
but lack those encoding gene products necessary for particle
assembly; the structural genes of the alphavirus genome are
replaced by sequences encoding a heterologous protein. Upon
delivery of the replicons to eukaryotic cells, the
positive-stranded RNA is translated to produce four non-structural
proteins, which together replicate the genomic RNA and transcribe
abundant subgenomic mRNAs encoding the heterologous gene product or
gene of interest (GOI). Due to the lack of expression of the
alphavirus structural proteins, replicons are incapable of inducing
the generation of infectious particles. A bacteriophage (T7 or SP6)
promoter upstream of the alphavirus cDNA facilitates the synthesis
of the replicon RNA in vitro and the hepatitis delta virus (HDV)
ribozyme immediately downstream of the poly(A)-tail generates the
correct 3'-end through its self-cleaving activity.
[0245] In order to allow the formation of an antigenic protein
complex, the expression of the individual components of said
complex in the same cell is of paramount importance. In theory,
this can be accomplished by co-transfecting cells with the genes
encoding the individual components. However, in case of non-virally
or VRP delivered alphavirus replicon RNAs, this strategy is
hampered by inefficient co-delivery of multiple RNAs to the same
cell or, alternatively, by inefficient launch of multiple
self-replicating RNAs in an individual cell. A potentially more
efficient way to facilitate co-expression of components of a
protein complex is to deliver the respective genes as part of the
same self-replicating RNA molecule. To this end, we engineered
alphavirus replicon constructs encoding multiple genes of interest.
Every GOI is preceded by its own subgenomic promoter which is
recognized by the alphavirus transcription machinery. Thereby,
multiple subgenomic messenger RNA species are synthesized in an
individual cell allowing the assembly of multi-component protein
complexes.
[0246] Following linearization of the plasmid DNA downstream of the
HDV ribozyme with a suitable restriction endonuclease, run-off
transcripts were synthesized in vitro using T7 bacteriophage
derived DNA-dependent RNA polymerase. Transcriptions were performed
for 2 hours at 37.degree. C. in the presence of 7.5 mM of each of
the nucleoside triphosphates (ATP, CTP, GTP and UTP) following the
instructions provided by the manufacturer (Ambion, Austin, Tex.).
Following transcription, the template DNA was digested with TURBO
DNase (Ambion, Austin, Tex.). The replicon RNA was precipitated
with LiCl and reconstituted in nuclease-free water. Uncapped RNA
was capped post-transcripionally with Vaccinia Capping Enzyme (VCE)
using the ScriptCap m.sup.7G Capping System (Epicentre
Biotechnologies, Madison, Wis.) as outlined in the user manual.
Post-transcriptionally capped RNA was precipitated with LiCl and
reconstituted in nuclease-free water. The concentration of the RNA
samples was determined by measuring the optical density at 260 nm.
Integrity of the in vitro transcripts was confirmed by denaturing
agarose gel electrophoresis.
[0247] Lipid Nanoparticle (LNP) Formulation
[0248] 1,2-dilinoleyloxy-N,N-dimethyl-3-aminopropane (DlinDMA) was
synthesized using a previously published procedure [Heyes, J.,
Palmer, L., Bremner, K., MacLachlan, I. Cationic lipid saturation
influences intracellular delivery of encapsulated nucleic acids.
Journal of Controlled Release, 107: 276-287 (2005)].
1,2-Diastearoyl-sn-glycero-3-phosphocholine (DSPC) was purchased
from Genzyme. Cholesterol was obtained from Sigma-Aldrich (St.
Lois, Mo.).
1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene
glycol)-2000] (ammonium salt) (PEG DMG 2000), was obtained from
Avanti Polar Lipids.
[0249] LNPs (RV01(14)) were formulated using the following method.
150 .mu.g batch, (PES hollow fibers and no mustang): Fresh lipid
stock solutions in ethanol were prepared. 37 mg of DlinDMA, 11.8 mg
of DSPC, 27.8 mg of Cholesterol and 8.07 mg of PEG DMG 2000 were
weighed and dissolved in 7.55 mL of ethanol. The freshly prepared
lipid stock solution was gently rocked at 37.degree. C. for about
15 min to form a homogenous mixture. Then, 453 .mu.l of the stock
was added to 1.547 mL ethanol to make a working lipid stock
solution of 2 mL. This amount of lipids was used to form LNPs with
150 .mu.g RNA at a 8:1 N:P (Nitrogen to Phosphate) ratio. The
protonatable nitrogen on DlinDMA (the cationic lipid) and
phosphates on the RNA are used for this calculation. Each .mu.g of
self-replicating RNA molecule was assumed to contain 3 nmoles of
anionic phosphate, each .mu.g of DlinDMA was assumed to contains
1.6 nmoles of cationic nitrogen. A 2 mL working solution of RNA was
also prepared from a stock solution of .about.1 .mu.g/.mu.L in 100
mM citrate buffer (pH 6) (Teknova). Three 20 mL glass vials (with
stir bars) were rinsed with RNase Away solution (Molecular
BioProducts) and washed with plenty of MilliQ water before use to
decontaminate the vials of RNAses. One of the vials was used for
the RNA working solution and the others for collecting the lipid
and RNA mixes (as described later). The working lipid and RNA
solutions were heated at 37.degree. C. for 10 min before being
loaded into 3 cc luer-lok syringes (BD Medical). 2 mL of citrate
buffer (pH 6) was loaded in another 3 cc syringe. Syringes
containing RNA and the lipids were connected to a T mixer (PEEK.TM.
500 .mu.m ID junction) using FEP tubing ([fluorinated
ethylene-propylene] 2 mm ID.times.3 mm OD, Idex Health Science, Oak
Harbor, Wash.). The outlet from the T mixer was also FEP tubing (2
mm ID.times.3 mm). The third syringe containing the citrate buffer
was connected to a separate piece of tubing (2 mm ID.times.3 mm
OD). All syringes were then driven at a flow rate of 7 mL/min using
a syringe pump (from kdScientific, model no. KDS-220). The tube
outlets were positioned to collect the mixtures in a 20 mL glass
vial (while stirring). The stir bar was taken out and the
ethanol/aqueous solution was allowed to equilibrate to room
temperature for 1 h. Then the mixture was loaded in a 5 cc syringe
(BD Medical), which was fitted to a piece of FEP tubing (2 mm
ID.times.3 mm OD) and in another 5 cc syringe with equal length of
FEP tubing, an equal volume of 100 mM citrate buffer (pH 6) was
loaded. The two syringes were driven at 7 mL/min flow rate using a
syringe pump and the final mixture collected in a 20 mL glass vial
(while stirring). Next, LNPs were concentrated to 2 mL and dialyzed
against 10-15 volumes of 1.times.PBS (from Teknova) using the
Tangential Flow Filtration (TFF) system before recovering the final
product. The TFF system and hollow fiber filtration membranes were
purchased from Spectrum Labs and were used according to the
manufacturer's guidelines. Polyethersulfone (PES) hollow fiber
filtration membranes (part number P-C1-100E-100-01N) with a 100 kD
pore size cutoff and 20 cm.sup.2 surface area were used. For in
vitro and in vivo experiments, formulations were diluted to the
required RNA concentration with 1.times.PBS (from Teknova).
[0250] Particle Size
[0251] Particle size was measured using a Zetasizer Nano ZS
(Malvern Instruments, Worcestershire, UK) according to the
manufacturer's instructions. Particle sizes are reported as the Z
average with the polydispersity index (pdi). Liposomes were diluted
in 1.times.PBS before measurement.
[0252] Encapsulation Efficiency and RNA Concentration
[0253] The percentage of encapsulated RNA and RNA concentration
were determined by
[0254] Quant-iT RiboGreen RNA reagent kit (Invitrogen).
Manufacturer's instructions were followed in the assay. The
ribosomal RNA standard provided in the kit was used to generate a
standard curve. LNPs either obtained from method 1 or methods 2-5
were diluted ten fold or one hundred fold respectively in lx TE
buffer (from kit), before addition of the dye. Separately, LNPs
were diluted ten or 100 fold in 1.times.TE buffer containing 0.5%
Triton X (Sigma-Aldrich), before addition of the dye. Thereafter an
equal amount of dye was added to each solution and then .about.180
.mu.L of each solution after dye addition was loaded in duplicate
into a 96 well tissue culture plate (obtained from VWR, catalog
#353072). The fluorescence (Ex 485 nm, Em 528 nm) was read on a
microplate reader (from BioTek Instruments, Inc.).
[0255] Triton X was used to disrupt the LNPs, providing a
fluorescence reading corresponding to the total RNA amount and the
sample without Triton X provided fluorescence corresponding to the
unencapsulated RNA. % RNA encapsulation was determined as follows:
LNP RNA Encapsulation (%)=[(F.sub.t-F.sub.i)/F.sub.t].times.100,
where F.sub.t is the fluorescence intensity of LNPs with triton X
addition and F.sub.i is the fluorescence intensity of the LNP
solution without detergent addition. These values (F.sub.t and
F.sub.i) were obtained after subtraction from blank (1.times.TE
buffer) fluorescence intensity. The concentration of encapsulated
RNA was obtained by comparing F.sub.t--F.sub.i with the standard
curve generated. All LNP formulations were dosed in vivo based on
the encapsulated dose.
[0256] Viral Replicon Particles (VRP)
[0257] To compare RNA vaccines to traditional RNA-vectored
approaches for achieving in vivo expression of reporter genes or
antigens, we utilized viral replicon particles (VRPs), produced in
BHK cells by the methods described by Perri et al. (J. Virol
77(19):10394-10403 (2003)), coding for expression of the same
antigens as the corresponding RNA constructs. In this system, the
antigen consisted of alphavirus chimeric replicons (VCR) derived
from the genome of Venezuelan equine encephalitis virus (VEEV)
engineered to contain the 3' terminal sequences (3' UTR) of Sindbis
virus and a Sindbis virus packaging signal (PS) (see FIG. 2 of
Perri et al). The replicons were packaged into VRPs by
co-electroporating them into baby hamster kidney (BHK) cells along
with defective helper RNAs encoding the Sindbis virus capsid and
glycoprotein genes (see FIG. 2 of Perri et al). The VRPs were then
harvested and partially purified by ultracentrifugation on a
sucrose cushion and concentrated on an Amicon concentrator. The
resulting VRP stock was titrated by standard methods and inoculated
into animals in culture fluid or other isotonic buffers. An
alphavirus replicon particle chimera derived from venezuelan equine
encephalitis and sindbis viruses is a potent gene-based vaccine
delivery vector. J. Virol. 77, 10394-10403.
[0258] Murine Immunogenicity Studies
[0259] Groups of 10 female BALB/c mice aged 8-10 weeks and weighing
about 20 g were immunized with 1.times.10.sup.6 IU (VRP) or 1.0
.mu.g (RNA) at day 0, 21 and 42 with bleeds taken 3 weeks after the
2.sup.nd and 3 weeks after the 3.sup.rd vaccinations. All animals
were injected in the quadriceps in the two hind legs each getting
an equivalent volume (50 .mu.l per site).
[0260] Micro Neutralization Assay
[0261] Serum samples were tested for the presence of neutralizing
antibodies by an infection reduction neutralization test. Two-fold
serial dilutions of HI-serum (in DMEM with 10% HI FBS) were added
to an equal volume of CMV (strain TB40 or clinical isolate 8819)
previously titered to give approximately 200 IU/50 .mu.l. The
VR1814, Towne, AD169 strains and the clinical isolate 8822 were
also used. Serum/virus mixtures were incubated for 2 hours at
37.degree. C. and 5% CO2, to allow virus neutralization to occur,
and then 50 .mu.l of this mixture (containing approximately 200 IU)
was inoculated on duplicate wells of ARPE-19 cells in 96 half well
plates. Plates were incubated for 40-44 hours. Unless otherwise
noted, the number of positive infected foci was determined by
immunostaining with an AlexaFluor 488 conjugated IE1 CMV monoclonal
antibody followed by automated counting. The neutralization titer
is defined as the reciprocal of the serum dilution producing a 50%
reduction in number of positive virus foci per well, relative to
controls (no serum).
[0262] Immunogenicity of gH/gL VRPs and LNP Formulated RNA
[0263] The A323 replicon that expresses the surface glycoprotein B
(gB) of CMV, the A160 replicon that expresses the membrane complex
of the full-length glycoprotein H and L (gH/gL) and the A322
replicon that expresses the membrane complex of the soluble form of
glycoprotein H and L (gHsol/gL) were used for this experiment.
BALB/c mice, 10 animals per group, were given bilateral
intramuscular vaccinations (50 .mu.L per leg) on days 0, 21 and 42
with VRPs expressing gB (1.times.10.sup.6 IU), VRPs expressing
gH/gL (1.times.10.sup.6 IU), VRP's expressing gHsol/gL
(1.times.10.sup.6 IU) and PBS as the controls. The three test
groups received self-replicating RNA (A160, A322 or A323)
formulated in LNP (RV01(14). Serum was collected for immunological
analysis on days 39 (3wp2) and 63 (3wp3).
Results
[0264] The sive and percentage of encapsulated RNA in the RV01(14)
formulations made for the experiment are shown in Table 3.
TABLE-US-00004 TABLE 3 pKa of Particle Lipid Composition (%
cationic Size Zav Percent RNA RV# moles of total) RNA lipid (nm)
pdI Encapsulation RV01 (14) DlinDMA 40%, DSPC- gB FL 5.8 170 0.098
88.3 10%, Chol- 48%, PEG DMG 2k-2% RV01 (14) DlinDMA 40%, DSPC- gH
FL/gL 5.8 168.8 0.144 87.4 10%, Chol- 48%, PEG DMG 2k-2% RV01 (14)
DlinDMA 40%, DSPC- gHsol/gL 5.8 162 0.131 90 10%, Chol- 48%, PEG
DMG 2k-2%
[0265] The 50% neutralizing titers for the terminal sera (day 63,
three weeks after final vaccination) are shown in Table 4.
TABLE-US-00005 TABLE 4 ARPE-19, ARPE-19, HCMV TB40 HCMV 8819 pool
pool aver- pool pool aver- #1 #2 age #1 #2 age Preimmune serum --
126 212 169 50 50 50 gB FL VRP 10.sup.6 IU 1332 295 814 5085 1031
3058 gB FL RNA- 1 .mu.g 686 179 433 1261 557 909 RV01(14) gH FL/gL
VRP 10.sup.6 IU 1425 1624 1525 2496 1374 1935 gH FL/gL RNA- 1 .mu.g
6196 6390 6293 5800 10267 8034 RV01(14) gH sol/gL VRP 10.sup.6 IU
2375 2254 2315 1733 1924 1829 gH sol/gL RNA- 1 .mu.g 4600 2062 3331
2912 1533 2223 RV01(14)
[0266] RNA expressing either a full-length or a presumed soluble
form of the HCMV gH/gL complex elicit high titers of neutralizing
antibody, as assayed on epithelial cells using two different HCMV
strains. The average titers elicited by the gH/gL RNAs are at least
as high as the average titer for the corresponding gH/gL VRPs (see
FIG. 17).
Example 6
Bicistronic and Pentacistronic Nucleic Acids Encoding CMV
Proteins
[0267] Additional bicistronic and pentacistronic alphavirus
replicons that express glycoprotein complexes from human
cytomegalovirus (HCMV) were prepared, and are shown schematically
in FIGS. 18 and 20. The alphavirus replicons were based on
venezuelan equine encephalitis virus (VEE). The replicons were
packaged into viral replicon particles (VRPs), encapsulated in
lipid nanoparticles (LNP), or formulated with a cationic
nanoemulsion (CNE). Expression of the encoded HCMV proteins and
protein complexes from each of the replicons was confirmed by
immunoblot, co-immunoprecipitation, and flow cytometry. Flow
cytometry was used to verify expression of the pentameric
gH/gL/UL128/UL130/UL131 complex from pentameric replicons encoding
the protein components of the complex, using human monoclonal
antibodies specific to conformational epitopes present on the
pentameric complex (Macagno et al (2010), J. Virol. 84(2):1005-13).
FIG. 19 shows that these antibodies bind to BHKV cells transfected
with replicon RNA expressing the HCMV gH/gL/UL128/UL130/UL131
pentameric complex (A527). Similar results were obtained when cells
were infected with VRPs made from the same replicon construct. This
shows that replicons designed to express the pentameric complex do
indeed express the desired antigen and not the potential byproduct
gH/gL.
[0268] The VRPs, RNA encaspulated in LNPs, and RNA formulated with
CNE were used to immunize Balb/c mice by intramuscular injections
in the rear quadriceps. The mice were immunized three times, three
weeks apart, and serum samples were collected prior to each
immunization as well as three weeks after the third and final
immunization. The sera were evaluated in microneutralization assays
to measure the potency of the neutralizing antibody response that
was elicited by the vaccinations. The titers are expressed as 50%
neutralizing titer.
[0269] The immunogenicity of a number of different configurations
of a bicistronic expression cassette for a soluble HCMV gH/gL
complex in VRPs was assessed. FIG. 20 shows that VRPs expressing
the membrane-anchored, full-length gH/gL complex elicited potent
neutralizing antibodies at slightly higher titers than the soluble
complex (gHsol/gL) expressed from a similar bicistronic expression
cassette. Changing the order of the genes encoding gHsol and gL or
replacing one of the subgenomic promoters with an IRES or an FMDV
2A site did not substantially improve immunogenicity.
[0270] The breadth and potency of HCMV neutralizing activity in
sera from mice immunized with VEE/SIN VRPs expressing gH/gL was
assessed by using the sera to block infection of fibroblasts and
epithelial cells with different strains of HCMV. Table 5 shows that
gH/gL immune sera were broadly and potently neutralizing against
six different strains of HCMV on both cell types in the absence of
complement. Addition of complement had a slight negative effect on
the neutralizing potency of the sera.
TABLE-US-00006 TABLE 5 Neutralizing antibody titers in sera from
mice immunized with pVCR-derived VRPs expressing gH/gL. Serum from
mice immunized with pVCR-derived VRPs expressing gH/gL Without With
HCMV Strain Cell complement complement Towne Fibroblasts 5244 4081
AD169 (MRC-5) 2126 2208 TB40-UL32-EGFP 678 505 VR1814 4764 2126
TB40-UL32-EGFP Epithelial cells 5602 3247 VR1814 (ARPE-19) 6510
2420 8819 (clinical isolate) 8706 5242 8822 (clinical isolate) 3427
2684
[0271] The immunogenicity of LNP-encapsulated RNAs encoding the
pentameric complex
[0272] (A526 and A527) compared to LNP-encapsulated RNA (A160) and
VRPs (pVCR modified gH-SGPgL) expressing gH/gL was assessed. Table
6 shows that replicons expressing the pentameric complex elicited
more potently neutralizing antibodies than replicons expressing
gH/gL.
TABLE-US-00007 TABLE 6 Neutralizing antibody titers. Titer Titer
Replicon Titer post 1.sup.st post 2.sup.nd post 3.sup.rd C313 pVCR
modified gH-SGP-gL 126 6,296 26,525 VRP 10.sup.6 IU A160 gH FL/gL 1
.mu.g LNP 347 9,848 42,319 A526 Pentameric 2A 1 .mu.g LNP 179
12,210 80,000 A527 Pentameric IRES 1 .mu.g LNP 1,510 51,200
130,000
[0273] The pentacistronic VEE-based RNA replicon that elicited the
highest titers of neutralizing antibodies (A527) was packaged as
VRPs and the immunogenicity of the VRPs were compared to
gH/gL-expressing VRPs and LNP-encapsulated replicons expressing
gH/gL and pentameric complex. Table 7 shows that VRPs expressing
the pentameric complex elicited higher titers of neutralizing
antibodies than VRPs expressing gH/gL. Moreover, 10.sup.6
infectious units of VRPs are at least as potent as 1 .mu.g of
LNP-encapsulated RNA when the VRPs and the RNA encoded the same
protein complexes.
TABLE-US-00008 TABLE 7 Neutralizing antibody titers. Sera were
collected three weeks after the second immunization. Replicon 50%
Neutralizing Titer A160 gH FL/gL VRP 10.sup.6 IU 14,833 A527
Pentameric IRES VRP 10.sup.6 IU 51,200 A160 gH FL/gL LNP 0.01 .mu.g
4,570 A160 gH FL/gL LNP 0.1 .mu.g 9,415 A160 gH FL/gL LNP 1 .mu.g
14,427 A527 Pentameric IRES 0.01 .mu.g LNP 12,693 A527 Pentameric
IRES 0.1 .mu.g LNP 10,309 A527 Pentameric IRES 1 .mu.g LNP
43,157
[0274] The breadth and potency of HCMV neutralizing activity in
sera from mice immunized with VEE-based RNA encoding the pentameric
complex (A527) was assessed by using the sera to block infection of
fibroblasts and epithelial cells with different strains of HCMV.
Table 8 shows that anti-gH/gL/UL128/UL130/UL131 immune sera broadly
and potently neutralized infection of epithelial cells. This effect
was complement independent. In contrast, the sera had a reduced or
not detectable effect on infection of fibroblasts. These results
are what is expected for immune sera that contains mostly
antibodies specific for the gH/gL/UL128/UL130/UL131 pentameric
complex, because the pentameric complex is not required for
infection of fibroblasts and, consequently, antibodies to UL128,
UL130, and UL131 do not block infection of fibroblasts (Adler et al
(2006), J. Gen. Virol. 87(Pt. 9):2451-60; Wang and Shenk (2005),
Proc. Natl. Acad. Sci. USA 102(50):18153-8). Thus, these data
demonstrate that the pentameric replicons encoding the
gH/gL/UL128/UL130/UL131 pentameric complex specifically elicit
antibodies to the complex in vivo.
TABLE-US-00009 TABLE 8 Neutralizing antibody titers in sera from
mice immunized with the A527 RNA replicon encapsulated in LNPs. The
replicon expresses the HCMV pentameric complex using subgenomic
promoters and IRESes. Serum from mice immunized with A527
pentameric IRES RNA in LNPs Without With HCMV Strain Cell
complement complement Towne Fibroblasts 3433 1574 AD169 (MRC-5)
2292 <1000 TB40-UL32-EGFP <1000 <1000 VR1814 4683 1324
TB40-UL32-EGFP Epithelial cells 86991 59778 VR1814 (ARPE-19) 82714
37293 8819 (clinical isolate) 94418 43269 8822 (clinical isolate)
85219 49742
[0275] To see if bicistronic and pentacistronic replicons
expressing the gH/gL and pentameric complexes would elicit
neutralizing antibodies in different formulations, cotton rats were
immunized with bicistronic or pentacistronic replicons mixed with a
cationic nanoemulsion (CNE). Table 9 shows that replicons in CNE
elicited comparable neutralizing antibody titers to the same
replicons encapsulated in LNPs.
TABLE-US-00010 TABLE 9 Neutralizing antibody titers. The sera were
collected three weeks after the second immunization. Replicon 50%
Neutralizing Titer A160 gH FL/gL VRP 10.sup.6 IU 594 A160 gH FL/gL
1 .mu.g LNP 141 A527 Pentameric IRES 1 .mu.g LNP 4,416 A160 gH
FL/gL 1 .mu.g CNE 413 A527 Pentameric IRES 1 .mu.g CNE 4,411
Example 7
Replicons Encoding VZV Proteins
[0276] Nucleic acids encoding VZV proteins were cloned into a VEE
replicon vector to produce monocystronic replicons that encode gB,
gH, gL, gE, and gI, and to produce bicistronic replicons that
encode gH/gL or gE/gI. In the bicistronic replicons, expression of
each VZV open reading frame was driven by a separate subgenomic
promoter.
[0277] To prepare replicon RNA, plasmid encoding the replicon was
linearized by digestion with PmeI, and the linearized plasmid was
extracted with phenol/chloroform/isoamylalchohol, precipitated in
sodium acetate/ethanol and resuspended in 20 .mu.l of RNase-free
water.
[0278] RNA was prepared by In vitro transcription of 1 .mu.g of
linearized DNA using the MEGAscript T7 kit (AMBION# AM1333). A 20
.mu.l reaction was set up according to the manufacturer's
instruction without cap analog and incubated for 2 hours at
32.degree. C. TURBO DNase (1 .mu.l) was added and the mixture was
incubate for 30 min. at 32.degree. C. RNase-free water (30 .mu.l)
and ammonium acetate solution (30 .mu.l) were added. The solution
was mixed and chilled for at least 30 min at -20.degree. C. Then
the solution was centrifuged at maximum speed for 25 min. at
4.degree. C. The supernatant was discarded, and the pellet was
rinsed with 70% ethanol, and again centrifuged at maximum speed for
10 min. at 4.degree. C. The pellet was air dried and resuspended in
50 .mu.l of RNase-free water. The concentration of RNA was measured
and quality was check on a denaturing gel.
[0279] The RNA was capped using the ScriptCap m7G Capping System
(Epicentre #SCCE0625). The reaction was scaled by combining the RNA
and RNase-free water. The RNA was then denatured for 5-10 min. at
65.degree. C. The denatured RNA was transferred quickly to ice and
the following reagents were added in the following order: ScriptCap
Capping Buffer, 10 mM GTP, 2 mM SAM fresh prepared, ScriptGuard
RNase inhibitor, and ScriptCap Capping Enzyme. The mixture was
incubated for 60 min. at 37.degree. C. The reaction was stopped by
adding RNase-free water and 7.5 M LiCl, mixing well and storing the
mixture for at least 30 min at -20.degree. C. Then, the mixture was
centrifuged at maximum speed for 25 min. at 4.degree. C., the
pellet was rinsed with 70% ethanol, again centrifuged at maximum
speed for 10 min. at 4.degree. C. and the pellet was air dried. The
pellet was resuspended in RNase-free water. The concentration of
RNA was measured and quality was checked on a denaturing gel.
RNA Transfection
[0280] Cells (BHK-V cells) were seeded on 6-well plates brought to
90-95% confluence at the time of transfection. For each
transfection 3 .mu.g of RNA was diluted in 50 mL OPTIMEM media in a
first tube. Lipofectamine 2000 was added to a second tube contained
50 mL OPTIMEM media. The first and second tubes were combined and
kept for 20 min. at room temperature. The culture media in the
6-well plates were replaced with fresh media, and the
RNA-Lipofectamine complex was placed onto the cells, and mixed by
gently rocking the plate. The plates were incubated for 24 hours at
37.degree. C. in a CO.sub.2 incubator.
[0281] Expression of the VZV proteins in transfected cells was
assessed by western blot and immunofluorescence. For western blots,
lysates of transfected cells were separated by electrophoresis (5
.mu.g total proteins/lane) and blotted. A cleared viral suspension
(7 .mu.g total protein/lane) derived from the OKA/Merck vaccine
strain was used as a positive control. Blots were probed using
commercially available antibodies (1:1000 dilution) that bind VZV
proteins.
[0282] For immunofluorescence, transfected cells were harvested and
seeded in 96 well plate, and intracellular staining was performed
using commercially available mouse mAbs (dilution range 1:100
1:400). Cell pellets were fixed and permeabilized with
Citofix-Citoperm solutions. A secondary reagent, Alexa488 labelled
goat anti-mouse F(ab').sub.2 (1:400 final dilution), was used.
[0283] Expression of VZV proteins gE and gI was detected in cells
transfected with monocistronic constructs (gE or gI), and
expression of both gE and gI was detected in cells transfected with
a bicistronic gE/gI construct in western blots using commercially
available mouse antibodies, 13B1 for gE and 8C4 for gI. Expression
of VZV protein gB was detected in cells transfected with a
monocistronic construct encoding gB, by immunofluorescence using
commercially available antibody 10G6. Expression of the VZV protein
complex gH/gL, was detected by immunofluorescence in cells
transfected with monocistronic gH and monocistronic gL, or with a
bicistronic gH/gL construct. The gH/gL complex was detected using
commercially available antibody SG3.
[0284] Murine Immunogenicity Studies
[0285] Groups of 8 female BALB/c mice aged 6-8 weeks and weighing
about 20 g were immunized intramuscularly with 7.0 or 1.0 .mu.g of
replicon RNA formulated with a CNE or LNP(RV01) at day 0, 21 and
42. Blood samples were taken from the immunized animals 3 weeks
after the 2nd immunization and 3 weeks after the 3rd immunization.
The groups are shown in Table 10.
TABLE-US-00011 TABLE 10 Dose Group Antigen (micrograms) Formulation
Study 1 1 YFP 7 CNE 2 YFP 1 CNE 3 gB 7 CNE 4 gB 1 CNE 5 gE 7 CNE 6
gE 1 CNE 7 gH 7 CNE 8 gH 1 CNE 9 gI 7 CNE 10 gI 1 CNE 11 gL 7 CNE
12 gL 1 CNE 13 gE/gI 7 CNE 14 gE/gI 1 CNE 15 gH/gL 7 CNE 16 gH/gL 1
CNE Study 2 1 gB 1 RV01 2 gE 1 RV01 3 gH 1 RV01 4 gI 1 RV01 5 gL 1
RV01 6 gE/gI 1 RV01 7 gH/gL 1 RV01
Immune Response to VZV Antigens
[0286] Serum samples were tested for the presence of antibodies to
gB, by intracellular staining of VZV-replicon transfected MRC-5
cells. MRC-5 cells were maintained in Dulbecco Modified Eagle's
Medium with 10% fetal bovine serum. VZV Oka strain inoculum
(obtained from ATCC) was used to infect MRC-5 cell culture and
infected whole cells were used for subpassage of virus. The ratio
between infected and un-infected cells was 1:10. 30 hrs post
infection cells were trypsin-dispersed for seeding in a 96 well
plate to perform an intracellular staining with pools of mice sera
(dilution range 1:200 to 1:800) obtained after immunization.
Commercial mAbs were used as controls to quantify the infection
level. Cell pellets ware fixed and permeabilized with
Citofix-Citoperm solutions. A secondary reagent, Alexa488 labelled
goat anti-mouse F(ab').sub.2 was used (1:400 final dilution).
[0287] Commercial antibodies to gB (10G6), gH(SG3), and gE (13B1
(SBA) and 8612 (Millipore)) were used as positive controls, and
each intracellularly stained infected MRC-5 cells. Immune sera
obtained 3 weeks after the third immunization with either 1 or 7
.mu.g of RNA formulated with CNE or LNP were diluted 1/200, 1/400
and 1/800 and used to intracellulary stain infected MRC-5 cells.
The results are shown in FIG. 21 (Study 1, groups 1, 5, 7, 9, 11,
13 and 15, CNE formulation) and FIG. 22 (Study 2, groups 1-7, LNP
formulation).
Neutralizing Assay
[0288] Each immunized mouse serum was serially diluted by two fold
increments starting at 1:20 in standard culture medium, and added
to the equal volume of VZV suspension in the presence of guinea pig
complement. After incubation for 1 hour at 37.degree. C., the human
epithelial cell line A549, was added. Infected cells can be
measured after one week of culture by counting plaques formed in
the culture under microscope. From the plaque number the %
inhibition at each serum dilution was calculated. A chart for each
serum sample was made by plotting the value of % inhibition against
the logarithmic scale the dilution factor. Subsequently an
approximate line of relationship between dilution factor and %
inhibition was drawn. Then the 50% neutralization titer was
determined as the dilution factor where the line crossed at the
value of 50% inhibition.
[0289] Table 11 shows that sera obtained from mice immunized with
monocistronic gE, bicistrnic gE/gl, and bicistronic gH/gL contained
robust neutralizing antibody titers.
TABLE-US-00012 TABLE 11 Neutralization titers of pooled sera from
mice immunized with 7 .mu.g RNA Control (YFP) gB gE gI gE/gI gH gL
gH/gL <20 <20 1111 <20 440 <20 <20 1070 <20
<20 413 51 >2560 <20 <20 >2560 <20 <20
>2560 <20 1031 <20 <20 >2560 <20 20 2128 <20
1538 <20 <20 >2560 <20 20 861 <20 636 20 <20
>2560 <20 <20 1390 <20 2339 <20 <20 >2560
<20 <20 969 <20 1903 <20 <20 900 <20 <20 1011
20 1969 20 <20 >2560 <20* <20* <20* <20* <20*
<20* <20* <20* *pre-immune pooled sera
REFERENCES
[0290] Britt W J, Alford C A. Cytomegalovirus. In Fields B N, Knipe
D M, Howley P M (ed.). Fields Virology, 3.sup.rd edition,
Philadelphia, Pa.: Lippincott/Raven; 1996. p. 2493-523. [0291] Chee
M S, Bankier A T, Beck S, Bohni R, Brown C M, Cerny R, Horsnell T,
Hutchinson C A, Kouzarides T, Martignetti J A, Preddie E, Satchwell
S C, Tomlinson P, Weston K M and Barrell B G. 1990. Analysis of the
protein-coding content of the sequence of human cytomegalovirus
strain AD169. Curr. Top. Microbiol. Immunol. 154:125-70. [0292]
Davison A J, Dolan A, Akter P, Addison C, Dargan D J, Alcendor D J,
McGeoch D J and Hayward G S. 2003. The human cytomegalovirus genome
revisited: comparison with the chimpanzee cytomegalovirus genome.
J. Gen. Virol. 84:17-28. (Erratum, 84:1053). [0293] Crumpacker C S
and Wadhwa S. 2005. Cytomegalovirus, p 1786-1800. In G. L. Mandell,
J. E. Bennett, and R. Dolin (ed.), Principles and practice of
infectious diseases, vol 2. Elsevier, Philadelphia, Pa. [0294]
Pomeroy C and Englund J A. 1987. Cyotmegalovirus: epidemiology and
infection control. Am J Infect Control 15: 107-119. [0295] Murphy
E, Yu D, Grimwood J, Schmutz J, Dickson M, Jarvis M A, Nelson J A,
Myers R M and Shenk T E. 2003. Coding potential of laboratory and
clinical strains of cytomegalovirus. Proc. Natl. Acad. Sci. USA
100:14976-81. [0296] Mocarski E S and Tan Courcelle C. 2001.
Cytomegalovirus and their replication, p. 2629-73. In D M Knipe and
P M Howley (ed.) Fields Virology, 4.sup.th edition, vol. 2.
Lippincott Williams and Wilkins, Philadelphia, Pa. [0297] Compton
T. 2004. Receptors and immune sensors: the complex entry path of
human cytomegalovirus. Trends Cell. Bio. 14(1): 5-8. [0298] Britt W
J and Alford C A. 2004. Human cytomegalovirus virion proteins. Hum.
Immunol. 65:395-402. [0299] Varnum S M, Streblow D N, Monroe M E,
Smith P, Auberry K J, Pasa-Tolic L, Wang D, Camp II DG, Rodland K,
Wiley, Britt W, Shenk T, Smith R D and Nelson J A. 2004.
Identification of proteins in human cytomegalovirus (HCMV)
particles: the HCMV proteome. J. Virol. 78:10960-66. (Erratum,
78:13395). [0300] Ljungman P, Griffiths P and Paya C. 2002.
Definitions of cytomegalovirus infection and disease in transplant
recipients. Clin. Infect. Dis. 34:1094-97. [0301] Rubin R. 2002.
Clinical approach to infection in the compromised host, p. 573-679.
In R. Rubin and LS Young (ed), Infection in the organ transplant
recipient. Kluwer Academic Press, New York, N.Y. [0302] Stagno S
and Britt W J. 2005. Cytomegalovirus, p. 389-424. In J S Remington
and J O Klein (ed), Infectious diseases of the fetus and newborn
infant, 6htt edition. WB Saunders, Phliadelphia, Pa. [0303] Britt W
J, Vugler L, Butfiloski E J and Stephens E B. 1990. Cell surface
expression of human cytomegalovirus (HCMV) gp55-116 (gB): use of
HCMV-vaccinia recombinant virus infected cells in analysis of the
human neutralizing antibody response. J. Virol. 64:1079-85. [0304]
Reap E A, Dryga S A, Morris J, Rivers B, Norberg P K, Olmsted R A
and Chulay J D. 2007. Cellular and Humoral Immune Responses to
Alphavirus Replicon Vaccines expressing Cytomegalovirus pp 65, ILl
and gB proteins. Clin. Vacc. Immunol. 14:748-55. [0305] Balasuriya
U B R, Heidner H W, Hedges J F, Williams J C, Davis N L, Johnston R
E and MacLachlan N J. 2000. Expression of the two major envelope
proteins of equine arteritis virus as a heterodimer is necessary
for induction of neutralizing antibodies in mice immunized with
recombinant Venezuelan equine encephalitis virus replicon
particles. J. Virol. 74:10623-30. [0306] Dunn W, Chou C, Li H, Hai
R, Patterson D, Stoic V, Zhu H and Liu F. 2003. Functional
profiling of a human cytomegalovirus genome. Proc. Natl. Acad. Sci.
USA 100:14223-28. [0307] Hobom U, Brune W, Messerle M, Hahn G and
Kosinowski U H. 2000. Fast screening procedures for random
transposon libraries of cloned herpesvirus genomes: mutational
analysis of human cytomegalovirus envelope glycoprotein genes. J.
Virol. 74:7720-29. [0308] Ryckman B J, Chase M C and Johnson D C.
2009. HCMV TR strain glycoprotein O acts as a chaperone promoting
gH/gL incorporation into virions, but is not present in virions. J.
Virol. [0309] Wille P T, Knoche A J, Nelson J A, Jarvis M A and
Johnson J C. 2009. An HCMV gO-null mutant fails to incorporate
gH/gL into the virion envelope and is unable to enter fibroblasts,
epithelial, and endothelial cells. J. Virol. [0310] Shimamura M,
Mach M and Britt W J. 2006. Human Cytomegalovirus infection elicits
a glycoprotein M (gM)/gN-specific virus-neutralizing antibody
response. J. Virol. 80:4591-4600. [0311] Cha T A, Tom E, Kemble G
W, Duke G M, Mocarski E S and Spaete R R. 1996. Human
cytomegalovirus clinical isolates carry at least 19 genes not found
in laboratory strains. J. Virol. 70:78-83. [0312] Wang D and Shenk
T. 2005. Human cytomegalovirus virion protein complex required for
epithelial and endothelial cell tropism. Proc. Natl. Acad. Sci. USA
102:18153-58. [0313] Adler B, Scrivano L, Ruzcics Z, Rupp B,
Sinzger C and Kosinowski U. 2006. Role of human cytomegalovirus
UL131A in cell type-specific virus entry and release. J. Gen.
Virol. 87:2451-60. [0314] Ryckman B J, Rainish B L, Chase M C,
Borton J A, Nelson J A, Jarvis J A and Johnson D C. 2008.
Characterization of the human cytomegalovirus gH/gL/UL128-UL131
complex that mediates entry into epithelial and endothelial cells.
J. Virol. 82: 60-70.
SEQUENCES
TABLE-US-00013 [0315] CMV gB FL: 1 -
atggaaagccggatctggtgcctggtcgtgtgcgtgaacctgtgcatcgtgtgcctgggagc
cgccgtgagcagcagcagcaccagaggcaccagcgccacacacagccaccacagcagccaca
ccacctctgccgcccacagcagatccggcagcgtgtcccagagagtgaccagcagccagacc
gtgtcccacggcgtgaacgagacaatctacaacaccaccctgaagtacggcgacgtcgtggg
cgtgaataccaccaagtacccctacagagtgtgcagcatggcccagggcaccgacctgatca
gattcgagcggaacatcgtgtgcaccagcatgaagcccatcaacgaggacctggacgagggc
atcatggtggtgtacaagagaaacatcgtggcccacaccttcaaagtgcgggtgtaccagaa
ggtgctgaccttccggcggagctacgcctacatccacaccacatacctgctgggcagcaaca
ccgagtacgtggcccctcccatgtgggagatccaccacatcaacagccacagccagtgctac
agcagctacagccgcgtgatcgccggcacagtgttcgtggcctaccaccgggacagctacga
gaacaagaccatgcagctgatgcccgacgactacagcaacacccacagcaccagatacgtga
ccgtgaaggaccagtggcacagcagaggcagcacctggctgtaccgggagacatgcaacctg
aactgcatggtcaccatcaccaccgccagaagcaagtacccttaccacttcttcgccacctc
caccggcgacgtggtggacatcagccccttctacaacggcaccaaccggaacgccagctact
tcggcgagaacgccgacaagttcttcatcttccccaactacaccatcgtgtccgacttcggc
agacccaacagcgctctggaaacccacagactggtggcctttctggaacgggccgacagcgt
gatcagctgggacatccaggacgagaagaacgtgacctgccagctgaccttctgggaggcct
ctgagagaaccatcagaagcgaggccgaggacagctaccacttcagcagcgccaagatgacc
gccaccttcctgagcaagaaacaggaagtgaacatgagcgactccgccctggactgcgtgag
ggacgaggccatcaacaagctgcagcagatcttcaacaccagctacaaccagacctacgaga
agtatggcaatgtgtccgtgttcgagacaacaggcggcctggtggtgttctggcagggcatc
aagcagaaaagcctggtggagctggaacggctcgccaaccggtccagcctgaacctgaccca
caaccggaccaagcggagcaccgacggcaacaacgcaacccacctgtccaacatggaaagcg
tgcacaacctggtgtacgcacagctgcagttcacctacgacaccctgcggggctacatcaac
agagccctggcccagatcgccgaggcttggtgcgtggaccagcggcggaccctggaagtgtt
caaagagctgtccaagatcaaccccagcgccatcctgagcgccatctacaacaagcctatcg
ccgccagattcatgggcgacgtgctgggcctggccagctgcgtgaccatcaaccagaccagc
gtgaaggtgctgcgggacatgaacgtgaaagagagcccaggccgctgctactccagacccgt
ggtcatcttcaacttcgccaacagctcctacgtgcagtacggccagctgggcgaggacaacg
agatcctgctggggaaccaccggaccgaggaatgccagctgcccagcctgaagatctttatc
gccggcaacagcgcctacgagtatgtggactacctgttcaagcggatgatcgacctgagcag
catctccaccgtggacagcatgatcgccctggacatcgaccccctggaaaacaccgacttcc
gggtgctggaactgtacagccagaaagagctgcggagcagcaacgtgttcgacctggaagag
atcatgcgggagttcaacagctacaagcagcgcgtgaaatacgtggaggacaaggtggtgga
ccccctgcctccttacctgaagggcctggacgacctgatgagcggactgggcgctgccggaa
aagccgtgggagtggccattggagctgtgggcggagctgtggcctctgtcgtggaaggcgtc
gccacctttctgaagaaccccttcggcgccttcaccatcatcctggtggccattgccgtcgt
gatcatcacctacctgatctacacccggcagcggagactgtgtacccagcccctgcagaacc
tgttcccctacctggtgtccgccgatggcaccacagtgaccagcggctccaccaaggatacc
agcctgcaggccccacccagctacgaagagagcgtgtacaacagcggcagaaagggccctgg
ccctcccagctctgatgccagcacagccgcccctccctacaccaacgagcaggcctaccaga
tgctgctggccctggctagactggatgccgagcagagggcccagcagaacggcaccgacagc
ctggatggcagaaccggcacccaggacaagggccagaagcccaacctgctggaccggctgcg
gcaccggaagaacggctaccggcacctgaaggacagcgacgaggaagagaacgtctgataa -
2727 CMV gB FL
MESRIWCLWCVNLCIVCLGAAVSSSSTRGTSATHSHHSSHTTSAAHSRSGSVSQRVTSSQT
VSHGVNETIYNTTLKYGDWGVNTTKYPYRVCSMAQGTDLIRFERNIVCTSMKPINEDLDEG
IMWYKRNIVAHTFKVRVYQKVLTFRRSYAYIHTTYLLGSNTEYVAPPMWEIHHINSHSQCY
SSYSRVIAGTVFVAYHRDSYENKTMQLMPDDYSNTHSTRYVTVKDQWHSRGSTWLYRETCNL
NCMVTITTARSKYPYHFFATSTGDWDISPFYNGTNRNASYFGENADKFFIFPNYTIVSDFG
RPNSALETHRLVAFLERADSVISWDIQDEKNVTCQLTFWEASERTIRSEAEDSYHFSSAKMT
ATFLSKKQEVNMSDSALDCVRDEAINKLQQIFNTSYNQTYEKYGNVSVFETTGGLWFWQGI
KQKSLVELERLANRSSLNLTHNRTKRSTDGNNATHLSNMESVHNLVYAQLQFTYDTLRGYIN
RALAQIAEAWCVDQRRTLEVFKELSKINPSAILSAIYNKPIAARFMGDVLGLASCVTINQTS
VKVLRDMNVKESPGRCYSRPWIFNFANSSYVQYGQLGEDNEILLGNHRTEECQLPSLKIFI
AGNSAYEYVDYLFKRMIDLSSISTVDSMIALDIDPLENTDFRVLELYSQKELRSSNVFDLEE
IMREFNSYKQRVKYVEDKWDPLPPYLKGLDDLMSGLGAAGKAVGVAIGAVGGAVASWEGV
ATFLKNPFGAFTIILVAIAWIITYLIYTRQRRLCTQPLQNLFPYLVSADGTTVTSGSTKDT
SLQAPPSYEESVYNSGRKGPGPPSSDASTAAPPYTNEQAYQMLLALARLDAEQRAQQNGTDS
LDGRTGTQDKGQKPNLLDRLRHRKNGYRHLKDSDEEENV--
TABLE-US-00014 CMV gB sol 750: 1-
atggaaagccggatctggtgcctggtcgtgtgcgtgaacctgtgcatcgtgtgcctgggagc
cgccgtgagcagcagcagcaccagaggcaccagcgccacacacagccaccacagcagccaca
ccacctctgccgcccacagcagatccggcagcgtgtcccagagagtgaccagcagccagacc
gtgtcccacggcgtgaacgagacaatctacaacaccaccctgaagtacggcgacgtcgtggg
cgtgaataccaccaagtacccctacagagtgtgcagcatggcccagggcaccgacctgatca
gattcgagcggaacatcgtgtgcaccagcatgaagcccatcaacgaggacctggacgagggc
atcatggtggtgtacaagagaaacatcgtggcccacaccttcaaagtgcgggtgtaccagaa
ggtgctgaccttccggcggagctacgcctacatccacaccacatacctgctgggcagcaaca
ccgagtacgtggcccctcccatgtgggagatccaccacatcaacagccacagccagtgctac
agcagctacagccgcgtgatcgccggcacagtgttcgtggcctaccaccgggacagctacga
gaacaagaccatgcagctgatgcccgacgactacagcaacacccacagcaccagatacgtga
ccgtgaaggaccagtggcacagcagaggcagcacctggctgtaccgggagacatgcaacctg
aactgcatggtcaccatcaccaccgccagaagcaagtacccttaccacttcttcgccacctc
caccggcgacgtggtggacatcagccccttctacaacggcaccaaccggaacgccagctact
tcggcgagaacgccgacaagttcttcatcttccccaactacaccatcgtgtccgacttcggc
agacccaacagcgctctggaaacccacagactggtggcctttctggaacgggccgacagcgt
gatcagctgggacatccaggacgagaagaacgtgacctgccagctgaccttctgggaggcct
ctgagagaaccatcagaagcgaggccgaggacagctaccacttcagcagcgccaagatgacc
gccaccttcctgagcaagaaacaggaagtgaacatgagcgactccgccctggactgcgtgag
ggacgaggccatcaacaagctgcagcagatcttcaacaccagctacaaccagacctacgaga
agtatggcaatgtgtccgtgttcgagacaacaggcggcctggtggtgttctggcagggcatc
aagcagaaaagcctggtggagctggaacggctcgccaaccggtccagcctgaacctgaccca
caaccggaccaagcggagcaccgacggcaacaacgcaacccacctgtccaacatggaaagcg
tgcacaacctggtgtacgcacagctgcagttcacctacgacaccctgcggggctacatcaac
agagccctggcccagatcgccgaggcttggtgcgtggaccagcggcggaccctggaagtgtt
caaagagctgtccaagatcaaccccagcgccatcctgagcgccatctacaacaagcctatcg
ccgccagattcatgggcgacgtgctgggcctggccagctgcgtgaccatcaaccagaccagc
gtgaaggtgctgcgggacatgaacgtgaaagagagcccaggccgctgctactccagacccgt
ggtcatcttcaacttcgccaacagctcctacgtgcagtacggccagctgggcgaggacaacg
agatcctgctggggaaccaccggaccgaggaatgccagctgcccagcctgaagatctttatc
gccggcaacagcgcctacgagtatgtggactacctgttcaagcggatgatcgacctgagcag
catctccaccgtggacagcatgatcgccctggacatcgaccccctggaaaacaccgacttcc
gggtgctggaactgtacagccagaaagagctgcggagcagcaacgtgttcgacctggaagag
atcatgcgggagttcaacagctacaagcagcgcgtgaaatacgtggaggacaaggtggtgga
ccccctgcctccttacctgaagggcctggacgacctgatgagcggactgggcgctgccggaa
aagccgtgggagtggccattggagctgtgggcggagctgtggcctctgtcgtggaaggcgtc
gccacctttctgaagaactgataa - 2256 Cmv gB sol 750
MESRIWCLWCVNLCIVCLGAAVSSSSTRGTSATHSHHSSHTTSAAHSRSGSVSQRVTSSQT
VSHGVNETIYNTTLKYGDWGVNTTKYPYRVCSMAQGTDLIRFERNIVCTSMKPINEDLDEG
IMWYKRNIVAHTFKVRVYQKVLTFRRSYAYIHTTYLLGSNTEYVAPPMWEIHHINSHSQCY
SSYSRVIAGTVFVAYHRDSYENKTMQLMPDDYSNTHSTRYVTVKDQWHSRGSTWLYRETCNL
NCMVTITTARSKYPYHFFATSTGDWDISPFYNGTNRNASYFGENADKFFIFPNYTIVSDFG
RPNSALETHRLVAFLERADSVISWDIQDEKNVTCQLTFWEASERTIRSEAEDSYHFSSAKMT
ATFLSKKQEVNMSDSALDCVRDEAINKLQQIFNTSYNQTYEKYGNVSVFETTGGLWFWQGI
KQKSLVELERLANRSSLNLTHNRTKRSTDGNNATHLSNMESVHNLVYAQLQFTYDTLRGYIN
RALAQIAEAWCVDQRRTLEVFKELSKINPSAILSAIYNKPIAARFMGDVLGLASCVTINQTS
VKVLRDMNVKESPGRCYSRPWIFNFANSSYVQYGQLGEDNEILLGNHRTEECQLPSLKIFI
AGNSAYEYVDYLFKRMIDLSSISTVDSMIALDIDPLENTDFRVLELYSQKELRSSNVFDLEE
IMREFNSYKQRVKYVEDKWDPLPPYLKGLDDLMSGLGAAGKAVGVAIGAVGGAVASWEGV
ATFLKN--
TABLE-US-00015 CMV gB sol 692: 1-
atggaaagccggatctggtgcctggtcgtgtgcgtgaacctgtgcatcgtgtgcctgggagc
cgccgtgagcagcagcagcaccagaggcaccagcgccacacacagccaccacagcagccaca
ccacctctgccgcccacagcagatccggcagcgtgtcccagagagtgaccagcagccagacc
gtgtcccacggcgtgaacgagacaatctacaacaccaccctgaagtacggcgacgtcgtggg
cgtgaataccaccaagtacccctacagagtgtgcagcatggcccagggcaccgacctgatca
gattcgagcggaacatcgtgtgcaccagcatgaagcccatcaacgaggacctggacgagggc
atcatggtggtgtacaagagaaacatcgtggcccacaccttcaaagtgcgggtgtaccagaa
ggtgctgaccttccggcggagctacgcctacatccacaccacatacctgctgggcagcaaca
ccgagtacgtggcccctcccatgtgggagatccaccacatcaacagccacagccagtgctac
agcagctacagccgcgtgatcgccggcacagtgttcgtggcctaccaccgggacagctacga
gaacaagaccatgcagctgatgcccgacgactacagcaacacccacagcaccagatacgtga
ccgtgaaggaccagtggcacagcagaggcagcacctggctgtaccgggagacatgcaacctg
aactgcatggtcaccatcaccaccgccagaagcaagtacccttaccacttcttcgccacctc
caccggcgacgtggtggacatcagccccttctacaacggcaccaaccggaacgccagctact
tcggcgagaacgccgacaagttcttcatcttccccaactacaccatcgtgtccgacttcggc
agacccaacagcgctctggaaacccacagactggtggcctttctggaacgggccgacagcgt
gatcagctgggacatccaggacgagaagaacgtgacctgccagctgaccttctgggaggcct
ctgagagaaccatcagaagcgaggccgaggacagctaccacttcagcagcgccaagatgacc
gccaccttcctgagcaagaaacaggaagtgaacatgagcgactccgccctggactgcgtgag
ggacgaggccatcaacaagctgcagcagatcttcaacaccagctacaaccagacctacgaga
agtatggcaatgtgtccgtgttcgagacaacaggcggcctggtggtgttctggcagggcatc
aagcagaaaagcctggtggagctggaacggctcgccaaccggtccagcctgaacctgaccca
caaccggaccaagcggagcaccgacggcaacaacgcaacccacctgtccaacatggaaagcg
tgcacaacctggtgtacgcacagctgcagttcacctacgacaccctgcggggctacatcaac
agagccctggcccagatcgccgaggcttggtgcgtggaccagcggcggaccctggaagtgtt
caaagagctgtccaagatcaaccccagcgccatcctgagcgccatctacaacaagcctatcg
ccgccagattcatgggcgacgtgctgggcctggccagctgcgtgaccatcaaccagaccagc
gtgaaggtgctgcgggacatgaacgtgaaagagagcccaggccgctgctactccagacccgt
ggtcatcttcaacttcgccaacagctcctacgtgcagtacggccagctgggcgaggacaacg
agatcctgctggggaaccaccggaccgaggaatgccagctgcccagcctgaagatctttatc
gccggcaacagcgcctacgagtatgtggactacctgttcaagcggatgatcgacctgagcag
catctccaccgtggacagcatgatcgccctggacatcgaccccctggaaaacaccgacttcc
gggtgctggaactgtacagccagaaagagctgcggagcagcaacgtgttcgacctggaagag
atcatgcgggagttcaacagctacaagcagtgataa - 2082 Cmv gB sol 692;
MESRIWCLVVCVNLCIVCLGAAVSSSSTRGTSATHSHHSSHTTSAAHSRSGSVSQRVTSSQTVSHGVNETIYNT-
T
LKYGDVVGVNTTKYPYRVCSMAQGTDLIRFERNIVCTSMKPINEDLDEGIMVVYKRNIVAHTFKVRVYQKVLTF-
R
RSYAYIHTTYLLGSNTEYVAPPMWEIHHINSHSQCYSSYSRVIAGTVFVAYHRDSYENKTMQLMPDDYSNTHST-
R
YVTVKDQWHSRGSTWLYRETCNLNCMVTITTARSKYPYHFFATSTGDVVDISPFYNGTNRNASYFGENADKFFI-
F
PNYTIVSDFGRPNSALETHRLVAFLERADSVISWDIQDEKNVTCQLTFWEASERTIRSEAEDSYHFSSAKMTAT-
F
LSKKQEVNMSDSALDCVRDEAINKLQQIFNTSYNQTYEKYGNVSVFETTGGLVVFWQGIKQKSLVELERLANRS-
S
LNLTHNRTKRSTDGNNATHLSNMESVHNLVYAQLQFTYDTLRGYINRALAQIAEAWCVDQRRTLEVFKELSKIN-
P
SAILSAIYNKPIAARFMGDVLGLASCVTINQTSVKVLRDMNVKESPGRCYSRPVVIFNFANSSYVQYGQLGEDN-
E
ILLGNHRTEECQLPSLKIFIAGNSAYEYVDYLFKRMIDLSSISTVDSMIALDIDPLENTDFRVLELYSQKELRS-
S NVFDLEEIMREFNSYKQ-
TABLE-US-00016 CMV gH FL: 1-
atgaggcctggcctgccctcctacctgatcatcctggccgtgtgcctgttcagccacctgctgtccagcagata-
c
ggcgccgaggccgtgagcgagcccctggacaaggctttccacctgctgctgaacacctacggcagacccatccg-
g
tttctgcgggagaacaccacccagtgcacctacaacagcagcctgcggaacagcaccgtcgtgagagagaacgc-
c
atcagcttcaactttttccagagctacaaccagtactacgtgttccacatgcccagatgcctgtttgccggccc-
t
ctggccgagcagttcctgaaccaggtggacctgaccgagacactggaaagataccagcagcggctgaataccta-
c
gccctggtgtccaaggacctggccagctaccggtcctttagccagcagctcaaggctcaggatagcctcggcga-
g
cagcctaccaccgtgccccctcccatcgacctgagcatcccccacgtgtggatgcctccccagaccacccctca-
c
ggctggaccgagagccacaccacctccggcctgcacagaccccacttcaaccagacctgcatcctgttcgacgg-
c
cacgacctgctgtttagcaccgtgaccccctgcctgcaccagggcttctacctgatcgacgagctgagatacgt-
g
aagatcaccctgaccgaggatttcttcgtggtcaccgtgtccatcgacgacgacacccccatgctgctgatctt-
c
ggccacctgcccagagtgctgttcaaggccccctaccagcgggacaacttcatcctgcggcagaccgagaagca-
c
gagctgctggtgctggtcaagaaggaccagctgaaccggcactcctacctgaaggaccccgacttcctggacgc-
c
gccctggacttcaactacctggacctgagcgccctgctgagaaacagcttccacagatacgccgtggacgtgct-
g
aagtccggacggtgccagatgctcgatcggcggaccgtggagatggccttcgcctatgccctcgccctgttcgc-
c
gctgccagacaggaagaggctggcgcccaggtgtcagtgcccagagccctggatagacaggccgccctgctgca-
g
atccaggaattcatgatcacctgcctgagccagaccccccctagaaccaccctgctgctgtaccccacagccgt-
g
gatctggccaagagggccctgtggacccccaaccagatcaccgacatcacaagcctcgtgcggctcgtgtacat-
c
ctgagcaagcagaaccagcagcacctgatcccccagtgggccctgagacagatcgccgacttcgccctgaagct-
g
cacaagacccatctggccagctttctgagcgccttcgccaggcaggaactgtacctgatgggcagcctggtcca-
c
agcatgctggtgcataccaccgagcggcgggagatcttcatcgtggagacaggcctgtgtagcctggccgagct-
g
tcccactttacccagctgctggcccaccctcaccacgagtacctgagcgacctgtacaccccctgcagcagcag-
c
ggcagacgggaccacagcctggaacggctgaccagactgttccccgatgccaccgtgcctgctacagtgcctgc-
c
gccctgtccatcctgtccaccatgcagcccagcaccctggaaaccttccccgacctgttctgcctgcccctggg-
c
gagagctttagcgccctgaccgtgtccgagcacgtgtcctacatcgtgaccaatcagtacctgatcaagggcat-
c
agctaccccgtgtccaccacagtcgtgggccagagcctgatcatcacccagaccgacagccagaccaagtgcga-
g
ctgacccggaacatgcacaccacacacagcatcaccgtggccctgaacatcagcctggaaaactgcgctttctg-
t
cagtctgccctgctggaatacgacgatacccagggcgtgatcaacatcatgtacatgcacgacagcgacgacgt-
g
ctgttcgccctggacccctacaacgaggtggtggtgtccagcccccggacccactacctgatgctgctgaagaa-
c
ggcaccgtgctggaagtgaccgacgtggtggtggacgccaccgacagcagactgctgatgatgagcgtgtacgc-
c ctgagcgccatcatcggcatctacctgctgtaccggatgctgaaaacctgctgataa -
2232
TABLE-US-00017 Cmv gH FL;
MRPGLPSYLIILAVCLFSHLLSSRYGAEAVSEPLDKAFHLLLNTYGRPIR
FLRENTTQCTYNSSLRNSTWRENAISFNFFQSYNQYYVFHMPRCLFAG
PLAEQFLNQVDLTETLERYQQRLNTYALVSKDLASYRSFSQQLKAQD
SLGEQPTTVPPPIDLSIPHVWMPPQTTPHGWTESHTTSGLHRPHFNQ
TCILFDGHDLLFSTVTPCLHQGFYLIDELRYVKITLTEDFFWTVSIDDD
TPMLLIFGHLPRVLFKAPYQRDNFILRQTEKHELLVLVKKDQLNRHSY
LKDPDFLDAALDFNYLDLSALLRNSFHRYAVDVLKSGRCQMLDRRT
VEMAFAYALALFAAARQEEAGAQVSVPRALDRQAALLQIQEFMITCL
SQTPPRTTLLLYPTAVDLAKRALWTPNQITDITSLVRLVYILSKQNQQHL
IPQWALRQIADFALKLHKTHLASFLSAFARQELYLMGSLVHSMLVHTT
ERREIFIVETGLCSLAELSHFTQLLAHPHHEYLSDLYTPCSSSGRRDH
SLERLTRLFPDATVPATVPAALSILSTMQPSTLETFPDLFCLPLGESF
SALTVSEHVSYIVTNQYLIKGISYPVSTTWGQSLIITQTDSQTKCELTRN
MHTTHSITVALNISLENCAFCQSALLEYDDTQGVINIMYMHDSDDVLF
ALDPYNEVVVSSPRTHYLMLLKNGTVLEVTDVVVDATDSRLLMMSV
YALSAIIGIYLLYRMLKTC--
TABLE-US-00018 CMV gH sol: 1-
atgaggcctggcctgccctcctacctgatcatcctggccgtgtgcctgttcagccacctgct
gtccagcagatacggcgccgaggccgtgagcgagcccctggacaaggctttccacctgctgc
tgaacacctacggcagacccatccggtttctgcgggagaacaccacccagtgcacctacaac
agcagcctgcggaacagcaccgtcgtgagagagaacgccatcagcttcaactttttccagag
ctacaaccagtactacgtgttccacatgcccagatgcctgtttgccggccctctggccgagc
agttcctgaaccaggtggacctgaccgagacactggaaagataccagcagcggctgaatacc
tacgccctggtgtccaaggacctggccagctaccggtcctttagccagcagctcaaggctca
ggatagcctcggcgagcagcctaccaccgtgccccctcccatcgacctgagcatcccccacg
tgtggatgcctccccagaccacccctcacggctggaccgagagccacaccacctccggcctg
cacagaccccacttcaaccagacctgcatcctgttcgacggccacgacctgctgtttagcac
cgtgaccccctgcctgcaccagggcttctacctgatcgacgagctgagatacgtgaagatca
ccctgaccgaggatttcttcgtggtcaccgtgtccatcgacgacgacacccccatgctgctg
atcttcggccacctgcccagagtgctgttcaaggccccctaccagcgggacaacttcatcct
gcggcagaccgagaagcacgagctgctggtgctggtcaagaaggaccagctgaaccggcact
cctacctgaaggaccccgacttcctggacgccgccctggacttcaactacctggacctgagc
gccctgctgagaaacagcttccacagatacgccgtggacgtgctgaagtccggacggtgcca
gatgctcgatcggcggaccgtggagatggccttcgcctatgccctcgccctgttcgccgctg
ccagacaggaagaggctggcgcccaggtgtcagtgcccagagccctggatagacaggccgcc
ctgctgcagatccaggaattcatgatcacctgcctgagccagaccccccctagaaccaccct
gctgctgtaccccacagccgtggatctggccaagagggccctgtggacccccaaccagatca
ccgacatcacaagcctcgtgcggctcgtgtacatcctgagcaagcagaaccagcagcacctg
atcccccagtgggccctgagacagatcgccgacttcgccctgaagctgcacaagacccatct
ggccagctttctgagcgccttcgccaggcaggaactgtacctgatgggcagcctggtccaca
gcatgctggtgcataccaccgagcggcgggagatcttcatcgtggagacaggcctgtgtagc
ctggccgagctgtcccactttacccagctgctggcccaccctcaccacgagtacctgagcga
cctgtacaccccctgcagcagcagcggcagacgggaccacagcctggaacggctgaccagac
tgttccccgatgccaccgtgcctgctacagtgcctgccgccctgtccatcctgtccaccatg
cagcccagcaccctggaaaccttccccgacctgttctgcctgcccctgggcgagagctttag
cgccctgaccgtgtccgagcacgtgtcctacatcgtgaccaatcagtacctgatcaagggca
tcagetaccccgtgtccaccacagtcgtgggccagagcctgatcatcacccagaccgacagc
cagaccaagtgcgagctgacccggaacatgcacaccacacacagcatcaccgtggccctgaa
catcagcctggaaaactgcgctttctgtcagtctgccctgctggaatacgacgatacccagg
gcgtgatcaacatcatgtacatgcacgacagcgacgacgtgctgttcgccctggacccctac
aacgaggtggtggtgtccagcccccggacccactacctgatgctgctgaagaacggcaccgt
gctggaagtgaccgacgtggtggtggacgccaccgactgataa - 2151
TABLE-US-00019 MV gH sol;
MRPGLPSYLIILAVCLFSHLLSSRYGAEAVSEPLDKAFHLLLNTYGR
PIRFLRENTTQCTYNSSLRNSTWRENAISFNFFQSYNQYYVFHMPRC
LFAGPLAEQFLNQVDLTETLERYQQRLNTYALVSKDLASYRSFSQQ
LKAQDSLGEQPTTVPPPIDLSIPHVWMPPQTTPHGWTESHTTSGL
HRPHFNQTCILFDGHDLLFSTVTPCLHQGFYLIDELRYVKITLTEDFFW
TVSIDDDTPMLLIFGHLPRVLFKAPYQRDNFILRQTEKHELLVLVKKD
QLNRHSYLKDPDFLDAALDFNYLDLSALLRNSFHRYAVDVLKSGRC
QMLDRRTVEMAFAYALALFAAARQEEAGAQVSVPRALDRQAA
LLQIQEFMITCLSQTPPRTTLLLYPTAVDLAKRALWTPNQITDITSLVR
LVYILSKQNQQHLIPQWALRQIADFALKLHKTHLASFLSAFARQELYL
MGSLVHSMLVHTTERREIFIVETGLCSLAELSHFTQLLAHPHHEYLS
DLYTPCSSSGRRDHSLERLTRLFPDATVPATVPAALSILSTM
QPSTLETFPDLFCLPLGESFSALTVSEHVSYIVTNQYLIKGISYPVST
TWGQSLIITQTDSQTKCELTRNMHTTHSITVALNISLENCAFCQSALL
EYDDTQGVINIMYMHDSDDVLFALDPYNEVVVSSPRTHYLMLLKNG TVLEVTDVVVDATD--
TABLE-US-00020 CMV gL fl: 1-
atgtgcagaaggcccgactgcggcttcagcttcagccctggacccgtgatcctgctgtggtg
ctgcctgctgctgcctatcgtgtcctctgccgccgtgtctgtggcccctacagccgccgaga
aggtgccagccgagtgccccgagctgaccagaagatgcctgctgggcgaggtgttcgagggc
gacaagtacgagagctggctgcggcccctggtcaacgtgaccggcagagatggccccctgag
ccagctgatccggtacagacccgtgacccccgaggccgccaatagcgtgctgctggacgagg
ccttcctggataccctggccctgctgtacaacaaccccgaccagctgagagccctgctgacc
ctgctgtccagcgacaccgcccccagatggatgaccgtgatgcggggctacagcgagtgtgg
agatggcagccctgccgtgtacacctgcgtggacgacctgtgcagaggctacgacctgacca
gactgagctacggccggtccatcttcacagagcacgtgctgggcttcgagctggtgcccccc
agcctgttcaacgtggtggtggccatccggaacgaggccaccagaaccaacagagccgtgcg
gctgcctgtgtctacagccgctgcacctgagggcatcacactgttctacggcctgtacaacg
ccgtgaaagagttctgcctccggcaccagctggatccccccctgctgagacacctggacaag
tactacgccggcctgcccccagagctgaagcagaccagagtgaacctgcccgcccacagcag
atatggccctcaggccgtggacgccagatgataa - 840
TABLE-US-00021 CMV gL FL;
MCRRPDCGFSFSPGPVILLWCCLLLPIVSSAAVSVAPTAAEKVPA
ECPELTRRCLLGEVFEGDKYESWLRPLVNVTGRDGPLSQLIRYRPVT
PEAANSVLLDEAFLDTLALLYNNPDQLRALLTLLSSDTAPRWMTVMR
GYSECGDGSPAVYTCVDDLCRGYDLTRLSYGRSIFTEHVLGFELVPP
SLFNVVVAIRNEATRTNRAVRLPVSTAAAPEGITLFYGLYNAVKEFCLR
HQLDPPLLRHLDKYYAGLPPELKQTRVNLPAHSRYGPQAVDAR--
TABLE-US-00022 CMV gM FL: 1-
atggcccccagccacgtggacaaagtgaacacccggacttggagcgccagcatcgtgttcat
ggtgctgaccttcgtgaacgtgtccgtgcacctggtgctgtccaacttcccccacctgggct
acccctgcgtgtactaccacgtggtggacttcgagcggctgaacatgagcgcctacaacgtg
atgcacctgcacacccccatgctgtttctggacagcgtgcagctcgtgtgctacgccgtgtt
catgcagctggtgtttctggccgtgaccatctactacctcgtgtgctggatcaagatcagca
tgcggaaggacaagggcatgagcctgaaccagagcacccgggacatcagctacatgggcgac
agcctgaccgccttcctgttcatcctgagcatggacaccttccagctgttcaccctgaccat
gagcttccggctgcccagcatgatcgccttcatggccgccgtgcactttttctgtctgacca
tcttcaacgtgtccatggtcacccagtaccggtcctacaagcggagcctgttcttcttctcc
cggctgcaccccaagctgaagggcaccgtgcagttccggaccctgatcgtgaacctggtgga
ggtggccctgggcttcaataccaccgtggtggctatggccctgtgctacggcttcggcaaca
acttcttcgtgcggaccggccatatggtgctggccgtgttcgtggtgtacgccatcatcagc
atcatctactttctgctgatcgaggccgtgttcttccagtacgtgaaggtgcagttcggcta
ccatctgggcgcctttttcggcctgtgcggcctgatctaccccatcgtgcagtacgacacct
tcctgagcaacgagtaccggaccggcatcagctggtccttcggaatgctgttcttcatctgg
gccatgttcaccacctgcagagccgtgcggtacttcagaggcagaggcagcggctccgtgaa
gtaccaggccctggccacagcctctggcgaagaggtggccgccctgagccaccacgacagcc
tggaaagcagacggctgcgggaggaagaggacgacgacgacgaggacttcgaggacgcctga taa
- 1119
TABLE-US-00023 CMV gM FL;
MAPSHVDKVNTRTWSASIVFMVLTFVNVSVHLVLSNFPHLGYPCVY
YHWDFERLNMSAYNVMHLHTPMLFLDSVQLVCYAVFMQLVFLAVTIY
YLVCWIKISMRKDKGMSLNQSTRDISYMGDSLTAFLFILSMDTFQLFT
LTMSFRLPSMIAFMAAVHFFCLTIFNVSMVTQYRSYKRSLFFFSRLHP
KLKGTVQFRTLIVNLVEVALGFNTTWAMALCYGFGNNFFVRTGHMVLA
VFWYAIISIIYFLLIEAVFFQYVKVQFGYHLGAFFGLCGLIYPIVQYDTF
LSNEYRTGISWSFGMLFFIWAMFTTCRAVRYFRGRGSGSVKYQALATA
SGEEVAALSHHDSLESRRLREEEDDDDEDFEDA--
TABLE-US-00024 CMV gN FL: 1-
atggaatggaacaccctggtcctgggcctgctggtgctgtctgtcgtggc
cagcagcaacaacacatccacagccagcacccctagacctagca
gcagcacccacgccagcactaccgtgaaggctaccaccgtggcca
ccacaagcaccaccactgctaccagcaccagctccaccacctctgcc
aagcctggctctaccacacacgaccccaacgtgatgaggccccacg
cccacaacgacttctacaacgctcactgcaccagccacatgtacgag
ctgtccctgagcagctttgccgcctggtggaccatgctgaacgccctga
tcctgatgggcgccttctgcatcgtgctgcggcactgctgcttc
cagaacttcaccgccaccaccaccaagggctactgataa - 411
TABLE-US-00025 CMV gN FL;
MEWNTLVLGLLVLSWASSNNTSTASTPRPSSSTHASTTVKATTVATTSTTTATSTSSTTSA
KPGSTTHDPNVMRPHAHNDFYNAHCTSHMYELSLSSFAAWWTMLNALILMGAFCIVLRHCCF
QNFTATTTKGY--
TABLE-US-00026 CMV gO FL: 1-
atgggcaagaaagaaatgatcatggtcaagggcatccccaagatcatgctgctgattagcat
cacctttctgctgctgtccctgatcaactgcaacgtgctggtcaacagccggggcaccagaa
gatcctggccctacaccgtgctgtcctaccggggcaaagagatcctgaagaagcagaaagag
gacatcctgaagcggctgatgagcaccagcagcgacggctaccggttcctgatgtaccccag
ccagcagaaattccacgccatcgtgatcagcatggacaagttcccccaggactacatcctgg
ccggacccatccggaacgacagcatcacccacatgtggttcgacttctacagcacccagctg
cggaagcccgccaaatacgtgtacagcgagtacaaccacaccgcccacaagatcaccctgag
gcctcccccttgtggcaccgtgcccagcatgaactgcctgagcgagatgctgaacgtgtcca
agcggaacgacaccggcgagaagggctgcggcaacttcaccaccttcaaccccatgttcttc
aacgtgccccggtggaacaccaagctgtacatcggcagcaacaaagtgaacgtggacagcca
gaccatctactttctgggcctgaccgccctgctgctgagatacgcccagcggaactgcaccc
ggtccttctacctggtcaacgccatgagccggaacctgttccgggtgcccaagtacatcaac
ggcaccaagctgaagaacaccatgcggaagctgaagcggaagcaggccctggtcaaagagca
gccccagaagaagaacaagaagtcccagagcaccaccaccccctacctgagctacaccacct
ccaccgccttcaacgtgaccaccaacgtgacctacagcgccacagccgccgtgaccagagtg
gccacaagcaccaccggctaccggcccgacagcaactttatgaagtccatcatggccaccca
gctgagagatctggccacctgggtgtacaccaccctgcggtacagaaacgagcccttctgca
agcccgaccggaacagaaccgccgtgagcgagttcatgaagaatacccacgtgctgatcaga
aacgagacaccctacaccatctacggcaccctggacatgagcagcctgtactacaacgagac
aatgagcgtggagaacgagacagccagcgacaacaacgaaaccacccccacctcccccagca
cccggttccagcggaccttcatcgaccccctgtgggactacctggacagcctgctgttcctg
gacaagatccggaacttcagcctgcagctgcccgcctacggcaatctgaccccccctgagca
cagaagggccgccaacctgagcaccctgaacagcctgtggtggtggagccagtgataa-
1422
TABLE-US-00027 CMV gO FL;
MGKKEMIMVKGIPKIMLLISITFLLLSLINCNVLVNSRGTRRSWPYTVLSYRGKEILKKQKE
DILKRLMSTSSDGYRFLMYPSQQKFHAIVISMDKFPQDYILAGPIRNDSITHMWFDFYSTQL
RKPAKYVYSEYNHTAHKITLRPPPCGTVPSMNCLSEMLNVSKRNDTGEKGCGNFTTFNPMFF
NVPRWNTKLYIGSNKVNVDSQTIYFLGLTALLLRYAQRNCTRSFYLVNAMSRNLFRVPKYIN
GTKLKNTMRKLKRKQALVKEQPQKKNKKSQSTTTPYLSYTTSTAFNVTTNVTYSATAAVTRV
ATSTTGYRPDSNFMKSIMATQLRDLATWVYTTLRYRNEPFCKPDRNRTAVSEFMKNTHVLIR
NETPYTIYGTLDMSSLYYNETMSVENETASDNNETTPTSPSTRFQRTFIDPLWDYLDSLLFL
DKIRNFSLQLPAYGNLTPPEHRRAANLSTLNSLWWWSQ--
TABLE-US-00028 CMV UL128 FL: 1-
atgagccccaaggacctgacccccttcctgacaaccctgtggctgctcctgggccatagcag
agtgcctagagtgcgggccgaggaatgctgcgagttcatcaacgtgaaccacccccccgagc
ggtgctacgacttcaagatgtgcaaccggttcaccgtggccctgagatgccccgacggcgaa
gtgtgctacagccccgagaaaaccgccgagatccggggcatcgtgaccaccatgacccacag
cctgacccggcaggtggtgcacaacaagctgaccagctgcaactacaaccccctgtacctgg
aagccgacggccggatcagatgcggcaaagtgaacgacaaggcccagtacctgctgggagcc
gccggaagcgtgccctaccggtggatcaacctggaatacgacaagatcacccggatcgtggg
cctggaccagtacctggaaagcgtgaagaagcacaagcggctggacgtgtgcagagccaaga
tgggctacatgctgcagtgataa-519
TABLE-US-00029 CMV UL128 FL;
MSPKDLTPFLTTLWLLLGHSRVPRVRAEECCEFINVNHPPERCYDFKMCNRFTVALRCPDGE
VCYSPEKTAEIRGIVTTMTHSLTRQWHNKLTSCNYNPLYLEADGRIRCGKVNDKAQYLLGA
AGSVPYRWINLEYDKITRIVGLDQYLESVKKHKRLDVCRAKMGYMLQ--
TABLE-US-00030 CMV UL130 FL: 1-
atgctgcggctgctgctgagacaccacttccactgcctgctgctgtgtgccgtgtgggccac
cccttgtctggccagcccttggagcaccctgaccgccaaccagaaccctagccccccttggt
ccaagctgacctacagcaagccccacgacgccgccaccttctactgcccctttctgtacccc
agccctcccagaagccccctgcagttcagcggcttccagagagtgtccaccggccctgagtg
ccggaacgagacactgtacctgctgtacaaccgggagggccagacactggtggagcggagca
gcacctgggtgaaaaaagtgatctggtatctgagcggccggaaccagaccatcctgcagcgg
atgcccagaaccgccagcaagcccagcgacggcaacgtgcagatcagcgtggaggacgccaa
aatcttcggcgcccacatggtgcccaagcagaccaagctgctgagattcgtggtcaacgacg
gcaccagatatcagatgtgcgtgatgaagctggaaagctgggcccacgtgttccgggactac
tccgtgagcttccaggtccggctgaccttcaccgaggccaacaaccagacctacaccttctg
cacccaccccaacctgatcgtgtgataa-648
TABLE-US-00031 CMV UL130 FL;
MLRLLLRHHFHCLLLCAVWATPCLASPWSTLTANQNPSPPWSKLTYSKPHDAATFYCPFLYP
SPPRSPLQFSGFQRVSTGPECRNETLYLLYNREGQTLVERSSTWVKKVIWYLSGRNQTILQR
MPRTASKPSDGNVQISVEDAKIFGAHMVPKQTKLLRFWNDGTRYQMCVMKLESWAHVFRDY
SVSFQVRLTFTEANNQTYTFCTHPNLIV--
TABLE-US-00032 CMV UL131 FL: 1-
atgcggctgtgcagagtgtggctgtccgtgtgcctgtgtgccgtggtgctgggccagtgcca
gagagagacagccgagaagaacgactactaccgggtgccccactactgggatgcctgcagca
gagccctgcccgaccagacccggtacaaatacgtggagcagctcgtggacctgaccctgaac
taccactacgacgccagccacggcctggacaacttcgacgtgctgaagcggatcaacgtgac
cgaggtgtccctgctgatcagcgacttccggcggcagaacagaagaggcggcaccaacaagc
ggaccaccttcaacgccgctggctctctggcccctcacgccagatccctggaattcagcgtg
cggctgttcgccaactgataa-393
TABLE-US-00033 CMV UL131 FL;
MRLCRVWLSVCLCAWLGQCQRETAEKNDYYRVPHYWDACSRALPDQTRYKYVEQLVDLTLN
YHYDASHGLDNFDVLKRINVTEVSLLISDFRRQNRRGGTNKRTTFNAAGSLAPHARSLEFSV
RLFAN--
TABLE-US-00034 EMCV IRES nucleotide sequence;
aacgttactggccgaagccgcttggaataaggccggtgtgcgtttgtctatatgttattttc
caccatattgccgtcttttggcaatgtgagggcccggaaacctggccctgtcttcttgacga
gcattcctaggggtctttcccctctcgccaaaggaatgcaaggtctgttgaatgtcgtgaag
gaagcagttcctctggaagcttcttgaagacaaacaacgtctgtagcgaccctttgcaggca
gcggaaccccccacctggcgacaggtgcctctgcggccaaaagccacgtgtataagatacac
ctgcaaaggcggcacaaccccagtgccacgttgtgagttggatagttgtggaaagagtcaaa
tggctctcctcaagcgtattcaacaaggggctgaaggatgcccagaaggtaccccattgtat
gggatctgatctggggcctcggtgcacatgctttacatgtgtttagtcgaggttaaaaaaac
gtctaggccccccgaaccacggggacgtggttttcctttgaaaaacacgataat
TABLE-US-00035 EV71 IRES nucleotide sequence;
gtacctttgtacgcctgttttataccccctccctgatttgcaacttagaagcaacgc
aaaccagatcaatagtaggtgtgacataccagtcgcatcttgatcaagcacttctgtatccc
cggaccgagtatcaatagactgtgcacacggttgaaggagaaaacgtccgttacccggctaa
ctacttcgagaagcctagtaacgccattgaagttgcagagtgtttcgctcagcactcccccc
gtgtagatcaggtcgatgagtcaccgcattccccacgggcgaccgtggcggtggctgcgttg
gcggcctgcctatggggtaacccataggacgctctaatacggacatggcgtgaagagtctat
tgagctagttagtagtcctccggcccctgaatgcggctaatcctaactgcggagcacatacc
cttaatccaaagggcagtgtgtcgtaacgggcaactctgcagcggaaccgactactttgggt
gtccgtgtttctttttattcttgtattggctgcttatggtgacaattaaagaattgttacca
tatagctattggattggccatccagtgtcaaacagagctattgtatatctctttgttggatt
cacacctctcactcttgaaacgttacacaccctcaattacattatactgctgaacacgaagc
g
TABLE-US-00036 VEE Subgenomic Promoter
5'-CTCTCTACGGCTAACCTGAATGGA-3'
TABLE-US-00037 pVCR modified vector gH sol-SGP gL
cgcgtcggctacaattaatacataaccttatgtatcatacacatacgatttaggtgacacta
tagatgggcggcgcatgagagaagcccagaccaattacctacccaaaatggagaaagttcac
gttgacatcgaggaagacagcccattcctcagagctttgcagcggagcttcccgcagtttga
ggtagaagccaagcaggtcactgataatgaccatgctaatgccagagcgttttcgcatctgg
cttcaaaactgatcgaaacggaggtggacccatccgacacgatccttgacattggaagtgcg
cccgcccgcagaatgtattctaagcacaagtatcattgtatctgtccgatgagatgtgcgga
agatccggacagattgtataagtatgcaactaagctgaagaaaaactgtaaggaaataactg
ataaggaattggacaagaaaatgaaggagctcgccgccgtcatgagcgaccctgacctggaa
actgagactatgtgcctccacgacgacgagtcgtgtcgctacgaagggcaagtcgctgttta
ccaggatgtatacgcggttgacggaccgacaagtctctatcaccaagccaataagggagtta
gagtcgcctactggataggctttgacaccaccccttttatgtttaagaacttggctggagca
tatccatcatactctaccaactgggccgacgaaaccgtgttaacggctcgtaacataggcct
atgcagctctgacgttatggagcggtcacgtagagggatgtccattcttagaaagaagtatt
tgaaaccatccaacaatgttctattctctgttggctcgaccatctaccacgagaagagggac
ttactgaggagctggcacctgccgtctgtatttcacttacgtggcaagcaaaattacacatg
tcggtgtgagactatagttagttgcgacgggtacgtcgttaaaagaatagctatcagtccag
gcctgtatgggaagccttcaggctatgctgctacgatgcaccgcgagggattcttgtgctgc
aaagtgacagacacattgaacggggagagggtctcttttcccgtgtgcacgtatgtgccagc
tacattgtgtgaccaaatgactggcatactggcaacagatgtcagtgcggacgacgcgcaaa
aactgctggttgggctcaaccagcgtatagtcgtcaacggtcgcacccagagaaacaccaat
accatgaaaaattaccttttgcccgtagtggcccaggcatttgctaggtgggcaaaggaata
taaggaagatcaagaagatgaaaggccactaggactacgagatagacagttagtcatggggt
gttgttgggcttttagaaggcacaagataacatctatttataagcgcccggatacccaaacc
atcatcaaagtgaacagcgatttccactcattcgtgctgcccaggataggcagtaacacatt
ggagatcgggctgagaacaagaatcaggaaaatgttagaggagcacaaggagccgtcacctc
tcattaccgccgaggacgtacaagaagctaagtgcgcagccgatgaggctaaggaggtgcgt
gaagccgaggagttgcgcgcagctctaccacctttggcagctgatgttgaggagcccactct
ggaagccgatgtagacttgatgttacaagaggctggggccggctcagtggagacacctcgtg
gcttgataaaggttaccagctacgctggcgaggacaagatcggctcttacgctgtgctttct
ccgcaggctgtactcaagagtgaaaaattatcttgcatccaccctctcgctgaacaagtcat
agtgataacacactctggccgaaaagggcgttatgccgtggaaccataccatggtaaagtag
tggtgccagagggacatgcaatacccgtccaggactttcaagctctgagtgaaagtgccacc
attgtgtacaacgaacgtgagttcgtaaacaggtacctgcaccatattgccacacatggagg
agcgctgaacactgatgaagaatattacaaaactgtcaagcccagcgagcacgacggcgaat
acctgtacgacatcgacaggaaacagtgcgtcaagaaagaactagtcactgggctagggctc
acaggcgagctggtggatcctcccttccatgaattcgcctacgagagtctgagaacacgacc
agccgctccttaccaagtaccaaccataggggtgtatggcgtgccaggatcaggcaagtctg
gcatcattaaaagcgcagtcaccaaaaaagatctagtggtgagcgccaagaaagaaaactgt
gcagaaattataagggacgtcaagaaaatgaaagggctggacgtcaatgccagaactgtgga
ctcagtgctcttgaatggatgcaaacaccccgtagagaccctgtatattgacgaagcttttg
cttgtcatgcaggtactctcagagcgctcatagccattataagacctaaaaaggcagtgctc
tgcggggatcccaaacagtgcggtttttttaacatgatgtgcctgaaagtgcattttaacca
cgagatttgcacacaagtcttccacaaaagcatctctcgccgttgcactaaatctgtgactt
cggtcgtctcaaccttgttttacgacaaaaaaatgagaacgacgaatccgaaagagactaag
attgtgattgacactaccggcagtaccaaacctaagcaggacgatctcattctcacttgttt
cagagggtgggtgaagcagttgcaaatagattacaaaggcaacgaaataatgacggcagctg
cctctcaagggctgacccgtaaaggtgtgtatgccgttcggtacaaggtgaatgaaaatcct
ctgtacgcacccacctcagaacatgtgaacgtcctactgacccgcacggaggaccgcatcgt
gtggaaaacactagccggcgacccatggataaaaacactgactgccaagtaccctgggaatt
tcactgccacgatagaggagtggcaagcagagcatgatgccatcatgaggcacatcttggag
agaccggaccctaccgacgtcttccagaataaggcaaacgtgtgttgggccaaggctttagt
gccggtgctgaagaccgctggcatagacatgaccactgaacaatggaacactgtggattatt
ttgaaacggacaaagctcactcagcagagatagtattgaaccaactatgcgtgaggttcttt
ggactcgatctggactccggtctattttctgcacccactgttccgttatccattaggaataa
tcactgggataactccccgtcgcctaacatgtacgggctgaataaagaagtggtccgtcagc
tctctcgcaggtacccacaactgcctcgggcagttgccactggaagagtctatgacatgaac
actggtacactgcgcaattatgatccgcgcataaacctagtacctgtaaacagaagactgcc
tcatgctttagtcctccaccataatgaacacccacagagtgacttttcttcattcgtcagca
aattgaagggcagaactgtcctggtggtcggggaaaagttgtccgtcccaggcaaaatggtt
gactggttgtcagaccggcctgaggctaccttcagagctcggctggatttaggcatcccagg
tgatgtgcccaaatatgacataatatttgttaatgtgaggaccccatataaataccatcact
atcagcagtgtgaagaccatgccattaagcttagcatgttgaccaagaaagcttgtctgcat
ctgaatcccggcggaacctgtgtcagcataggttatggttacgctgacagggccagcgaaag
catcattggtgctatagcgcggcagttcaagttttcccgggtatgcaaaccgaaatcctcac
ttgaagagacggaagttctgtttgtattcattgggtacgatcgcaaggcccgtacgcacaat
ccttacaagctttcatcaaccttgaccaacatttatacaggttccagactccacgaagccgg
atgtgcaccctcatatcatgtggtgcgaggggatattgccacggccaccgaaggagtgatta
taaatgctgctaacagcaaaggacaacctggcggaggggtgtgcggagcgctgtataagaaa
ttcccggaaagcttcgatttacagccgatcgaagtaggaaaagcgcgactggtcaaaggtgc
agctaaacatatcattcatgccgtaggaccaaacttcaacaaagtttcggaggttgaaggtg
acaaacagttggcagaggcttatgagtccatcgctaagattgtcaacgataacaattacaag
tcagtagcgattccactgttgtccaccggcatcttttccgggaacaaagatcgactaaccca
atcattgaaccatttgctgacagctttagacaccactgatgcagatgtagccatatactgca
gggacaagaaatgggaaatgactctcaaggaagcagtggctaggagagaagcagtggaggag
atatgcatatccgacgactcttcagtgacagaacctgatgcagagctggtgagggtgcatcc
gaagagttctttggctggaaggaagggctacagcacaagcgatggcaaaactttctcatatt
tggaagggaccaagtttcaccaggcggccaaggatatagcagaaattaatgccatgtggccc
gttgcaacggaggccaatgagcaggtatgcatgtatatcctcggagaaagcatgagcagtat
taggtcgaaatgccccgtcgaagagtcggaagcctcctcaccacctagcacgctgccttgct
tgtgcatccatgccatgactccagaaagagtacagcgcctaaaagcctcacgtccagaacaa
attactgtgtgctcatcctttccattgccgaagtatagaatcactggtgtgcagaagatcca
atgctcccagcctatattgttctcaccgaaagtgcctgcgtatattcatccaaggaagtatc
tcgtggaaacaccaccggtagacgagactccggagccatcggcagagaaccaatccacagag
gggacacctgaacaaccaccacttataaccgaggatgagaccaggactagaacgcctgagcc
gatcatcatcgaagaggaagaagaggatagcataagtttgctgtcagatggcccgacccacc
aggtgctgcaagtcgaggcagacattcacgggccgccctctgtatctagctcatcctggtcc
attcctcatgcatccgactttgatgtggacagtttatccatacttgacaccctggagggagc
tagcgtgaccagcggggcaacgtcagccgagactaactcttacttcgcaaagagtatggagt
ttctggcgcgaccggtgcctgcgcctcgaacagtattcaggaaccctccacatcccgctccg
cgcacaagaacaccgtcacttgcacccagcagggcctgctcgagagggatcacgggagaaac
cgtgggatacgcggttacacacaatagcgagggcttcttgctatgcaaagttactgacacag
taaaaggagaacgggtatcgttccctgtgtgcacgtacatcccggccaccataaactcgaga
accagcctggtctccaacccgccaggcgtaaatagggtgattacaagagaggagtttgaggc
gttcgtagcacaacaacaatgacggtttgatgcgggtgcatacatcttttcctccgacaccg
gtcaagggcatttacaacaaaaatcagtaaggcaaacggtgctatccgaagtggtgttggag
aggaccgaattggagatttcgtatgccccgcgcctcgaccaagaaaaagaagaattactacg
caagaaattacagttaaatcccacacctgctaacagaagcagataccagtccaggaaggtgg
agaacatgaaagccataacagctagacgtattctgcaaggcctagggcattatttgaaggca
gaaggaaaagtggagtgctaccgaaccctgcatcctgttcctttgtattcatctagtgtgaa
ccgtgccttttcaagccccaaggtcgcagtggaagcctgtaacgccatgttgaaagagaact
ttccgactgtggcttcttactgtattattccagagtacgatgcctatttggacatggttgac
ggagcttcatgctgcttagacactgccagtttttgccctgcaaagctgcgcagctttccaaa
gaaacactcctatttggaacccacaatacgatcggcagtgccttcagcgatccagaacacgc
tccagaacgtcctggcagctgccacaaaaagaaattgcaatgtcacgcaaatgagagaattg
cccgtattggattcggcggcctttaatgtggaatgcttcaagaaatatgcgtgtaataatga
atattgggaaacgtttaaagaaaaccccatcaggcttactgaagaaaacgtggtaaattaca
ttaccaaattaaaaggaccaaaagctgctgctctttttgcgaagacacataatttgaatatg
ttgcaggacataccaatggacaggtttgtaatggacttaaagagagacgtgaaagtgactcc
aggaacaaaacatactgaagaacggcccaaggtacaggtgatccaggctgccgatccgctag
caacagcgtatctgtgcggaatccaccgagagctggttaggagattaaatgcggtcctgctt
ccgaacattcatacactgtttgatatgtcggctgaagactttgacgctattatagccgagca
cttccagcctggggattgtgttctggaaactgacatcgcgtcgtttgataaaagtgaggacg
acgccatggctctgaccgcgttaatgattctggaagacttaggtgtggacgcagagctgttg
acgctgattgaggcggctttcggcgaaatttcatcaatacatttgcccactaaaactaaatt
taaattcggagccatgatgaaatctggaatgttcctcacactgtttgtgaacacagtcatta
acattgtaatcgcaagcagagtgttgagagaacggctaaccggatcaccatgtgcagcattc
attggagatgacaatatcgtgaaaggagtcaaatcggacaaattaatggcagacaggtgcgc
cacctggttgaatatggaagtcaagattatagatgctgtggtgggcgagaaagcgccttatt
tctgtggagggtttattttgtgtgactccgtgaccggcacagcgtgccgtgtggcagacccc
ctaaaaaggctgtttaagcttggcaaacctctggcagcagacgatgaacatgatgatgacag
gagaagggcattgcatgaagagtcaacacgctggaaccgagtgggtattctttcagagctgt
gcaaggcagtagaatcaaggtatgaaaccgtaggaacttccatcatagttatggccatgact
actctagctagcagtgttaaatcattcagctacctgagaggggcccctataactctctacgg
ctaacctgaatggactacgacatagtctagtcgacgccaccatgaggcctggcctgccctcc
tacctgatcatcctggccgtgtgcctgttcagccacctgctgtccagcagatacggcgccga
ggccgtgagcgagcccctggacaaggctttccacctgctgctgaacacctacggcagaccca
tccggtttctgcgggagaacaccacccagtgcacctacaacagcagcctgcggaacagcacc
gtcgtgagagagaacgccatcagcttcaactttttccagagctacaaccagtactacgtgtt
ccacatgcccagatgcctgtttgccggccctctggccgagcagttcctgaaccaggtggacc
tgaccgagacactggaaagataccagcagcggctgaatacctacgccctggtgtccaaggac
ctggccagctaccggtcctttagccagcagctcaaggctcaggatagcctcggcgagcagcc
taccaccgtgccccctcccatcgacctgagcatcccccacgtgtggatgcctccccagacca
cccctcacggctggaccgagagccacaccacctccggcctgcacagaccccacttcaaccag
acctgcatcctgttcgacggccacgacctgctgtttagcaccgtgaccccctgcctgcacca
gggcttctacctgatcgacgagctgagatacgtgaagatcaccctgaccgaggatttcttcg
tggtcaccgtgtccatcgacgacgacacccccatgctgctgatcttcggccacctgcccaga
gtgctgttcaaggccccctaccagcgggacaacttcatcctgcggcagaccgagaagcacga
gctgctggtgctggtcaagaaggaccagctgaaccggcactcctacctgaaggaccccgact
tcctggacgccgccctggacttcaactacctggacctgagcgccctgctgagaaacagcttc
cacagatacgccgtggacgtgctgaagtccggacggtgccagatgctcgatcggcggaccgt
ggagatggccttcgcctatgccctcgccctgttcgccgctgccagacaggaagaggctggcg
cccaggtgtcagtgcccagagccctggatagacaggccgccctgctgcagatccaggaattc
atgatcacctgcctgagccagaccccccctagaaccaccctgctgctgtaccccacagccgt
ggatctggccaagagggccctgtggacccccaaccagatcaccgacatcacaagcctcgtgc
ggctcgtgtacatcctgagcaagcagaaccagcagcacctgatcccccagtgggccctgaga
cagatcgccgacttcgccctgaagctgcacaagacccatctggccagctttctgagcgcctt
cgccaggcaggaactgtacctgatgggcagcctggtccacagcatgctggtgcataccaccg
agcggcgggagatcttcatcgtggagacaggcctgtgtagcctggccgagctgtcccacttt
acccagctgctggcccaccctcaccacgagtacctgagcgacctgtacaccccctgcagcag
cagcggcagacgggaccacagcctggaacggctgaccagactgttccccgatgccaccgtgc
ctgctacagtgcctgccgccctgtccatcctgtccaccatgcagcccagcaccctggaaacc
ttccccgacctgttctgcctgcccctgggcgagagctttagcgccctgaccgtgtccgagca
cgtgtcctacatcgtgaccaatcagtacctgatcaagggcatcagctaccccgtgtccacca
cagtcgtgggccagagcctgatcatcacccagaccgacagccagaccaagtgcgagctgacc
cggaacatgcacaccacacacagcatcaccgtggccctgaacatcagcctggaaaactgcgc
tttctgtcagtctgccctgctggaatacgacgatacccagggcgtgatcaacatcatgtaca
tgcacgacagcgacgacgtgctgttcgccctggacccctacaacgaggtggtggtgtccagc
ccccggacccactacctgatgctgctgaagaacggcaccgtgctggaagtgaccgacgtggt
ggtggacgccaccgactgataatctagacggcgcgcccacccagcggccgcctataactctc
tacggctaacctgaatggactacgacatagtctagtcgacgccaccatgtgcagaaggcccg
actgcggcttcagcttcagccctggacccgtgatcctgctgtggtgctgcctgctgctgcct
atcgtgtcctctgccgccgtgtctgtggcccctacagccgccgagaaggtgccagccgagtg
ccccgagctgaccagaagatgcctgctgggcgaggtgttcgagggcgacaagtacgagagct
ggctgcggcccctggtcaacgtgaccggcagagatggccccctgagccagctgatccggtac
agacccgtgacccccgaggccgccaatagcgtgctgctggacgaggccttcctggataccct
ggccctgctgtacaacaaccccgaccagctgagagccctgctgaccctgctgtccagcgaca
ccgcccccagatggatgaccgtgatgcggggctacagcgagtgtggagatggcagccctgcc
gtgtacacctgcgtggacgacctgtgcagaggctacgacctgaccagactgagctacggccg
gtccatcttcacagagcacgtgctgggcttcgagctggtgccccccagcctgttcaacgtgg
tggtggccatccggaacgaggccaccagaaccaacagagccgtgcggctgcctgtgtctaca
gccgctgcacctgagggcatcacactgttctacggcctgtacaacgccgtgaaagagttctg
cctccggcaccagctggatccccccctgctgagacacctggacaagtactacgccggcctgc
ccccagagctgaagcagaccagagtgaacctgcccgcccacagcagatatggccctcaggcc
gtggacgccagatgataatctagacggcgcgcccacccaatcgatgtacttccgaggaactc
acgtgcataatgcatcaggctggtacattagatccccgcttaccgcgggcaatatagcaaca
ctaaaaactcgatgtacttccgaggaagcgcagtgcataatgctgcgcagtgttgccacata
accactatattaaccatttatctagcggacgccaaaaactcaatgtatttctgaggaagcgt
ggtgcataatgccacgcagcgtctgcataacttttattatttcttttattaatcaacaaaat
tttgtttttaacatttcaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaagggtc
ggcatggcatctccacctcctcgcggtccgacctgggcatccgaaggaggacgcacgtccac
tcggatggctaagggagagccacgagctcctgtttaaaccagctccaattcgccctatagtg
agtcgtattacgcgcgctcactggccgtcgttttacaacgtcgtgactgggaaaaccctggc
gttacccaacttaatcgccttgcagcacatccccctttcgccagctggcgtaatagcgaaga
ggcccgcaccgatcgcccttcccaacagttgcgcagcctgaatggcgaatgggacgcgccct
gtagcggcgcattaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacacttgcc
agcgccctagcgcccgctcctttcgctttcttcccttcctttctcgccacgttcgccggctt
tccccgtcaagctctaaatcgggggctccctttagggttccgatttagtgctttacggcacc
tcgaccccaaaaaacttgattagggtgatggttcacgtagtgggccatcgccctgatagacg
gtttttcgccctttgacgttggagtccacgttctttaatagtggactcttgttccaaactgg
aacaacactcaaccctatctcggtctattcttttgatttataagggattttgccgatttcgg
cctattggttaaaaaatgagctgatttaacaaaaatttaacgcgaattttaacaaaatatta
acgcttacaatttaggtggcacttttcggggaaatgtgcgcggaacccctatttgtttattt
ttctaaatacattcaaatatgtatccgctcatgagacaataaccctgataaatgcttcaata
atattgaaaaaggaagagtatgagtattcaacatttccgtgtcgcccttattcccttttttg
cggcattttgccttcctgtttttgctcacccagaaacgctggtgaaagtaaaagatgctgaa
gatcagttgggtgcacgagtgggttacatcgaactggatctcaacagcggtaagatccttga
gagttttcgccccgaagaacgttttccaatgatgagcacttttaaagttctgctatgtggcg
cggtattatcccgtattgacgccgggcaagagcaactcggtcgccgcatacactattctcag
aatgacttggttgagtactcaccagtcacagaaaagcatcttacggatggcatgacagtaag
agaattatgcagtgctgccataaccatgagtgataacactgcggccaacttacttctgacaa
cgatcggaggaccgaaggagctaaccgcttttttgcacaacatgggggatcatgtaactcgc
cttgatcgttgggaaccggagctgaatgaagccataccaaacgacgagcgtgacaccacgat
gcctgtagcaatggcaacaacgttgcgcaaactattaactggcgaactacttactctagctt
cccggcaacaattaatagactggatggaggcggataaagttgcaggaccacttctgcgctcg
gcccttccggctggctggtttattgctgataaatctggagccggtgagcgtgggtctcgcgg
tatcattgcagcactggggccagatggtaagccctcccgtatcgtagttatctacacgacgg
ggagtcaggcaactatggatgaacgaaatagacagatcgctgagataggtgcctcactgatt
aagcattggtaactgtcagaccaagtttactcatatatactttagattgatttaaaacttca
tttttaatttaaaaggatctaggtgaagatcctttttgataatctcatgaccaaaatccctt
aacgtgagttttcgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttga
gatcctttttttctgcgcgtaatctgctgcttgcaaacaaaaaaaccaccgctaccagcggt
ggtttgtttgccggatcaagagctaccaactctttttccgaaggtaactggcttcagcagag
cgcagataccaaatactgttcttctagtgtagccgtagttaggccaccacttcaagaactct
gtagcaccgcctacatacctcgctctgctaatcctgttaccagtggctgctgccagtggcga
taagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcagcggtcgg
gctgaacggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactgaga
tacctacagcgtgagctatgagaaagcgccacgcttcccgaagggagaaaggcggacaggta
tccggtaagcggcagggtcggaacaggagagcgcacgagggagcttccagggggaaacgcct
ggtatctttatagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgc
tcgtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggc
cttttgctggccttttgctcacatgttctttcctgcgttatcccctgattctgtggataacc
gtattaccgcctttgagtgagctgataccgctcgccgcagccgaacgaccgagcgcagcgag
tcagtgagcgaggaagcggaagagcgcccaatacgcaaaccgcctctccccgcgcgttggcc
gattcattaatgcagctggcacgacaggtttcccgactggaaagcgggcagtgagcgcaacg
caattaatgtgagttagctcactcattaggcaccccaggctttacactttatgctcccggct
cgtatgttgtgtggaattgtgagcggataacaatttcacacaggaaacagctatgaccatga
ttacgccaagcgcgcaattaaccctcactaaagggaacaaaagctgggtaccggcgcca
TABLE-US-00038 pVCR modified vector gH FL-SGP gL
cgcgtcggctacaattaatacataaccttatgtatcatacacatacgatttaggtgacacta
tagatgggcggcgcatgagagaagcccagaccaattacctacccaaaatggagaaagttcac
gttgacatcgaggaagacagcccattcctcagagctttgcagcggagcttcccgcagtttga
ggtagaagccaagcaggtcactgataatgaccatgctaatgccagagcgttttcgcatctgg
cttcaaaactgatcgaaacggaggtggacccatccgacacgatccttgacattggaagtgcg
cccgcccgcagaatgtattctaagcacaagtatcattgtatctgtccgatgagatgtgcgga
agatccggacagattgtataagtatgcaactaagctgaagaaaaactgtaaggaaataactg
ataaggaattggacaagaaaatgaaggagctcgccgccgtcatgagcgaccctgacctggaa
actgagactatgtgcctccacgacgacgagtcgtgtcgctacgaagggcaagtcgctgttta
ccaggatgtatacgcggttgacggaccgacaagtctctatcaccaagccaataagggagtta
gagtcgcctactggataggctttgacaccaccccttttatgtttaagaacttggctggagca
tatccatcatactctaccaactgggccgacgaaaccgtgttaacggctcgtaacataggcct
atgcagctctgacgttatggagcggtcacgtagagggatgtccattcttagaaagaagtatt
tgaaaccatccaacaatgttctattctctgttggctcgaccatctaccacgagaagagggac
ttactgaggagctggcacctgccgtctgtatttcacttacgtggcaagcaaaattacacatg
tcggtgtgagactatagttagttgcgacgggtacgtcgttaaaagaatagctatcagtccag
gcctgtatgggaagccttcaggctatgctgctacgatgcaccgcgagggattcttgtgctgc
aaagtgacagacacattgaacggggagagggtctcttttcccgtgtgcacgtatgtgccagc
tacattgtgtgaccaaatgactggcatactggcaacagatgtcagtgcggacgacgcgcaaa
aactgctggttgggctcaaccagcgtatagtcgtcaacggtcgcacccagagaaacaccaat
accatgaaaaattaccttttgcccgtagtggcccaggcatttgctaggtgggcaaaggaata
taaggaagatcaagaagatgaaaggccactaggactacgagatagacagttagtcatggggt
gttgttgggcttttagaaggcacaagataacatctatttataagcgcccggatacccaaacc
atcatcaaagtgaacagcgatttccactcattcgtgctgcccaggataggcagtaacacatt
ggagatcgggctgagaacaagaatcaggaaaatgttagaggagcacaaggagccgtcacctc
tcattaccgccgaggacgtacaagaagctaagtgcgcagccgatgaggctaaggaggtgcgt
gaagccgaggagttgcgcgcagctctaccacctttggcagctgatgttgaggagcccactct
ggaagccgatgtagacttgatgttacaagaggctggggccggctcagtggagacacctcgtg
gcttgataaaggttaccagctacgctggcgaggacaagatcggctcttacgctgtgctttct
ccgcaggctgtactcaagagtgaaaaattatcttgcatccaccctctcgctgaacaagtcat
agtgataacacactctggccgaaaagggcgttatgccgtggaaccataccatggtaaagtag
tggtgccagagggacatgcaatacccgtccaggactttcaagctctgagtgaaagtgccacc
attgtgtacaacgaacgtgagttcgtaaacaggtacctgcaccatattgccacacatggagg
agcgctgaacactgatgaagaatattacaaaactgtcaagcccagcgagcacgacggcgaat
acctgtacgacatcgacaggaaacagtgcgtcaagaaagaactagtcactgggctagggctc
acaggcgagctggtggatcctcccttccatgaattcgcctacgagagtctgagaacacgacc
agccgctccttaccaagtaccaaccataggggtgtatggcgtgccaggatcaggcaagtctg
gcatcattaaaagcgcagtcaccaaaaaagatctagtggtgagcgccaagaaagaaaactgt
gcagaaattataagggacgtcaagaaaatgaaagggctggacgtcaatgccagaactgtgga
ctcagtgctcttgaatggatgcaaacaccccgtagagaccctgtatattgacgaagcttttg
cttgtcatgcaggtactctcagagcgctcatagccattataagacctaaaaaggcagtgctc
tgcggggatcccaaacagtgcggtttttttaacatgatgtgcctgaaagtgcattttaacca
cgagatttgcacacaagtcttccacaaaagcatctctcgccgttgcactaaatctgtgactt
cggtcgtctcaaccttgttttacgacaaaaaaatgagaacgacgaatccgaaagagactaag
attgtgattgacactaccggcagtaccaaacctaagcaggacgatctcattctcacttgttt
cagagggtgggtgaagcagttgcaaatagattacaaaggcaacgaaataatgacggcagctg
cctctcaagggctgacccgtaaaggtgtgtatgccgttcggtacaaggtgaatgaaaatcct
ctgtacgcacccacctcagaacatgtgaacgtcctactgacccgcacggaggaccgcatcgt
gtggaaaacactagccggcgacccatggataaaaacactgactgccaagtaccctgggaatt
tcactgccacgatagaggagtggcaagcagagcatgatgccatcatgaggcacatcttggag
agaccggaccctaccgacgtcttccagaataaggcaaacgtgtgttgggccaaggctttagt
gccggtgctgaagaccgctggcatagacatgaccactgaacaatggaacactgtggattatt
ttgaaacggacaaagctcactcagcagagatagtattgaaccaactatgcgtgaggttcttt
ggactcgatctggactccggtctattttctgcacccactgttccgttatccattaggaataa
tcactgggataactccccgtcgcctaacatgtacgggctgaataaagaagtggtccgtcagc
tctctcgcaggtacccacaactgcctcgggcagttgccactggaagagtctatgacatgaac
actggtacactgcgcaattatgatccgcgcataaacctagtacctgtaaacagaagactgcc
tcatgctttagtcctccaccataatgaacacccacagagtgacttttcttcattcgtcagca
aattgaagggcagaactgtcctggtggtcggggaaaagttgtccgtcccaggcaaaatggtt
gactggttgtcagaccggcctgaggctaccttcagagctcggctggatttaggcatcccagg
tgatgtgcccaaatatgacataatatttgttaatgtgaggaccccatataaataccatcact
atcagcagtgtgaagaccatgccattaagcttagcatgttgaccaagaaagcttgtctgcat
ctgaatcccggcggaacctgtgtcagcataggttatggttacgctgacagggccagcgaaag
catcattggtgctatagcgcggcagttcaagttttcccgggtatgcaaaccgaaatcctcac
ttgaagagacggaagttctgtttgtattcattgggtacgatcgcaaggcccgtacgcacaat
ccttacaagctttcatcaaccttgaccaacatttatacaggttccagactccacgaagccgg
atgtgcaccctcatatcatgtggtgcgaggggatattgccacggccaccgaaggagtgatta
taaatgctgctaacagcaaaggacaacctggcggaggggtgtgcggagcgctgtataagaaa
ttcccggaaagcttcgatttacagccgatcgaagtaggaaaagcgcgactggtcaaaggtgc
agctaaacatatcattcatgccgtaggaccaaacttcaacaaagtttcggaggttgaaggtg
acaaacagttggcagaggcttatgagtccatcgctaagattgtcaacgataacaattacaag
tcagtagcgattccactgttgtccaccggcatcttttccgggaacaaagatcgactaaccca
atcattgaaccatttgctgacagctttagacaccactgatgcagatgtagccatatactgca
gggacaagaaatgggaaatgactctcaaggaagcagtggctaggagagaagcagtggaggag
atatgcatatccgacgactcttcagtgacagaacctgatgcagagctggtgagggtgcatcc
gaagagttctttggctggaaggaagggctacagcacaagcgatggcaaaactttctcatatt
tggaagggaccaagtttcaccaggcggccaaggatatagcagaaattaatgccatgtggccc
gttgcaacggaggccaatgagcaggtatgcatgtatatcctcggagaaagcatgagcagtat
taggtcgaaatgccccgtcgaagagtcggaagcctcctcaccacctagcacgctgccttgct
tgtgcatccatgccatgactccagaaagagtacagcgcctaaaagcctcacgtccagaacaa
attactgtgtgctcatcctttccattgccgaagtatagaatcactggtgtgcagaagatcca
atgctcccagcctatattgttctcaccgaaagtgcctgcgtatattcatccaaggaagtatc
tcgtggaaacaccaccggtagacgagactccggagccatcggcagagaaccaatccacagag
gggacacctgaacaaccaccacttataaccgaggatgagaccaggactagaacgcctgagcc
gatcatcatcgaagaggaagaagaggatagcataagtttgctgtcagatggcccgacccacc
aggtgctgcaagtcgaggcagacattcacgggccgccctctgtatctagctcatcctggtcc
attcctcatgcatccgactttgatgtggacagtttatccatacttgacaccctggagggagc
tagcgtgaccagcggggcaacgtcagccgagactaactcttacttcgcaaagagtatggagt
ttctggcgcgaccggtgcctgcgcctcgaacagtattcaggaaccctccacatcccgctccg
cgcacaagaacaccgtcacttgcacccagcagggcctgctcgagagggatcacgggagaaac
cgtgggatacgcggttacacacaatagcgagggcttcttgctatgcaaagttactgacacag
taaaaggagaacgggtatcgttccctgtgtgcacgtacatcccggccaccataaactcgaga
accagcctggtctccaacccgccaggcgtaaatagggtgattacaagagaggagtttgaggc
gttcgtagcacaacaacaatgacggtttgatgcgggtgcatacatcttttcctccgacaccg
gtcaagggcatttacaacaaaaatcagtaaggcaaacggtgctatccgaagtggtgttggag
aggaccgaattggagatttcgtatgccccgcgcctcgaccaagaaaaagaagaattactacg
caagaaattacagttaaatcccacacctgctaacagaagcagataccagtccaggaaggtgg
agaacatgaaagccataacagctagacgtattctgcaaggcctagggcattatttgaaggca
gaaggaaaagtggagtgctaccgaaccctgcatcctgttcctttgtattcatctagtgtgaa
ccgtgccttttcaagccccaaggtcgcagtggaagcctgtaacgccatgttgaaagagaact
ttccgactgtggcttcttactgtattattccagagtacgatgcctatttggacatggttgac
ggagcttcatgctgcttagacactgccagtttttgccctgcaaagctgcgcagctttccaaa
gaaacactcctatttggaacccacaatacgatcggcagtgccttcagcgatccagaacacgc
tccagaacgtcctggcagctgccacaaaaagaaattgcaatgtcacgcaaatgagagaattg
cccgtattggattcggcggcctttaatgtggaatgcttcaagaaatatgcgtgtaataatga
atattgggaaacgtttaaagaaaaccccatcaggcttactgaagaaaacgtggtaaattaca
ttaccaaattaaaaggaccaaaagctgctgctctttttgcgaagacacataatttgaatatg
ttgcaggacataccaatggacaggtttgtaatggacttaaagagagacgtgaaagtgactcc
aggaacaaaacatactgaagaacggcccaaggtacaggtgatccaggctgccgatccgctag
caacagcgtatctgtgcggaatccaccgagagctggttaggagattaaatgcggtcctgctt
ccgaacattcatacactgtttgatatgtcggctgaagactttgacgctattatagccgagca
cttccagcctggggattgtgttctggaaactgacatcgcgtcgtttgataaaagtgaggacg
acgccatggctctgaccgcgttaatgattctggaagacttaggtgtggacgcagagctgttg
acgctgattgaggcggctttcggcgaaatttcatcaatacatttgcccactaaaactaaatt
taaattcggagccatgatgaaatctggaatgttcctcacactgtttgtgaacacagtcatta
acattgtaatcgcaagcagagtgttgagagaacggctaaccggatcaccatgtgcagcattc
attggagatgacaatatcgtgaaaggagtcaaatcggacaaattaatggcagacaggtgcgc
cacctggttgaatatggaagtcaagattatagatgctgtggtgggcgagaaagcgccttatt
tctgtggagggtttattttgtgtgactccgtgaccggcacagcgtgccgtgtggcagacccc
ctaaaaaggctgtttaagcttggcaaacctctggcagcagacgatgaacatgatgatgacag
gagaagggcattgcatgaagagtcaacacgctggaaccgagtgggtattctttcagagctgt
gcaaggcagtagaatcaaggtatgaaaccgtaggaacttccatcatagttatggccatgact
actctagctagcagtgttaaatcattcagctacctgagaggggcccctataactctctacgg
ctaacctgaatggactacgacatagtctagtcgacgccaccatgaggcctggcctgccctcc
tacctgatcatcctggccgtgtgcctgttcagccacctgctgtccagcagatacggcgccga
ggccgtgagcgagcccctggacaaggctttccacctgctgctgaacacctacggcagaccca
tccggtttctgcgggagaacaccacccagtgcacctacaacagcagcctgcggaacagcacc
gtcgtgagagagaacgccatcagcttcaactttttccagagctacaaccagtactacgtgtt
ccacatgcccagatgcctgtttgccggccctctggccgagcagttcctgaaccaggtggacc
tgaccgagacactggaaagataccagcagcggctgaatacctacgccctggtgtccaaggac
ctggccagctaccggtcctttagccagcagctcaaggctcaggatagcctcggcgagcagcc
taccaccgtgccccctcccatcgacctgagcatcccccacgtgtggatgcctccccagacca
cccctcacggctggaccgagagccacaccacctccggcctgcacagaccccacttcaaccag
acctgcatcctgttcgacggccacgacctgctgtttagcaccgtgaccccctgcctgcacca
gggcttctacctgatcgacgagctgagatacgtgaagatcaccctgaccgaggatttcttcg
tggtcaccgtgtccatcgacgacgacacccccatgctgctgatcttcggccacctgcccaga
gtgctgttcaaggccccctaccagcgggacaacttcatcctgcggcagaccgagaagcacga
gctgctggtgctggtcaagaaggaccagctgaaccggcactcctacctgaaggaccccgact
tcctggacgccgccctggacttcaactacctggacctgagcgccctgctgagaaacagcttc
cacagatacgccgtggacgtgctgaagtccggacggtgccagatgctcgatcggcggaccgt
ggagatggccttcgcctatgccctcgccctgttcgccgctgccagacaggaagaggctggcg
cccaggtgtcagtgcccagagccctggatagacaggccgccctgctgcagatccaggaattc
atgatcacctgcctgagccagaccccccctagaaccaccctgctgctgtaccccacagccgt
ggatctggccaagagggccctgtggacccccaaccagatcaccgacatcacaagcctcgtgc
ggctcgtgtacatcctgagcaagcagaaccagcagcacctgatcccccagtgggccctgaga
cagatcgccgacttcgccctgaagctgcacaagacccatctggccagctttctgagcgcctt
cgccaggcaggaactgtacctgatgggcagcctggtccacagcatgctggtgcataccaccg
agcggcgggagatcttcatcgtggagacaggcctgtgtagcctggccgagctgtcccacttt
acccagctgctggcccaccctcaccacgagtacctgagcgacctgtacaccccctgcagcag
cagcggcagacgggaccacagcctggaacggctgaccagactgttccccgatgccaccgtgc
ctgctacagtgcctgccgccctgtccatcctgtccaccatgcagcccagcaccctggaaacc
ttccccgacctgttctgcctgcccctgggcgagagctttagcgccctgaccgtgtccgagca
cgtgtcctacatcgtgaccaatcagtacctgatcaagggcatcagctaccccgtgtccacca
cagtcgtgggccagagcctgatcatcacccagaccgacagccagaccaagtgcgagctgacc
cggaacatgcacaccacacacagcatcaccgtggccctgaacatcagcctggaaaactgcgc
tttctgtcagtctgccctgctggaatacgacgatacccagggcgtgatcaacatcatgtaca
tgcacgacagcgacgacgtgctgttcgccctggacccctacaacgaggtggtggtgtccagc
ccccggacccactacctgatgctgctgaagaacggcaccgtgctggaagtgaccgacgtggt
ggtggacgccaccgacagcagactgctgatgatgagcgtgtacgccctgagcgccatcatcg
gcatctacctgctgtaccggatgctgaaaacctgctgataatctagacggcgcgcccaccca
gcggccgcctataactctctacggctaacctgaatggactacgacatagtctagtcgacgcc
accatgtgcagaaggcccgactgcggcttcagcttcagccctggacccgtgatcctgctgtg
gtgctgcctgctgctgcctatcgtgtcctctgccgccgtgtctgtggcccctacagccgccg
agaaggtgccagccgagtgccccgagctgaccagaagatgcctgctgggcgaggtgttcgag
ggcgacaagtacgagagctggctgcggcccctggtcaacgtgaccggcagagatggccccct
gagccagctgatccggtacagacccgtgacccccgaggccgccaatagcgtgctgctggacg
aggccttcctggataccctggccctgctgtacaacaaccccgaccagctgagagccctgctg
accctgctgtccagcgacaccgcccccagatggatgaccgtgatgcggggctacagcgagtg
tggagatggcagccctgccgtgtacacctgcgtggacgacctgtgcagaggctacgacctga
ccagactgagctacggccggtccatcttcacagagcacgtgctgggcttcgagctggtgccc
cccagcctgttcaacgtggtggtggccatccggaacgaggccaccagaaccaacagagccgt
gcggctgcctgtgtctacagccgctgcacctgagggcatcacactgttctacggcctgtaca
acgccgtgaaagagttctgcctccggcaccagctggatccccccctgctgagacacctggac
aagtactacgccggcctgcccccagagctgaagcagaccagagtgaacctgcccgcccacag
cagatatggccctcaggccgtggacgccagatgataatctagacggcgcgcccacccaatcg
atgtacttccgaggaactcacgtgcataatgcatcaggctggtacattagatccccgcttac
cgcgggcaatatagcaacactaaaaactcgatgtacttccgaggaagcgcagtgcataatgc
tgcgcagtgttgccacataaccactatattaaccatttatctagcggacgccaaaaactcaa
tgtatttctgaggaagcgtggtgcataatgccacgcagcgtctgcataacttttattatttc
ttttattaatcaacaaaattttgtttttaacatttcaaaaaaaaaaaaaaaaaaaaaaaaaa
aaaaaaaaaaaaaagggtcggcatggcatctccacctcctcgcggtccgacctgggcatccg
aaggaggacgcacgtccactcggatggctaagggagagccacgagctcctgtttaaaccagc
tccaattcgccctatagtgagtcgtattacgcgcgctcactggccgtcgttttacaacgtcg
tgactgggaaaaccctggcgttacccaacttaatcgccttgcagcacatccccctttcgcca
gctggcgtaatagcgaagaggcccgcaccgatcgcccttcccaacagttgcgcagcctgaat
ggcgaatgggacgcgccctgtagcggcgcattaagcgcggcgggtgtggtggttacgcgcag
cgtgaccgctacacttgccagcgccctagcgcccgctcctttcgctttcttcccttcctttc
tcgccacgttcgccggctttccccgtcaagctctaaatcgggggctccctttagggttccga
tttagtgctttacggcacctcgaccccaaaaaacttgattagggtgatggttcacgtagtgg
gccatcgccctgatagacggtttttcgccctttgacgttggagtccacgttctttaatagtg
gactcttgttccaaactggaacaacactcaaccctatctcggtctattcttttgatttataa
gggattttgccgatttcggcctattggttaaaaaatgagctgatttaacaaaaatttaacgc
gaattttaacaaaatattaacgcttacaatttaggtggcacttttcggggaaatgtgcgcgg
aacccctatttgtttatttttctaaatacattcaaatatgtatccgctcatgagacaataac
cctgataaatgcttcaataatattgaaaaaggaagagtatgagtattcaacatttccgtgtc
gcccttattcccttttttgcggcattttgccttcctgtttttgctcacccagaaacgctggt
gaaagtaaaagatgctgaagatcagttgggtgcacgagtgggttacatcgaactggatctca
acagcggtaagatccttgagagttttcgccccgaagaacgttttccaatgatgagcactttt
aaagttctgctatgtggcgcggtattatcccgtattgacgccgggcaagagcaactcggtcg
ccgcatacactattctcagaatgacttggttgagtactcaccagtcacagaaaagcatctta
cggatggcatgacagtaagagaattatgcagtgctgccataaccatgagtgataacactgcg
gccaacttacttctgacaacgatcggaggaccgaaggagctaaccgcttttttgcacaacat
gggggatcatgtaactcgccttgatcgttgggaaccggagctgaatgaagccataccaaacg
acgagcgtgacaccacgatgcctgtagcaatggcaacaacgttgcgcaaactattaactggc
gaactacttactctagcttcccggcaacaattaatagactggatggaggcggataaagttgc
aggaccacttctgcgctcggcccttccggctggctggtttattgctgataaatctggagccg
gtgagcgtgggtctcgcggtatcattgcagcactggggccagatggtaagccctcccgtatc
gtagttatctacacgacggggagtcaggcaactatggatgaacgaaatagacagatcgctga
gataggtgcctcactgattaagcattggtaactgtcagaccaagtttactcatatatacttt
agattgatttaaaacttcatttttaatttaaaaggatctaggtgaagatcctttttgataat
ctcatgaccaaaatcccttaacgtgagttttcgttccactgagcgtcagaccccgtagaaaa
gatcaaaggatcttcttgagatcctttttttctgcgcgtaatctgctgcttgcaaacaaaaa
aaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctttttccgaag
gtaactggcttcagcagagcgcagataccaaatactgttcttctagtgtagccgtagttagg
ccaccacttcaagaactctgtagcaccgcctacatacctcgctctgctaatcctgttaccag
tggctgctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccg
gataaggcgcagcggtcgggctgaacggggggttcgtgcacacagcccagcttggagcgaac
gacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgcttcccgaag
ggagaaaggcggacaggtatccggtaagcggcagggtcggaacaggagagcgcacgagggag
cttccagggggaaacgcctggtatctttatagtcctgtcgggtttcgccacctctgacttga
gcgtcgatttttgtgatgctcgtcaggggggcggagcctatggaaaaacgccagcaacgcgg
cctttttacggttcctggccttttgctggccttttgctcacatgttctttcctgcgttatcc
cctgattctgtggataaccgtattaccgcctttgagtgagctgataccgctcgccgcagccg
aacgaccgagcgcagcgagtcagtgagcgaggaagcggaagagcgcccaatacgcaaaccgc
ctctccccgcgcgttggccgattcattaatgcagctggcacgacaggtttcccgactggaaa
gcgggcagtgagcgcaacgcaattaatgtgagttagctcactcattaggcaccccaggcttt
acactttatgctcccggctcgtatgttgtgtggaattgtgagcggataacaatttcacacag
gaaacagctatgaccatgattacgccaagcgcgcaattaaccctcactaaagggaacaaaag
ctgggtaccggcgcca
TABLE-US-00039 pVCR modified vector gH sol-SGP gL-SGP gO
cgcgtcggctacaattaatacataaccttatgtatcatacacatacgatttaggtgacacta
tagatgggcggcgcatgagagaagcccagaccaattacctacccaaaatggagaaagttcac
gttgacatcgaggaagacagcccattcctcagagctttgcagcggagcttcccgcagtttga
ggtagaagccaagcaggtcactgataatgaccatgctaatgccagagcgttttcgcatctgg
cttcaaaactgatcgaaacggaggtggacccatccgacacgatccttgacattggaagtgcg
cccgcccgcagaatgtattctaagcacaagtatcattgtatctgtccgatgagatgtgcgga
agatccggacagattgtataagtatgcaactaagctgaagaaaaactgtaaggaaataactg
ataaggaattggacaagaaaatgaaggagctcgccgccgtcatgagcgaccctgacctggaa
actgagactatgtgcctccacgacgacgagtcgtgtcgctacgaagggcaagtcgctgttta
ccaggatgtatacgcggttgacggaccgacaagtctctatcaccaagccaataagggagtta
gagtcgcctactggataggctttgacaccaccccttttatgtttaagaacttggctggagca
tatccatcatactctaccaactgggccgacgaaaccgtgttaacggctcgtaacataggcct
atgcagctctgacgttatggagcggtcacgtagagggatgtccattcttagaaagaagtatt
tgaaaccatccaacaatgttctattctctgttggctcgaccatctaccacgagaagagggac
ttactgaggagctggcacctgccgtctgtatttcacttacgtggcaagcaaaattacacatg
tcggtgtgagactatagttagttgcgacgggtacgtcgttaaaagaatagctatcagtccag
gcctgtatgggaagccttcaggctatgctgctacgatgcaccgcgagggattcttgtgctgc
aaagtgacagacacattgaacggggagagggtctcttttcccgtgtgcacgtatgtgccagc
tacattgtgtgaccaaatgactggcatactggcaacagatgtcagtgcggacgacgcgcaaa
aactgctggttgggctcaaccagcgtatagtcgtcaacggtcgcacccagagaaacaccaat
accatgaaaaattaccttttgcccgtagtggcccaggcatttgctaggtgggcaaaggaata
taaggaagatcaagaagatgaaaggccactaggactacgagatagacagttagtcatggggt
gttgttgggcttttagaaggcacaagataacatctatttataagcgcccggatacccaaacc
atcatcaaagtgaacagcgatttccactcattcgtgctgcccaggataggcagtaacacatt
ggagatcgggctgagaacaagaatcaggaaaatgttagaggagcacaaggagccgtcacctc
tcattaccgccgaggacgtacaagaagctaagtgcgcagccgatgaggctaaggaggtgcgt
gaagccgaggagttgcgcgcagctctaccacctttggcagctgatgttgaggagcccactct
ggaagccgatgtagacttgatgttacaagaggctggggccggctcagtggagacacctcgtg
gcttgataaaggttaccagctacgctggcgaggacaagatcggctcttacgctgtgctttct
ccgcaggctgtactcaagagtgaaaaattatcttgcatccaccctctcgctgaacaagtcat
agtgataacacactctggccgaaaagggcgttatgccgtggaaccataccatggtaaagtag
tggtgccagagggacatgcaatacccgtccaggactttcaagctctgagtgaaagtgccacc
attgtgtacaacgaacgtgagttcgtaaacaggtacctgcaccatattgccacacatggagg
agcgctgaacactgatgaagaatattacaaaactgtcaagcccagcgagcacgacggcgaat
acctgtacgacatcgacaggaaacagtgcgtcaagaaagaactagtcactgggctagggctc
acaggcgagctggtggatcctcccttccatgaattcgcctacgagagtctgagaacacgacc
agccgctccttaccaagtaccaaccataggggtgtatggcgtgccaggatcaggcaagtctg
gcatcattaaaagcgcagtcaccaaaaaagatctagtggtgagcgccaagaaagaaaactgt
gcagaaattataagggacgtcaagaaaatgaaagggctggacgtcaatgccagaactgtgga
ctcagtgctcttgaatggatgcaaacaccccgtagagaccctgtatattgacgaagcttttg
cttgtcatgcaggtactctcagagcgctcatagccattataagacctaaaaaggcagtgctc
tgcggggatcccaaacagtgcggtttttttaacatgatgtgcctgaaagtgcattttaacca
cgagatttgcacacaagtcttccacaaaagcatctctcgccgttgcactaaatctgtgactt
cggtcgtctcaaccttgttttacgacaaaaaaatgagaacgacgaatccgaaagagactaag
attgtgattgacactaccggcagtaccaaacctaagcaggacgatctcattctcacttgttt
cagagggtgggtgaagcagttgcaaatagattacaaaggcaacgaaataatgacggcagctg
cctctcaagggctgacccgtaaaggtgtgtatgccgttcggtacaaggtgaatgaaaatcct
ctgtacgcacccacctcagaacatgtgaacgtcctactgacccgcacggaggaccgcatcgt
gtggaaaacactagccggcgacccatggataaaaacactgactgccaagtaccctgggaatt
tcactgccacgatagaggagtggcaagcagagcatgatgccatcatgaggcacatcttggag
agaccggaccctaccgacgtcttccagaataaggcaaacgtgtgttgggccaaggctttagt
gccggtgctgaagaccgctggcatagacatgaccactgaacaatggaacactgtggattatt
ttgaaacggacaaagctcactcagcagagatagtattgaaccaactatgcgtgaggttcttt
ggactcgatctggactccggtctattttctgcacccactgttccgttatccattaggaataa
tcactgggataactccccgtcgcctaacatgtacgggctgaataaagaagtggtccgtcagc
tctctcgcaggtacccacaactgcctcgggcagttgccactggaagagtctatgacatgaac
actggtacactgcgcaattatgatccgcgcataaacctagtacctgtaaacagaagactgcc
tcatgctttagtcctccaccataatgaacacccacagagtgacttttcttcattcgtcagca
aattgaagggcagaactgtcctggtggtcggggaaaagttgtccgtcccaggcaaaatggtt
gactggttgtcagaccggcctgaggctaccttcagagctcggctggatttaggcatcccagg
tgatgtgcccaaatatgacataatatttgttaatgtgaggaccccatataaataccatcact
atcagcagtgtgaagaccatgccattaagcttagcatgttgaccaagaaagcttgtctgcat
ctgaatcccggcggaacctgtgtcagcataggttatggttacgctgacagggccagcgaaag
catcattggtgctatagcgcggcagttcaagttttcccgggtatgcaaaccgaaatcctcac
ttgaagagacggaagttctgtttgtattcattgggtacgatcgcaaggcccgtacgcacaat
ccttacaagctttcatcaaccttgaccaacatttatacaggttccagactccacgaagccgg
atgtgcaccctcatatcatgtggtgcgaggggatattgccacggccaccgaaggagtgatta
taaatgctgctaacagcaaaggacaacctggcggaggggtgtgcggagcgctgtataagaaa
ttcccggaaagcttcgatttacagccgatcgaagtaggaaaagcgcgactggtcaaaggtgc
agctaaacatatcattcatgccgtaggaccaaacttcaacaaagtttcggaggttgaaggtg
acaaacagttggcagaggcttatgagtccatcgctaagattgtcaacgataacaattacaag
tcagtagcgattccactgttgtccaccggcatcttttccgggaacaaagatcgactaaccca
atcattgaaccatttgctgacagctttagacaccactgatgcagatgtagccatatactgca
gggacaagaaatgggaaatgactctcaaggaagcagtggctaggagagaagcagtggaggag
atatgcatatccgacgactcttcagtgacagaacctgatgcagagctggtgagggtgcatcc
gaagagttctttggctggaaggaagggctacagcacaagcgatggcaaaactttctcatatt
tggaagggaccaagtttcaccaggcggccaaggatatagcagaaattaatgccatgtggccc
gttgcaacggaggccaatgagcaggtatgcatgtatatcctcggagaaagcatgagcagtat
taggtcgaaatgccccgtcgaagagtcggaagcctcctcaccacctagcacgctgccttgct
tgtgcatccatgccatgactccagaaagagtacagcgcctaaaagcctcacgtccagaacaa
attactgtgtgctcatcctttccattgccgaagtatagaatcactggtgtgcagaagatcca
atgctcccagcctatattgttctcaccgaaagtgcctgcgtatattcatccaaggaagtatc
tcgtggaaacaccaccggtagacgagactccggagccatcggcagagaaccaatccacagag
gggacacctgaacaaccaccacttataaccgaggatgagaccaggactagaacgcctgagcc
gatcatcatcgaagaggaagaagaggatagcataagtttgctgtcagatggcccgacccacc
aggtgctgcaagtcgaggcagacattcacgggccgccctctgtatctagctcatcctggtcc
attcctcatgcatccgactttgatgtggacagtttatccatacttgacaccctggagggagc
tagcgtgaccagcggggcaacgtcagccgagactaactcttacttcgcaaagagtatggagt
ttctggcgcgaccggtgcctgcgcctcgaacagtattcaggaaccctccacatcccgctccg
cgcacaagaacaccgtcacttgcacccagcagggcctgctcgagagggatcacgggagaaac
cgtgggatacgcggttacacacaatagcgagggcttcttgctatgcaaagttactgacacag
taaaaggagaacgggtatcgttccctgtgtgcacgtacatcccggccaccataaactcgaga
accagcctggtctccaacccgccaggcgtaaatagggtgattacaagagaggagtttgaggc
gttcgtagcacaacaacaatgacggtttgatgcgggtgcatacatcttttcctccgacaccg
gtcaagggcatttacaacaaaaatcagtaaggcaaacggtgctatccgaagtggtgttggag
aggaccgaattggagatttcgtatgccccgcgcctcgaccaagaaaaagaagaattactacg
caagaaattacagttaaatcccacacctgctaacagaagcagataccagtccaggaaggtgg
agaacatgaaagccataacagctagacgtattctgcaaggcctagggcattatttgaaggca
gaaggaaaagtggagtgctaccgaaccctgcatcctgttcctttgtattcatctagtgtgaa
ccgtgccttttcaagccccaaggtcgcagtggaagcctgtaacgccatgttgaaagagaact
ttccgactgtggcttcttactgtattattccagagtacgatgcctatttggacatggttgac
ggagcttcatgctgcttagacactgccagtttttgccctgcaaagctgcgcagctttccaaa
gaaacactcctatttggaacccacaatacgatcggcagtgccttcagcgatccagaacacgc
tccagaacgtcctggcagctgccacaaaaagaaattgcaatgtcacgcaaatgagagaattg
cccgtattggattcggcggcctttaatgtggaatgcttcaagaaatatgcgtgtaataatga
atattgggaaacgtttaaagaaaaccccatcaggcttactgaagaaaacgtggtaaattaca
ttaccaaattaaaaggaccaaaagctgctgctctttttgcgaagacacataatttgaatatg
ttgcaggacataccaatggacaggtttgtaatggacttaaagagagacgtgaaagtgactcc
aggaacaaaacatactgaagaacggcccaaggtacaggtgatccaggctgccgatccgctag
caacagcgtatctgtgcggaatccaccgagagctggttaggagattaaatgcggtcctgctt
ccgaacattcatacactgtttgatatgtcggctgaagactttgacgctattatagccgagca
cttccagcctggggattgtgttctggaaactgacatcgcgtcgtttgataaaagtgaggacg
acgccatggctctgaccgcgttaatgattctggaagacttaggtgtggacgcagagctgttg
acgctgattgaggcggctttcggcgaaatttcatcaatacatttgcccactaaaactaaatt
taaattcggagccatgatgaaatctggaatgttcctcacactgtttgtgaacacagtcatta
acattgtaatcgcaagcagagtgttgagagaacggctaaccggatcaccatgtgcagcattc
attggagatgacaatatcgtgaaaggagtcaaatcggacaaattaatggcagacaggtgcgc
cacctggttgaatatggaagtcaagattatagatgctgtggtgggcgagaaagcgccttatt
tctgtggagggtttattttgtgtgactccgtgaccggcacagcgtgccgtgtggcagacccc
ctaaaaaggctgtttaagcttggcaaacctctggcagcagacgatgaacatgatgatgacag
gagaagggcattgcatgaagagtcaacacgctggaaccgagtgggtattctttcagagctgt
gcaaggcagtagaatcaaggtatgaaaccgtaggaacttccatcatagttatggccatgact
actctagctagcagtgttaaatcattcagctacctgagaggggcccctataactctctacgg
ctaacctgaatggactacgacatagtctagtcgacgccaccatgaggcctggcctgccctcc
tacctgatcatcctggccgtgtgcctgttcagccacctgctgtccagcagatacggcgccga
ggccgtgagcgagcccctggacaaggctttccacctgctgctgaacacctacggcagaccca
tccggtttctgcgggagaacaccacccagtgcacctacaacagcagcctgcggaacagcacc
gtcgtgagagagaacgccatcagcttcaactttttccagagctacaaccagtactacgtgtt
ccacatgcccagatgcctgtttgccggccctctggccgagcagttcctgaaccaggtggacc
tgaccgagacactggaaagataccagcagcggctgaatacctacgccctggtgtccaaggac
ctggccagctaccggtcctttagccagcagctcaaggctcaggatagcctcggcgagcagcc
taccaccgtgccccctcccatcgacctgagcatcccccacgtgtggatgcctccccagacca
cccctcacggctggaccgagagccacaccacctccggcctgcacagaccccacttcaaccag
acctgcatcctgttcgacggccacgacctgctgtttagcaccgtgaccccctgcctgcacca
gggcttctacctgatcgacgagctgagatacgtgaagatcaccctgaccgaggatttcttcg
tggtcaccgtgtccatcgacgacgacacccccatgctgctgatcttcggccacctgcccaga
gtgctgttcaaggccccctaccagcgggacaacttcatcctgcggcagaccgagaagcacga
gctgctggtgctggtcaagaaggaccagctgaaccggcactcctacctgaaggaccccgact
tcctggacgccgccctggacttcaactacctggacctgagcgccctgctgagaaacagcttc
cacagatacgccgtggacgtgctgaagtccggacggtgccagatgctcgatcggcggaccgt
ggagatggccttcgcctatgccctcgccctgttcgccgctgccagacaggaagaggctggcg
cccaggtgtcagtgcccagagccctggatagacaggccgccctgctgcagatccaggaattc
atgatcacctgcctgagccagaccccccctagaaccaccctgctgctgtaccccacagccgt
ggatctggccaagagggccctgtggacccccaaccagatcaccgacatcacaagcctcgtgc
ggctcgtgtacatcctgagcaagcagaaccagcagcacctgatcccccagtgggccctgaga
cagatcgccgacttcgccctgaagctgcacaagacccatctggccagctttctgagcgcctt
cgccaggcaggaactgtacctgatgggcagcctggtccacagcatgctggtgcataccaccg
agcggcgggagatcttcatcgtggagacaggcctgtgtagcctggccgagctgtcccacttt
acccagctgctggcccaccctcaccacgagtacctgagcgacctgtacaccccctgcagcag
cagcggcagacgggaccacagcctggaacggctgaccagactgttccccgatgccaccgtgc
ctgctacagtgcctgccgccctgtccatcctgtccaccatgcagcccagcaccctggaaacc
ttccccgacctgttctgcctgcccctgggcgagagctttagcgccctgaccgtgtccgagca
cgtgtcctacatcgtgaccaatcagtacctgatcaagggcatcagctaccccgtgtccacca
cagtcgtgggccagagcctgatcatcacccagaccgacagccagaccaagtgcgagctgacc
cggaacatgcacaccacacacagcatcaccgtggccctgaacatcagcctggaaaactgcgc
tttctgtcagtctgccctgctggaatacgacgatacccagggcgtgatcaacatcatgtaca
tgcacgacagcgacgacgtgctgttcgccctggacccctacaacgaggtggtggtgtccagc
ccccggacccactacctgatgctgctgaagaacggcaccgtgctggaagtgaccgacgtggt
ggtggacgccaccgactgataatctagacggcgcgcccacccagcggccgcctataactctc
tacggctaacctgaatggactacgacatagtctagtcgacgccaccatgtgcagaaggcccg
actgcggcttcagcttcagccctggacccgtgatcctgctgtggtgctgcctgctgctgcct
atcgtgtcctctgccgccgtgtctgtggcccctacagccgccgagaaggtgccagccgagtg
ccccgagctgaccagaagatgcctgctgggcgaggtgttcgagggcgacaagtacgagagct
ggctgcggcccctggtcaacgtgaccggcagagatggccccctgagccagctgatccggtac
agacccgtgacccccgaggccgccaatagcgtgctgctggacgaggccttcctggataccct
ggccctgctgtacaacaaccccgaccagctgagagccctgctgaccctgctgtccagcgaca
ccgcccccagatggatgaccgtgatgcggggctacagcgagtgtggagatggcagccctgcc
gtgtacacctgcgtggacgacctgtgcagaggctacgacctgaccagactgagctacggccg
gtccatcttcacagagcacgtgctgggcttcgagctggtgccccccagcctgttcaacgtgg
tggtggccatccggaacgaggccaccagaaccaacagagccgtgcggctgcctgtgtctaca
gccgctgcacctgagggcatcacactgttctacggcctgtacaacgccgtgaaagagttctg
cctccggcaccagctggatccccccctgctgagacacctggacaagtactacgccggcctgc
ccccagagctgaagcagaccagagtgaacctgcccgcccacagcagatatggccctcaggcc
gtggacgccagatgataatctagacggcgcgcccacccaatcgatctataactctctacggc
taacctgaatggactacgacatagtctagtcgacgccaccatgggcaagaaagaaatgatca
tggtcaagggcatccccaagatcatgctgctgattagcatcacctttctgctgctgtccctg
atcaactgcaacgtgctggtcaacagccggggcaccagaagatcctggccctacaccgtgct
gtcctaccggggcaaagagatcctgaagaagcagaaagaggacatcctgaagcggctgatga
gcaccagcagcgacggctaccggttcctgatgtaccccagccagcagaaattccacgccatc
gtgatcagcatggacaagttcccccaggactacatcctggccggacccatccggaacgacag
catcacccacatgtggttcgacttctacagcacccagctgcggaagcccgccaaatacgtgt
acagcgagtacaaccacaccgcccacaagatcaccctgaggcctcccccttgtggcaccgtg
cccagcatgaactgcctgagcgagatgctgaacgtgtccaagcggaacgacaccggcgagaa
gggctgcggcaacttcaccaccttcaaccccatgttcttcaacgtgccccggtggaacacca
agctgtacatcggcagcaacaaagtgaacgtggacagccagaccatctactttctgggcctg
accgccctgctgctgagatacgcccagcggaactgcacccggtccttctacctggtcaacgc
catgagccggaacctgttccgggtgcccaagtacatcaacggcaccaagctgaagaacacca
tgcggaagctgaagcggaagcaggccctggtcaaagagcagccccagaagaagaacaagaag
tcccagagcaccaccaccccctacctgagctacaccacctccaccgccttcaacgtgaccac
caacgtgacctacagcgccacagccgccgtgaccagagtggccacaagcaccaccggctacc
ggcccgacagcaactttatgaagtccatcatggccacccagctgagagatctggccacctgg
gtgtacaccaccctgcggtacagaaacgagcccttctgcaagcccgaccggaacagaaccgc
cgtgagcgagttcatgaagaatacccacgtgctgatcagaaacgagacaccctacaccatct
acggcaccctggacatgagcagcctgtactacaacgagacaatgagcgtggagaacgagaca
gccagcgacaacaacgaaaccacccccacctcccccagcacccggttccagcggaccttcat
cgaccccctgtgggactacctggacagcctgctgttcctggacaagatccggaacttcagcc
tgcagctgcccgcctacggcaatctgaccccccctgagcacagaagggccgccaacctgagc
accctgaacagcctgtggtggtggagccagtgataatctagacggcgcgcccacccaccgcg
ggcaatatagcaacactaaaaactcgatgtacttccgaggaagcgcagtgcataatgctgcg
cagtgttgccacataaccactatattaaccatttatctagcggacgccaaaaactcaatgta
tttctgaggaagcgtggtgcataatgccacgcagcgtctgcataacttttattatttctttt
attaatcaacaaaattttgtttttaacatttcaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa
aaaaaaaaaagggtcggcatggcatctccacctcctcgcggtccgacctgggcatccgaagg
aggacgcacgtccactcggatggctaagggagagccacgagctcctgtttaaaccagctcca
attcgccctatagtgagtcgtattacgcgcgctcactggccgtcgttttacaacgtcgtgac
tgggaaaaccctggcgttacccaacttaatcgccttgcagcacatccccctttcgccagctg
gcgtaatagcgaagaggcccgcaccgatcgcccttcccaacagttgcgcagcctgaatggcg
aatgggacgcgccctgtagcggcgcattaagcgcggcgggtgtggtggttacgcgcagcgtg
accgctacacttgccagcgccctagcgcccgctcctttcgctttcttcccttcctttctcgc
cacgttcgccggctttccccgtcaagctctaaatcgggggctccctttagggttccgattta
gtgctttacggcacctcgaccccaaaaaacttgattagggtgatggttcacgtagtgggcca
tcgccctgatagacggtttttcgccctttgacgttggagtccacgttctttaatagtggact
cttgttccaaactggaacaacactcaaccctatctcggtctattcttttgatttataaggga
ttttgccgatttcggcctattggttaaaaaatgagctgatttaacaaaaatttaacgcgaat
tttaacaaaatattaacgcttacaatttaggtggcacttttcggggaaatgtgcgcggaacc
cctatttgtttatttttctaaatacattcaaatatgtatccgctcatgagacaataaccctg
ataaatgcttcaataatattgaaaaaggaagagtatgagtattcaacatttccgtgtcgccc
ttattcccttttttgcggcattttgccttcctgtttttgctcacccagaaacgctggtgaaa
gtaaaagatgctgaagatcagttgggtgcacgagtgggttacatcgaactggatctcaacag
cggtaagatccttgagagttttcgccccgaagaacgttttccaatgatgagcacttttaaag
ttctgctatgtggcgcggtattatcccgtattgacgccgggcaagagcaactcggtcgccgc
atacactattctcagaatgacttggttgagtactcaccagtcacagaaaagcatcttacgga
tggcatgacagtaagagaattatgcagtgctgccataaccatgagtgataacactgcggcca
acttacttctgacaacgatcggaggaccgaaggagctaaccgcttttttgcacaacatgggg
gatcatgtaactcgccttgatcgttgggaaccggagctgaatgaagccataccaaacgacga
gcgtgacaccacgatgcctgtagcaatggcaacaacgttgcgcaaactattaactggcgaac
tacttactctagcttcccggcaacaattaatagactggatggaggcggataaagttgcagga
ccacttctgcgctcggcccttccggctggctggtttattgctgataaatctggagccggtga
gcgtgggtctcgcggtatcattgcagcactggggccagatggtaagccctcccgtatcgtag
ttatctacacgacggggagtcaggcaactatggatgaacgaaatagacagatcgctgagata
ggtgcctcactgattaagcattggtaactgtcagaccaagtttactcatatatactttagat
tgatttaaaacttcatttttaatttaaaaggatctaggtgaagatcctttttgataatctca
tgaccaaaatcccttaacgtgagttttcgttccactgagcgtcagaccccgtagaaaagatc
aaaggatcttcttgagatcctttttttctgcgcgtaatctgctgcttgcaaacaaaaaaacc
accgctaccagcggtggtttgtttgccggatcaagagctaccaactctttttccgaaggtaa
ctggcttcagcagagcgcagataccaaatactgttcttctagtgtagccgtagttaggccac
cacttcaagaactctgtagcaccgcctacatacctcgctctgctaatcctgttaccagtggc
tgctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggata
aggcgcagcggtcgggctgaacggggggttcgtgcacacagcccagcttggagcgaacgacc
tacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgcttcccgaagggag
aaaggcggacaggtatccggtaagcggcagggtcggaacaggagagcgcacgagggagcttc
cagggggaaacgcctggtatctttatagtcctgtcgggtttcgccacctctgacttgagcgt
cgatttttgtgatgctcgtcaggggggcggagcctatggaaaaacgccagcaacgcggcctt
tttacggttcctggccttttgctggccttttgctcacatgttctttcctgcgttatcccctg
attctgtggataaccgtattaccgcctttgagtgagctgataccgctcgccgcagccgaacg
accgagcgcagcgagtcagtgagcgaggaagcggaagagcgcccaatacgcaaaccgcctct
ccccgcgcgttggccgattcattaatgcagctggcacgacaggtttcccgactggaaagcgg
gcagtgagcgcaacgcaattaatgtgagttagctcactcattaggcaccccaggctttacac
tttatgctcccggctcgtatgttgtgtggaattgtgagcggataacaatttcacacaggaaa
cagctatgaccatgattacgccaagcgcgcaattaaccctcactaaagggaacaaaagctgg
gtaccggcgcca
TABLE-US-00040 pVCR modified vector gH FL-SGP gL-SGP gO
cgcgtcggctacaattaatacataaccttatgtatcatacacatacgatttaggtgacacta
tagatgggcggcgcatgagagaagcccagaccaattacctacccaaaatggagaaagttcac
gttgacatcgaggaagacagcccattcctcagagctttgcagcggagcttcccgcagtttga
ggtagaagccaagcaggtcactgataatgaccatgctaatgccagagcgttttcgcatctgg
cttcaaaactgatcgaaacggaggtggacccatccgacacgatccttgacattggaagtgcg
cccgcccgcagaatgtattctaagcacaagtatcattgtatctgtccgatgagatgtgcgga
agatccggacagattgtataagtatgcaactaagctgaagaaaaactgtaaggaaataactg
ataaggaattggacaagaaaatgaaggagctcgccgccgtcatgagcgaccctgacctggaa
actgagactatgtgcctccacgacgacgagtcgtgtcgctacgaagggcaagtcgctgttta
ccaggatgtatacgcggttgacggaccgacaagtctctatcaccaagccaataagggagtta
gagtcgcctactggataggctttgacaccaccccttttatgtttaagaacttggctggagca
tatccatcatactctaccaactgggccgacgaaaccgtgttaacggctcgtaacataggcct
atgcagctctgacgttatggagcggtcacgtagagggatgtccattcttagaaagaagtatt
tgaaaccatccaacaatgttctattctctgttggctcgaccatctaccacgagaagagggac
ttactgaggagctggcacctgccgtctgtatttcacttacgtggcaagcaaaattacacatg
tcggtgtgagactatagttagttgcgacgggtacgtcgttaaaagaatagctatcagtccag
gcctgtatgggaagccttcaggctatgctgctacgatgcaccgcgagggattcttgtgctgc
aaagtgacagacacattgaacggggagagggtctcttttcccgtgtgcacgtatgtgccagc
tacattgtgtgaccaaatgactggcatactggcaacagatgtcagtgcggacgacgcgcaaa
aactgctggttgggctcaaccagcgtatagtcgtcaacggtcgcacccagagaaacaccaat
accatgaaaaattaccttttgcccgtagtggcccaggcatttgctaggtgggcaaaggaata
taaggaagatcaagaagatgaaaggccactaggactacgagatagacagttagtcatggggt
gttgttgggcttttagaaggcacaagataacatctatttataagcgcccggatacccaaacc
atcatcaaagtgaacagcgatttccactcattcgtgctgcccaggataggcagtaacacatt
ggagatcgggctgagaacaagaatcaggaaaatgttagaggagcacaaggagccgtcacctc
tcattaccgccgaggacgtacaagaagctaagtgcgcagccgatgaggctaaggaggtgcgt
gaagccgaggagttgcgcgcagctctaccacctttggcagctgatgttgaggagcccactct
ggaagccgatgtagacttgatgttacaagaggctggggccggctcagtggagacacctcgtg
gcttgataaaggttaccagctacgctggcgaggacaagatcggctcttacgctgtgctttct
ccgcaggctgtactcaagagtgaaaaattatcttgcatccaccctctcgctgaacaagtcat
agtgataacacactctggccgaaaagggcgttatgccgtggaaccataccatggtaaagtag
tggtgccagagggacatgcaatacccgtccaggactttcaagctctgagtgaaagtgccacc
attgtgtacaacgaacgtgagttcgtaaacaggtacctgcaccatattgccacacatggagg
agcgctgaacactgatgaagaatattacaaaactgtcaagcccagcgagcacgacggcgaat
acctgtacgacatcgacaggaaacagtgcgtcaagaaagaactagtcactgggctagggctc
acaggcgagctggtggatcctcccttccatgaattcgcctacgagagtctgagaacacgacc
agccgctccttaccaagtaccaaccataggggtgtatggcgtgccaggatcaggcaagtctg
gcatcattaaaagcgcagtcaccaaaaaagatctagtggtgagcgccaagaaagaaaactgt
gcagaaattataagggacgtcaagaaaatgaaagggctggacgtcaatgccagaactgtgga
ctcagtgctcttgaatggatgcaaacaccccgtagagaccctgtatattgacgaagcttttg
cttgtcatgcaggtactctcagagcgctcatagccattataagacctaaaaaggcagtgctc
tgcggggatcccaaacagtgcggtttttttaacatgatgtgcctgaaagtgcattttaacca
cgagatttgcacacaagtcttccacaaaagcatctctcgccgttgcactaaatctgtgactt
cggtcgtctcaaccttgttttacgacaaaaaaatgagaacgacgaatccgaaagagactaag
attgtgattgacactaccggcagtaccaaacctaagcaggacgatctcattctcacttgttt
cagagggtgggtgaagcagttgcaaatagattacaaaggcaacgaaataatgacggcagctg
cctctcaagggctgacccgtaaaggtgtgtatgccgttcggtacaaggtgaatgaaaatcct
ctgtacgcacccacctcagaacatgtgaacgtcctactgacccgcacggaggaccgcatcgt
gtggaaaacactagccggcgacccatggataaaaacactgactgccaagtaccctgggaatt
tcactgccacgatagaggagtggcaagcagagcatgatgccatcatgaggcacatcttggag
agaccggaccctaccgacgtcttccagaataaggcaaacgtgtgttgggccaaggctttagt
gccggtgctgaagaccgctggcatagacatgaccactgaacaatggaacactgtggattatt
ttgaaacggacaaagctcactcagcagagatagtattgaaccaactatgcgtgaggttcttt
ggactcgatctggactccggtctattttctgcacccactgttccgttatccattaggaataa
tcactgggataactccccgtcgcctaacatgtacgggctgaataaagaagtggtccgtcagc
tctctcgcaggtacccacaactgcctcgggcagttgccactggaagagtctatgacatgaac
actggtacactgcgcaattatgatccgcgcataaacctagtacctgtaaacagaagactgcc
tcatgctttagtcctccaccataatgaacacccacagagtgacttttcttcattcgtcagca
aattgaagggcagaactgtcctggtggtcggggaaaagttgtccgtcccaggcaaaatggtt
gactggttgtcagaccggcctgaggctaccttcagagctcggctggatttaggcatcccagg
tgatgtgcccaaatatgacataatatttgttaatgtgaggaccccatataaataccatcact
atcagcagtgtgaagaccatgccattaagcttagcatgttgaccaagaaagcttgtctgcat
ctgaatcccggcggaacctgtgtcagcataggttatggttacgctgacagggccagcgaaag
catcattggtgctatagcgcggcagttcaagttttcccgggtatgcaaaccgaaatcctcac
ttgaagagacggaagttctgtttgtattcattgggtacgatcgcaaggcccgtacgcacaat
ccttacaagctttcatcaaccttgaccaacatttatacaggttccagactccacgaagccgg
atgtgcaccctcatatcatgtggtgcgaggggatattgccacggccaccgaaggagtgatta
taaatgctgctaacagcaaaggacaacctggcggaggggtgtgcggagcgctgtataagaaa
ttcccggaaagcttcgatttacagccgatcgaagtaggaaaagcgcgactggtcaaaggtgc
agctaaacatatcattcatgccgtaggaccaaacttcaacaaagtttcggaggttgaaggtg
acaaacagttggcagaggcttatgagtccatcgctaagattgtcaacgataacaattacaag
tcagtagcgattccactgttgtccaccggcatcttttccgggaacaaagatcgactaaccca
atcattgaaccatttgctgacagctttagacaccactgatgcagatgtagccatatactgca
gggacaagaaatgggaaatgactctcaaggaagcagtggctaggagagaagcagtggaggag
atatgcatatccgacgactcttcagtgacagaacctgatgcagagctggtgagggtgcatcc
gaagagttctttggctggaaggaagggctacagcacaagcgatggcaaaactttctcatatt
tggaagggaccaagtttcaccaggcggccaaggatatagcagaaattaatgccatgtggccc
gttgcaacggaggccaatgagcaggtatgcatgtatatcctcggagaaagcatgagcagtat
taggtcgaaatgccccgtcgaagagtcggaagcctcctcaccacctagcacgctgccttgct
tgtgcatccatgccatgactccagaaagagtacagcgcctaaaagcctcacgtccagaacaa
attactgtgtgctcatcctttccattgccgaagtatagaatcactggtgtgcagaagatcca
atgctcccagcctatattgttctcaccgaaagtgcctgcgtatattcatccaaggaagtatc
tcgtggaaacaccaccggtagacgagactccggagccatcggcagagaaccaatccacagag
gggacacctgaacaaccaccacttataaccgaggatgagaccaggactagaacgcctgagcc
gatcatcatcgaagaggaagaagaggatagcataagtttgctgtcagatggcccgacccacc
aggtgctgcaagtcgaggcagacattcacgggccgccctctgtatctagctcatcctggtcc
attcctcatgcatccgactttgatgtggacagtttatccatacttgacaccctggagggagc
tagcgtgaccagcggggcaacgtcagccgagactaactcttacttcgcaaagagtatggagt
ttctggcgcgaccggtgcctgcgcctcgaacagtattcaggaaccctccacatcccgctccg
cgcacaagaacaccgtcacttgcacccagcagggcctgctcgagagggatcacgggagaaac
cgtgggatacgcggttacacacaatagcgagggcttcttgctatgcaaagttactgacacag
taaaaggagaacgggtatcgttccctgtgtgcacgtacatcccggccaccataaactcgaga
accagcctggtctccaacccgccaggcgtaaatagggtgattacaagagaggagtttgaggc
gttcgtagcacaacaacaatgacggtttgatgcgggtgcatacatcttttcctccgacaccg
gtcaagggcatttacaacaaaaatcagtaaggcaaacggtgctatccgaagtggtgttggag
aggaccgaattggagatttcgtatgccccgcgcctcgaccaagaaaaagaagaattactacg
caagaaattacagttaaatcccacacctgctaacagaagcagataccagtccaggaaggtgg
agaacatgaaagccataacagctagacgtattctgcaaggcctagggcattatttgaaggca
gaaggaaaagtggagtgctaccgaaccctgcatcctgttcctttgtattcatctagtgtgaa
ccgtgccttttcaagccccaaggtcgcagtggaagcctgtaacgccatgttgaaagagaact
ttccgactgtggcttcttactgtattattccagagtacgatgcctatttggacatggttgac
ggagcttcatgctgcttagacactgccagtttttgccctgcaaagctgcgcagctttccaaa
gaaacactcctatttggaacccacaatacgatcggcagtgccttcagcgatccagaacacgc
tccagaacgtcctggcagctgccacaaaaagaaattgcaatgtcacgcaaatgagagaattg
cccgtattggattcggcggcctttaatgtggaatgcttcaagaaatatgcgtgtaataatga
atattgggaaacgtttaaagaaaaccccatcaggcttactgaagaaaacgtggtaaattaca
ttaccaaattaaaaggaccaaaagctgctgctctttttgcgaagacacataatttgaatatg
ttgcaggacataccaatggacaggtttgtaatggacttaaagagagacgtgaaagtgactcc
aggaacaaaacatactgaagaacggcccaaggtacaggtgatccaggctgccgatccgctag
caacagcgtatctgtgcggaatccaccgagagctggttaggagattaaatgcggtcctgctt
ccgaacattcatacactgtttgatatgtcggctgaagactttgacgctattatagccgagca
cttccagcctggggattgtgttctggaaactgacatcgcgtcgtttgataaaagtgaggacg
acgccatggctctgaccgcgttaatgattctggaagacttaggtgtggacgcagagctgttg
acgctgattgaggcggctttcggcgaaatttcatcaatacatttgcccactaaaactaaatt
taaattcggagccatgatgaaatctggaatgttcctcacactgtttgtgaacacagtcatta
acattgtaatcgcaagcagagtgttgagagaacggctaaccggatcaccatgtgcagcattc
attggagatgacaatatcgtgaaaggagtcaaatcggacaaattaatggcagacaggtgcgc
cacctggttgaatatggaagtcaagattatagatgctgtggtgggcgagaaagcgccttatt
tctgtggagggtttattttgtgtgactccgtgaccggcacagcgtgccgtgtggcagacccc
ctaaaaaggctgtttaagcttggcaaacctctggcagcagacgatgaacatgatgatgacag
gagaagggcattgcatgaagagtcaacacgctggaaccgagtgggtattctttcagagctgt
gcaaggcagtagaatcaaggtatgaaaccgtaggaacttccatcatagttatggccatgact
actctagctagcagtgttaaatcattcagctacctgagaggggcccctataactctctacgg
ctaacctgaatggactacgacatagtctagtcgacgccaccatgaggcctggcctgccctcc
tacctgatcatcctggccgtgtgcctgttcagccacctgctgtccagcagatacggcgccga
ggccgtgagcgagcccctggacaaggctttccacctgctgctgaacacctacggcagaccca
tccggtttctgcgggagaacaccacccagtgcacctacaacagcagcctgcggaacagcacc
gtcgtgagagagaacgccatcagcttcaactttttccagagctacaaccagtactacgtgtt
ccacatgcccagatgcctgtttgccggccctctggccgagcagttcctgaaccaggtggacc
tgaccgagacactggaaagataccagcagcggctgaatacctacgccctggtgtccaaggac
ctggccagctaccggtcctttagccagcagctcaaggctcaggatagcctcggcgagcagcc
taccaccgtgccccctcccatcgacctgagcatcccccacgtgtggatgcctccccagacca
cccctcacggctggaccgagagccacaccacctccggcctgcacagaccccacttcaaccag
acctgcatcctgttcgacggccacgacctgctgtttagcaccgtgaccccctgcctgcacca
gggcttctacctgatcgacgagctgagatacgtgaagatcaccctgaccgaggatttcttcg
tggtcaccgtgtccatcgacgacgacacccccatgctgctgatcttcggccacctgcccaga
gtgctgttcaaggccccctaccagcgggacaacttcatcctgcggcagaccgagaagcacga
gctgctggtgctggtcaagaaggaccagctgaaccggcactcctacctgaaggaccccgact
tcctggacgccgccctggacttcaactacctggacctgagcgccctgctgagaaacagcttc
cacagatacgccgtggacgtgctgaagtccggacggtgccagatgctcgatcggcggaccgt
ggagatggccttcgcctatgccctcgccctgttcgccgctgccagacaggaagaggctggcg
cccaggtgtcagtgcccagagccctggatagacaggccgccctgctgcagatccaggaattc
atgatcacctgcctgagccagaccccccctagaaccaccctgctgctgtaccccacagccgt
ggatctggccaagagggccctgtggacccccaaccagatcaccgacatcacaagcctcgtgc
ggctcgtgtacatcctgagcaagcagaaccagcagcacctgatcccccagtgggccctgaga
cagatcgccgacttcgccctgaagctgcacaagacccatctggccagctttctgagcgcctt
cgccaggcaggaactgtacctgatgggcagcctggtccacagcatgctggtgcataccaccg
agcggcgggagatcttcatcgtggagacaggcctgtgtagcctggccgagctgtcccacttt
acccagctgctggcccaccctcaccacgagtacctgagcgacctgtacaccccctgcagcag
cagcggcagacgggaccacagcctggaacggctgaccagactgttccccgatgccaccgtgc
ctgctacagtgcctgccgccctgtccatcctgtccaccatgcagcccagcaccctggaaacc
ttccccgacctgttctgcctgcccctgggcgagagctttagcgccctgaccgtgtccgagca
cgtgtcctacatcgtgaccaatcagtacctgatcaagggcatcagctaccccgtgtccacca
cagtcgtgggccagagcctgatcatcacccagaccgacagccagaccaagtgcgagctgacc
cggaacatgcacaccacacacagcatcaccgtggccctgaacatcagcctggaaaactgcgc
tttctgtcagtctgccctgctggaatacgacgatacccagggcgtgatcaacatcatgtaca
tgcacgacagcgacgacgtgctgttcgccctggacccctacaacgaggtggtggtgtccagc
ccccggacccactacctgatgctgctgaagaacggcaccgtgctggaagtgaccgacgtggt
ggtggacgccaccgacagcagactgctgatgatgagcgtgtacgccctgagcgccatcatcg
gcatctacctgctgtaccggatgctgaaaacctgctgataatctagacggcgcgcccaccca
gcggccgcctataactctctacggctaacctgaatggactacgacatagtctagtcgacgcc
accatgtgcagaaggcccgactgcggcttcagcttcagccctggacccgtgatcctgctgtg
gtgctgcctgctgctgcctatcgtgtcctctgccgccgtgtctgtggcccctacagccgccg
agaaggtgccagccgagtgccccgagctgaccagaagatgcctgctgggcgaggtgttcgag
ggcgacaagtacgagagctggctgcggcccctggtcaacgtgaccggcagagatggccccct
gagccagctgatccggtacagacccgtgacccccgaggccgccaatagcgtgctgctggacg
aggccttcctggataccctggccctgctgtacaacaaccccgaccagctgagagccctgctg
accctgctgtccagcgacaccgcccccagatggatgaccgtgatgcggggctacagcgagtg
tggagatggcagccctgccgtgtacacctgcgtggacgacctgtgcagaggctacgacctga
ccagactgagctacggccggtccatcttcacagagcacgtgctgggcttcgagctggtgccc
cccagcctgttcaacgtggtggtggccatccggaacgaggccaccagaaccaacagagccgt
gcggctgcctgtgtctacagccgctgcacctgagggcatcacactgttctacggcctgtaca
acgccgtgaaagagttctgcctccggcaccagctggatccccccctgctgagacacctggac
aagtactacgccggcctgcccccagagctgaagcagaccagagtgaacctgcccgcccacag
cagatatggccctcaggccgtggacgccagatgataatctagacggcgcgcccacccaatcg
atctataactctctacggctaacctgaatggactacgacatagtctagtcgacgccaccatg
ggcaagaaagaaatgatcatggtcaagggcatccccaagatcatgctgctgattagcatcac
ctttctgctgctgtccctgatcaactgcaacgtgctggtcaacagccggggcaccagaagat
cctggccctacaccgtgctgtcctaccggggcaaagagatcctgaagaagcagaaagaggac
atcctgaagcggctgatgagcaccagcagcgacggctaccggttcctgatgtaccccagcca
gcagaaattccacgccatcgtgatcagcatggacaagttcccccaggactacatcctggccg
gacccatccggaacgacagcatcacccacatgtggttcgacttctacagcacccagctgcgg
aagcccgccaaatacgtgtacagcgagtacaaccacaccgcccacaagatcaccctgaggcc
tcccccttgtggcaccgtgcccagcatgaactgcctgagcgagatgctgaacgtgtccaagc
ggaacgacaccggcgagaagggctgcggcaacttcaccaccttcaaccccatgttcttcaac
gtgccccggtggaacaccaagctgtacatcggcagcaacaaagtgaacgtggacagccagac
catctactttctgggcctgaccgccctgctgctgagatacgcccagcggaactgcacccggt
ccttctacctggtcaacgccatgagccggaacctgttccgggtgcccaagtacatcaacggc
accaagctgaagaacaccatgcggaagctgaagcggaagcaggccctggtcaaagagcagcc
ccagaagaagaacaagaagtcccagagcaccaccaccccctacctgagctacaccacctcca
ccgccttcaacgtgaccaccaacgtgacctacagcgccacagccgccgtgaccagagtggcc
acaagcaccaccggctaccggcccgacagcaactttatgaagtccatcatggccacccagct
gagagatctggccacctgggtgtacaccaccctgcggtacagaaacgagcccttctgcaagc
ccgaccggaacagaaccgccgtgagcgagttcatgaagaatacccacgtgctgatcagaaac
gagacaccctacaccatctacggcaccctggacatgagcagcctgtactacaacgagacaat
gagcgtggagaacgagacagccagcgacaacaacgaaaccacccccacctcccccagcaccc
ggttccagcggaccttcatcgaccccctgtgggactacctggacagcctgctgttcctggac
aagatccggaacttcagcctgcagctgcccgcctacggcaatctgaccccccctgagcacag
aagggccgccaacctgagcaccctgaacagcctgtggtggtggagccagtgataatctagac
ggcgcgcccacccaccgcgggcaatatagcaacactaaaaactcgatgtacttccgaggaag
cgcagtgcataatgctgcgcagtgttgccacataaccactatattaaccatttatctagcgg
acgccaaaaactcaatgtatttctgaggaagcgtggtgcataatgccacgcagcgtctgcat
aacttttattatttcttttattaatcaacaaaattttgtttttaacatttcaaaaaaaaaaa
aaaaaaaaaaaaaaaaaaaaaaaaaaaaagggtcggcatggcatctccacctcctcgcggtc
cgacctgggcatccgaaggaggacgcacgtccactcggatggctaagggagagccacgagct
cctgtttaaaccagctccaattcgccctatagtgagtcgtattacgcgcgctcactggccgt
cgttttacaacgtcgtgactgggaaaaccctggcgttacccaacttaatcgccttgcagcac
atccccctttcgccagctggcgtaatagcgaagaggcccgcaccgatcgcccttcccaacag
ttgcgcagcctgaatggcgaatgggacgcgccctgtagcggcgcattaagcgcggcgggtgt
ggtggttacgcgcagcgtgaccgctacacttgccagcgccctagcgcccgctcctttcgctt
tcttcccttcctttctcgccacgttcgccggctttccccgtcaagctctaaatcgggggctc
cctttagggttccgatttagtgctttacggcacctcgaccccaaaaaacttgattagggtga
tggttcacgtagtgggccatcgccctgatagacggtttttcgccctttgacgttggagtcca
cgttctttaatagtggactcttgttccaaactggaacaacactcaaccctatctcggtctat
tcttttgatttataagggattttgccgatttcggcctattggttaaaaaatgagctgattta
acaaaaatttaacgcgaattttaacaaaatattaacgcttacaatttaggtggcacttttcg
gggaaatgtgcgcggaacccctatttgtttatttttctaaatacattcaaatatgtatccgc
tcatgagacaataaccctgataaatgcttcaataatattgaaaaaggaagagtatgagtatt
caacatttccgtgtcgcccttattcccttttttgcggcattttgccttcctgtttttgctca
cccagaaacgctggtgaaagtaaaagatgctgaagatcagttgggtgcacgagtgggttaca
tcgaactggatctcaacagcggtaagatccttgagagttttcgccccgaagaacgttttcca
atgatgagcacttttaaagttctgctatgtggcgcggtattatcccgtattgacgccgggca
agagcaactcggtcgccgcatacactattctcagaatgacttggttgagtactcaccagtca
cagaaaagcatcttacggatggcatgacagtaagagaattatgcagtgctgccataaccatg
agtgataacactgcggccaacttacttctgacaacgatcggaggaccgaaggagctaaccgc
ttttttgcacaacatgggggatcatgtaactcgccttgatcgttgggaaccggagctgaatg
aagccataccaaacgacgagcgtgacaccacgatgcctgtagcaatggcaacaacgttgcgc
aaactattaactggcgaactacttactctagcttcccggcaacaattaatagactggatgga
ggcggataaagttgcaggaccacttctgcgctcggcccttccggctggctggtttattgctg
ataaatctggagccggtgagcgtgggtctcgcggtatcattgcagcactggggccagatggt
aagccctcccgtatcgtagttatctacacgacggggagtcaggcaactatggatgaacgaaa
tagacagatcgctgagataggtgcctcactgattaagcattggtaactgtcagaccaagttt
actcatatatactttagattgatttaaaacttcatttttaatttaaaaggatctaggtgaag
atcctttttgataatctcatgaccaaaatcccttaacgtgagttttcgttccactgagcgtc
agaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaatctgct
gcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctacca
actctttttccgaaggtaactggcttcagcagagcgcagataccaaatactgttcttctagt
gtagccgtagttaggccaccacttcaagaactctgtagcaccgcctacatacctcgctctgc
taatcctgttaccagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactca
agacgatagttaccggataaggcgcagcggtcgggctgaacggggggttcgtgcacacagcc
cagcttggagcgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcg
ccacgcttcccgaagggagaaaggcggacaggtatccggtaagcggcagggtcggaacagga
gagcgcacgagggagcttccagggggaaacgcctggtatctttatagtcctgtcgggtttcg
ccacctctgacttgagcgtcgatttttgtgatgctcgtcaggggggcggagcctatggaaaa
acgccagcaacgcggcctttttacggttcctggccttttgctggccttttgctcacatgttc
tttcctgcgttatcccctgattctgtggataaccgtattaccgcctttgagtgagctgatac
cgctcgccgcagccgaacgaccgagcgcagcgagtcagtgagcgaggaagcggaagagcgcc
caatacgcaaaccgcctctccccgcgcgttggccgattcattaatgcagctggcacgacagg
tttcccgactggaaagcgggcagtgagcgcaacgcaattaatgtgagttagctcactcatta
ggcaccccaggctttacactttatgctcccggctcgtatgttgtgtggaattgtgagcggat
aacaatttcacacaggaaacagctatgaccatgattacgccaagcgcgcaattaaccctcac
taaagggaacaaaagctgggtaccggcgcca
TABLE-US-00041 A526 Vector:
SGP-gH-SGP-gL-SGP-UL128-2A-UL130-2Amod-UL131
ATAGGCGGCGCATGAGAGAAGCCCAGACCAATTACCTACCCAAAATGGAGAAAGTTCACGTTGACATCGAGGAA-
G
ACAGCCCATTCCTCAGAGCTTTGCAGCGGAGCTTCCCGCAGTTTGAGGTAGAAGCCAAGCAGGTCACTGATAAT-
G
ACCATGCTAATGCCAGAGCGTTTTCGCATCTGGCTTCAAAACTGATCGAAACGGAGGTGGACCCATCCGACACG-
A
TCCTTGACATTGGAAGTGCGCCCGCCCGCAGAATGTATTCTAAGCACAAGTATCATTGTATCTGTCCGATGAGA-
T
GTGCGGAAGATCCGGACAGATTGTATAAGTATGCAACTAAGCTGAAGAAAAACTGTAAGGAAATAACTGATAAG-
G
AATTGGACAAGAAAATGAAGGAGCTCGCCGCCGTCATGAGCGACCCTGACCTGGAAACTGAGACTATGTGCCTC-
C
ACGACGACGAGTCGTGTCGCTACGAAGGGCAAGTCGCTGTTTACCAGGATGTATACGCGGTTGACGGACCGACA-
A
GTCTCTATCACCAAGCCAATAAGGGAGTTAGAGTCGCCTACTGGATAGGCTTTGACACCACCCCTTTTATGTTT-
A
AGAACTTGGCTGGAGCATATCCATCATACTCTACCAACTGGGCCGACGAAACCGTGTTAACGGCTCGTAACATA-
G
GCCTATGCAGCTCTGACGTTATGGAGCGGTCACGTAGAGGGATGTCCATTCTTAGAAAGAAGTATTTGAAACCA-
T
CCAACAATGTTCTATTCTCTGTTGGCTCGACCATCTACCACGAGAAGAGGGACTTACTGAGGAGCTGGCACCTG-
C
CGTCTGTATTTCACTTACGTGGCAAGCAAAATTACACATGTCGGTGTGAGACTATAGTTAGTTGCGACGGGTAC-
G
TCGTTAAAAGAATAGCTATCAGTCCAGGCCTGTATGGGAAGCCTTCAGGCTATGCTGCTACGATGCACCGCGAG-
G
GATTCTTGTGCTGCAAAGTGACAGACACATTGAACGGGGAGAGGGTCTCTTTTCCCGTGTGCACGTATGTGCCA-
G
CTACATTGTGTGACCAAATGACTGGCATACTGGCAACAGATGTCAGTGCGGACGACGCGCAAAAACTGCTGGTT-
G
GGCTCAACCAGCGTATAGTCGTCAACGGTCGCACCCAGAGAAACACCAATACCATGAAAAATTACCTTTTGCCC-
G
TAGTGGCCCAGGCATTTGCTAGGTGGGCAAAGGAATATAAGGAAGATCAAGAAGATGAAAGGCCACTAGGACTA-
C
GAGATAGACAGTTAGTCATGGGGTGTTGTTGGGCTTTTAGAAGGCACAAGATAACATCTATTTATAAGCGCCCG-
G
ATACCCAAACCATCATCAAAGTGAACAGCGATTTCCACTCATTCGTGCTGCCCAGGATAGGCAGTAACACATTG-
G
AGATCGGGCTGAGAACAAGAATCAGGAAAATGTTAGAGGAGCACAAGGAGCCGTCACCTCTCATTACCGCCGAG-
G
ACGTACAAGAAGCTAAGTGCGCAGCCGATGAGGCTAAGGAGGTGCGTGAAGCCGAGGAGTTGCGCGCAGCTCTA-
C
CACCTTTGGCAGCTGATGTTGAGGAGCCCACTCTGGAAGCCGATGTAGACTTGATGTTACAAGAGGCTGGGGCC-
G
GCTCAGTGGAGACACCTCGTGGCTTGATAAAGGTTACCAGCTACGATGGCGAGGACAAGATCGGCTCTTACGCT-
G
TGCTTTCTCCGCAGGCTGTACTCAAGAGTGAAAAATTATCTTGCATCCACCCTCTCGCTGAACAAGTCATAGTG-
A
TAACACACTCTGGCCGAAAAGGGCGTTATGCCGTGGAACCATACCATGGTAAAGTAGTGGTGCCAGAGGGACAT-
G
CAATACCCGTCCAGGACTTTCAAGCTCTGAGTGAAAGTGCCACCATTGTGTACAACGAACGTGAGTTCGTAAAC-
A
GGTACCTGCACCATATTGCCACACATGGAGGAGCGCTGAACACTGATGAAGAATATTACAAAACTGTCAAGCCC-
A
GCGAGCACGACGGCGAATACCTGTACGACATCGACAGGAAACAGTGCGTCAAGAAAGAACTAGTCACTGGGCTA-
G
GGCTCACAGGCGAGCTGGTGGATCCTCCCTTCCATGAATTCGCCTACGAGAGTCTGAGAACACGACCAGCCGCT-
C
CTTACCAAGTACCAACCATAGGGGTGTATGGCGTGCCAGGATCAGGCAAGTCTGGCATCATTAAAAGCGCAGTC-
A
CCAAAAAAGATCTAGTGGTGAGCGCCAAGAAAGAAAACTGTGCAGAAATTATAAGGGACGTCAAGAAAATGAAA-
G
GGCTGGACGTCAATGCCAGAACTGTGGACTCAGTGCTCTTGAATGGATGCAAACACCCCGTAGAGACCCTGTAT-
A
TTGACGAAGCTTTTGCTTGTCATGCAGGTACTCTCAGAGCGCTCATAGCCATTATAAGACCTAAAAAGGCAGTG-
C
TCTGCGGGGATCCCAAACAGTGCGGTTTTTTTAACATGATGTGCCTGAAAGTGCATTTTAACCACGAGATTTGC-
A
CACAAGTCTTCCACAAAAGCATCTCTCGCCGTTGCACTAAATCTGTGACTTCGGTCGTCTCAACCTTGTTTTAC-
G
ACAAAAAAATGAGAACGACGAATCCGAAAGAGACTAAGATTGTGATTGACACTACCGGCAGTACCAAACCTAAG-
C
AGGACGATCTCATTCTCACTTGTTTCAGAGGGTGGGTGAAGCAGTTGCAAATAGATTACAAAGGCAACGAAATA-
A
TGACGGCAGCTGCCTCTCAAGGGCTGACCCGTAAAGGTGTGTATGCCGTTCGGTACAAGGTGAATGAAAATCCT-
C
TGTACGCACCCACCTCAGAACATGTGAACGTCCTACTGACCCGCACGGAGGACCGCATCGTGTGGAAAACACTA-
G
CCGGCGACCCATGGATAAAAACACTGACTGCCAAGTACCCTGGGAATTTCACTGCCACGATAGAGGAGTGGCAA-
G
CAGAGCATGATGCCATCATGAGGCACATCTTGGAGAGACCGGACCCTACCGACGTCTTCCAGAATAAGGCAAAC-
G
TGTGTTGGGCCAAGGCTTTAGTGCCGGTGCTGAAGACCGCTGGCATAGACATGACCACTGAACAATGGAACACT-
G
TGGATTATTTTGAAACGGACAAAGCTCACTCAGCAGAGATAGTATTGAACCAACTATGCGTGAGGTTCTTTGGA-
C
TCGATCTGGACTCCGGTCTATTTTCTGCACCCACTGTTCCGTTATCCATTAGGAATAATCACTGGGATAACTCC-
C
CGTCGCCTAACATGTACGGGCTGAATAAAGAAGTGGTCCGTCAGCTCTCTCGCAGGTACCCACAACTGCCTCGG-
G
CAGTTGCCACTGGAAGAGTCTATGACATGAACACTGGTACACTGCGCAATTATGATCCGCGCATAAACCTAGTA-
C
CTGTAAACAGAAGACTGCCTCATGCTTTAGTCCTCCACCATAATGAACACCCACAGAGTGACTTTTCTTCATTC-
G
TCAGCAAATTGAAGGGCAGAACTGTCCTGGTGGTCGGGGAAAAGTTGTCCGTCCCAGGCAAAATGGTTGACTGG-
T
TGTCAGACCGGCCTGAGGCTACCTTCAGAGCTCGGCTGGATTTAGGCATCCCAGGTGATGTGCCCAAATATGAC-
A
TAATATTTGTTAATGTGAGGACCCCATATAAATACCATCACTATCAGCAGTGTGAAGACCATGCCATTAAGCTT-
A
GCATGTTGACCAAGAAAGCTTGTCTGCATCTGAATCCCGGCGGAACCTGTGTCAGCATAGGTTATGGTTACGCT-
G
ACAGGGCCAGCGAAAGCATCATTGGTGCTATAGCGCGGCAGTTCAAGTTTTCCCGGGTATGCAAACCGAAATCC-
T
CACTTGAAGAGACGGAAGTTCTGTTTGTATTCATTGGGTACGATCGCAAGGCCCGTACGCACAATCCTTACAAG-
C
TTTCATCAACCTTGACCAACATTTATACAGGTTCCAGACTCCACGAAGCCGGATGTGCACCCTCATATCATGTG-
G
TGCGAGGGGATATTGCCACGGCCACCGAAGGAGTGATTATAAATGCTGCTAACAGCAAAGGACAACCTGGCGGA-
G
GGGTGTGCGGAGCGCTGTATAAGAAATTCCCGGAAAGCTTCGATTTACAGCCGATCGAAGTAGGAAAAGCGCGA-
C
TGGTCAAAGGTGCAGCTAAACATATCATTCATGCCGTAGGACCAAACTTCAACAAAGTTTCGGAGGTTGAAGGT-
G
ACAAACAGTTGGCAGAGGCTTATGAGTCCATCGCTAAGATTGTCAACGATAACAATTACAAGTCAGTAGCGATT-
C
CACTGTTGTCCACCGGCATCTTTTCCGGGAACAAAGATCGACTAACCCAATCATTGAACCATTTGCTGACAGCT-
T
TAGACACCACTGATGCAGATGTAGCCATATACTGCAGGGACAAGAAATGGGAAATGACTCTCAAGGAAGCAGTG-
G
CTAGGAGAGAAGCAGTGGAGGAGATATGCATATCCGACGACTCTTCAGTGACAGAACCTGATGCAGAGCTGGTG-
A
GGGTGCATCCGAAGAGTTCTTTGGCTGGAAGGAAGGGCTACAGCACAAGCGATGGCAAAACTTTCTCATATTTG-
G
AAGGGACCAAGTTTCACCAGGCGGCCAAGGATATAGCAGAAATTAATGCCATGTGGCCCGTTGCAACGGAGGCC-
A
ATGAGCAGGTATGCATGTATATCCTCGGAGAAAGCATGAGCAGTATTAGGTCGAAATGCCCCGTCGAAGAGTCG-
G
AAGCCTCCACACCACCTAGCACGCTGCCTTGCTTGTGCATCCATGCCATGACTCCAGAAAGAGTACAGCGCCTA-
A
AAGCCTCACGTCCAGAACAAATTACTGTGTGCTCATCCTTTCCATTGCCGAAGTATAGAATCACTGGTGTGCAG-
A
AGATCCAATGCTCCCAGCCTATATTGTTCTCACCGAAAGTGCCTGCGTATATTCATCCAAGGAAGTATCTCGTG-
G
AAACACCACCGGTAGACGAGACTCCGGAGCCATCGGCAGAGAACCAATCCACAGAGGGGACACCTGAACAACCA-
C
CACTTATAACCGAGGATGAGACCAGGACTAGAACGCCTGAGCCGATCATCATCGAAGAGGAAGAAGAGGATAGC-
A
TAAGTTTGCTGTCAGATGGCCCGACCCACCAGGTGCTGCAAGTCGAGGCAGACATTCACGGGCCGCCCTCTGTA-
T
CTAGCTCATCCTGGTCCATTCCTCATGCATCCGACTTTGATGTGGACAGTTTATCCATACTTGACACCCTGGAG-
G
GAGCTAGCGTGACCAGCGGGGCAACGTCAGCCGAGACTAACTCTTACTTCGCAAAGAGTATGGAGTTTCTGGCG-
C
GACCGGTGCCTGCGCCTCGAACAGTATTCAGGAACCCTCCACATCCCGCTCCGCGCACAAGAACACCGTCACTT-
G
CACCCAGCAGGGCCTGCTCGAGAACCAGCCTAGTTTCCACCCCGCCAGGCGTGAATAGGGTGATCACTAGAGAG-
G
AGCTCGAGGCGCTTACCCCGTCACGCACTCCTAGCAGGTCGGTCTCGAGAACCAGCCTGGTCTCCAACCCGCCA-
G
GCGTAAATAGGGTGATTACAAGAGAGGAGTTTGAGGCGTTCGTAGCACAACAACAATGACGGTTTGATGCGGGT-
G
CATACATCTTTTCCTCCGACACCGGTCAAGGGCATTTACAACAAAAATCAGTAAGGCAAACGGTGCTATCCGAA-
G
TGGTGTTGGAGAGGACCGAATTGGAGATTTCGTATGCCCCGCGCCTCGACCAAGAAAAAGAAGAATTACTACGC-
A
AGAAATTACAGTTAAATCCCACACCTGCTAACAGAAGCAGATACCAGTCCAGGAAGGTGGAGAACATGAAAGCC-
A
TAACAGCTAGACGTATTCTGCAAGGCCTAGGGCATTATTTGAAGGCAGAAGGAAAAGTGGAGTGCTACCGAACC-
C
TGCATCCTGTTCCTTTGTATTCATCTAGTGTGAACCGTGCCTTTTCAAGCCCCAAGGTCGCAGTGGAAGCCTGT-
A
ACGCCATGTTGAAAGAGAACTTTCCGACTGTGGCTTCTTACTGTATTATTCCAGAGTACGATGCCTATTTGGAC-
A
TGGTTGACGGAGCTTCATGCTGCTTAGACACTGCCAGTTTTTGCCCTGCAAAGCTGCGCAGCTTTCCAAAGAAA-
C
ACTCCTATTTGGAACCCACAATACGATCGGCAGTGCCTTCAGCGATCCAGAACACGCTCCAGAACGTCCTGGCA-
G
CTGCCACAAAAAGAAATTGCAATGTCACGCAAATGAGAGAATTGCCCGTATTGGATTCGGCGGCCTTTAATGTG-
G
AATGCTTCAAGAAATATGCGTGTAATAATGAATATTGGGAAACGTTTAAAGAAAACCCCATCAGGCTTACTGAA-
G
AAAACGTGGTAAATTACATTACCAAATTAAAAGGACCAAAAGCTGCTGCTCTTTTTGCGAAGACACATAATTTG-
A
ATATGTTGCAGGACATACCAATGGACAGGTTTGTAATGGACTTAAAGAGAGACGTGAAAGTGACTCCAGGAACA-
A
AACATACTGAAGAACGGCCCAAGGTACAGGTGATCCAGGCTGCCGATCCGCTAGCAACAGCGTATCTGTGCGGA-
A
TCCACCGAGAGCTGGTTAGGAGATTAAATGCGGTCCTGCTTCCGAACATTCATACACTGTTTGATATGTCGGCT-
G
AAGACTTTGACGCTATTATAGCCGAGCACTTCCAGCCTGGGGATTGTGTTCTGGAAACTGACATCGCGTCGTTT-
G
ATAAAAGTGAGGACGACGCCATGGCTCTGACCGCGTTAATGATTCTGGAAGACTTAGGTGTGGACGCAGAGCTG-
T
TGACGCTGATTGAGGCGGCTTTCGGCGAAATTTCATCAATACATTTGCCCACTAAAACTAAATTTAAATTCGGA-
G
CCATGATGAAATCTGGAATGTTCCTCACACTGTTTGTGAACACAGTCATTAACATTGTAATCGCAAGCAGAGTG-
T
TGAGAGAACGGCTAACCGGATCACCATGTGCAGCATTCATTGGAGATGACAATATCGTGAAAGGAGTCAAATCG-
G
ACAAATTAATGGCAGACAGGTGCGCCACCTGGTTGAATATGGAAGTCAAGATTATAGATGCTGTGGTGGGCGAG-
A
AAGCGCCTTATTTCTGTGGAGGGTTTATTTTGTGTGACTCCGTGACCGGCACAGCGTGCCGTGTGGCAGACCCC-
C
TAAAAAGGCTGTTTAAGCTTGGCAAACCTCTGGCAGCAGACGATGAACATGATGATGACAGGAGAAGGGCATTG-
C
ATGAAGAGTCAACACGCTGGAACCGAGTGGGTATTCTTTCAGAGCTGTGCAAGGCAGTAGAATCAAGGTATGAA-
A
CCGTAGGAACTTCCATCATAGTTATGGCCATGACTACTCTAGCTAGCAGTGTTAAATCATTCAGCTACCTGAGA-
G ##STR00001## ##STR00002## ##STR00003##
CAGCAGCAATTGGCAAGCTGCTTACATAGAACTCGCGGCGATTGGCATGCCGCCTTAAAATTTTTATTTTATTT-
T
TCTTTTCTTTTCCGAATCGGATTTTGTTTTTAATATTTCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA-
G
GGTCGGCATGGCATCTCCACCTCCTCGCGGTCCGACCTGGGCATCCGAAGGAGGACGCACGTCCACTCGGATGG-
C
TAAGGGAGAGCCACGTTTAAACGCTAGAGCAAGACGTTTCCCGTTGAATATGGCTCATAACACCCCTTGTATTA-
C
TGTTTATGTAAGCAGACAGTTTTATTGTTCATGATGATATATTTTTATCTTGTGCAATGTAACATCAGAGATTT-
T
GAGACACAACGTGGCTTTGTTGAATAAATCGAACTTTTGCTGAGTTGAAGGATCAGATCACGCATCTTCCCGAC-
A
ACGCAGACCGTTCCGTGGCAAAGCAAAAGTTCAAAATCACCAACTGGTCCACCTACAACAAAGCTCTCATCAAC-
C
GTGGCTCCCTCACTTTCTGGCTGGATGATGGGGCGATTCAGGCCTGGTATGAGTCAGCAACACCTTCTTCACGA-
G
GCAGACCTCAGCGCTAGCGGAGTGTATACTGGCTTACTATGTTGGCACTGATGAGGGTGTCAGTGAAGTGCTTC-
A
TGTGGCAGGAGAAAAAAGGCTGCACCGGTGCGTCAGCAGAATATGTGATACAGGATATATTCCGCTTCCTCGCT-
C
ACTGACTCGCTACGCTCGGTCGTTCGACTGCGGCGAGCGGAAATGGCTTACGAACGGGGCGGAGATTTCCTGGA-
A
GATGCCAGGAAGATACTTAACAGGGAAGTGAGAGGGCCGCGGCAAAGCCGTTTTTCCATAGGCTCCGCCCCCCT-
G
ACAAGCATCACGAAATCTGACGCTCAAATCAGTGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTT-
C
CCCTGGCGGCTCCCTCGTGCGCTCTCCTGTTCCTGCCTTTCGGTTTACCGGTGTCATTCCGCTGTTATGGCCGC-
G
TTTGTCTCATTCCACGCCTGACACTCAGTTCCGGGTAGGCAGTTCGCTCCAAGCTGGACTGTATGCACGAACCC-
C
CCGTTCAGTCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGAAAGACATGCAAAAGCA-
C
CACTGGCAGCAGCCACTGGTAATTGATTTAGAGGAGTTAGTCTTGAAGTCATGCGCCGGTTAAGGCTAAACTGA-
A
AGGACAAGTTTTGGTGACTGCGCTCCTCCAAGCCAGTTACCTCGGTTCAAAGAGTTGGTAGCTCAGAGAACCTT-
C
GAAAAACCGCCCTGCAAGGCGGTTTTTTCGTTTTCAGAGCAAGAGATTACGCGCAGACCAAAACGATCTCAAGA-
A
GATCATCTTATTAAGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATC-
A
AAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAAC-
T
TGGTCTGACAGTTATTAGAAAAATTCATCCAGCAGACGATAAAACGCAATACGCTGGCTATCCGGTGCCGCAAT-
G
CCATACAGCACCAGAAAACGATCCGCCCATTCGCCGCCCAGTTCTTCCGCAATATCACGGGTGGCCAGCGCAAT-
A
TCCTGATAACGATCCGCCACGCCCAGACGGCCGCAATCAATAAAGCCGCTAAAACGGCCATTTTCCACCATAAT-
G
TTCGGCAGGCACGCATCACCATGGGTCACCACCAGATCTTCGCCATCCGGCATGCTCGCTTTCAGACGCGCAAA-
C
AGCTCTGCCGGTGCCAGGCCCTGATGTTCTTCATCCAGATCATCCTGATCCACCAGGCCCGCTTCCATACGGGT-
A
CGCGCACGTTCAATACGATGTTTCGCCTGATGATCAAACGGACAGGTCGCCGGGTCCAGGGTATGCAGACGACG-
C
ATGGCATCCGCCATAATGCTCACTTTTTCTGCCGGCGCCAGATGGCTAGACAGCAGATCCTGACCCGGCACTTC-
G
CCCAGCAGCAGCCAATCACGGCCCGCTTCGGTCACCACATCCAGCACCGCCGCACACGGAACACCGGTGGTGGC-
C
AGCCAGCTCAGACGCGCCGCTTCATCCTGCAGCTCGTTCAGCGCACCGCTCAGATCGGTTTTCACAAACAGCAC-
C
GGACGACCCTGCGCGCTCAGACGAAACACCGCCGCATCAGAGCAGCCAATGGTCTGCTGCGCCCAATCATAGCC-
A
AACAGACGTTCCACCCACGCTGCCGGGCTACCCGCATGCAGGCCATCCTGTTCAATCATACTCTTCCTTTTTCA-
A
TATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACA-
A
ATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTAAATTGTAAGCGTTAATATTTTGTTAAAATTCGCG-
T
TAAATTTTTGTTAAATCAGCTCATTTTTTAACCAATAGGCCGAAATCGGCAAAATCCCTTATAAATCAAAAGAA-
T
AGACCGAGATAGGGTTGAGTGGCCGCTACAGGGCGCTCCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGG-
G
CGTTTCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGG-
T AACGCCAGGGTTTTCCCAGTCACACGCGTAATACGACTCACTATAG
TABLE-US-00042 A527 Vector:
SGP-gH-SGP-gL-SGP-UL128-EMCV-UL130-EV71-UL131
ATAGGCGGCGCATGAGAGAAGCCCAGACCAATTACCTACCCAAAATGGAGAAAGTTCACGTTGACATCGAGGAA-
G
ACAGCCCATTCCTCAGAGCTTTGCAGCGGAGCTTCCCGCAGTTTGAGGTAGAAGCCAAGCAGGTCACTGATAAT-
G
ACCATGCTAATGCCAGAGCGTTTTCGCATCTGGCTTCAAAACTGATCGAAACGGAGGTGGACCCATCCGACACG-
A
TCCTTGACATTGGAAGTGCGCCCGCCCGCAGAATGTATTCTAAGCACAAGTATCATTGTATCTGTCCGATGAGA-
T
GTGCGGAAGATCCGGACAGATTGTATAAGTATGCAACTAAGCTGAAGAAAAACTGTAAGGAAATAACTGATAAG-
G
AATTGGACAAGAAAATGAAGGAGCTCGCCGCCGTCATGAGCGACCCTGACCTGGAAACTGAGACTATGTGCCTC-
C
ACGACGACGAGTCGTGTCGCTACGAAGGGCAAGTCGCTGTTTACCAGGATGTATACGCGGTTGACGGACCGACA-
A
GTCTCTATCACCAAGCCAATAAGGGAGTTAGAGTCGCCTACTGGATAGGCTTTGACACCACCCCTTTTATGTTT-
A
AGAACTTGGCTGGAGCATATCCATCATACTCTACCAACTGGGCCGACGAAACCGTGTTAACGGCTCGTAACATA-
G
GCCTATGCAGCTCTGACGTTATGGAGCGGTCACGTAGAGGGATGTCCATTCTTAGAAAGAAGTATTTGAAACCA-
T
CCAACAATGTTCTATTCTCTGTTGGCTCGACCATCTACCACGAGAAGAGGGACTTACTGAGGAGCTGGCACCTG-
C
CGTCTGTATTTCACTTACGTGGCAAGCAAAATTACACATGTCGGTGTGAGACTATAGTTAGTTGCGACGGGTAC-
G
TCGTTAAAAGAATAGCTATCAGTCCAGGCCTGTATGGGAAGCCTTCAGGCTATGCTGCTACGATGCACCGCGAG-
G
GATTCTTGTGCTGCAAAGTGACAGACACATTGAACGGGGAGAGGGTCTCTTTTCCCGTGTGCACGTATGTGCCA-
G
CTACATTGTGTGACCAAATGACTGGCATACTGGCAACAGATGTCAGTGCGGACGACGCGCAAAAACTGCTGGTT-
G
GGCTCAACCAGCGTATAGTCGTCAACGGTCGCACCCAGAGAAACACCAATACCATGAAAAATTACCTTTTGCCC-
G
TAGTGGCCCAGGCATTTGCTAGGTGGGCAAAGGAATATAAGGAAGATCAAGAAGATGAAAGGCCACTAGGACTA-
C
GAGATAGACAGTTAGTCATGGGGTGTTGTTGGGCTTTTAGAAGGCACAAGATAACATCTATTTATAAGCGCCCG-
G
ATACCCAAACCATCATCAAAGTGAACAGCGATTTCCACTCATTCGTGCTGCCCAGGATAGGCAGTAACACATTG-
G
AGATCGGGCTGAGAACAAGAATCAGGAAAATGTTAGAGGAGCACAAGGAGCCGTCACCTCTCATTACCGCCGAG-
G
ACGTACAAGAAGCTAAGTGCGCAGCCGATGAGGCTAAGGAGGTGCGTGAAGCCGAGGAGTTGCGCGCAGCTCTA-
C
CACCTTTGGCAGCTGATGTTGAGGAGCCCACTCTGGAAGCCGATGTAGACTTGATGTTACAAGAGGCTGGGGCC-
G
GCTCAGTGGAGACACCTCGTGGCTTGATAAAGGTTACCAGCTACGATGGCGAGGACAAGATCGGCTCTTACGCT-
G
TGCTTTCTCCGCAGGCTGTACTCAAGAGTGAAAAATTATCTTGCATCCACCCTCTCGCTGAACAAGTCATAGTG-
A
TAACACACTCTGGCCGAAAAGGGCGTTATGCCGTGGAACCATACCATGGTAAAGTAGTGGTGCCAGAGGGACAT-
G
CAATACCCGTCCAGGACTTTCAAGCTCTGAGTGAAAGTGCCACCATTGTGTACAACGAACGTGAGTTCGTAAAC-
A
GGTACCTGCACCATATTGCCACACATGGAGGAGCGCTGAACACTGATGAAGAATATTACAAAACTGTCAAGCCC-
A
GCGAGCACGACGGCGAATACCTGTACGACATCGACAGGAAACAGTGCGTCAAGAAAGAACTAGTCACTGGGCTA-
G
GGCTCACAGGCGAGCTGGTGGATCCTCCCTTCCATGAATTCGCCTACGAGAGTCTGAGAACACGACCAGCCGCT-
C
CTTACCAAGTACCAACCATAGGGGTGTATGGCGTGCCAGGATCAGGCAAGTCTGGCATCATTAAAAGCGCAGTC-
A
CCAAAAAAGATCTAGTGGTGAGCGCCAAGAAAGAAAACTGTGCAGAAATTATAAGGGACGTCAAGAAAATGAAA-
G
GGCTGGACGTCAATGCCAGAACTGTGGACTCAGTGCTCTTGAATGGATGCAAACACCCCGTAGAGACCCTGTAT-
A
TTGACGAAGCTTTTGCTTGTCATGCAGGTACTCTCAGAGCGCTCATAGCCATTATAAGACCTAAAAAGGCAGTG-
C
TCTGCGGGGATCCCAAACAGTGCGGTTTTTTTAACATGATGTGCCTGAAAGTGCATTTTAACCACGAGATTTGC-
A
CACAAGTCTTCCACAAAAGCATCTCTCGCCGTTGCACTAAATCTGTGACTTCGGTCGTCTCAACCTTGTTTTAC-
G
ACAAAAAAATGAGAACGACGAATCCGAAAGAGACTAAGATTGTGATTGACACTACCGGCAGTACCAAACCTAAG-
C
AGGACGATCTCATTCTCACTTGTTTCAGAGGGTGGGTGAAGCAGTTGCAAATAGATTACAAAGGCAACGAAATA-
A
TGACGGCAGCTGCCTCTCAAGGGCTGACCCGTAAAGGTGTGTATGCCGTTCGGTACAAGGTGAATGAAAATCCT-
C
TGTACGCACCCACCTCAGAACATGTGAACGTCCTACTGACCCGCACGGAGGACCGCATCGTGTGGAAAACACTA-
G
CCGGCGACCCATGGATAAAAACACTGACTGCCAAGTACCCTGGGAATTTCACTGCCACGATAGAGGAGTGGCAA-
G
CAGAGCATGATGCCATCATGAGGCACATCTTGGAGAGACCGGACCCTACCGACGTCTTCCAGAATAAGGCAAAC-
G
TGTGTTGGGCCAAGGCTTTAGTGCCGGTGCTGAAGACCGCTGGCATAGACATGACCACTGAACAATGGAACACT-
G
TGGATTATTTTGAAACGGACAAAGCTCACTCAGCAGAGATAGTATTGAACCAACTATGCGTGAGGTTCTTTGGA-
C
TCGATCTGGACTCCGGTCTATTTTCTGCACCCACTGTTCCGTTATCCATTAGGAATAATCACTGGGATAACTCC-
C
CGTCGCCTAACATGTACGGGCTGAATAAAGAAGTGGTCCGTCAGCTCTCTCGCAGGTACCCACAACTGCCTCGG-
G
CAGTTGCCACTGGAAGAGTCTATGACATGAACACTGGTACACTGCGCAATTATGATCCGCGCATAAACCTAGTA-
C
CTGTAAACAGAAGACTGCCTCATGCTTTAGTCCTCCACCATAATGAACACCCACAGAGTGACTTTTCTTCATTC-
G
TCAGCAAATTGAAGGGCAGAACTGTCCTGGTGGTCGGGGAAAAGTTGTCCGTCCCAGGCAAAATGGTTGACTGG-
T
TGTCAGACCGGCCTGAGGCTACCTTCAGAGCTCGGCTGGATTTAGGCATCCCAGGTGATGTGCCCAAATATGAC-
A
TAATATTTGTTAATGTGAGGACCCCATATAAATACCATCACTATCAGCAGTGTGAAGACCATGCCATTAAGCTT-
A
GCATGTTGACCAAGAAAGCTTGTCTGCATCTGAATCCCGGCGGAACCTGTGTCAGCATAGGTTATGGTTACGCT-
G
ACAGGGCCAGCGAAAGCATCATTGGTGCTATAGCGCGGCAGTTCAAGTTTTCCCGGGTATGCAAACCGAAATCC-
T
CACTTGAAGAGACGGAAGTTCTGTTTGTATTCATTGGGTACGATCGCAAGGCCCGTACGCACAATCCTTACAAG-
C
TTTCATCAACCTTGACCAACATTTATACAGGTTCCAGACTCCACGAAGCCGGATGTGCACCCTCATATCATGTG-
G
TGCGAGGGGATATTGCCACGGCCACCGAAGGAGTGATTATAAATGCTGCTAACAGCAAAGGACAACCTGGCGGA-
G
GGGTGTGCGGAGCGCTGTATAAGAAATTCCCGGAAAGCTTCGATTTACAGCCGATCGAAGTAGGAAAAGCGCGA-
C
TGGTCAAAGGTGCAGCTAAACATATCATTCATGCCGTAGGACCAAACTTCAACAAAGTTTCGGAGGTTGAAGGT-
G
ACAAACAGTTGGCAGAGGCTTATGAGTCCATCGCTAAGATTGTCAACGATAACAATTACAAGTCAGTAGCGATT-
C
CACTGTTGTCCACCGGCATCTTTTCCGGGAACAAAGATCGACTAACCCAATCATTGAACCATTTGCTGACAGCT-
T
TAGACACCACTGATGCAGATGTAGCCATATACTGCAGGGACAAGAAATGGGAAATGACTCTCAAGGAAGCAGTG-
G
CTAGGAGAGAAGCAGTGGAGGAGATATGCATATCCGACGACTCTTCAGTGACAGAACCTGATGCAGAGCTGGTG-
A
GGGTGCATCCGAAGAGTTCTTTGGCTGGAAGGAAGGGCTACAGCACAAGCGATGGCAAAACTTTCTCATATTTG-
G
AAGGGACCAAGTTTCACCAGGCGGCCAAGGATATAGCAGAAATTAATGCCATGTGGCCCGTTGCAACGGAGGCC-
A
ATGAGCAGGTATGCATGTATATCCTCGGAGAAAGCATGAGCAGTATTAGGTCGAAATGCCCCGTCGAAGAGTCG-
G
AAGCCTCCACACCACCTAGCACGCTGCCTTGCTTGTGCATCCATGCCATGACTCCAGAAAGAGTACAGCGCCTA-
A
AAGCCTCACGTCCAGAACAAATTACTGTGTGCTCATCCTTTCCATTGCCGAAGTATAGAATCACTGGTGTGCAG-
A
AGATCCAATGCTCCCAGCCTATATTGTTCTCACCGAAAGTGCCTGCGTATATTCATCCAAGGAAGTATCTCGTG-
G
AAACACCACCGGTAGACGAGACTCCGGAGCCATCGGCAGAGAACCAATCCACAGAGGGGACACCTGAACAACCA-
C
CACTTATAACCGAGGATGAGACCAGGACTAGAACGCCTGAGCCGATCATCATCGAAGAGGAAGAAGAGGATAGC-
A
TAAGTTTGCTGTCAGATGGCCCGACCCACCAGGTGCTGCAAGTCGAGGCAGACATTCACGGGCCGCCCTCTGTA-
T
CTAGCTCATCCTGGTCCATTCCTCATGCATCCGACTTTGATGTGGACAGTTTATCCATACTTGACACCCTGGAG-
G
GAGCTAGCGTGACCAGCGGGGCAACGTCAGCCGAGACTAACTCTTACTTCGCAAAGAGTATGGAGTTTCTGGCG-
C
GACCGGTGCCTGCGCCTCGAACAGTATTCAGGAACCCTCCACATCCCGCTCCGCGCACAAGAACACCGTCACTT-
G
CACCCAGCAGGGCCTGCTCGAGAACCAGCCTAGTTTCCACCCCGCCAGGCGTGAATAGGGTGATCACTAGAGAG-
G
AGCTCGAGGCGCTTACCCCGTCACGCACTCCTAGCAGGTCGGTCTCGAGAACCAGCCTGGTCTCCAACCCGCCA-
G
GCGTAAATAGGGTGATTACAAGAGAGGAGTTTGAGGCGTTCGTAGCACAACAACAATGACGGTTTGATGCGGGT-
G
CATACATCTTTTCCTCCGACACCGGTCAAGGGCATTTACAACAAAAATCAGTAAGGCAAACGGTGCTATCCGAA-
G
TGGTGTTGGAGAGGACCGAATTGGAGATTTCGTATGCCCCGCGCCTCGACCAAGAAAAAGAAGAATTACTACGC-
A
AGAAATTACAGTTAAATCCCACACCTGCTAACAGAAGCAGATACCAGTCCAGGAAGGTGGAGAACATGAAAGCC-
A
TAACAGCTAGACGTATTCTGCAAGGCCTAGGGCATTATTTGAAGGCAGAAGGAAAAGTGGAGTGCTACCGAACC-
C
TGCATCCTGTTCCTTTGTATTCATCTAGTGTGAACCGTGCCTTTTCAAGCCCCAAGGTCGCAGTGGAAGCCTGT-
A
ACGCCATGTTGAAAGAGAACTTTCCGACTGTGGCTTCTTACTGTATTATTCCAGAGTACGATGCCTATTTGGAC-
A
TGGTTGACGGAGCTTCATGCTGCTTAGACACTGCCAGTTTTTGCCCTGCAAAGCTGCGCAGCTTTCCAAAGAAA-
C
ACTCCTATTTGGAACCCACAATACGATCGGCAGTGCCTTCAGCGATCCAGAACACGCTCCAGAACGTCCTGGCA-
G
CTGCCACAAAAAGAAATTGCAATGTCACGCAAATGAGAGAATTGCCCGTATTGGATTCGGCGGCCTTTAATGTG-
G
AATGCTTCAAGAAATATGCGTGTAATAATGAATATTGGGAAACGTTTAAAGAAAACCCCATCAGGCTTACTGAA-
G
AAAACGTGGTAAATTACATTACCAAATTAAAAGGACCAAAAGCTGCTGCTCTTTTTGCGAAGACACATAATTTG-
A
ATATGTTGCAGGACATACCAATGGACAGGTTTGTAATGGACTTAAAGAGAGACGTGAAAGTGACTCCAGGAACA-
A
AACATACTGAAGAACGGCCCAAGGTACAGGTGATCCAGGCTGCCGATCCGCTAGCAACAGCGTATCTGTGCGGA-
A
TCCACCGAGAGCTGGTTAGGAGATTAAATGCGGTCCTGCTTCCGAACATTCATACACTGTTTGATATGTCGGCT-
G
AAGACTTTGACGCTATTATAGCCGAGCACTTCCAGCCTGGGGATTGTGTTCTGGAAACTGACATCGCGTCGTTT-
G
ATAAAAGTGAGGACGACGCCATGGCTCTGACCGCGTTAATGATTCTGGAAGACTTAGGTGTGGACGCAGAGCTG-
T
TGACGCTGATTGAGGCGGCTTTCGGCGAAATTTCATCAATACATTTGCCCACTAAAACTAAATTTAAATTCGGA-
G
CCATGATGAAATCTGGAATGTTCCTCACACTGTTTGTGAACACAGTCATTAACATTGTAATCGCAAGCAGAGTG-
T
TGAGAGAACGGCTAACCGGATCACCATGTGCAGCATTCATTGGAGATGACAATATCGTGAAAGGAGTCAAATCG-
G
ACAAATTAATGGCAGACAGGTGCGCCACCTGGTTGAATATGGAAGTCAAGATTATAGATGCTGTGGTGGGCGAG-
A
AAGCGCCTTATTTCTGTGGAGGGTTTATTTTGTGTGACTCCGTGACCGGCACAGCGTGCCGTGTGGCAGACCCC-
C
TAAAAAGGCTGTTTAAGCTTGGCAAACCTCTGGCAGCAGACGATGAACATGATGATGACAGGAGAAGGGCATTG-
C
ATGAAGAGTCAACACGCTGGAACCGAGTGGGTATTCTTTCAGAGCTGTGCAAGGCAGTAGAATCAAGGTATGAA-
A
CCGTAGGAACTTCCATCATAGTTATGGCCATGACTACTCTAGCTAGCAGTGTTAAATCATTCAGCTACCTGAGA-
G ##STR00004## ##STR00005## ##STR00006## ##STR00007## ##STR00008##
CCGGTGTGCGTTTGTCTATATGTTATTTTCCACCATATTGCCGTCTTTTGGCAATGTGAGGGCCCGGAAACCTG-
G
CCCTGTCTTCTTGACGAGCATTCCTAGGGGTCTTTCCCCTCTCGCCAAAGGAATGCAAGGTCTGTTGAATGTCG-
T
GAAGGAAGCAGTTCCTCTGGAAGCTTCTTGAAGACAAACAACGTCTGTAGCGACCCTTTGCAGGCAGCGGAACC-
C
CCCACCTGGCGACAGGTGCCTCTGCGGCCAAAAGCCACGTGTATAAGATACACCTGCAAAGGCGGCACAACCCC-
A
GTGCCACGTTGTGAGTTGGATAGTTGTGGAAAGAGTCAAATGGCTCTCCTCAAGCGTATTCAACAAGGGGCTGA-
A
GGATGCCCAGAAGGTACCCCATTGTATGGGATCTGATCTGGGGCCTCGGTGCACATGCTTTACATGTGTTTAGT-
C ##STR00009##
GATTTGCAACTTAGAAGCAACGCAAACCAGATCAATAGTAGGTGTGACATACCAGTCGCATCTTGATCAAGCAC-
T
TCTGTATCCCCGGACCGAGTATCAATAGACTGTGCACACGGTTGAAGGAGAAAACGTCCGTTACCCGGCTAACT-
A
CTTCGAGAAGCCTAGTAACGCCATTGAAGTTGCAGAGTGTTTCGCTCAGCACTCCCCCCGTGTAGATCAGGTCG-
A
TGAGTCACCGCATTCCCCACGGGCGACCGTGGCGGTGGCTGCGTTGGCGGCCTGCCTATGGGGTAACCCATAGG-
A
CGCTCTAATACGGACATGGCGTGAAGAGTCTATTGAGCTAGTTAGTAGTCCTCCGGCCCCTGAATGCGGCTAAT-
C
CTAACTGCGGAGCACATACCCTTAATCCAAAGGGCAGTGTGTCGTAACGGGCAACTCTGCAGCGGAACCGACTA-
C
TTTGGGTGTCCGTGTTTCTTTTTATTCTTGTATTGGCTGCTTATGGTGACAATTAAAGAATTGTTACCATATAG-
C
TATTGGATTGGCCATCCAGTGTCAAACAGAGCTATTGTATATCTCTTTGTTGGATTCACACCTCTCACTCTTGA-
A ##STR00010## ##STR00011##
TGCAGGATACAGCAGCAATTGGCAAGCTGCTTACATAGAACTCGCGGCGATTGGCATGCCGCCTTAAAATTTTT-
A
TTTTATTTTTCTTTTCTTTTCCGAATCGGATTTTGTTTTTAATATTTCAAAAAAAAAAAAAAAAAAAAAAAAAA-
A
AAAAAAAAGGGTCGGCATGGCATCTCCACCTCCTCGCGGTCCGACCTGGGCATCCGAAGGAGGACGCACGTCCA-
C
TCGGATGGCTAAGGGAGAGCCACGTTTAAACGCTAGAGCAAGACGTTTCCCGTTGAATATGGCTCATAACACCC-
C
TTGTATTACTGTTTATGTAAGCAGACAGTTTTATTGTTCATGATGATATATTTTTATCTTGTGCAATGTAACAT-
C
AGAGATTTTGAGACACAACGTGGCTTTGTTGAATAAATCGAACTTTTGCTGAGTTGAAGGATCAGATCACGCAT-
C
TTCCCGACAACGCAGACCGTTCCGTGGCAAAGCAAAAGTTCAAAATCACCAACTGGTCCACCTACAACAAAGCT-
C
TCATCAACCGTGGCTCCCTCACTTTCTGGCTGGATGATGGGGCGATTCAGGCCTGGTATGAGTCAGCAACACCT-
T
CTTCACGAGGCAGACCTCAGCGCTAGCGGAGTGTATACTGGCTTACTATGTTGGCACTGATGAGGGTGTCAGTG-
A
AGTGCTTCATGTGGCAGGAGAAAAAAGGCTGCACCGGTGCGTCAGCAGAATATGTGATACAGGATATATTCCGC-
T
TCCTCGCTCACTGACTCGCTACGCTCGGTCGTTCGACTGCGGCGAGCGGAAATGGCTTACGAACGGGGCGGAGA-
T
TTCCTGGAAGATGCCAGGAAGATACTTAACAGGGAAGTGAGAGGGCCGCGGCAAAGCCGTTTTTCCATAGGCTC-
C
GCCCCCCTGACAAGCATCACGAAATCTGACGCTCAAATCAGTGGTGGCGAAACCCGACAGGACTATAAAGATAC-
C
AGGCGTTTCCCCTGGCGGCTCCCTCGTGCGCTCTCCTGTTCCTGCCTTTCGGTTTACCGGTGTCATTCCGCTGT-
T
ATGGCCGCGTTTGTCTCATTCCACGCCTGACACTCAGTTCCGGGTAGGCAGTTCGCTCCAAGCTGGACTGTATG-
C
ACGAACCCCCCGTTCAGTCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGAAAGACAT-
G
CAAAAGCACCACTGGCAGCAGCCACTGGTAATTGATTTAGAGGAGTTAGTCTTGAAGTCATGCGCCGGTTAAGG-
C
TAAACTGAAAGGACAAGTTTTGGTGACTGCGCTCCTCCAAGCCAGTTACCTCGGTTCAAAGAGTTGGTAGCTCA-
G
AGAACCTTCGAAAAACCGCCCTGCAAGGCGGTTTTTTCGTTTTCAGAGCAAGAGATTACGCGCAGACCAAAACG-
A
TCTCAAGAAGATCATCTTATTAAGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCAT-
G
AGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATA-
T
GAGTAAACTTGGTCTGACAGTTATTAGAAAAATTCATCCAGCAGACGATAAAACGCAATACGCTGGCTATCCGG-
T
GCCGCAATGCCATACAGCACCAGAAAACGATCCGCCCATTCGCCGCCCAGTTCTTCCGCAATATCACGGGTGGC-
C
AGCGCAATATCCTGATAACGATCCGCCACGCCCAGACGGCCGCAATCAATAAAGCCGCTAAAACGGCCATTTTC-
C
ACCATAATGTTCGGCAGGCACGCATCACCATGGGTCACCACCAGATCTTCGCCATCCGGCATGCTCGCTTTCAG-
A
CGCGCAAACAGCTCTGCCGGTGCCAGGCCCTGATGTTCTTCATCCAGATCATCCTGATCCACCAGGCCCGCTTC-
C
ATACGGGTACGCGCACGTTCAATACGATGTTTCGCCTGATGATCAAACGGACAGGTCGCCGGGTCCAGGGTATG-
C
AGACGACGCATGGCATCCGCCATAATGCTCACTTTTTCTGCCGGCGCCAGATGGCTAGACAGCAGATCCTGACC-
C
GGCACTTCGCCCAGCAGCAGCCAATCACGGCCCGCTTCGGTCACCACATCCAGCACCGCCGCACACGGAACACC-
G
GTGGTGGCCAGCCAGCTCAGACGCGCCGCTTCATCCTGCAGCTCGTTCAGCGCACCGCTCAGATCGGTTTTCAC-
A
AACAGCACCGGACGACCCTGCGCGCTCAGACGAAACACCGCCGCATCAGAGCAGCCAATGGTCTGCTGCGCCCA-
A
TCATAGCCAAACAGACGTTCCACCCACGCTGCCGGGCTACCCGCATGCAGGCCATCCTGTTCAATCATACTCTT-
C
CTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAA-
A
AATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTAAATTGTAAGCGTTAATATTTTGTTA-
A
AATTCGCGTTAAATTTTTGTTAAATCAGCTCATTTTTTAACCAATAGGCCGAAATCGGCAAAATCCCTTATAAA-
T
CAAAAGAATAGACCGAGATAGGGTTGAGTGGCCGCTACAGGGCGCTCCCATTCGCCATTCAGGCTGCGCAACTG-
T
TGGGAAGGGCGTTTCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGAT-
T AAGTTGGGTAACGCCAGGGTTTTCCCAGTCACACGCGTAATACGACTCACTATAG
TABLE-US-00043 A531 Vector: SGP-gHsol-SGP-gL
ATAGGCGGCGCATGAGAGAAGCCCAGACCAATTACCTACCCAAAATGGAGAAAGTTCACGTTGACATCGAGGAA-
G
ACAGCCCATTCCTCAGAGCTTTGCAGCGGAGCTTCCCGCAGTTTGAGGTAGAAGCCAAGCAGGTCACTGATAAT-
G
ACCATGCTAATGCCAGAGCGTTTTCGCATCTGGCTTCAAAACTGATCGAAACGGAGGTGGACCCATCCGACACG-
A
TCCTTGACATTGGAAGTGCGCCCGCCCGCAGAATGTATTCTAAGCACAAGTATCATTGTATCTGTCCGATGAGA-
T
GTGCGGAAGATCCGGACAGATTGTATAAGTATGCAACTAAGCTGAAGAAAAACTGTAAGGAAATAACTGATAAG-
G
AATTGGACAAGAAAATGAAGGAGCTCGCCGCCGTCATGAGCGACCCTGACCTGGAAACTGAGACTATGTGCCTC-
C
ACGACGACGAGTCGTGTCGCTACGAAGGGCAAGTCGCTGTTTACCAGGATGTATACGCGGTTGACGGACCGACA-
A
GTCTCTATCACCAAGCCAATAAGGGAGTTAGAGTCGCCTACTGGATAGGCTTTGACACCACCCCTTTTATGTTT-
A
AGAACTTGGCTGGAGCATATCCATCATACTCTACCAACTGGGCCGACGAAACCGTGTTAACGGCTCGTAACATA-
G
GCCTATGCAGCTCTGACGTTATGGAGCGGTCACGTAGAGGGATGTCCATTCTTAGAAAGAAGTATTTGAAACCA-
T
CCAACAATGTTCTATTCTCTGTTGGCTCGACCATCTACCACGAGAAGAGGGACTTACTGAGGAGCTGGCACCTG-
C
CGTCTGTATTTCACTTACGTGGCAAGCAAAATTACACATGTCGGTGTGAGACTATAGTTAGTTGCGACGGGTAC-
G
TCGTTAAAAGAATAGCTATCAGTCCAGGCCTGTATGGGAAGCCTTCAGGCTATGCTGCTACGATGCACCGCGAG-
G
GATTCTTGTGCTGCAAAGTGACAGACACATTGAACGGGGAGAGGGTCTCTTTTCCCGTGTGCACGTATGTGCCA-
G
CTACATTGTGTGACCAAATGACTGGCATACTGGCAACAGATGTCAGTGCGGACGACGCGCAAAAACTGCTGGTT-
G
GGCTCAACCAGCGTATAGTCGTCAACGGTCGCACCCAGAGAAACACCAATACCATGAAAAATTACCTTTTGCCC-
G
TAGTGGCCCAGGCATTTGCTAGGTGGGCAAAGGAATATAAGGAAGATCAAGAAGATGAAAGGCCACTAGGACTA-
C
GAGATAGACAGTTAGTCATGGGGTGTTGTTGGGCTTTTAGAAGGCACAAGATAACATCTATTTATAAGCGCCCG-
G
ATACCCAAACCATCATCAAAGTGAACAGCGATTTCCACTCATTCGTGCTGCCCAGGATAGGCAGTAACACATTG-
G
AGATCGGGCTGAGAACAAGAATCAGGAAAATGTTAGAGGAGCACAAGGAGCCGTCACCTCTCATTACCGCCGAG-
G
ACGTACAAGAAGCTAAGTGCGCAGCCGATGAGGCTAAGGAGGTGCGTGAAGCCGAGGAGTTGCGCGCAGCTCTA-
C
CACCTTTGGCAGCTGATGTTGAGGAGCCCACTCTGGAAGCCGATGTCGACTTGATGTTACAAGAGGCTGGGGCC-
G
GCTCAGTGGAGACACCTCGTGGCTTGATAAAGGTTACCAGCTACGATGGCGAGGACAAGATCGGCTCTTACGCT-
G
TGCTTTCTCCGCAGGCTGTACTCAAGAGTGAAAAATTATCTTGCATCCACCCTCTCGCTGAACAAGTCATAGTG-
A
TAACACACTCTGGCCGAAAAGGGCGTTATGCCGTGGAACCATACCATGGTAAAGTAGTGGTGCCAGAGGGACAT-
G
CAATACCCGTCCAGGACTTTCAAGCTCTGAGTGAAAGTGCCACCATTGTGTACAACGAACGTGAGTTCGTAAAC-
A
GGTACCTGCACCATATTGCCACACATGGAGGAGCGCTGAACACTGATGAAGAATATTACAAAACTGTCAAGCCC-
A
GCGAGCACGACGGCGAATACCTGTACGACATCGACAGGAAACAGTGCGTCAAGAAAGAACTAGTCACTGGGCTA-
G
GGCTCACAGGCGAGCTGGTGGATCCTCCCTTCCATGAATTCGCCTACGAGAGTCTGAGAACACGACCAGCCGCT-
C
CTTACCAAGTACCAACCATAGGGGTGTATGGCGTGCCAGGATCAGGCAAGTCTGGCATCATTAAAAGCGCAGTC-
A
CCAAAAAAGATCTAGTGGTGAGCGCCAAGAAAGAAAACTGTGCAGAAATTATAAGGGACGTCAAGAAAATGAAA-
G
GGCTGGACGTCAATGCCAGAACTGTGGACTCAGTGCTCTTGAATGGATGCAAACACCCCGTAGAGACCCTGTAT-
A
TTGACGAAGCTTTTGCTTGTCATGCAGGTACTCTCAGAGCGCTCATAGCCATTATAAGACCTAAAAAGGCAGTG-
C
TCTGCGGGGATCCCAAACAGTGCGGTTTTTTTAACATGATGTGCCTGAAAGTGCATTTTAACCACGAGATTTGC-
A
CACAAGTCTTCCACAAAAGCATCTCTCGCCGTTGCACTAAATCTGTGACTTCGGTCGTCTCAACCTTGTTTTAC-
G
ACAAAAAAATGAGAACGACGAATCCGAAAGAGACTAAGATTGTGATTGACACTACCGGCAGTACCAAACCTAAG-
C
AGGACGATCTCATTCTCACTTGTTTCAGAGGGTGGGTGAAGCAGTTGCAAATAGATTACAAAGGCAACGAAATA-
A
TGACGGCAGCTGCCTCTCAAGGGCTGACCCGTAAAGGTGTGTATGCCGTTCGGTACAAGGTGAATGAAAATCCT-
C
TGTACGCACCCACCTCAGAACATGTGAACGTCCTACTGACCCGCACGGAGGACCGCATCGTGTGGAAAACACTA-
G
CCGGCGACCCATGGATAAAAACACTGACTGCCAAGTACCCTGGGAATTTCACTGCCACGATAGAGGAGTGGCAA-
G
CAGAGCATGATGCCATCATGAGGCACATCTTGGAGAGACCGGACCCTACCGACGTCTTCCAGAATAAGGCAAAC-
G
TGTGTTGGGCCAAGGCTTTAGTGCCGGTGCTGAAGACCGCTGGCATAGACATGACCACTGAACAATGGAACACT-
G
TGGATTATTTTGAAACGGACAAAGCTCACTCAGCAGAGATAGTATTGAACCAACTATGCGTGAGGTTCTTTGGA-
C
TCGATCTGGACTCCGGTCTATTTTCTGCACCCACTGTTCCGTTATCCATTAGGAATAATCACTGGGATAACTCC-
C
CGTCGCCTAACATGTACGGGCTGAATAAAGAAGTGGTCCGTCAGCTCTCTCGCAGGTACCCACAACTGCCTCGG-
G
CAGTTGCCACTGGAAGAGTCTATGACATGAACACTGGTACACTGCGCAATTATGATCCGCGCATAAACCTAGTA-
C
CTGTAAACAGAAGACTGCCTCATGCTTTAGTCCTCCACCATAATGAACACCCACAGAGTGACTTTTCTTCATTC-
G
TCAGCAAATTGAAGGGCAGAACTGTCCTGGTGGTCGGGGAAAAGTTGTCCGTCCCAGGCAAAATGGTTGACTGG-
T
TGTCAGACCGGCCTGAGGCTACCTTCAGAGCTCGGCTGGATTTAGGCATCCCAGGTGATGTGCCCAAATATGAC-
A
TAATATTTGTTAATGTGAGGACCCCATATAAATACCATCACTATCAGCAGTGTGAAGACCATGCCATTAAGCTT-
A
GCATGTTGACCAAGAAAGCTTGTCTGCATCTGAATCCCGGCGGAACCTGTGTCAGCATAGGTTATGGTTACGCT-
G
ACAGGGCCAGCGAAAGCATCATTGGTGCTATAGCGCGGCAGTTCAAGTTTTCCCGGGTATGCAAACCGAAATCC-
T
CACTTGAAGAGACGGAAGTTCTGTTTGTATTCATTGGGTACGATCGCAAGGCCCGTACGCACAATCCTTACAAG-
C
TTTCATCAACCTTGACCAACATTTATACAGGTTCCAGACTCCACGAAGCCGGATGTGCACCCTCATATCATGTG-
G
TGCGAGGGGATATTGCCACGGCCACCGAAGGAGTGATTATAAATGCTGCTAACAGCAAAGGACAACCTGGCGGA-
G
GGGTGTGCGGAGCGCTGTATAAGAAATTCCCGGAAAGCTTCGATTTACAGCCGATCGAAGTAGGAAAAGCGCGA-
C
TGGTCAAAGGTGCAGCTAAACATATCATTCATGCCGTAGGACCAAACTTCAACAAAGTTTCGGAGGTTGAAGGT-
G
ACAAACAGTTGGCAGAGGCTTATGAGTCCATCGCTAAGATTGTCAACGATAACAATTACAAGTCAGTAGCGATT-
C
CACTGTTGTCCACCGGCATCTTTTCCGGGAACAAAGATCGACTAACCCAATCATTGAACCATTTGCTGACAGCT-
T
TAGACACCACTGATGCAGATGTAGCCATATACTGCAGGGACAAGAAATGGGAAATGACTCTCAAGGAAGCAGTG-
G
CTAGGAGAGAAGCAGTGGAGGAGATATGCATATCCGACGACTCTTCAGTGACAGAACCTGATGCAGAGCTGGTG-
A
GGGTGCATCCGAAGAGTTCTTTGGCTGGAAGGAAGGGCTACAGCACAAGCGATGGCAAAACTTTCTCATATTTG-
G
AAGGGACCAAGTTTCACCAGGCGGCCAAGGATATAGCAGAAATTAATGCCATGTGGCCCGTTGCAACGGAGGCC-
A
ATGAGCAGGTATGCATGTATATCCTCGGAGAAAGCATGAGCAGTATTAGGTCGAAATGCCCCGTCGAAGAGTCG-
G
AAGCCTCCACACCACCTAGCACGCTGCCTTGCTTGTGCATCCATGCCATGACTCCAGAAAGAGTACAGCGCCTA-
A
AAGCCTCACGTCCAGAACAAATTACTGTGTGCTCATCCTTTCCATTGCCGAAGTATAGAATCACTGGTGTGCAG-
A
AGATCCAATGCTCCCAGCCTATATTGTTCTCACCGAAAGTGCCTGCGTATATTCATCCAAGGAAGTATCTCGTG-
G
AAACACCACCGGTAGACGAGACTCCGGAGCCATCGGCAGAGAACCAATCCACAGAGGGGACACCTGAACAACCA-
C
CACTTATAACCGAGGATGAGACCAGGACTAGAACGCCTGAGCCGATCATCATCGAAGAGGAAGAAGAGGATAGC-
A
TAAGTTTGCTGTCAGATGGCCCGACCCACCAGGTGCTGCAAGTCGAGGCAGACATTCACGGGCCGCCCTCTGTA-
T
CTAGCTCATCCTGGTCCATTCCTCATGCATCCGACTTTGATGTGGACAGTTTATCCATACTTGACACCCTGGAG-
G
GAGCTAGCGTGACCAGCGGGGCAACGTCAGCCGAGACTAACTCTTACTTCGCAAAGAGTATGGAGTTTCTGGCG-
C
GACCGGTGCCTGCGCCTCGAACAGTATTCAGGAACCCTCCACATCCCGCTCCGCGCACAAGAACACCGTCACTT-
G
CACCCAGCAGGGCCTGCTCGAGAACCAGCCTAGTTTCCACCCCGCCAGGCGTGAATAGGGTGATCACTAGAGAG-
G
AGCTCGAGGCGCTTACCCCGTCACGCACTCCTAGCAGGTCGGTCTCGAGAACCAGCCTGGTCTCCAACCCGCCA-
G
GCGTAAATAGGGTGATTACAAGAGAGGAGTTTGAGGCGTTCGTAGCACAACAACAATGACGGTTTGATGCGGGT-
G
CATACATCTTTTCCTCCGACACCGGTCAAGGGCATTTACAACAAAAATCAGTAAGGCAAACGGTGCTATCCGAA-
G
TGGTGTTGGAGAGGACCGAATTGGAGATTTCGTATGCCCCGCGCCTCGACCAAGAAAAAGAAGAATTACTACGC-
A
AGAAATTACAGTTAAATCCCACACCTGCTAACAGAAGCAGATACCAGTCCAGGAAGGTGGAGAACATGAAAGCC-
A
TAACAGCTAGACGTATTCTGCAAGGCCTAGGGCATTATTTGAAGGCAGAAGGAAAAGTGGAGTGCTACCGAACC-
C
TGCATCCTGTTCCTTTGTATTCATCTAGTGTGAACCGTGCCTTTTCAAGCCCCAAGGTCGCAGTGGAAGCCTGT-
A
ACGCCATGTTGAAAGAGAACTTTCCGACTGTGGCTTCTTACTGTATTATTCCAGAGTACGATGCCTATTTGGAC-
A
TGGTTGACGGAGCTTCATGCTGCTTAGACACTGCCAGTTTTTGCCCTGCAAAGCTGCGCAGCTTTCCAAAGAAA-
C
ACTCCTATTTGGAACCCACAATACGATCGGCAGTGCCTTCAGCGATCCAGAACACGCTCCAGAACGTCCTGGCA-
G
CTGCCACAAAAAGAAATTGCAATGTCACGCAAATGAGAGAATTGCCCGTATTGGATTCGGCGGCCTTTAATGTG-
G
AATGCTTCAAGAAATATGCGTGTAATAATGAATATTGGGAAACGTTTAAAGAAAACCCCATCAGGCTTACTGAA-
G
AAAACGTGGTAAATTACATTACCAAATTAAAAGGACCAAAAGCTGCTGCTCTTTTTGCGAAGACACATAATTTG-
A
ATATGTTGCAGGACATACCAATGGACAGGTTTGTAATGGACTTAAAGAGAGACGTGAAAGTGACTCCAGGAACA-
A
AACATACTGAAGAACGGCCCAAGGTACAGGTGATCCAGGCTGCCGATCCGCTAGCAACAGCGTATCTGTGCGGA-
A
TCCACCGAGAGCTGGTTAGGAGATTAAATGCGGTCCTGCTTCCGAACATTCATACACTGTTTGATATGTCGGCT-
G
AAGACTTTGACGCTATTATAGCCGAGCACTTCCAGCCTGGGGATTGTGTTCTGGAAACTGACATCGCGTCGTTT-
G
ATAAAAGTGAGGACGACGCCATGGCTCTGACCGCGTTAATGATTCTGGAAGACTTAGGTGTGGACGCAGAGCTG-
T
TGACGCTGATTGAGGCGGCTTTCGGCGAAATTTCATCAATACATTTGCCCACTAAAACTAAATTTAAATTCGGA-
G
CCATGATGAAATCTGGAATGTTCCTCACACTGTTTGTGAACACAGTCATTAACATTGTAATCGCAAGCAGAGTG-
T
TGAGAGAACGGCTAACCGGATCACCATGTGCAGCATTCATTGGAGATGACAATATCGTGAAAGGAGTCAAATCG-
G
ACAAATTAATGGCAGACAGGTGCGCCACCTGGTTGAATATGGAAGTCAAGATTATAGATGCTGTGGTGGGCGAG-
A
AAGCGCCTTATTTCTGTGGAGGGTTTATTTTGTGTGACTCCGTGACCGGCACAGCGTGCCGTGTGGCAGACCCC-
C
TAAAAAGGCTGTTTAAGCTTGGCAAACCTCTGGCAGCAGACGATGAACATGATGATGACAGGAGAAGGGCATTG-
C
ATGAAGAGTCAACACGCTGGAACCGAGTGGGTATTCTTTCAGAGCTGTGCAAGGCAGTAGAATCAAGGTATGAA-
A
CCGTAGGAACTTCCATCATAGTTATGGCCATGACTACTCTAGCTAGCAGTGTTAAATCATTCAGCTACCTGAGA-
G ##STR00012## ##STR00013## ##STR00014## ##STR00015## ##STR00016##
TTACATAGAACTCGCGGCGATTGGCATGCCGCCTTAAAATTTTTATTTTATTTTTCTTTTCTTTTCCGAATCGG-
A
TTTTGTTTTTAATATTTCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGGGTCGGCATGGCATCTCCAC-
C
TCCTCGCGGTCCGACCTGGGCATCCGAAGGAGGACGCACGTCCACTCGGATGGCTAAGGGAGAGCCACGTTTAA-
A
CACGTGATATCTGGCCTCATGGGCCTTCCTTTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGC-
A
TTAACATGGTCATAGCTGTTTCCTTGCGTATTGGGCGCTCTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGG-
T
CGTTCGGGTAAAGCCTGGGGTGCCTAATGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTT-
G
CTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAA-
C
CCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCC-
G
CTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCT-
C
AGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTT-
A
TCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAG-
G
ATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAG-
A
ACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAA-
A
CAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGA-
A
GATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAG-
A
TTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGA-
G
TAAACTTGGTCTGACAGTTATTAGAAAAATTCATCCAGCAGACGATAAAACGCAATACGCTGGCTATCCGGTGC-
C
GCAATGCCATACAGCACCAGAAAACGATCCGCCCATTCGCCGCCCAGTTCTTCCGCAATATCACGGGTGGCCAG-
C
GCAATATCCTGATAACGATCCGCCACGCCCAGACGGCCGCAATCAATAAAGCCGCTAAAACGGCCATTTTCCAC-
C
ATAATGTTCGGCAGGCACGCATCACCATGGGTCACCACCAGATCTTCGCCATCCGGCATGCTCGCTTTCAGACG-
C
GCAAACAGCTCTGCCGGTGCCAGGCCCTGATGTTCTTCATCCAGATCATCCTGATCCACCAGGCCCGCTTCCAT-
A
CGGGTACGCGCACGTTCAATACGATGTTTCGCCTGATGATCAAACGGACAGGTCGCCGGGTCCAGGGTATGCAG-
A
CGACGCATGGCATCCGCCATAATGCTCACTTTTTCTGCCGGCGCCAGATGGCTAGACAGCAGATCCTGACCCGG-
C
ACTTCGCCCAGCAGCAGCCAATCACGGCCCGCTTCGGTCACCACATCCAGCACCGCCGCACACGGAACACCGGT-
G
GTGGCCAGCCAGCTCAGACGCGCCGCTTCATCCTGCAGCTCGTTCAGCGCACCGCTCAGATCGGTTTTCACAAA-
C
AGCACCGGACGACCCTGCGCGCTCAGACGAAACACCGCCGCATCAGAGCAGCCAATGGTCTGCTGCGCCCAATC-
A
TAGCCAAACAGACGTTCCACCCACGCTGCCGGGCTACCCGCATGCAGGCCATCCTGTTCAATCATACTCTTCCT-
T
TTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAA-
T
AAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTAAATTGTAAGCGTTAATATTTTGTTAAAA-
T
TCGCGTTAAATTTTTGTTAAATCAGCTCATTTTTTAACCAATAGGCCGAAATCGGCAAAATCCCTTATAAATCA-
A
AAGAATAGACCGAGATAGGGTTGAGTGGCCGCTACAGGGCGCTCCCATTCGCCATTCAGGCTGCGCAACTGTTG-
G
GAAGGGCGTTTCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAA-
G TTGGGTAACGCCAGGGTTTTCCCAGTCACACGCGTAATACGACTCACTATAG
TABLE-US-00044 A532 Vector: SGP-gHsol-2A-gL
ATAGGCGGCGCATGAGAGAAGCCCAGACCAATTACCTACCCAAAATGGAGAAAGTTCACGTTGACATCGAGGAA-
G
ACAGCCCATTCCTCAGAGCTTTGCAGCGGAGCTTCCCGCAGTTTGAGGTAGAAGCCAAGCAGGTCACTGATAAT-
G
ACCATGCTAATGCCAGAGCGTTTTCGCATCTGGCTTCAAAACTGATCGAAACGGAGGTGGACCCATCCGACACG-
A
TCCTTGACATTGGAAGTGCGCCCGCCCGCAGAATGTATTCTAAGCACAAGTATCATTGTATCTGTCCGATGAGA-
T
GTGCGGAAGATCCGGACAGATTGTATAAGTATGCAACTAAGCTGAAGAAAAACTGTAAGGAAATAACTGATAAG-
G
AATTGGACAAGAAAATGAAGGAGCTCGCCGCCGTCATGAGCGACCCTGACCTGGAAACTGAGACTATGTGCCTC-
C
ACGACGACGAGTCGTGTCGCTACGAAGGGCAAGTCGCTGTTTACCAGGATGTATACGCGGTTGACGGACCGACA-
A
GTCTCTATCACCAAGCCAATAAGGGAGTTAGAGTCGCCTACTGGATAGGCTTTGACACCACCCCTTTTATGTTT-
A
AGAACTTGGCTGGAGCATATCCATCATACTCTACCAACTGGGCCGACGAAACCGTGTTAACGGCTCGTAACATA-
G
GCCTATGCAGCTCTGACGTTATGGAGCGGTCACGTAGAGGGATGTCCATTCTTAGAAAGAAGTATTTGAAACCA-
T
CCAACAATGTTCTATTCTCTGTTGGCTCGACCATCTACCACGAGAAGAGGGACTTACTGAGGAGCTGGCACCTG-
C
CGTCTGTATTTCACTTACGTGGCAAGCAAAATTACACATGTCGGTGTGAGACTATAGTTAGTTGCGACGGGTAC-
G
TCGTTAAAAGAATAGCTATCAGTCCAGGCCTGTATGGGAAGCCTTCAGGCTATGCTGCTACGATGCACCGCGAG-
G
GATTCTTGTGCTGCAAAGTGACAGACACATTGAACGGGGAGAGGGTCTCTTTTCCCGTGTGCACGTATGTGCCA-
G
CTACATTGTGTGACCAAATGACTGGCATACTGGCAACAGATGTCAGTGCGGACGACGCGCAAAAACTGCTGGTT-
G
GGCTCAACCAGCGTATAGTCGTCAACGGTCGCACCCAGAGAAACACCAATACCATGAAAAATTACCTTTTGCCC-
G
TAGTGGCCCAGGCATTTGCTAGGTGGGCAAAGGAATATAAGGAAGATCAAGAAGATGAAAGGCCACTAGGACTA-
C
GAGATAGACAGTTAGTCATGGGGTGTTGTTGGGCTTTTAGAAGGCACAAGATAACATCTATTTATAAGCGCCCG-
G
ATACCCAAACCATCATCAAAGTGAACAGCGATTTCCACTCATTCGTGCTGCCCAGGATAGGCAGTAACACATTG-
G
AGATCGGGCTGAGAACAAGAATCAGGAAAATGTTAGAGGAGCACAAGGAGCCGTCACCTCTCATTACCGCCGAG-
G
ACGTACAAGAAGCTAAGTGCGCAGCCGATGAGGCTAAGGAGGTGCGTGAAGCCGAGGAGTTGCGCGCAGCTCTA-
C
CACCTTTGGCAGCTGATGTTGAGGAGCCCACTCTGGAAGCCGATGTCGACTTGATGTTACAAGAGGCTGGGGCC-
G
GCTCAGTGGAGACACCTCGTGGCTTGATAAAGGTTACCAGCTACGATGGCGAGGACAAGATCGGCTCTTACGCT-
G
TGCTTTCTCCGCAGGCTGTACTCAAGAGTGAAAAATTATCTTGCATCCACCCTCTCGCTGAACAAGTCATAGTG-
A
TAACACACTCTGGCCGAAAAGGGCGTTATGCCGTGGAACCATACCATGGTAAAGTAGTGGTGCCAGAGGGACAT-
G
CAATACCCGTCCAGGACTTTCAAGCTCTGAGTGAAAGTGCCACCATTGTGTACAACGAACGTGAGTTCGTAAAC-
A
GGTACCTGCACCATATTGCCACACATGGAGGAGCGCTGAACACTGATGAAGAATATTACAAAACTGTCAAGCCC-
A
GCGAGCACGACGGCGAATACCTGTACGACATCGACAGGAAACAGTGCGTCAAGAAAGAACTAGTCACTGGGCTA-
G
GGCTCACAGGCGAGCTGGTGGATCCTCCCTTCCATGAATTCGCCTACGAGAGTCTGAGAACACGACCAGCCGCT-
C
CTTACCAAGTACCAACCATAGGGGTGTATGGCGTGCCAGGATCAGGCAAGTCTGGCATCATTAAAAGCGCAGTC-
A
CCAAAAAAGATCTAGTGGTGAGCGCCAAGAAAGAAAACTGTGCAGAAATTATAAGGGACGTCAAGAAAATGAAA-
G
GGCTGGACGTCAATGCCAGAACTGTGGACTCAGTGCTCTTGAATGGATGCAAACACCCCGTAGAGACCCTGTAT-
A
TTGACGAAGCTTTTGCTTGTCATGCAGGTACTCTCAGAGCGCTCATAGCCATTATAAGACCTAAAAAGGCAGTG-
C
TCTGCGGGGATCCCAAACAGTGCGGTTTTTTTAACATGATGTGCCTGAAAGTGCATTTTAACCACGAGATTTGC-
A
CACAAGTCTTCCACAAAAGCATCTCTCGCCGTTGCACTAAATCTGTGACTTCGGTCGTCTCAACCTTGTTTTAC-
G
ACAAAAAAATGAGAACGACGAATCCGAAAGAGACTAAGATTGTGATTGACACTACCGGCAGTACCAAACCTAAG-
C
AGGACGATCTCATTCTCACTTGTTTCAGAGGGTGGGTGAAGCAGTTGCAAATAGATTACAAAGGCAACGAAATA-
A
TGACGGCAGCTGCCTCTCAAGGGCTGACCCGTAAAGGTGTGTATGCCGTTCGGTACAAGGTGAATGAAAATCCT-
C
TGTACGCACCCACCTCAGAACATGTGAACGTCCTACTGACCCGCACGGAGGACCGCATCGTGTGGAAAACACTA-
G
CCGGCGACCCATGGATAAAAACACTGACTGCCAAGTACCCTGGGAATTTCACTGCCACGATAGAGGAGTGGCAA-
G
CAGAGCATGATGCCATCATGAGGCACATCTTGGAGAGACCGGACCCTACCGACGTCTTCCAGAATAAGGCAAAC-
G
TGTGTTGGGCCAAGGCTTTAGTGCCGGTGCTGAAGACCGCTGGCATAGACATGACCACTGAACAATGGAACACT-
G
TGGATTATTTTGAAACGGACAAAGCTCACTCAGCAGAGATAGTATTGAACCAACTATGCGTGAGGTTCTTTGGA-
C
TCGATCTGGACTCCGGTCTATTTTCTGCACCCACTGTTCCGTTATCCATTAGGAATAATCACTGGGATAACTCC-
C
CGTCGCCTAACATGTACGGGCTGAATAAAGAAGTGGTCCGTCAGCTCTCTCGCAGGTACCCACAACTGCCTCGG-
G
CAGTTGCCACTGGAAGAGTCTATGACATGAACACTGGTACACTGCGCAATTATGATCCGCGCATAAACCTAGTA-
C
CTGTAAACAGAAGACTGCCTCATGCTTTAGTCCTCCACCATAATGAACACCCACAGAGTGACTTTTCTTCATTC-
G
TCAGCAAATTGAAGGGCAGAACTGTCCTGGTGGTCGGGGAAAAGTTGTCCGTCCCAGGCAAAATGGTTGACTGG-
T
TGTCAGACCGGCCTGAGGCTACCTTCAGAGCTCGGCTGGATTTAGGCATCCCAGGTGATGTGCCCAAATATGAC-
A
TAATATTTGTTAATGTGAGGACCCCATATAAATACCATCACTATCAGCAGTGTGAAGACCATGCCATTAAGCTT-
A
GCATGTTGACCAAGAAAGCTTGTCTGCATCTGAATCCCGGCGGAACCTGTGTCAGCATAGGTTATGGTTACGCT-
G
ACAGGGCCAGCGAAAGCATCATTGGTGCTATAGCGCGGCAGTTCAAGTTTTCCCGGGTATGCAAACCGAAATCC-
T
CACTTGAAGAGACGGAAGTTCTGTTTGTATTCATTGGGTACGATCGCAAGGCCCGTACGCACAATCCTTACAAG-
C
TTTCATCAACCTTGACCAACATTTATACAGGTTCCAGACTCCACGAAGCCGGATGTGCACCCTCATATCATGTG-
G
TGCGAGGGGATATTGCCACGGCCACCGAAGGAGTGATTATAAATGCTGCTAACAGCAAAGGACAACCTGGCGGA-
G
GGGTGTGCGGAGCGCTGTATAAGAAATTCCCGGAAAGCTTCGATTTACAGCCGATCGAAGTAGGAAAAGCGCGA-
C
TGGTCAAAGGTGCAGCTAAACATATCATTCATGCCGTAGGACCAAACTTCAACAAAGTTTCGGAGGTTGAAGGT-
G
ACAAACAGTTGGCAGAGGCTTATGAGTCCATCGCTAAGATTGTCAACGATAACAATTACAAGTCAGTAGCGATT-
C
CACTGTTGTCCACCGGCATCTTTTCCGGGAACAAAGATCGACTAACCCAATCATTGAACCATTTGCTGACAGCT-
T
TAGACACCACTGATGCAGATGTAGCCATATACTGCAGGGACAAGAAATGGGAAATGACTCTCAAGGAAGCAGTG-
G
CTAGGAGAGAAGCAGTGGAGGAGATATGCATATCCGACGACTCTTCAGTGACAGAACCTGATGCAGAGCTGGTG-
A
GGGTGCATCCGAAGAGTTCTTTGGCTGGAAGGAAGGGCTACAGCACAAGCGATGGCAAAACTTTCTCATATTTG-
G
AAGGGACCAAGTTTCACCAGGCGGCCAAGGATATAGCAGAAATTAATGCCATGTGGCCCGTTGCAACGGAGGCC-
A
ATGAGCAGGTATGCATGTATATCCTCGGAGAAAGCATGAGCAGTATTAGGTCGAAATGCCCCGTCGAAGAGTCG-
G
AAGCCTCCACACCACCTAGCACGCTGCCTTGCTTGTGCATCCATGCCATGACTCCAGAAAGAGTACAGCGCCTA-
A
AAGCCTCACGTCCAGAACAAATTACTGTGTGCTCATCCTTTCCATTGCCGAAGTATAGAATCACTGGTGTGCAG-
A
AGATCCAATGCTCCCAGCCTATATTGTTCTCACCGAAAGTGCCTGCGTATATTCATCCAAGGAAGTATCTCGTG-
G
AAACACCACCGGTAGACGAGACTCCGGAGCCATCGGCAGAGAACCAATCCACAGAGGGGACACCTGAACAACCA-
C
CACTTATAACCGAGGATGAGACCAGGACTAGAACGCCTGAGCCGATCATCATCGAAGAGGAAGAAGAGGATAGC-
A
TAAGTTTGCTGTCAGATGGCCCGACCCACCAGGTGCTGCAAGTCGAGGCAGACATTCACGGGCCGCCCTCTGTA-
T
CTAGCTCATCCTGGTCCATTCCTCATGCATCCGACTTTGATGTGGACAGTTTATCCATACTTGACACCCTGGAG-
G
GAGCTAGCGTGACCAGCGGGGCAACGTCAGCCGAGACTAACTCTTACTTCGCAAAGAGTATGGAGTTTCTGGCG-
C
GACCGGTGCCTGCGCCTCGAACAGTATTCAGGAACCCTCCACATCCCGCTCCGCGCACAAGAACACCGTCACTT-
G
CACCCAGCAGGGCCTGCTCGAGAACCAGCCTAGTTTCCACCCCGCCAGGCGTGAATAGGGTGATCACTAGAGAG-
G
AGCTCGAGGCGCTTACCCCGTCACGCACTCCTAGCAGGTCGGTCTCGAGAACCAGCCTGGTCTCCAACCCGCCA-
G
GCGTAAATAGGGTGATTACAAGAGAGGAGTTTGAGGCGTTCGTAGCACAACAACAATGACGGTTTGATGCGGGT-
G
CATACATCTTTTCCTCCGACACCGGTCAAGGGCATTTACAACAAAAATCAGTAAGGCAAACGGTGCTATCCGAA-
G
TGGTGTTGGAGAGGACCGAATTGGAGATTTCGTATGCCCCGCGCCTCGACCAAGAAAAAGAAGAATTACTACGC-
A
AGAAATTACAGTTAAATCCCACACCTGCTAACAGAAGCAGATACCAGTCCAGGAAGGTGGAGAACATGAAAGCC-
A
TAACAGCTAGACGTATTCTGCAAGGCCTAGGGCATTATTTGAAGGCAGAAGGAAAAGTGGAGTGCTACCGAACC-
C
TGCATCCTGTTCCTTTGTATTCATCTAGTGTGAACCGTGCCTTTTCAAGCCCCAAGGTCGCAGTGGAAGCCTGT-
A
ACGCCATGTTGAAAGAGAACTTTCCGACTGTGGCTTCTTACTGTATTATTCCAGAGTACGATGCCTATTTGGAC-
A
TGGTTGACGGAGCTTCATGCTGCTTAGACACTGCCAGTTTTTGCCCTGCAAAGCTGCGCAGCTTTCCAAAGAAA-
C
ACTCCTATTTGGAACCCACAATACGATCGGCAGTGCCTTCAGCGATCCAGAACACGCTCCAGAACGTCCTGGCA-
G
CTGCCACAAAAAGAAATTGCAATGTCACGCAAATGAGAGAATTGCCCGTATTGGATTCGGCGGCCTTTAATGTG-
G
AATGCTTCAAGAAATATGCGTGTAATAATGAATATTGGGAAACGTTTAAAGAAAACCCCATCAGGCTTACTGAA-
G
AAAACGTGGTAAATTACATTACCAAATTAAAAGGACCAAAAGCTGCTGCTCTTTTTGCGAAGACACATAATTTG-
A
ATATGTTGCAGGACATACCAATGGACAGGTTTGTAATGGACTTAAAGAGAGACGTGAAAGTGACTCCAGGAACA-
A
AACATACTGAAGAACGGCCCAAGGTACAGGTGATCCAGGCTGCCGATCCGCTAGCAACAGCGTATCTGTGCGGA-
A
TCCACCGAGAGCTGGTTAGGAGATTAAATGCGGTCCTGCTTCCGAACATTCATACACTGTTTGATATGTCGGCT-
G
AAGACTTTGACGCTATTATAGCCGAGCACTTCCAGCCTGGGGATTGTGTTCTGGAAACTGACATCGCGTCGTTT-
G
ATAAAAGTGAGGACGACGCCATGGCTCTGACCGCGTTAATGATTCTGGAAGACTTAGGTGTGGACGCAGAGCTG-
T
TGACGCTGATTGAGGCGGCTTTCGGCGAAATTTCATCAATACATTTGCCCACTAAAACTAAATTTAAATTCGGA-
G
CCATGATGAAATCTGGAATGTTCCTCACACTGTTTGTGAACACAGTCATTAACATTGTAATCGCAAGCAGAGTG-
T
TGAGAGAACGGCTAACCGGATCACCATGTGCAGCATTCATTGGAGATGACAATATCGTGAAAGGAGTCAAATCG-
G
ACAAATTAATGGCAGACAGGTGCGCCACCTGGTTGAATATGGAAGTCAAGATTATAGATGCTGTGGTGGGCGAG-
A
AAGCGCCTTATTTCTGTGGAGGGTTTATTTTGTGTGACTCCGTGACCGGCACAGCGTGCCGTGTGGCAGACCCC-
C
TAAAAAGGCTGTTTAAGCTTGGCAAACCTCTGGCAGCAGACGATGAACATGATGATGACAGGAGAAGGGCATTG-
C
ATGAAGAGTCAACACGCTGGAACCGAGTGGGTATTCTTTCAGAGCTGTGCAAGGCAGTAGAATCAAGGTATGAA-
A ##STR00017## ##STR00018## ##STR00019## ##STR00020##
GGCGATTGGCATGCCGCCTTAAAATTTTTATTTTATTTTTCTTTTCTTTTCCGAATCGGATTTTGTTTTTAATA-
T
TTCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGGGTCGGCATGGCATCTCCACCTCCTCGCGGTCCGA-
C
CTGGGCATCCGAAGGAGGACGCACGTCCACTCGGATGGCTAAGGGAGAGCCACGTTTAAACACGTGATATCTGG-
C
CTCATGGGCCTTCCTTTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAACATGGTCATA-
G
CTGTTTCCTTGCGTATTGGGCGCTCTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGGTAAAGC-
C
TGGGGTGCCTAATGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCA-
T
AGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATA-
A
AGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCT-
G
TCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGT-
C
GTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCG-
T
CTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAG-
G
TATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTAT-
C
TGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGG-
T
AGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTT-
T
TCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGAT-
C
TTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGA-
C
AGTTATTAGAAAAATTCATCCAGCAGACGATAAAACGCAATACGCTGGCTATCCGGTGCCGCAATGCCATACAG-
C
ACCAGAAAACGATCCGCCCATTCGCCGCCCAGTTCTTCCGCAATATCACGGGTGGCCAGCGCAATATCCTGATA-
A
CGATCCGCCACGCCCAGACGGCCGCAATCAATAAAGCCGCTAAAACGGCCATTTTCCACCATAATGTTCGGCAG-
G
CACGCATCACCATGGGTCACCACCAGATCTTCGCCATCCGGCATGCTCGCTTTCAGACGCGCAAACAGCTCTGC-
C
GGTGCCAGGCCCTGATGTTCTTCATCCAGATCATCCTGATCCACCAGGCCCGCTTCCATACGGGTACGCGCACG-
T
TCAATACGATGTTTCGCCTGATGATCAAACGGACAGGTCGCCGGGTCCAGGGTATGCAGACGACGCATGGCATC-
C
GCCATAATGCTCACTTTTTCTGCCGGCGCCAGATGGCTAGACAGCAGATCCTGACCCGGCACTTCGCCCAGCAG-
C
AGCCAATCACGGCCCGCTTCGGTCACCACATCCAGCACCGCCGCACACGGAACACCGGTGGTGGCCAGCCAGCT-
C
AGACGCGCCGCTTCATCCTGCAGCTCGTTCAGCGCACCGCTCAGATCGGTTTTCACAAACAGCACCGGACGACC-
C
TGCGCGCTCAGACGAAACACCGCCGCATCAGAGCAGCCAATGGTCTGCTGCGCCCAATCATAGCCAAACAGACG-
T
TCCACCCACGCTGCCGGGCTACCCGCATGCAGGCCATCCTGTTCAATCATACTCTTCCTTTTTCAATATTATTG-
A
AGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGT-
T
CCGCGCACATTTCCCCGAAAAGTGCCACCTAAATTGTAAGCGTTAATATTTTGTTAAAATTCGCGTTAAATTTT-
T
GTTAAATCAGCTCATTTTTTAACCAATAGGCCGAAATCGGCAAAATCCCTTATAAATCAAAAGAATAGACCGAG-
A
TAGGGTTGAGTGGCCGCTACAGGGCGCTCCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGTTTCGG-
T
GCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAG-
G GTTTTCCCAGTCACACGCGTAATACGACTCACTATAG
TABLE-US-00045 A533 Vector: SGP-gHsol-EV71-gL
ATAGGCGGCGCATGAGAGAAGCCCAGACCAATTACCTACCCAAAATGGAGAAAGTTCACGTTGACATCGAGGAA-
G
ACAGCCCATTCCTCAGAGCTTTGCAGCGGAGCTTCCCGCAGTTTGAGGTAGAAGCCAAGCAGGTCACTGATAAT-
G
ACCATGCTAATGCCAGAGCGTTTTCGCATCTGGCTTCAAAACTGATCGAAACGGAGGTGGACCCATCCGACACG-
A
TCCTTGACATTGGAAGTGCGCCCGCCCGCAGAATGTATTCTAAGCACAAGTATCATTGTATCTGTCCGATGAGA-
T
GTGCGGAAGATCCGGACAGATTGTATAAGTATGCAACTAAGCTGAAGAAAAACTGTAAGGAAATAACTGATAAG-
G
AATTGGACAAGAAAATGAAGGAGCTCGCCGCCGTCATGAGCGACCCTGACCTGGAAACTGAGACTATGTGCCTC-
C
ACGACGACGAGTCGTGTCGCTACGAAGGGCAAGTCGCTGTTTACCAGGATGTATACGCGGTTGACGGACCGACA-
A
GTCTCTATCACCAAGCCAATAAGGGAGTTAGAGTCGCCTACTGGATAGGCTTTGACACCACCCCTTTTATGTTT-
A
AGAACTTGGCTGGAGCATATCCATCATACTCTACCAACTGGGCCGACGAAACCGTGTTAACGGCTCGTAACATA-
G
GCCTATGCAGCTCTGACGTTATGGAGCGGTCACGTAGAGGGATGTCCATTCTTAGAAAGAAGTATTTGAAACCA-
T
CCAACAATGTTCTATTCTCTGTTGGCTCGACCATCTACCACGAGAAGAGGGACTTACTGAGGAGCTGGCACCTG-
C
CGTCTGTATTTCACTTACGTGGCAAGCAAAATTACACATGTCGGTGTGAGACTATAGTTAGTTGCGACGGGTAC-
G
TCGTTAAAAGAATAGCTATCAGTCCAGGCCTGTATGGGAAGCCTTCAGGCTATGCTGCTACGATGCACCGCGAG-
G
GATTCTTGTGCTGCAAAGTGACAGACACATTGAACGGGGAGAGGGTCTCTTTTCCCGTGTGCACGTATGTGCCA-
G
CTACATTGTGTGACCAAATGACTGGCATACTGGCAACAGATGTCAGTGCGGACGACGCGCAAAAACTGCTGGTT-
G
GGCTCAACCAGCGTATAGTCGTCAACGGTCGCACCCAGAGAAACACCAATACCATGAAAAATTACCTTTTGCCC-
G
TAGTGGCCCAGGCATTTGCTAGGTGGGCAAAGGAATATAAGGAAGATCAAGAAGATGAAAGGCCACTAGGACTA-
C
GAGATAGACAGTTAGTCATGGGGTGTTGTTGGGCTTTTAGAAGGCACAAGATAACATCTATTTATAAGCGCCCG-
G
ATACCCAAACCATCATCAAAGTGAACAGCGATTTCCACTCATTCGTGCTGCCCAGGATAGGCAGTAACACATTG-
G
AGATCGGGCTGAGAACAAGAATCAGGAAAATGTTAGAGGAGCACAAGGAGCCGTCACCTCTCATTACCGCCGAG-
G
ACGTACAAGAAGCTAAGTGCGCAGCCGATGAGGCTAAGGAGGTGCGTGAAGCCGAGGAGTTGCGCGCAGCTCTA-
C
CACCTTTGGCAGCTGATGTTGAGGAGCCCACTCTGGAAGCCGATGTCGACTTGATGTTACAAGAGGCTGGGGCC-
G
GCTCAGTGGAGACACCTCGTGGCTTGATAAAGGTTACCAGCTACGATGGCGAGGACAAGATCGGCTCTTACGCT-
G
TGCTTTCTCCGCAGGCTGTACTCAAGAGTGAAAAATTATCTTGCATCCACCCTCTCGCTGAACAAGTCATAGTG-
A
TAACACACTCTGGCCGAAAAGGGCGTTATGCCGTGGAACCATACCATGGTAAAGTAGTGGTGCCAGAGGGACAT-
G
CAATACCCGTCCAGGACTTTCAAGCTCTGAGTGAAAGTGCCACCATTGTGTACAACGAACGTGAGTTCGTAAAC-
A
GGTACCTGCACCATATTGCCACACATGGAGGAGCGCTGAACACTGATGAAGAATATTACAAAACTGTCAAGCCC-
A
GCGAGCACGACGGCGAATACCTGTACGACATCGACAGGAAACAGTGCGTCAAGAAAGAACTAGTCACTGGGCTA-
G
GGCTCACAGGCGAGCTGGTGGATCCTCCCTTCCATGAATTCGCCTACGAGAGTCTGAGAACACGACCAGCCGCT-
C
CTTACCAAGTACCAACCATAGGGGTGTATGGCGTGCCAGGATCAGGCAAGTCTGGCATCATTAAAAGCGCAGTC-
A
CCAAAAAAGATCTAGTGGTGAGCGCCAAGAAAGAAAACTGTGCAGAAATTATAAGGGACGTCAAGAAAATGAAA-
G
GGCTGGACGTCAATGCCAGAACTGTGGACTCAGTGCTCTTGAATGGATGCAAACACCCCGTAGAGACCCTGTAT-
A
TTGACGAAGCTTTTGCTTGTCATGCAGGTACTCTCAGAGCGCTCATAGCCATTATAAGACCTAAAAAGGCAGTG-
C
TCTGCGGGGATCCCAAACAGTGCGGTTTTTTTAACATGATGTGCCTGAAAGTGCATTTTAACCACGAGATTTGC-
A
CACAAGTCTTCCACAAAAGCATCTCTCGCCGTTGCACTAAATCTGTGACTTCGGTCGTCTCAACCTTGTTTTAC-
G
ACAAAAAAATGAGAACGACGAATCCGAAAGAGACTAAGATTGTGATTGACACTACCGGCAGTACCAAACCTAAG-
C
AGGACGATCTCATTCTCACTTGTTTCAGAGGGTGGGTGAAGCAGTTGCAAATAGATTACAAAGGCAACGAAATA-
A
TGACGGCAGCTGCCTCTCAAGGGCTGACCCGTAAAGGTGTGTATGCCGTTCGGTACAAGGTGAATGAAAATCCT-
C
TGTACGCACCCACCTCAGAACATGTGAACGTCCTACTGACCCGCACGGAGGACCGCATCGTGTGGAAAACACTA-
G
CCGGCGACCCATGGATAAAAACACTGACTGCCAAGTACCCTGGGAATTTCACTGCCACGATAGAGGAGTGGCAA-
G
CAGAGCATGATGCCATCATGAGGCACATCTTGGAGAGACCGGACCCTACCGACGTCTTCCAGAATAAGGCAAAC-
G
TGTGTTGGGCCAAGGCTTTAGTGCCGGTGCTGAAGACCGCTGGCATAGACATGACCACTGAACAATGGAACACT-
G
TGGATTATTTTGAAACGGACAAAGCTCACTCAGCAGAGATAGTATTGAACCAACTATGCGTGAGGTTCTTTGGA-
C
TCGATCTGGACTCCGGTCTATTTTCTGCACCCACTGTTCCGTTATCCATTAGGAATAATCACTGGGATAACTCC-
C
CGTCGCCTAACATGTACGGGCTGAATAAAGAAGTGGTCCGTCAGCTCTCTCGCAGGTACCCACAACTGCCTCGG-
G
CAGTTGCCACTGGAAGAGTCTATGACATGAACACTGGTACACTGCGCAATTATGATCCGCGCATAAACCTAGTA-
C
CTGTAAACAGAAGACTGCCTCATGCTTTAGTCCTCCACCATAATGAACACCCACAGAGTGACTTTTCTTCATTC-
G
TCAGCAAATTGAAGGGCAGAACTGTCCTGGTGGTCGGGGAAAAGTTGTCCGTCCCAGGCAAAATGGTTGACTGG-
T
TGTCAGACCGGCCTGAGGCTACCTTCAGAGCTCGGCTGGATTTAGGCATCCCAGGTGATGTGCCCAAATATGAC-
A
TAATATTTGTTAATGTGAGGACCCCATATAAATACCATCACTATCAGCAGTGTGAAGACCATGCCATTAAGCTT-
A
GCATGTTGACCAAGAAAGCTTGTCTGCATCTGAATCCCGGCGGAACCTGTGTCAGCATAGGTTATGGTTACGCT-
G
ACAGGGCCAGCGAAAGCATCATTGGTGCTATAGCGCGGCAGTTCAAGTTTTCCCGGGTATGCAAACCGAAATCC-
T
CACTTGAAGAGACGGAAGTTCTGTTTGTATTCATTGGGTACGATCGCAAGGCCCGTACGCACAATCCTTACAAG-
C
TTTCATCAACCTTGACCAACATTTATACAGGTTCCAGACTCCACGAAGCCGGATGTGCACCCTCATATCATGTG-
G
TGCGAGGGGATATTGCCACGGCCACCGAAGGAGTGATTATAAATGCTGCTAACAGCAAAGGACAACCTGGCGGA-
G
GGGTGTGCGGAGCGCTGTATAAGAAATTCCCGGAAAGCTTCGATTTACAGCCGATCGAAGTAGGAAAAGCGCGA-
C
TGGTCAAAGGTGCAGCTAAACATATCATTCATGCCGTAGGACCAAACTTCAACAAAGTTTCGGAGGTTGAAGGT-
G
ACAAACAGTTGGCAGAGGCTTATGAGTCCATCGCTAAGATTGTCAACGATAACAATTACAAGTCAGTAGCGATT-
C
CACTGTTGTCCACCGGCATCTTTTCCGGGAACAAAGATCGACTAACCCAATCATTGAACCATTTGCTGACAGCT-
T
TAGACACCACTGATGCAGATGTAGCCATATACTGCAGGGACAAGAAATGGGAAATGACTCTCAAGGAAGCAGTG-
G
CTAGGAGAGAAGCAGTGGAGGAGATATGCATATCCGACGACTCTTCAGTGACAGAACCTGATGCAGAGCTGGTG-
A
GGGTGCATCCGAAGAGTTCTTTGGCTGGAAGGAAGGGCTACAGCACAAGCGATGGCAAAACTTTCTCATATTTG-
G
AAGGGACCAAGTTTCACCAGGCGGCCAAGGATATAGCAGAAATTAATGCCATGTGGCCCGTTGCAACGGAGGCC-
A
ATGAGCAGGTATGCATGTATATCCTCGGAGAAAGCATGAGCAGTATTAGGTCGAAATGCCCCGTCGAAGAGTCG-
G
AAGCCTCCACACCACCTAGCACGCTGCCTTGCTTGTGCATCCATGCCATGACTCCAGAAAGAGTACAGCGCCTA-
A
AAGCCTCACGTCCAGAACAAATTACTGTGTGCTCATCCTTTCCATTGCCGAAGTATAGAATCACTGGTGTGCAG-
A
AGATCCAATGCTCCCAGCCTATATTGTTCTCACCGAAAGTGCCTGCGTATATTCATCCAAGGAAGTATCTCGTG-
G
AAACACCACCGGTAGACGAGACTCCGGAGCCATCGGCAGAGAACCAATCCACAGAGGGGACACCTGAACAACCA-
C
CACTTATAACCGAGGATGAGACCAGGACTAGAACGCCTGAGCCGATCATCATCGAAGAGGAAGAAGAGGATAGC-
A
TAAGTTTGCTGTCAGATGGCCCGACCCACCAGGTGCTGCAAGTCGAGGCAGACATTCACGGGCCGCCCTCTGTA-
T
CTAGCTCATCCTGGTCCATTCCTCATGCATCCGACTTTGATGTGGACAGTTTATCCATACTTGACACCCTGGAG-
G
GAGCTAGCGTGACCAGCGGGGCAACGTCAGCCGAGACTAACTCTTACTTCGCAAAGAGTATGGAGTTTCTGGCG-
C
GACCGGTGCCTGCGCCTCGAACAGTATTCAGGAACCCTCCACATCCCGCTCCGCGCACAAGAACACCGTCACTT-
G
CACCCAGCAGGGCCTGCTCGAGAACCAGCCTAGTTTCCACCCCGCCAGGCGTGAATAGGGTGATCACTAGAGAG-
G
AGCTCGAGGCGCTTACCCCGTCACGCACTCCTAGCAGGTCGGTCTCGAGAACCAGCCTGGTCTCCAACCCGCCA-
G
GCGTAAATAGGGTGATTACAAGAGAGGAGTTTGAGGCGTTCGTAGCACAACAACAATGACGGTTTGATGCGGGT-
G
CATACATCTTTTCCTCCGACACCGGTCAAGGGCATTTACAACAAAAATCAGTAAGGCAAACGGTGCTATCCGAA-
G
TGGTGTTGGAGAGGACCGAATTGGAGATTTCGTATGCCCCGCGCCTCGACCAAGAAAAAGAAGAATTACTACGC-
A
AGAAATTACAGTTAAATCCCACACCTGCTAACAGAAGCAGATACCAGTCCAGGAAGGTGGAGAACATGAAAGCC-
A
TAACAGCTAGACGTATTCTGCAAGGCCTAGGGCATTATTTGAAGGCAGAAGGAAAAGTGGAGTGCTACCGAACC-
C
TGCATCCTGTTCCTTTGTATTCATCTAGTGTGAACCGTGCCTTTTCAAGCCCCAAGGTCGCAGTGGAAGCCTGT-
A
ACGCCATGTTGAAAGAGAACTTTCCGACTGTGGCTTCTTACTGTATTATTCCAGAGTACGATGCCTATTTGGAC-
A
TGGTTGACGGAGCTTCATGCTGCTTAGACACTGCCAGTTTTTGCCCTGCAAAGCTGCGCAGCTTTCCAAAGAAA-
C
ACTCCTATTTGGAACCCACAATACGATCGGCAGTGCCTTCAGCGATCCAGAACACGCTCCAGAACGTCCTGGCA-
G
CTGCCACAAAAAGAAATTGCAATGTCACGCAAATGAGAGAATTGCCCGTATTGGATTCGGCGGCCTTTAATGTG-
G
AATGCTTCAAGAAATATGCGTGTAATAATGAATATTGGGAAACGTTTAAAGAAAACCCCATCAGGCTTACTGAA-
G
AAAACGTGGTAAATTACATTACCAAATTAAAAGGACCAAAAGCTGCTGCTCTTTTTGCGAAGACACATAATTTG-
A
ATATGTTGCAGGACATACCAATGGACAGGTTTGTAATGGACTTAAAGAGAGACGTGAAAGTGACTCCAGGAACA-
A
AACATACTGAAGAACGGCCCAAGGTACAGGTGATCCAGGCTGCCGATCCGCTAGCAACAGCGTATCTGTGCGGA-
A
TCCACCGAGAGCTGGTTAGGAGATTAAATGCGGTCCTGCTTCCGAACATTCATACACTGTTTGATATGTCGGCT-
G
AAGACTTTGACGCTATTATAGCCGAGCACTTCCAGCCTGGGGATTGTGTTCTGGAAACTGACATCGCGTCGTTT-
G
ATAAAAGTGAGGACGACGCCATGGCTCTGACCGCGTTAATGATTCTGGAAGACTTAGGTGTGGACGCAGAGCTG-
T
TGACGCTGATTGAGGCGGCTTTCGGCGAAATTTCATCAATACATTTGCCCACTAAAACTAAATTTAAATTCGGA-
G
CCATGATGAAATCTGGAATGTTCCTCACACTGTTTGTGAACACAGTCATTAACATTGTAATCGCAAGCAGAGTG-
T
TGAGAGAACGGCTAACCGGATCACCATGTGCAGCATTCATTGGAGATGACAATATCGTGAAAGGAGTCAAATCG-
G
ACAAATTAATGGCAGACAGGTGCGCCACCTGGTTGAATATGGAAGTCAAGATTATAGATGCTGTGGTGGGCGAG-
A
AAGCGCCTTATTTCTGTGGAGGGTTTATTTTGTGTGACTCCGTGACCGGCACAGCGTGCCGTGTGGCAGACCCC-
C
TAAAAAGGCTGTTTAAGCTTGGCAAACCTCTGGCAGCAGACGATGAACATGATGATGACAGGAGAAGGGCATTG-
C
ATGAAGAGTCAACACGCTGGAACCGAGTGGGTATTCTTTCAGAGCTGTGCAAGGCAGTAGAATCAAGGTATGAA-
A ##STR00021## ##STR00022## ##STR00023##
GGCCCACTGGGCGCTAGCACTCTGATTTTACGAAATCCTTGTGCGCCTGTTTTATATCCCTTCCCTAATTCGAA-
A
CGTAGAAGCAATGCGCACCACTGATCAATAGTAGGCGTAACGCGCCAGTTACGTCATGATCAAGCATATCTGTT-
C
CCCCGGACTGAGTATCAATAGACTGCTTACGCGGTTGAAGGAGAAAACGTTCGTTATCCGGCTAACTACTTCGA-
G
AAGCCCAGTAACACCATGGAAGCTGCAGGGTGTTTCGCTCAGCACTTCCCCCGTGTAGATCAGGTCGATGAGCC-
A
CTGCAATCCCCACAGGTGACTGTGGCAGTGGCTGCGTTGGCGGCCTGCCTATGGGGAGACCCATAGGACGCTCT-
A
ATGTGGACATGGTGCGAAGAGCCTATTGAGCTAGTTAGTAGTCCTCCGGCCCCTGAATGCGGCTAATCCTAACT-
G
CGGAGCACATGCCTTCAACCCAGAGGGTAGTGTGTCGTAATGGGCAACTCTGCAGCGGAACCGACTACTTTGGG-
T
GTCCGTGTTTCTTTTTATTCTTATATTGGCTGCTTATGGTGACAATTACAGAATTGTTACCATATAGCTATTGG-
A
TTGGCCATCCGGTGTGTAATAGAGCTGTTATATACCTATTTGTTGGCTTTGTACCACTAACTTTAAAATCTATA-
A ##STR00024##
TGGCAAGCTGCTTACATAGAACTCGCGGCGATTGGCATGCCGCCTTAAAATTTTTATTTTATTTTTCTTTTCTT-
T
TCCGAATCGGATTTTGTTTTTAATATTTCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGGGTCGGCAT-
G
GCATCTCCACCTCCTCGCGGTCCGACCTGGGCATCCGAAGGAGGACGCACGTCCACTCGGATGGCTAAGGGAGA-
G
CCACGTTTAAACACGTGATATCTGGCCTCATGGGCCTTCCTTTCACTGCCCGCTTTCCAGTCGGGAAACCTGTC-
G
TGCCAGCTGCATTAACATGGTCATAGCTGTTTCCTTGCGTATTGGGCGCTCTCCGCTTCCTCGCTCACTGACTC-
G
CTGCGCTCGGTCGTTCGGGTAAAGCCTGGGGTGCCTAATGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAA-
A
AGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAG-
A
GGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTT-
C
CGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGC-
T
GTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGAC-
C
GCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCC-
A
CTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGC-
T
ACACTAGAAGAACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCT-
T
GATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAA-
G
GATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATT-
T
TGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAA-
A
GTATATATGAGTAAACTTGGTCTGACAGTTATTAGAAAAATTCATCCAGCAGACGATAAAACGCAATACGCTGG-
C
TATCCGGTGCCGCAATGCCATACAGCACCAGAAAACGATCCGCCCATTCGCCGCCCAGTTCTTCCGCAATATCA-
C
GGGTGGCCAGCGCAATATCCTGATAACGATCCGCCACGCCCAGACGGCCGCAATCAATAAAGCCGCTAAAACGG-
C
CATTTTCCACCATAATGTTCGGCAGGCACGCATCACCATGGGTCACCACCAGATCTTCGCCATCCGGCATGCTC-
G
CTTTCAGACGCGCAAACAGCTCTGCCGGTGCCAGGCCCTGATGTTCTTCATCCAGATCATCCTGATCCACCAGG-
C
CCGCTTCCATACGGGTACGCGCACGTTCAATACGATGTTTCGCCTGATGATCAAACGGACAGGTCGCCGGGTCC-
A
GGGTATGCAGACGACGCATGGCATCCGCCATAATGCTCACTTTTTCTGCCGGCGCCAGATGGCTAGACAGCAGA-
T
CCTGACCCGGCACTTCGCCCAGCAGCAGCCAATCACGGCCCGCTTCGGTCACCACATCCAGCACCGCCGCACAC-
G
GAACACCGGTGGTGGCCAGCCAGCTCAGACGCGCCGCTTCATCCTGCAGCTCGTTCAGCGCACCGCTCAGATCG-
G
TTTTCACAAACAGCACCGGACGACCCTGCGCGCTCAGACGAAACACCGCCGCATCAGAGCAGCCAATGGTCTGC-
T
GCGCCCAATCATAGCCAAACAGACGTTCCACCCACGCTGCCGGGCTACCCGCATGCAGGCCATCCTGTTCAATC-
A
TACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGT-
A
TTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTAAATTGTAAGCGTTAATA-
T
TTTGTTAAAATTCGCGTTAAATTTTTGTTAAATCAGCTCATTTTTTAACCAATAGGCCGAAATCGGCAAAATCC-
C
TTATAAATCAAAAGAATAGACCGAGATAGGGTTGAGTGGCCGCTACAGGGCGCTCCCATTCGCCATTCAGGCTG-
C
GCAACTGTTGGGAAGGGCGTTTCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGC-
A
AGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACACGCGTAATACGACTCACTATAG
TABLE-US-00046 A534 Vector: SGP-gL-EV71-gH
ATAGGCGGCGCATGAGAGAAGCCCAGACCAATTACCTACCCAAAATGGAGAAAGTTCACGTTGACATCGAGGAA-
G
ACAGCCCATTCCTCAGAGCTTTGCAGCGGAGCTTCCCGCAGTTTGAGGTAGAAGCCAAGCAGGTCACTGATAAT-
G
ACCATGCTAATGCCAGAGCGTTTTCGCATCTGGCTTCAAAACTGATCGAAACGGAGGTGGACCCATCCGACACG-
A
TCCTTGACATTGGAAGTGCGCCCGCCCGCAGAATGTATTCTAAGCACAAGTATCATTGTATCTGTCCGATGAGA-
T
GTGCGGAAGATCCGGACAGATTGTATAAGTATGCAACTAAGCTGAAGAAAAACTGTAAGGAAATAACTGATAAG-
G
AATTGGACAAGAAAATGAAGGAGCTCGCCGCCGTCATGAGCGACCCTGACCTGGAAACTGAGACTATGTGCCTC-
C
ACGACGACGAGTCGTGTCGCTACGAAGGGCAAGTCGCTGTTTACCAGGATGTATACGCGGTTGACGGACCGACA-
A
GTCTCTATCACCAAGCCAATAAGGGAGTTAGAGTCGCCTACTGGATAGGCTTTGACACCACCCCTTTTATGTTT-
A
AGAACTTGGCTGGAGCATATCCATCATACTCTACCAACTGGGCCGACGAAACCGTGTTAACGGCTCGTAACATA-
G
GCCTATGCAGCTCTGACGTTATGGAGCGGTCACGTAGAGGGATGTCCATTCTTAGAAAGAAGTATTTGAAACCA-
T
CCAACAATGTTCTATTCTCTGTTGGCTCGACCATCTACCACGAGAAGAGGGACTTACTGAGGAGCTGGCACCTG-
C
CGTCTGTATTTCACTTACGTGGCAAGCAAAATTACACATGTCGGTGTGAGACTATAGTTAGTTGCGACGGGTAC-
G
TCGTTAAAAGAATAGCTATCAGTCCAGGCCTGTATGGGAAGCCTTCAGGCTATGCTGCTACGATGCACCGCGAG-
G
GATTCTTGTGCTGCAAAGTGACAGACACATTGAACGGGGAGAGGGTCTCTTTTCCCGTGTGCACGTATGTGCCA-
G
CTACATTGTGTGACCAAATGACTGGCATACTGGCAACAGATGTCAGTGCGGACGACGCGCAAAAACTGCTGGTT-
G
GGCTCAACCAGCGTATAGTCGTCAACGGTCGCACCCAGAGAAACACCAATACCATGAAAAATTACCTTTTGCCC-
G
TAGTGGCCCAGGCATTTGCTAGGTGGGCAAAGGAATATAAGGAAGATCAAGAAGATGAAAGGCCACTAGGACTA-
C
GAGATAGACAGTTAGTCATGGGGTGTTGTTGGGCTTTTAGAAGGCACAAGATAACATCTATTTATAAGCGCCCG-
G
ATACCCAAACCATCATCAAAGTGAACAGCGATTTCCACTCATTCGTGCTGCCCAGGATAGGCAGTAACACATTG-
G
AGATCGGGCTGAGAACAAGAATCAGGAAAATGTTAGAGGAGCACAAGGAGCCGTCACCTCTCATTACCGCCGAG-
G
ACGTACAAGAAGCTAAGTGCGCAGCCGATGAGGCTAAGGAGGTGCGTGAAGCCGAGGAGTTGCGCGCAGCTCTA-
C
CACCTTTGGCAGCTGATGTTGAGGAGCCCACTCTGGAAGCCGATGTCGACTTGATGTTACAAGAGGCTGGGGCC-
G
GCTCAGTGGAGACACCTCGTGGCTTGATAAAGGTTACCAGCTACGATGGCGAGGACAAGATCGGCTCTTACGCT-
G
TGCTTTCTCCGCAGGCTGTACTCAAGAGTGAAAAATTATCTTGCATCCACCCTCTCGCTGAACAAGTCATAGTG-
A
TAACACACTCTGGCCGAAAAGGGCGTTATGCCGTGGAACCATACCATGGTAAAGTAGTGGTGCCAGAGGGACAT-
G
CAATACCCGTCCAGGACTTTCAAGCTCTGAGTGAAAGTGCCACCATTGTGTACAACGAACGTGAGTTCGTAAAC-
A
GGTACCTGCACCATATTGCCACACATGGAGGAGCGCTGAACACTGATGAAGAATATTACAAAACTGTCAAGCCC-
A
GCGAGCACGACGGCGAATACCTGTACGACATCGACAGGAAACAGTGCGTCAAGAAAGAACTAGTCACTGGGCTA-
G
GGCTCACAGGCGAGCTGGTGGATCCTCCCTTCCATGAATTCGCCTACGAGAGTCTGAGAACACGACCAGCCGCT-
C
CTTACCAAGTACCAACCATAGGGGTGTATGGCGTGCCAGGATCAGGCAAGTCTGGCATCATTAAAAGCGCAGTC-
A
CCAAAAAAGATCTAGTGGTGAGCGCCAAGAAAGAAAACTGTGCAGAAATTATAAGGGACGTCAAGAAAATGAAA-
G
GGCTGGACGTCAATGCCAGAACTGTGGACTCAGTGCTCTTGAATGGATGCAAACACCCCGTAGAGACCCTGTAT-
A
TTGACGAAGCTTTTGCTTGTCATGCAGGTACTCTCAGAGCGCTCATAGCCATTATAAGACCTAAAAAGGCAGTG-
C
TCTGCGGGGATCCCAAACAGTGCGGTTTTTTTAACATGATGTGCCTGAAAGTGCATTTTAACCACGAGATTTGC-
A
CACAAGTCTTCCACAAAAGCATCTCTCGCCGTTGCACTAAATCTGTGACTTCGGTCGTCTCAACCTTGTTTTAC-
G
ACAAAAAAATGAGAACGACGAATCCGAAAGAGACTAAGATTGTGATTGACACTACCGGCAGTACCAAACCTAAG-
C
AGGACGATCTCATTCTCACTTGTTTCAGAGGGTGGGTGAAGCAGTTGCAAATAGATTACAAAGGCAACGAAATA-
A
TGACGGCAGCTGCCTCTCAAGGGCTGACCCGTAAAGGTGTGTATGCCGTTCGGTACAAGGTGAATGAAAATCCT-
C
TGTACGCACCCACCTCAGAACATGTGAACGTCCTACTGACCCGCACGGAGGACCGCATCGTGTGGAAAACACTA-
G
CCGGCGACCCATGGATAAAAACACTGACTGCCAAGTACCCTGGGAATTTCACTGCCACGATAGAGGAGTGGCAA-
G
CAGAGCATGATGCCATCATGAGGCACATCTTGGAGAGACCGGACCCTACCGACGTCTTCCAGAATAAGGCAAAC-
G
TGTGTTGGGCCAAGGCTTTAGTGCCGGTGCTGAAGACCGCTGGCATAGACATGACCACTGAACAATGGAACACT-
G
TGGATTATTTTGAAACGGACAAAGCTCACTCAGCAGAGATAGTATTGAACCAACTATGCGTGAGGTTCTTTGGA-
C
TCGATCTGGACTCCGGTCTATTTTCTGCACCCACTGTTCCGTTATCCATTAGGAATAATCACTGGGATAACTCC-
C
CGTCGCCTAACATGTACGGGCTGAATAAAGAAGTGGTCCGTCAGCTCTCTCGCAGGTACCCACAACTGCCTCGG-
G
CAGTTGCCACTGGAAGAGTCTATGACATGAACACTGGTACACTGCGCAATTATGATCCGCGCATAAACCTAGTA-
C
CTGTAAACAGAAGACTGCCTCATGCTTTAGTCCTCCACCATAATGAACACCCACAGAGTGACTTTTCTTCATTC-
G
TCAGCAAATTGAAGGGCAGAACTGTCCTGGTGGTCGGGGAAAAGTTGTCCGTCCCAGGCAAAATGGTTGACTGG-
T
TGTCAGACCGGCCTGAGGCTACCTTCAGAGCTCGGCTGGATTTAGGCATCCCAGGTGATGTGCCCAAATATGAC-
A
TAATATTTGTTAATGTGAGGACCCCATATAAATACCATCACTATCAGCAGTGTGAAGACCATGCCATTAAGCTT-
A
GCATGTTGACCAAGAAAGCTTGTCTGCATCTGAATCCCGGCGGAACCTGTGTCAGCATAGGTTATGGTTACGCT-
G
ACAGGGCCAGCGAAAGCATCATTGGTGCTATAGCGCGGCAGTTCAAGTTTTCCCGGGTATGCAAACCGAAATCC-
T
CACTTGAAGAGACGGAAGTTCTGTTTGTATTCATTGGGTACGATCGCAAGGCCCGTACGCACAATCCTTACAAG-
C
TTTCATCAACCTTGACCAACATTTATACAGGTTCCAGACTCCACGAAGCCGGATGTGCACCCTCATATCATGTG-
G
TGCGAGGGGATATTGCCACGGCCACCGAAGGAGTGATTATAAATGCTGCTAACAGCAAAGGACAACCTGGCGGA-
G
GGGTGTGCGGAGCGCTGTATAAGAAATTCCCGGAAAGCTTCGATTTACAGCCGATCGAAGTAGGAAAAGCGCGA-
C
TGGTCAAAGGTGCAGCTAAACATATCATTCATGCCGTAGGACCAAACTTCAACAAAGTTTCGGAGGTTGAAGGT-
G
ACAAACAGTTGGCAGAGGCTTATGAGTCCATCGCTAAGATTGTCAACGATAACAATTACAAGTCAGTAGCGATT-
C
CACTGTTGTCCACCGGCATCTTTTCCGGGAACAAAGATCGACTAACCCAATCATTGAACCATTTGCTGACAGCT-
T
TAGACACCACTGATGCAGATGTAGCCATATACTGCAGGGACAAGAAATGGGAAATGACTCTCAAGGAAGCAGTG-
G
CTAGGAGAGAAGCAGTGGAGGAGATATGCATATCCGACGACTCTTCAGTGACAGAACCTGATGCAGAGCTGGTG-
A
GGGTGCATCCGAAGAGTTCTTTGGCTGGAAGGAAGGGCTACAGCACAAGCGATGGCAAAACTTTCTCATATTTG-
G
AAGGGACCAAGTTTCACCAGGCGGCCAAGGATATAGCAGAAATTAATGCCATGTGGCCCGTTGCAACGGAGGCC-
A
ATGAGCAGGTATGCATGTATATCCTCGGAGAAAGCATGAGCAGTATTAGGTCGAAATGCCCCGTCGAAGAGTCG-
G
AAGCCTCCACACCACCTAGCACGCTGCCTTGCTTGTGCATCCATGCCATGACTCCAGAAAGAGTACAGCGCCTA-
A
AAGCCTCACGTCCAGAACAAATTACTGTGTGCTCATCCTTTCCATTGCCGAAGTATAGAATCACTGGTGTGCAG-
A
AGATCCAATGCTCCCAGCCTATATTGTTCTCACCGAAAGTGCCTGCGTATATTCATCCAAGGAAGTATCTCGTG-
G
AAACACCACCGGTAGACGAGACTCCGGAGCCATCGGCAGAGAACCAATCCACAGAGGGGACACCTGAACAACCA-
C
CACTTATAACCGAGGATGAGACCAGGACTAGAACGCCTGAGCCGATCATCATCGAAGAGGAAGAAGAGGATAGC-
A
TAAGTTTGCTGTCAGATGGCCCGACCCACCAGGTGCTGCAAGTCGAGGCAGACATTCACGGGCCGCCCTCTGTA-
T
CTAGCTCATCCTGGTCCATTCCTCATGCATCCGACTTTGATGTGGACAGTTTATCCATACTTGACACCCTGGAG-
G
GAGCTAGCGTGACCAGCGGGGCAACGTCAGCCGAGACTAACTCTTACTTCGCAAAGAGTATGGAGTTTCTGGCG-
C
GACCGGTGCCTGCGCCTCGAACAGTATTCAGGAACCCTCCACATCCCGCTCCGCGCACAAGAACACCGTCACTT-
G
CACCCAGCAGGGCCTGCTCGAGAACCAGCCTAGTTTCCACCCCGCCAGGCGTGAATAGGGTGATCACTAGAGAG-
G
AGCTCGAGGCGCTTACCCCGTCACGCACTCCTAGCAGGTCGGTCTCGAGAACCAGCCTGGTCTCCAACCCGCCA-
G
GCGTAAATAGGGTGATTACAAGAGAGGAGTTTGAGGCGTTCGTAGCACAACAACAATGACGGTTTGATGCGGGT-
G
CATACATCTTTTCCTCCGACACCGGTCAAGGGCATTTACAACAAAAATCAGTAAGGCAAACGGTGCTATCCGAA-
G
TGGTGTTGGAGAGGACCGAATTGGAGATTTCGTATGCCCCGCGCCTCGACCAAGAAAAAGAAGAATTACTACGC-
A
AGAAATTACAGTTAAATCCCACACCTGCTAACAGAAGCAGATACCAGTCCAGGAAGGTGGAGAACATGAAAGCC-
A
TAACAGCTAGACGTATTCTGCAAGGCCTAGGGCATTATTTGAAGGCAGAAGGAAAAGTGGAGTGCTACCGAACC-
C
TGCATCCTGTTCCTTTGTATTCATCTAGTGTGAACCGTGCCTTTTCAAGCCCCAAGGTCGCAGTGGAAGCCTGT-
A
ACGCCATGTTGAAAGAGAACTTTCCGACTGTGGCTTCTTACTGTATTATTCCAGAGTACGATGCCTATTTGGAC-
A
TGGTTGACGGAGCTTCATGCTGCTTAGACACTGCCAGTTTTTGCCCTGCAAAGCTGCGCAGCTTTCCAAAGAAA-
C
ACTCCTATTTGGAACCCACAATACGATCGGCAGTGCCTTCAGCGATCCAGAACACGCTCCAGAACGTCCTGGCA-
G
CTGCCACAAAAAGAAATTGCAATGTCACGCAAATGAGAGAATTGCCCGTATTGGATTCGGCGGCCTTTAATGTG-
G
AATGCTTCAAGAAATATGCGTGTAATAATGAATATTGGGAAACGTTTAAAGAAAACCCCATCAGGCTTACTGAA-
G
AAAACGTGGTAAATTACATTACCAAATTAAAAGGACCAAAAGCTGCTGCTCTTTTTGCGAAGACACATAATTTG-
A
ATATGTTGCAGGACATACCAATGGACAGGTTTGTAATGGACTTAAAGAGAGACGTGAAAGTGACTCCAGGAACA-
A
AACATACTGAAGAACGGCCCAAGGTACAGGTGATCCAGGCTGCCGATCCGCTAGCAACAGCGTATCTGTGCGGA-
A
TCCACCGAGAGCTGGTTAGGAGATTAAATGCGGTCCTGCTTCCGAACATTCATACACTGTTTGATATGTCGGCT-
G
AAGACTTTGACGCTATTATAGCCGAGCACTTCCAGCCTGGGGATTGTGTTCTGGAAACTGACATCGCGTCGTTT-
G
ATAAAAGTGAGGACGACGCCATGGCTCTGACCGCGTTAATGATTCTGGAAGACTTAGGTGTGGACGCAGAGCTG-
T
TGACGCTGATTGAGGCGGCTTTCGGCGAAATTTCATCAATACATTTGCCCACTAAAACTAAATTTAAATTCGGA-
G
CCATGATGAAATCTGGAATGTTCCTCACACTGTTTGTGAACACAGTCATTAACATTGTAATCGCAAGCAGAGTG-
T
TGAGAGAACGGCTAACCGGATCACCATGTGCAGCATTCATTGGAGATGACAATATCGTGAAAGGAGTCAAATCG-
G
ACAAATTAATGGCAGACAGGTGCGCCACCTGGTTGAATATGGAAGTCAAGATTATAGATGCTGTGGTGGGCGAG-
A
AAGCGCCTTATTTCTGTGGAGGGTTTATTTTGTGTGACTCCGTGACCGGCACAGCGTGCCGTGTGGCAGACCCC-
C
TAAAAAGGCTGTTTAAGCTTGGCAAACCTCTGGCAGCAGACGATGAACATGATGATGACAGGAGAAGGGCATTG-
C
ATGAAGAGTCAACACGCTGGAACCGAGTGGGTATTCTTTCAGAGCTGTGCAAGGCAGTAGAATCAAGGTATGAA-
A
CCGTAGGAACTTCCATCATAGTTATGGCCATGACTACTCTAGCTAGCAGTGTTAAATCATTCAGCTACCTGAGA-
G ##STR00025##
ATCTAGATTAAAACAGCTGTGGGTTGTTCCCACCCACAGGGCCCACTGGGCGCTAGCACTCTGATTTTACGAAA-
T
CCTTGTGCGCCTGTTTTATATCCCTTCCCTAATTCGAAACGTAGAAGCAATGCGCACCACTGATCAATAGTAGG-
C
GTAACGCGCCAGTTACGTCATGATCAAGCATATCTGTTCCCCCGGACTGAGTATCAATAGACTGCTTACGCGGT-
T
GAAGGAGAAAACGTTCGTTATCCGGCTAACTACTTCGAGAAGCCCAGTAACACCATGGAAGCTGCAGGGTGTTT-
C
GCTCAGCACTTCCCCCGTGTAGATCAGGTCGATGAGCCACTGCAATCCCCACAGGTGACTGTGGCAGTGGCTGC-
G
TTGGCGGCCTGCCTATGGGGAGACCCATAGGACGCTCTAATGTGGACATGGTGCGAAGAGCCTATTGAGCTAGT-
T
AGTAGTCCTCCGGCCCCTGAATGCGGCTAATCCTAACTGCGGAGCACATGCCTTCAACCCAGAGGGTAGTGTGT-
C
GTAATGGGCAACTCTGCAGCGGAACCGACTACTTTGGGTGTCCGTGTTTCTTTTTATTCTTATATTGGCTGCTT-
A
TGGTGACAATTACAGAATTGTTACCATATAGCTATTGGATTGGCCATCCGGTGTGTAATAGAGCTGTTATATAC-
C
TATTTGTTGGCTTTGTACCACTAACTTTAAAATCTATAACTACCCTCAACTTTATATTAACCCTCAATACAGTT-
G ##STR00026## ##STR00027## ##STR00028## ##STR00029##
TGGCAAGCTGCTTACATAGAACTCGCGGCGATTGGCATGCCGCCTTAAAATTTTTATTTTATTTTTCTTTTCTT-
T
TCCGAATCGGATTTTGTTTTTAATATTTCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGGGTCGGCAT-
G
GCATCTCCACCTCCTCGCGGTCCGACCTGGGCATCCGAAGGAGGACGCACGTCCACTCGGATGGCTAAGGGAGA-
G
CCACGTTTAAACACGTGATATCTGGCCTCATGGGCCTTCCTTTCACTGCCCGCTTTCCAGTCGGGAAACCTGTC-
G
TGCCAGCTGCATTAACATGGTCATAGCTGTTTCCTTGCGTATTGGGCGCTCTCCGCTTCCTCGCTCACTGACTC-
G
CTGCGCTCGGTCGTTCGGGTAAAGCCTGGGGTGCCTAATGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAA-
A
AGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAG-
A
GGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTT-
C
CGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGC-
T
GTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGAC-
C
GCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCC-
A
CTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGC-
T
ACACTAGAAGAACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCT-
T
GATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAA-
G
GATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATT-
T
TGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAA-
A
GTATATATGAGTAAACTTGGTCTGACAGTTATTAGAAAAATTCATCCAGCAGACGATAAAACGCAATACGCTGG-
C
TATCCGGTGCCGCAATGCCATACAGCACCAGAAAACGATCCGCCCATTCGCCGCCCAGTTCTTCCGCAATATCA-
C
GGGTGGCCAGCGCAATATCCTGATAACGATCCGCCACGCCCAGACGGCCGCAATCAATAAAGCCGCTAAAACGG-
C
CATTTTCCACCATAATGTTCGGCAGGCACGCATCACCATGGGTCACCACCAGATCTTCGCCATCCGGCATGCTC-
G
CTTTCAGACGCGCAAACAGCTCTGCCGGTGCCAGGCCCTGATGTTCTTCATCCAGATCATCCTGATCCACCAGG-
C
CCGCTTCCATACGGGTACGCGCACGTTCAATACGATGTTTCGCCTGATGATCAAACGGACAGGTCGCCGGGTCC-
A
GGGTATGCAGACGACGCATGGCATCCGCCATAATGCTCACTTTTTCTGCCGGCGCCAGATGGCTAGACAGCAGA-
T
CCTGACCCGGCACTTCGCCCAGCAGCAGCCAATCACGGCCCGCTTCGGTCACCACATCCAGCACCGCCGCACAC-
G
GAACACCGGTGGTGGCCAGCCAGCTCAGACGCGCCGCTTCATCCTGCAGCTCGTTCAGCGCACCGCTCAGATCG-
G
TTTTCACAAACAGCACCGGACGACCCTGCGCGCTCAGACGAAACACCGCCGCATCAGAGCAGCCAATGGTCTGC-
T
GCGCCCAATCATAGCCAAACAGACGTTCCACCCACGCTGCCGGGCTACCCGCATGCAGGCCATCCTGTTCAATC-
A
TACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGT-
A
TTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTAAATTGTAAGCGTTAATA-
T
TTTGTTAAAATTCGCGTTAAATTTTTGTTAAATCAGCTCATTTTTTAACCAATAGGCCGAAATCGGCAAAATCC-
C
TTATAAATCAAAAGAATAGACCGAGATAGGGTTGAGTGGCCGCTACAGGGCGCTCCCATTCGCCATTCAGGCTG-
C
GCAACTGTTGGGAAGGGCGTTTCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGC-
A
AGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACACGCGTAATACGACTCACTATAG
TABLE-US-00047 A535 Vector: SGP-342-EV71-gHsol-2A-gL
ATAGGCGGCGCATGAGAGAAGCCCAGACCAATTACCTACCCAAAATGGAGAAAGTTCACGTTGACATCGAGGAA-
G
ACAGCCCATTCCTCAGAGCTTTGCAGCGGAGCTTCCCGCAGTTTGAGGTAGAAGCCAAGCAGGTCACTGATAAT-
G
ACCATGCTAATGCCAGAGCGTTTTCGCATCTGGCTTCAAAACTGATCGAAACGGAGGTGGACCCATCCGACACG-
A
TCCTTGACATTGGAAGTGCGCCCGCCCGCAGAATGTATTCTAAGCACAAGTATCATTGTATCTGTCCGATGAGA-
T
GTGCGGAAGATCCGGACAGATTGTATAAGTATGCAACTAAGCTGAAGAAAAACTGTAAGGAAATAACTGATAAG-
G
AATTGGACAAGAAAATGAAGGAGCTCGCCGCCGTCATGAGCGACCCTGACCTGGAAACTGAGACTATGTGCCTC-
C
ACGACGACGAGTCGTGTCGCTACGAAGGGCAAGTCGCTGTTTACCAGGATGTATACGCGGTTGACGGACCGACA-
A
GTCTCTATCACCAAGCCAATAAGGGAGTTAGAGTCGCCTACTGGATAGGCTTTGACACCACCCCTTTTATGTTT-
A
AGAACTTGGCTGGAGCATATCCATCATACTCTACCAACTGGGCCGACGAAACCGTGTTAACGGCTCGTAACATA-
G
GCCTATGCAGCTCTGACGTTATGGAGCGGTCACGTAGAGGGATGTCCATTCTTAGAAAGAAGTATTTGAAACCA-
T
CCAACAATGTTCTATTCTCTGTTGGCTCGACCATCTACCACGAGAAGAGGGACTTACTGAGGAGCTGGCACCTG-
C
CGTCTGTATTTCACTTACGTGGCAAGCAAAATTACACATGTCGGTGTGAGACTATAGTTAGTTGCGACGGGTAC-
G
TCGTTAAAAGAATAGCTATCAGTCCAGGCCTGTATGGGAAGCCTTCAGGCTATGCTGCTACGATGCACCGCGAG-
G
GATTCTTGTGCTGCAAAGTGACAGACACATTGAACGGGGAGAGGGTCTCTTTTCCCGTGTGCACGTATGTGCCA-
G
CTACATTGTGTGACCAAATGACTGGCATACTGGCAACAGATGTCAGTGCGGACGACGCGCAAAAACTGCTGGTT-
G
GGCTCAACCAGCGTATAGTCGTCAACGGTCGCACCCAGAGAAACACCAATACCATGAAAAATTACCTTTTGCCC-
G
TAGTGGCCCAGGCATTTGCTAGGTGGGCAAAGGAATATAAGGAAGATCAAGAAGATGAAAGGCCACTAGGACTA-
C
GAGATAGACAGTTAGTCATGGGGTGTTGTTGGGCTTTTAGAAGGCACAAGATAACATCTATTTATAAGCGCCCG-
G
ATACCCAAACCATCATCAAAGTGAACAGCGATTTCCACTCATTCGTGCTGCCCAGGATAGGCAGTAACACATTG-
G
AGATCGGGCTGAGAACAAGAATCAGGAAAATGTTAGAGGAGCACAAGGAGCCGTCACCTCTCATTACCGCCGAG-
G
ACGTACAAGAAGCTAAGTGCGCAGCCGATGAGGCTAAGGAGGTGCGTGAAGCCGAGGAGTTGCGCGCAGCTCTA-
C
CACCTTTGGCAGCTGATGTTGAGGAGCCCACTCTGGAAGCCGATGTCGACTTGATGTTACAAGAGGCTGGGGCC-
G
GCTCAGTGGAGACACCTCGTGGCTTGATAAAGGTTACCAGCTACGATGGCGAGGACAAGATCGGCTCTTACGCT-
G
TGCTTTCTCCGCAGGCTGTACTCAAGAGTGAAAAATTATCTTGCATCCACCCTCTCGCTGAACAAGTCATAGTG-
A
TAACACACTCTGGCCGAAAAGGGCGTTATGCCGTGGAACCATACCATGGTAAAGTAGTGGTGCCAGAGGGACAT-
G
CAATACCCGTCCAGGACTTTCAAGCTCTGAGTGAAAGTGCCACCATTGTGTACAACGAACGTGAGTTCGTAAAC-
A
GGTACCTGCACCATATTGCCACACATGGAGGAGCGCTGAACACTGATGAAGAATATTACAAAACTGTCAAGCCC-
A
GCGAGCACGACGGCGAATACCTGTACGACATCGACAGGAAACAGTGCGTCAAGAAAGAACTAGTCACTGGGCTA-
G
GGCTCACAGGCGAGCTGGTGGATCCTCCCTTCCATGAATTCGCCTACGAGAGTCTGAGAACACGACCAGCCGCT-
C
CTTACCAAGTACCAACCATAGGGGTGTATGGCGTGCCAGGATCAGGCAAGTCTGGCATCATTAAAAGCGCAGTC-
A
CCAAAAAAGATCTAGTGGTGAGCGCCAAGAAAGAAAACTGTGCAGAAATTATAAGGGACGTCAAGAAAATGAAA-
G
GGCTGGACGTCAATGCCAGAACTGTGGACTCAGTGCTCTTGAATGGATGCAAACACCCCGTAGAGACCCTGTAT-
A
TTGACGAAGCTTTTGCTTGTCATGCAGGTACTCTCAGAGCGCTCATAGCCATTATAAGACCTAAAAAGGCAGTG-
C
TCTGCGGGGATCCCAAACAGTGCGGTTTTTTTAACATGATGTGCCTGAAAGTGCATTTTAACCACGAGATTTGC-
A
CACAAGTCTTCCACAAAAGCATCTCTCGCCGTTGCACTAAATCTGTGACTTCGGTCGTCTCAACCTTGTTTTAC-
G
ACAAAAAAATGAGAACGACGAATCCGAAAGAGACTAAGATTGTGATTGACACTACCGGCAGTACCAAACCTAAG-
C
AGGACGATCTCATTCTCACTTGTTTCAGAGGGTGGGTGAAGCAGTTGCAAATAGATTACAAAGGCAACGAAATA-
A
TGACGGCAGCTGCCTCTCAAGGGCTGACCCGTAAAGGTGTGTATGCCGTTCGGTACAAGGTGAATGAAAATCCT-
C
TGTACGCACCCACCTCAGAACATGTGAACGTCCTACTGACCCGCACGGAGGACCGCATCGTGTGGAAAACACTA-
G
CCGGCGACCCATGGATAAAAACACTGACTGCCAAGTACCCTGGGAATTTCACTGCCACGATAGAGGAGTGGCAA-
G
CAGAGCATGATGCCATCATGAGGCACATCTTGGAGAGACCGGACCCTACCGACGTCTTCCAGAATAAGGCAAAC-
G
TGTGTTGGGCCAAGGCTTTAGTGCCGGTGCTGAAGACCGCTGGCATAGACATGACCACTGAACAATGGAACACT-
G
TGGATTATTTTGAAACGGACAAAGCTCACTCAGCAGAGATAGTATTGAACCAACTATGCGTGAGGTTCTTTGGA-
C
TCGATCTGGACTCCGGTCTATTTTCTGCACCCACTGTTCCGTTATCCATTAGGAATAATCACTGGGATAACTCC-
C
CGTCGCCTAACATGTACGGGCTGAATAAAGAAGTGGTCCGTCAGCTCTCTCGCAGGTACCCACAACTGCCTCGG-
G
CAGTTGCCACTGGAAGAGTCTATGACATGAACACTGGTACACTGCGCAATTATGATCCGCGCATAAACCTAGTA-
C
CTGTAAACAGAAGACTGCCTCATGCTTTAGTCCTCCACCATAATGAACACCCACAGAGTGACTTTTCTTCATTC-
G
TCAGCAAATTGAAGGGCAGAACTGTCCTGGTGGTCGGGGAAAAGTTGTCCGTCCCAGGCAAAATGGTTGACTGG-
T
TGTCAGACCGGCCTGAGGCTACCTTCAGAGCTCGGCTGGATTTAGGCATCCCAGGTGATGTGCCCAAATATGAC-
A
TAATATTTGTTAATGTGAGGACCCCATATAAATACCATCACTATCAGCAGTGTGAAGACCATGCCATTAAGCTT-
A
GCATGTTGACCAAGAAAGCTTGTCTGCATCTGAATCCCGGCGGAACCTGTGTCAGCATAGGTTATGGTTACGCT-
G
ACAGGGCCAGCGAAAGCATCATTGGTGCTATAGCGCGGCAGTTCAAGTTTTCCCGGGTATGCAAACCGAAATCC-
T
CACTTGAAGAGACGGAAGTTCTGTTTGTATTCATTGGGTACGATCGCAAGGCCCGTACGCACAATCCTTACAAG-
C
TTTCATCAACCTTGACCAACATTTATACAGGTTCCAGACTCCACGAAGCCGGATGTGCACCCTCATATCATGTG-
G
TGCGAGGGGATATTGCCACGGCCACCGAAGGAGTGATTATAAATGCTGCTAACAGCAAAGGACAACCTGGCGGA-
G
GGGTGTGCGGAGCGCTGTATAAGAAATTCCCGGAAAGCTTCGATTTACAGCCGATCGAAGTAGGAAAAGCGCGA-
C
TGGTCAAAGGTGCAGCTAAACATATCATTCATGCCGTAGGACCAAACTTCAACAAAGTTTCGGAGGTTGAAGGT-
G
ACAAACAGTTGGCAGAGGCTTATGAGTCCATCGCTAAGATTGTCAACGATAACAATTACAAGTCAGTAGCGATT-
C
CACTGTTGTCCACCGGCATCTTTTCCGGGAACAAAGATCGACTAACCCAATCATTGAACCATTTGCTGACAGCT-
T
TAGACACCACTGATGCAGATGTAGCCATATACTGCAGGGACAAGAAATGGGAAATGACTCTCAAGGAAGCAGTG-
G
CTAGGAGAGAAGCAGTGGAGGAGATATGCATATCCGACGACTCTTCAGTGACAGAACCTGATGCAGAGCTGGTG-
A
GGGTGCATCCGAAGAGTTCTTTGGCTGGAAGGAAGGGCTACAGCACAAGCGATGGCAAAACTTTCTCATATTTG-
G
AAGGGACCAAGTTTCACCAGGCGGCCAAGGATATAGCAGAAATTAATGCCATGTGGCCCGTTGCAACGGAGGCC-
A
ATGAGCAGGTATGCATGTATATCCTCGGAGAAAGCATGAGCAGTATTAGGTCGAAATGCCCCGTCGAAGAGTCG-
G
AAGCCTCCACACCACCTAGCACGCTGCCTTGCTTGTGCATCCATGCCATGACTCCAGAAAGAGTACAGCGCCTA-
A
AAGCCTCACGTCCAGAACAAATTACTGTGTGCTCATCCTTTCCATTGCCGAAGTATAGAATCACTGGTGTGCAG-
A
AGATCCAATGCTCCCAGCCTATATTGTTCTCACCGAAAGTGCCTGCGTATATTCATCCAAGGAAGTATCTCGTG-
G
AAACACCACCGGTAGACGAGACTCCGGAGCCATCGGCAGAGAACCAATCCACAGAGGGGACACCTGAACAACCA-
C
CACTTATAACCGAGGATGAGACCAGGACTAGAACGCCTGAGCCGATCATCATCGAAGAGGAAGAAGAGGATAGC-
A
TAAGTTTGCTGTCAGATGGCCCGACCCACCAGGTGCTGCAAGTCGAGGCAGACATTCACGGGCCGCCCTCTGTA-
T
CTAGCTCATCCTGGTCCATTCCTCATGCATCCGACTTTGATGTGGACAGTTTATCCATACTTGACACCCTGGAG-
G
GAGCTAGCGTGACCAGCGGGGCAACGTCAGCCGAGACTAACTCTTACTTCGCAAAGAGTATGGAGTTTCTGGCG-
C
GACCGGTGCCTGCGCCTCGAACAGTATTCAGGAACCCTCCACATCCCGCTCCGCGCACAAGAACACCGTCACTT-
G
CACCCAGCAGGGCCTGCTCGAGAACCAGCCTAGTTTCCACCCCGCCAGGCGTGAATAGGGTGATCACTAGAGAG-
G
AGCTCGAGGCGCTTACCCCGTCACGCACTCCTAGCAGGTCGGTCTCGAGAACCAGCCTGGTCTCCAACCCGCCA-
G
GCGTAAATAGGGTGATTACAAGAGAGGAGTTTGAGGCGTTCGTAGCACAACAACAATGACGGTTTGATGCGGGT-
G
CATACATCTTTTCCTCCGACACCGGTCAAGGGCATTTACAACAAAAATCAGTAAGGCAAACGGTGCTATCCGAA-
G
TGGTGTTGGAGAGGACCGAATTGGAGATTTCGTATGCCCCGCGCCTCGACCAAGAAAAAGAAGAATTACTACGC-
A
AGAAATTACAGTTAAATCCCACACCTGCTAACAGAAGCAGATACCAGTCCAGGAAGGTGGAGAACATGAAAGCC-
A
TAACAGCTAGACGTATTCTGCAAGGCCTAGGGCATTATTTGAAGGCAGAAGGAAAAGTGGAGTGCTACCGAACC-
C
TGCATCCTGTTCCTTTGTATTCATCTAGTGTGAACCGTGCCTTTTCAAGCCCCAAGGTCGCAGTGGAAGCCTGT-
A
ACGCCATGTTGAAAGAGAACTTTCCGACTGTGGCTTCTTACTGTATTATTCCAGAGTACGATGCCTATTTGGAC-
A
TGGTTGACGGAGCTTCATGCTGCTTAGACACTGCCAGTTTTTGCCCTGCAAAGCTGCGCAGCTTTCCAAAGAAA-
C
ACTCCTATTTGGAACCCACAATACGATCGGCAGTGCCTTCAGCGATCCAGAACACGCTCCAGAACGTCCTGGCA-
G
CTGCCACAAAAAGAAATTGCAATGTCACGCAAATGAGAGAATTGCCCGTATTGGATTCGGCGGCCTTTAATGTG-
G
AATGCTTCAAGAAATATGCGTGTAATAATGAATATTGGGAAACGTTTAAAGAAAACCCCATCAGGCTTACTGAA-
G
AAAACGTGGTAAATTACATTACCAAATTAAAAGGACCAAAAGCTGCTGCTCTTTTTGCGAAGACACATAATTTG-
A
ATATGTTGCAGGACATACCAATGGACAGGTTTGTAATGGACTTAAAGAGAGACGTGAAAGTGACTCCAGGAACA-
A
AACATACTGAAGAACGGCCCAAGGTACAGGTGATCCAGGCTGCCGATCCGCTAGCAACAGCGTATCTGTGCGGA-
A
TCCACCGAGAGCTGGTTAGGAGATTAAATGCGGTCCTGCTTCCGAACATTCATACACTGTTTGATATGTCGGCT-
G
AAGACTTTGACGCTATTATAGCCGAGCACTTCCAGCCTGGGGATTGTGTTCTGGAAACTGACATCGCGTCGTTT-
G
ATAAAAGTGAGGACGACGCCATGGCTCTGACCGCGTTAATGATTCTGGAAGACTTAGGTGTGGACGCAGAGCTG-
T
TGACGCTGATTGAGGCGGCTTTCGGCGAAATTTCATCAATACATTTGCCCACTAAAACTAAATTTAAATTCGGA-
G
CCATGATGAAATCTGGAATGTTCCTCACACTGTTTGTGAACACAGTCATTAACATTGTAATCGCAAGCAGAGTG-
T
TGAGAGAACGGCTAACCGGATCACCATGTGCAGCATTCATTGGAGATGACAATATCGTGAAAGGAGTCAAATCG-
G
ACAAATTAATGGCAGACAGGTGCGCCACCTGGTTGAATATGGAAGTCAAGATTATAGATGCTGTGGTGGGCGAG-
A
AAGCGCCTTATTTCTGTGGAGGGTTTATTTTGTGTGACTCCGTGACCGGCACAGCGTGCCGTGTGGCAGACCCC-
C
TAAAAAGGCTGTTTAAGCTTGGCAAACCTCTGGCAGCAGACGATGAACATGATGATGACAGGAGAAGGGCATTG-
C
ATGAAGAGTCAACACGCTGGAACCGAGTGGGTATTCTTTCAGAGCTGTGCAAGGCAGTAGAATCAAGGTATGAA-
A
CCGTAGGAACTTCCATCATAGTTATGGCCATGACTACTCTAGCTAGCAGTGTTAAATCATTCAGCTACCTGAGA-
G
GGGCCCCTATAACTCTCTACGGCTAACCTGAATGGACTACGACATAGTCTAGTCCGCCAAGCTATTCCAGAAGT-
A
GTGAGGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTTGTATATCCATTTTCGGATCTGATCAAGAGAC-
A
GGATGAGGATCGTTTCGCATGATTGAATAAGATGGATTGCACGTAGGTTCTCCGGCCGCTTGGGTGGAGAGGCT-
A
TTCGGCTATGACTGGGCACAACTGACAATCGGCTGCTCTGATGCCGCCGTGATCCGGTTGTCAGCGCAGGGGCG-
C
CCGGTTCTTTTTGTCAAGACCGACCTGTCCGGTGCCCTGAATGAACTGAAGGACGAGGCAGCGCGGCTATCGTG-
G
CTGGCCACGACGGGCGTTCCTTGCGCAGTCTAGACTGGCGCGCCAAACCTGCAGGTTAAAACAGCTGTGGGTTG-
T
TCCCACCCACAGGGCCCACTGGGCGCTAGCACTCTGATTTTACGAAATCCTTGTGCGCCTGTTTTATATCCCTT-
C
CCTAATTCGAAACGTAGAAGCAATGCGCACCACTGATCAATAGTAGGCGTAACGCGCCAGTTACGTCATGATCA-
A
GCATATCTGTTCCCCCGGACTGAGTATCAATAGACTGCTTACGCGGTTGAAGGAGAAAACGTTCGTTATCCGGC-
T
AACTACTTCGAGAAGCCCAGTAACACCATGGAAGCTGCAGGGTGTTTCGCTCAGCACTTCCCCCGTGTAGATCA-
G
GTCGATGAGCCACTGCAATCCCCACAGGTGACTGTGGCAGTGGCTGCGTTGGCGGCCTGCCTATGGGGAGACCC-
A
TAGGACGCTCTAATGTGGACATGGTGCGAAGAGCCTATTGAGCTAGTTAGTAGTCCTCCGGCCCCTGAATGCGG-
C
TAATCCTAACTGCGGAGCACATGCCTTCAACCCAGAGGGTAGTGTGTCGTAATGGGCAACTCTGCAGCGGAACC-
G
ACTACTTTGGGTGTCCGTGTTTCTTTTTATTCTTATATTGGCTGCTTATGGTGACAATTACAGAATTGTTACCA-
T
ATAGCTATTGGATTGGCCATCCGGTGTGTAATAGAGCTGTTATATACCTATTTGTTGGCTTTGTACCACTAACT-
T ##STR00030## ##STR00031## ##STR00032## ##STR00033##
ATGCCGCCTTAAAATTTTTATTTTATTTTTCTTTTCTTTTCCGAATCGGATTTTGTTTTTAATATTTCAAAAAA-
A
AAAAAAAAAAAAAAAAAAAAAAAAAAAAGGGTCGGCATGGCATCTCCACCTCCTCGCGGTCCGACCTGGGCATC-
C
GAAGGAGGACGCACGTCCACTCGGATGGCTAAGGGAGAGCCACGTTTAAACACGTGATATCTGGCCTCATGGGC-
C
TTCCTTTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAACATGGTCATAGCTGTTTCCT-
T
GCGTATTGGGCGCTCTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGGTAAAGCCTGGGGTGCC-
T
AATGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGC-
C
CCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAG-
G
CGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTT-
C
TCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCC-
A
AGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCC-
A
ACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGC-
G
GTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCTGCGCTCTG-
C
TGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGT-
T
TTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGG-
T
CTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAG-
A
TCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTATTAG-
A
AAAATTCATCCAGCAGACGATAAAACGCAATACGCTGGCTATCCGGTGCCGCAATGCCATACAGCACCAGAAAA-
C
GATCCGCCCATTCGCCGCCCAGTTCTTCCGCAATATCACGGGTGGCCAGCGCAATATCCTGATAACGATCCGCC-
A
CGCCCAGACGGCCGCAATCAATAAAGCCGCTAAAACGGCCATTTTCCACCATAATGTTCGGCAGGCACGCATCA-
C
CATGGGTCACCACCAGATCTTCGCCATCCGGCATGCTCGCTTTCAGACGCGCAAACAGCTCTGCCGGTGCCAGG-
C
CCTGATGTTCTTCATCCAGATCATCCTGATCCACCAGGCCCGCTTCCATACGGGTACGCGCACGTTCAATACGA-
T
GTTTCGCCTGATGATCAAACGGACAGGTCGCCGGGTCCAGGGTATGCAGACGACGCATGGCATCCGCCATAATG-
C
TCACTTTTTCTGCCGGCGCCAGATGGCTAGACAGCAGATCCTGACCCGGCACTTCGCCCAGCAGCAGCCAATCA-
C
GGCCCGCTTCGGTCACCACATCCAGCACCGCCGCACACGGAACACCGGTGGTGGCCAGCCAGCTCAGACGCGCC-
G
CTTCATCCTGCAGCTCGTTCAGCGCACCGCTCAGATCGGTTTTCACAAACAGCACCGGACGACCCTGCGCGCTC-
A
GACGAAACACCGCCGCATCAGAGCAGCCAATGGTCTGCTGCGCCCAATCATAGCCAAACAGACGTTCCACCCAC-
G
CTGCCGGGCTACCCGCATGCAGGCCATCCTGTTCAATCATACTCTTCCTTTTTCAATATTATTGAAGCATTTAT-
C
AGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACA-
T
TTCCCCGAAAAGTGCCACCTAAATTGTAAGCGTTAATATTTTGTTAAAATTCGCGTTAAATTTTTGTTAAATCA-
G
CTCATTTTTTAACCAATAGGCCGAAATCGGCAAAATCCCTTATAAATCAAAAGAATAGACCGAGATAGGGTTGA-
G
TGGCCGCTACAGGGCGCTCCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGTTTCGGTGCGGGCCTC-
T
TCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCA-
G TCACACGCGTAATACGACTCACTATAG
TABLE-US-00048 A536 Vector: SGP-342-EV71-gHsol-EMCV-gL
ATAGGCGGCGCATGAGAGAAGCCCAGACCAATTACCTACCCAAAATGGAGAAAGTTCACGTTGACATCGAGGAA-
G
ACAGCCCATTCCTCAGAGCTTTGCAGCGGAGCTTCCCGCAGTTTGAGGTAGAAGCCAAGCAGGTCACTGATAAT-
G
ACCATGCTAATGCCAGAGCGTTTTCGCATCTGGCTTCAAAACTGATCGAAACGGAGGTGGACCCATCCGACACG-
A
TCCTTGACATTGGAAGTGCGCCCGCCCGCAGAATGTATTCTAAGCACAAGTATCATTGTATCTGTCCGATGAGA-
T
GTGCGGAAGATCCGGACAGATTGTATAAGTATGCAACTAAGCTGAAGAAAAACTGTAAGGAAATAACTGATAAG-
G
AATTGGACAAGAAAATGAAGGAGCTCGCCGCCGTCATGAGCGACCCTGACCTGGAAACTGAGACTATGTGCCTC-
C
ACGACGACGAGTCGTGTCGCTACGAAGGGCAAGTCGCTGTTTACCAGGATGTATACGCGGTTGACGGACCGACA-
A
GTCTCTATCACCAAGCCAATAAGGGAGTTAGAGTCGCCTACTGGATAGGCTTTGACACCACCCCTTTTATGTTT-
A
AGAACTTGGCTGGAGCATATCCATCATACTCTACCAACTGGGCCGACGAAACCGTGTTAACGGCTCGTAACATA-
G
GCCTATGCAGCTCTGACGTTATGGAGCGGTCACGTAGAGGGATGTCCATTCTTAGAAAGAAGTATTTGAAACCA-
T
CCAACAATGTTCTATTCTCTGTTGGCTCGACCATCTACCACGAGAAGAGGGACTTACTGAGGAGCTGGCACCTG-
C
CGTCTGTATTTCACTTACGTGGCAAGCAAAATTACACATGTCGGTGTGAGACTATAGTTAGTTGCGACGGGTAC-
G
TCGTTAAAAGAATAGCTATCAGTCCAGGCCTGTATGGGAAGCCTTCAGGCTATGCTGCTACGATGCACCGCGAG-
G
GATTCTTGTGCTGCAAAGTGACAGACACATTGAACGGGGAGAGGGTCTCTTTTCCCGTGTGCACGTATGTGCCA-
G
CTACATTGTGTGACCAAATGACTGGCATACTGGCAACAGATGTCAGTGCGGACGACGCGCAAAAACTGCTGGTT-
G
GGCTCAACCAGCGTATAGTCGTCAACGGTCGCACCCAGAGAAACACCAATACCATGAAAAATTACCTTTTGCCC-
G
TAGTGGCCCAGGCATTTGCTAGGTGGGCAAAGGAATATAAGGAAGATCAAGAAGATGAAAGGCCACTAGGACTA-
C
GAGATAGACAGTTAGTCATGGGGTGTTGTTGGGCTTTTAGAAGGCACAAGATAACATCTATTTATAAGCGCCCG-
G
ATACCCAAACCATCATCAAAGTGAACAGCGATTTCCACTCATTCGTGCTGCCCAGGATAGGCAGTAACACATTG-
G
AGATCGGGCTGAGAACAAGAATCAGGAAAATGTTAGAGGAGCACAAGGAGCCGTCACCTCTCATTACCGCCGAG-
G
ACGTACAAGAAGCTAAGTGCGCAGCCGATGAGGCTAAGGAGGTGCGTGAAGCCGAGGAGTTGCGCGCAGCTCTA-
C
CACCTTTGGCAGCTGATGTTGAGGAGCCCACTCTGGAAGCCGATGTCGACTTGATGTTACAAGAGGCTGGGGCC-
G
GCTCAGTGGAGACACCTCGTGGCTTGATAAAGGTTACCAGCTACGATGGCGAGGACAAGATCGGCTCTTACGCT-
G
TGCTTTCTCCGCAGGCTGTACTCAAGAGTGAAAAATTATCTTGCATCCACCCTCTCGCTGAACAAGTCATAGTG-
A
TAACACACTCTGGCCGAAAAGGGCGTTATGCCGTGGAACCATACCATGGTAAAGTAGTGGTGCCAGAGGGACAT-
G
CAATACCCGTCCAGGACTTTCAAGCTCTGAGTGAAAGTGCCACCATTGTGTACAACGAACGTGAGTTCGTAAAC-
A
GGTACCTGCACCATATTGCCACACATGGAGGAGCGCTGAACACTGATGAAGAATATTACAAAACTGTCAAGCCC-
A
GCGAGCACGACGGCGAATACCTGTACGACATCGACAGGAAACAGTGCGTCAAGAAAGAACTAGTCACTGGGCTA-
G
GGCTCACAGGCGAGCTGGTGGATCCTCCCTTCCATGAATTCGCCTACGAGAGTCTGAGAACACGACCAGCCGCT-
C
CTTACCAAGTACCAACCATAGGGGTGTATGGCGTGCCAGGATCAGGCAAGTCTGGCATCATTAAAAGCGCAGTC-
A
CCAAAAAAGATCTAGTGGTGAGCGCCAAGAAAGAAAACTGTGCAGAAATTATAAGGGACGTCAAGAAAATGAAA-
G
GGCTGGACGTCAATGCCAGAACTGTGGACTCAGTGCTCTTGAATGGATGCAAACACCCCGTAGAGACCCTGTAT-
A
TTGACGAAGCTTTTGCTTGTCATGCAGGTACTCTCAGAGCGCTCATAGCCATTATAAGACCTAAAAAGGCAGTG-
C
TCTGCGGGGATCCCAAACAGTGCGGTTTTTTTAACATGATGTGCCTGAAAGTGCATTTTAACCACGAGATTTGC-
A
CACAAGTCTTCCACAAAAGCATCTCTCGCCGTTGCACTAAATCTGTGACTTCGGTCGTCTCAACCTTGTTTTAC-
G
ACAAAAAAATGAGAACGACGAATCCGAAAGAGACTAAGATTGTGATTGACACTACCGGCAGTACCAAACCTAAG-
C
AGGACGATCTCATTCTCACTTGTTTCAGAGGGTGGGTGAAGCAGTTGCAAATAGATTACAAAGGCAACGAAATA-
A
TGACGGCAGCTGCCTCTCAAGGGCTGACCCGTAAAGGTGTGTATGCCGTTCGGTACAAGGTGAATGAAAATCCT-
C
TGTACGCACCCACCTCAGAACATGTGAACGTCCTACTGACCCGCACGGAGGACCGCATCGTGTGGAAAACACTA-
G
CCGGCGACCCATGGATAAAAACACTGACTGCCAAGTACCCTGGGAATTTCACTGCCACGATAGAGGAGTGGCAA-
G
CAGAGCATGATGCCATCATGAGGCACATCTTGGAGAGACCGGACCCTACCGACGTCTTCCAGAATAAGGCAAAC-
G
TGTGTTGGGCCAAGGCTTTAGTGCCGGTGCTGAAGACCGCTGGCATAGACATGACCACTGAACAATGGAACACT-
G
TGGATTATTTTGAAACGGACAAAGCTCACTCAGCAGAGATAGTATTGAACCAACTATGCGTGAGGTTCTTTGGA-
C
TCGATCTGGACTCCGGTCTATTTTCTGCACCCACTGTTCCGTTATCCATTAGGAATAATCACTGGGATAACTCC-
C
CGTCGCCTAACATGTACGGGCTGAATAAAGAAGTGGTCCGTCAGCTCTCTCGCAGGTACCCACAACTGCCTCGG-
G
CAGTTGCCACTGGAAGAGTCTATGACATGAACACTGGTACACTGCGCAATTATGATCCGCGCATAAACCTAGTA-
C
CTGTAAACAGAAGACTGCCTCATGCTTTAGTCCTCCACCATAATGAACACCCACAGAGTGACTTTTCTTCATTC-
G
TCAGCAAATTGAAGGGCAGAACTGTCCTGGTGGTCGGGGAAAAGTTGTCCGTCCCAGGCAAAATGGTTGACTGG-
T
TGTCAGACCGGCCTGAGGCTACCTTCAGAGCTCGGCTGGATTTAGGCATCCCAGGTGATGTGCCCAAATATGAC-
A
TAATATTTGTTAATGTGAGGACCCCATATAAATACCATCACTATCAGCAGTGTGAAGACCATGCCATTAAGCTT-
A
GCATGTTGACCAAGAAAGCTTGTCTGCATCTGAATCCCGGCGGAACCTGTGTCAGCATAGGTTATGGTTACGCT-
G
ACAGGGCCAGCGAAAGCATCATTGGTGCTATAGCGCGGCAGTTCAAGTTTTCCCGGGTATGCAAACCGAAATCC-
T
CACTTGAAGAGACGGAAGTTCTGTTTGTATTCATTGGGTACGATCGCAAGGCCCGTACGCACAATCCTTACAAG-
C
TTTCATCAACCTTGACCAACATTTATACAGGTTCCAGACTCCACGAAGCCGGATGTGCACCCTCATATCATGTG-
G
TGCGAGGGGATATTGCCACGGCCACCGAAGGAGTGATTATAAATGCTGCTAACAGCAAAGGACAACCTGGCGGA-
G
GGGTGTGCGGAGCGCTGTATAAGAAATTCCCGGAAAGCTTCGATTTACAGCCGATCGAAGTAGGAAAAGCGCGA-
C
TGGTCAAAGGTGCAGCTAAACATATCATTCATGCCGTAGGACCAAACTTCAACAAAGTTTCGGAGGTTGAAGGT-
G
ACAAACAGTTGGCAGAGGCTTATGAGTCCATCGCTAAGATTGTCAACGATAACAATTACAAGTCAGTAGCGATT-
C
CACTGTTGTCCACCGGCATCTTTTCCGGGAACAAAGATCGACTAACCCAATCATTGAACCATTTGCTGACAGCT-
T
TAGACACCACTGATGCAGATGTAGCCATATACTGCAGGGACAAGAAATGGGAAATGACTCTCAAGGAAGCAGTG-
G
CTAGGAGAGAAGCAGTGGAGGAGATATGCATATCCGACGACTCTTCAGTGACAGAACCTGATGCAGAGCTGGTG-
A
GGGTGCATCCGAAGAGTTCTTTGGCTGGAAGGAAGGGCTACAGCACAAGCGATGGCAAAACTTTCTCATATTTG-
G
AAGGGACCAAGTTTCACCAGGCGGCCAAGGATATAGCAGAAATTAATGCCATGTGGCCCGTTGCAACGGAGGCC-
A
ATGAGCAGGTATGCATGTATATCCTCGGAGAAAGCATGAGCAGTATTAGGTCGAAATGCCCCGTCGAAGAGTCG-
G
AAGCCTCCACACCACCTAGCACGCTGCCTTGCTTGTGCATCCATGCCATGACTCCAGAAAGAGTACAGCGCCTA-
A
AAGCCTCACGTCCAGAACAAATTACTGTGTGCTCATCCTTTCCATTGCCGAAGTATAGAATCACTGGTGTGCAG-
A
AGATCCAATGCTCCCAGCCTATATTGTTCTCACCGAAAGTGCCTGCGTATATTCATCCAAGGAAGTATCTCGTG-
G
AAACACCACCGGTAGACGAGACTCCGGAGCCATCGGCAGAGAACCAATCCACAGAGGGGACACCTGAACAACCA-
C
CACTTATAACCGAGGATGAGACCAGGACTAGAACGCCTGAGCCGATCATCATCGAAGAGGAAGAAGAGGATAGC-
A
TAAGTTTGCTGTCAGATGGCCCGACCCACCAGGTGCTGCAAGTCGAGGCAGACATTCACGGGCCGCCCTCTGTA-
T
CTAGCTCATCCTGGTCCATTCCTCATGCATCCGACTTTGATGTGGACAGTTTATCCATACTTGACACCCTGGAG-
G
GAGCTAGCGTGACCAGCGGGGCAACGTCAGCCGAGACTAACTCTTACTTCGCAAAGAGTATGGAGTTTCTGGCG-
C
GACCGGTGCCTGCGCCTCGAACAGTATTCAGGAACCCTCCACATCCCGCTCCGCGCACAAGAACACCGTCACTT-
G
CACCCAGCAGGGCCTGCTCGAGAACCAGCCTAGTTTCCACCCCGCCAGGCGTGAATAGGGTGATCACTAGAGAG-
G
AGCTCGAGGCGCTTACCCCGTCACGCACTCCTAGCAGGTCGGTCTCGAGAACCAGCCTGGTCTCCAACCCGCCA-
G
GCGTAAATAGGGTGATTACAAGAGAGGAGTTTGAGGCGTTCGTAGCACAACAACAATGACGGTTTGATGCGGGT-
G
CATACATCTTTTCCTCCGACACCGGTCAAGGGCATTTACAACAAAAATCAGTAAGGCAAACGGTGCTATCCGAA-
G
TGGTGTTGGAGAGGACCGAATTGGAGATTTCGTATGCCCCGCGCCTCGACCAAGAAAAAGAAGAATTACTACGC-
A
AGAAATTACAGTTAAATCCCACACCTGCTAACAGAAGCAGATACCAGTCCAGGAAGGTGGAGAACATGAAAGCC-
A
TAACAGCTAGACGTATTCTGCAAGGCCTAGGGCATTATTTGAAGGCAGAAGGAAAAGTGGAGTGCTACCGAACC-
C
TGCATCCTGTTCCTTTGTATTCATCTAGTGTGAACCGTGCCTTTTCAAGCCCCAAGGTCGCAGTGGAAGCCTGT-
A
ACGCCATGTTGAAAGAGAACTTTCCGACTGTGGCTTCTTACTGTATTATTCCAGAGTACGATGCCTATTTGGAC-
A
TGGTTGACGGAGCTTCATGCTGCTTAGACACTGCCAGTTTTTGCCCTGCAAAGCTGCGCAGCTTTCCAAAGAAA-
C
ACTCCTATTTGGAACCCACAATACGATCGGCAGTGCCTTCAGCGATCCAGAACACGCTCCAGAACGTCCTGGCA-
G
CTGCCACAAAAAGAAATTGCAATGTCACGCAAATGAGAGAATTGCCCGTATTGGATTCGGCGGCCTTTAATGTG-
G
AATGCTTCAAGAAATATGCGTGTAATAATGAATATTGGGAAACGTTTAAAGAAAACCCCATCAGGCTTACTGAA-
G
AAAACGTGGTAAATTACATTACCAAATTAAAAGGACCAAAAGCTGCTGCTCTTTTTGCGAAGACACATAATTTG-
A
ATATGTTGCAGGACATACCAATGGACAGGTTTGTAATGGACTTAAAGAGAGACGTGAAAGTGACTCCAGGAACA-
A
AACATACTGAAGAACGGCCCAAGGTACAGGTGATCCAGGCTGCCGATCCGCTAGCAACAGCGTATCTGTGCGGA-
A
TCCACCGAGAGCTGGTTAGGAGATTAAATGCGGTCCTGCTTCCGAACATTCATACACTGTTTGATATGTCGGCT-
G
AAGACTTTGACGCTATTATAGCCGAGCACTTCCAGCCTGGGGATTGTGTTCTGGAAACTGACATCGCGTCGTTT-
G
ATAAAAGTGAGGACGACGCCATGGCTCTGACCGCGTTAATGATTCTGGAAGACTTAGGTGTGGACGCAGAGCTG-
T
TGACGCTGATTGAGGCGGCTTTCGGCGAAATTTCATCAATACATTTGCCCACTAAAACTAAATTTAAATTCGGA-
G
CCATGATGAAATCTGGAATGTTCCTCACACTGTTTGTGAACACAGTCATTAACATTGTAATCGCAAGCAGAGTG-
T
TGAGAGAACGGCTAACCGGATCACCATGTGCAGCATTCATTGGAGATGACAATATCGTGAAAGGAGTCAAATCG-
G
ACAAATTAATGGCAGACAGGTGCGCCACCTGGTTGAATATGGAAGTCAAGATTATAGATGCTGTGGTGGGCGAG-
A
AAGCGCCTTATTTCTGTGGAGGGTTTATTTTGTGTGACTCCGTGACCGGCACAGCGTGCCGTGTGGCAGACCCC-
C
TAAAAAGGCTGTTTAAGCTTGGCAAACCTCTGGCAGCAGACGATGAACATGATGATGACAGGAGAAGGGCATTG-
C
ATGAAGAGTCAACACGCTGGAACCGAGTGGGTATTCTTTCAGAGCTGTGCAAGGCAGTAGAATCAAGGTATGAA-
A
CCGTAGGAACTTCCATCATAGTTATGGCCATGACTACTCTAGCTAGCAGTGTTAAATCATTCAGCTACCTGAGA-
G
GGGCCCCTATAACTCTCTACGGCTAACCTGAATGGACTACGACATAGTCTAGTCCGCCAAGCTATTCCAGAAGT-
A
GTGAGGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTTGTATATCCATTTTCGGATCTGATCAAGAGAC-
A
GGATGAGGATCGTTTCGCATGATTGAATAAGATGGATTGCACGTAGGTTCTCCGGCCGCTTGGGTGGAGAGGCT-
A
TTCGGCTATGACTGGGCACAACTGACAATCGGCTGCTCTGATGCCGCCGTGATCCGGTTGTCAGCGCAGGGGCG-
C
CCGGTTCTTTTTGTCAAGACCGACCTGTCCGGTGCCCTGAATGAACTGAAGGACGAGGCAGCGCGGCTATCGTG-
G
CTGGCCACGACGGGCGTTCCTTGCGCAGTCTAGACTGGCGCGCCAAACCTGCAGGTTAAAACAGCTGTGGGTTG-
T
TCCCACCCACAGGGCCCACTGGGCGCTAGCACTCTGATTTTACGAAATCCTTGTGCGCCTGTTTTATATCCCTT-
C
CCTAATTCGAAACGTAGAAGCAATGCGCACCACTGATCAATAGTAGGCGTAACGCGCCAGTTACGTCATGATCA-
A
GCATATCTGTTCCCCCGGACTGAGTATCAATAGACTGCTTACGCGGTTGAAGGAGAAAACGTTCGTTATCCGGC-
T
AACTACTTCGAGAAGCCCAGTAACACCATGGAAGCTGCAGGGTGTTTCGCTCAGCACTTCCCCCGTGTAGATCA-
G
GTCGATGAGCCACTGCAATCCCCACAGGTGACTGTGGCAGTGGCTGCGTTGGCGGCCTGCCTATGGGGAGACCC-
A
TAGGACGCTCTAATGTGGACATGGTGCGAAGAGCCTATTGAGCTAGTTAGTAGTCCTCCGGCCCCTGAATGCGG-
C
TAATCCTAACTGCGGAGCACATGCCTTCAACCCAGAGGGTAGTGTGTCGTAATGGGCAACTCTGCAGCGGAACC-
G
ACTACTTTGGGTGTCCGTGTTTCTTTTTATTCTTATATTGGCTGCTTATGGTGACAATTACAGAATTGTTACCA-
T
ATAGCTATTGGATTGGCCATCCGGTGTGTAATAGAGCTGTTATATACCTATTTGTTGGCTTTGTACCACTAACT-
T ##STR00034## ##STR00035##
GCCGGTGTGCGTTTGTCTATATGTTATTTTCCACCATATTGCCGTCTTTTGGCAATGTGAGGGCCCGGAAACCT-
G
GCCCTGTCTTCTTGACGAGCATTCCTAGGGGTCTTTCCCCTCTCGCCAAAGGAATGCAAGGTCTGTTGAATGTC-
G
TGAAGGAAGCAGTTCCTCTGGAAGCTTCTTGAAGACAAACAACGTCTGTAGCGACCCTTTGCAGGCAGCGGAAC-
C
CCCCACCTGGCGACAGGTGCCTCTGCGGCCAAAAGCCACGTGTATAAGATACACCTGCAAAGGCGGCACAACCC-
C
AGTGCCACGTTGTGAGTTGGATAGTTGTGGAAAGAGTCAAATGGCTCTCCTCAAGCGTATTCAACAAGGGGCTG-
A
AGGATGCCCAGAAGGTACCCCATTGTATGGGATCTGATCTGGGGCCTCGGTGCACATGCTTTACATGTGTTTAG-
T ##STR00036##
CCTTAAAATTTTTATTTTATTTTTCTTTTCTTTTCCGAATCGGATTTTGTTTTTAATATTTCAAAAAAAAAAAA-
A
AAAAAAAAAAAAAAAAAAAAAAGGGTCGGCATGGCATCTCCACCTCCTCGCGGTCCGACCTGGGCATCCGAAGG-
A
GGACGCACGTCCACTCGGATGGCTAAGGGAGAGCCACGTTTAAACACGTGATATCTGGCCTCATGGGCCTTCCT-
T
TCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAACATGGTCATAGCTGTTTCCTTGCGTA-
T
TGGGCGCTCTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGGTAAAGCCTGGGGTGCCTAATGA-
G
CAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCT-
G
ACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTT-
C
CCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCT-
T
CGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTG-
G
GCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCG-
G
TAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCT-
A
CAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCTGCGCTCTGCTGAAG-
C
CAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTT-
G
TTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGAC-
G
CTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTT-
T
TAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTATTAGAAAAAT-
T
CATCCAGCAGACGATAAAACGCAATACGCTGGCTATCCGGTGCCGCAATGCCATACAGCACCAGAAAACGATCC-
G
CCCATTCGCCGCCCAGTTCTTCCGCAATATCACGGGTGGCCAGCGCAATATCCTGATAACGATCCGCCACGCCC-
A
GACGGCCGCAATCAATAAAGCCGCTAAAACGGCCATTTTCCACCATAATGTTCGGCAGGCACGCATCACCATGG-
G
TCACCACCAGATCTTCGCCATCCGGCATGCTCGCTTTCAGACGCGCAAACAGCTCTGCCGGTGCCAGGCCCTGA-
T
GTTCTTCATCCAGATCATCCTGATCCACCAGGCCCGCTTCCATACGGGTACGCGCACGTTCAATACGATGTTTC-
G
CCTGATGATCAAACGGACAGGTCGCCGGGTCCAGGGTATGCAGACGACGCATGGCATCCGCCATAATGCTCACT-
T
TTTCTGCCGGCGCCAGATGGCTAGACAGCAGATCCTGACCCGGCACTTCGCCCAGCAGCAGCCAATCACGGCCC-
G
CTTCGGTCACCACATCCAGCACCGCCGCACACGGAACACCGGTGGTGGCCAGCCAGCTCAGACGCGCCGCTTCA-
T
CCTGCAGCTCGTTCAGCGCACCGCTCAGATCGGTTTTCACAAACAGCACCGGACGACCCTGCGCGCTCAGACGA-
A
ACACCGCCGCATCAGAGCAGCCAATGGTCTGCTGCGCCCAATCATAGCCAAACAGACGTTCCACCCACGCTGCC-
G
GGCTACCCGCATGCAGGCCATCCTGTTCAATCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGT-
T
ATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCC-
C
GAAAAGTGCCACCTAAATTGTAAGCGTTAATATTTTGTTAAAATTCGCGTTAAATTTTTGTTAAATCAGCTCAT-
T
TTTTAACCAATAGGCCGAAATCGGCAAAATCCCTTATAAATCAAAAGAATAGACCGAGATAGGGTTGAGTGGCC-
G
CTACAGGGCGCTCCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGTTTCGGTGCGGGCCTCTTCGCT-
A
TTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACA-
C GCGTAATACGACTCACTATAG
TABLE-US-00049 A537 Vector: SGP-342-EV71-gL-EMCV-gHsol
ATAGGCGGCGCATGAGAGAAGCCCAGACCAATTACCTACCCAAAATGGAGAAAGTTCACGTTGACATCGAGGAA-
G
ACAGCCCATTCCTCAGAGCTTTGCAGCGGAGCTTCCCGCAGTTTGAGGTAGAAGCCAAGCAGGTCACTGATAAT-
G
ACCATGCTAATGCCAGAGCGTTTTCGCATCTGGCTTCAAAACTGATCGAAACGGAGGTGGACCCATCCGACACG-
A
TCCTTGACATTGGAAGTGCGCCCGCCCGCAGAATGTATTCTAAGCACAAGTATCATTGTATCTGTCCGATGAGA-
T
GTGCGGAAGATCCGGACAGATTGTATAAGTATGCAACTAAGCTGAAGAAAAACTGTAAGGAAATAACTGATAAG-
G
AATTGGACAAGAAAATGAAGGAGCTCGCCGCCGTCATGAGCGACCCTGACCTGGAAACTGAGACTATGTGCCTC-
C
ACGACGACGAGTCGTGTCGCTACGAAGGGCAAGTCGCTGTTTACCAGGATGTATACGCGGTTGACGGACCGACA-
A
GTCTCTATCACCAAGCCAATAAGGGAGTTAGAGTCGCCTACTGGATAGGCTTTGACACCACCCCTTTTATGTTT-
A
AGAACTTGGCTGGAGCATATCCATCATACTCTACCAACTGGGCCGACGAAACCGTGTTAACGGCTCGTAACATA-
G
GCCTATGCAGCTCTGACGTTATGGAGCGGTCACGTAGAGGGATGTCCATTCTTAGAAAGAAGTATTTGAAACCA-
T
CCAACAATGTTCTATTCTCTGTTGGCTCGACCATCTACCACGAGAAGAGGGACTTACTGAGGAGCTGGCACCTG-
C
CGTCTGTATTTCACTTACGTGGCAAGCAAAATTACACATGTCGGTGTGAGACTATAGTTAGTTGCGACGGGTAC-
G
TCGTTAAAAGAATAGCTATCAGTCCAGGCCTGTATGGGAAGCCTTCAGGCTATGCTGCTACGATGCACCGCGAG-
G
GATTCTTGTGCTGCAAAGTGACAGACACATTGAACGGGGAGAGGGTCTCTTTTCCCGTGTGCACGTATGTGCCA-
G
CTACATTGTGTGACCAAATGACTGGCATACTGGCAACAGATGTCAGTGCGGACGACGCGCAAAAACTGCTGGTT-
G
GGCTCAACCAGCGTATAGTCGTCAACGGTCGCACCCAGAGAAACACCAATACCATGAAAAATTACCTTTTGCCC-
G
TAGTGGCCCAGGCATTTGCTAGGTGGGCAAAGGAATATAAGGAAGATCAAGAAGATGAAAGGCCACTAGGACTA-
C
GAGATAGACAGTTAGTCATGGGGTGTTGTTGGGCTTTTAGAAGGCACAAGATAACATCTATTTATAAGCGCCCG-
G
ATACCCAAACCATCATCAAAGTGAACAGCGATTTCCACTCATTCGTGCTGCCCAGGATAGGCAGTAACACATTG-
G
AGATCGGGCTGAGAACAAGAATCAGGAAAATGTTAGAGGAGCACAAGGAGCCGTCACCTCTCATTACCGCCGAG-
G
ACGTACAAGAAGCTAAGTGCGCAGCCGATGAGGCTAAGGAGGTGCGTGAAGCCGAGGAGTTGCGCGCAGCTCTA-
C
CACCTTTGGCAGCTGATGTTGAGGAGCCCACTCTGGAAGCCGATGTCGACTTGATGTTACAAGAGGCTGGGGCC-
G
GCTCAGTGGAGACACCTCGTGGCTTGATAAAGGTTACCAGCTACGATGGCGAGGACAAGATCGGCTCTTACGCT-
G
TGCTTTCTCCGCAGGCTGTACTCAAGAGTGAAAAATTATCTTGCATCCACCCTCTCGCTGAACAAGTCATAGTG-
A
TAACACACTCTGGCCGAAAAGGGCGTTATGCCGTGGAACCATACCATGGTAAAGTAGTGGTGCCAGAGGGACAT-
G
CAATACCCGTCCAGGACTTTCAAGCTCTGAGTGAAAGTGCCACCATTGTGTACAACGAACGTGAGTTCGTAAAC-
A
GGTACCTGCACCATATTGCCACACATGGAGGAGCGCTGAACACTGATGAAGAATATTACAAAACTGTCAAGCCC-
A
GCGAGCACGACGGCGAATACCTGTACGACATCGACAGGAAACAGTGCGTCAAGAAAGAACTAGTCACTGGGCTA-
G
GGCTCACAGGCGAGCTGGTGGATCCTCCCTTCCATGAATTCGCCTACGAGAGTCTGAGAACACGACCAGCCGCT-
C
CTTACCAAGTACCAACCATAGGGGTGTATGGCGTGCCAGGATCAGGCAAGTCTGGCATCATTAAAAGCGCAGTC-
A
CCAAAAAAGATCTAGTGGTGAGCGCCAAGAAAGAAAACTGTGCAGAAATTATAAGGGACGTCAAGAAAATGAAA-
G
GGCTGGACGTCAATGCCAGAACTGTGGACTCAGTGCTCTTGAATGGATGCAAACACCCCGTAGAGACCCTGTAT-
A
TTGACGAAGCTTTTGCTTGTCATGCAGGTACTCTCAGAGCGCTCATAGCCATTATAAGACCTAAAAAGGCAGTG-
C
TCTGCGGGGATCCCAAACAGTGCGGTTTTTTTAACATGATGTGCCTGAAAGTGCATTTTAACCACGAGATTTGC-
A
CACAAGTCTTCCACAAAAGCATCTCTCGCCGTTGCACTAAATCTGTGACTTCGGTCGTCTCAACCTTGTTTTAC-
G
ACAAAAAAATGAGAACGACGAATCCGAAAGAGACTAAGATTGTGATTGACACTACCGGCAGTACCAAACCTAAG-
C
AGGACGATCTCATTCTCACTTGTTTCAGAGGGTGGGTGAAGCAGTTGCAAATAGATTACAAAGGCAACGAAATA-
A
TGACGGCAGCTGCCTCTCAAGGGCTGACCCGTAAAGGTGTGTATGCCGTTCGGTACAAGGTGAATGAAAATCCT-
C
TGTACGCACCCACCTCAGAACATGTGAACGTCCTACTGACCCGCACGGAGGACCGCATCGTGTGGAAAACACTA-
G
CCGGCGACCCATGGATAAAAACACTGACTGCCAAGTACCCTGGGAATTTCACTGCCACGATAGAGGAGTGGCAA-
G
CAGAGCATGATGCCATCATGAGGCACATCTTGGAGAGACCGGACCCTACCGACGTCTTCCAGAATAAGGCAAAC-
G
TGTGTTGGGCCAAGGCTTTAGTGCCGGTGCTGAAGACCGCTGGCATAGACATGACCACTGAACAATGGAACACT-
G
TGGATTATTTTGAAACGGACAAAGCTCACTCAGCAGAGATAGTATTGAACCAACTATGCGTGAGGTTCTTTGGA-
C
TCGATCTGGACTCCGGTCTATTTTCTGCACCCACTGTTCCGTTATCCATTAGGAATAATCACTGGGATAACTCC-
C
CGTCGCCTAACATGTACGGGCTGAATAAAGAAGTGGTCCGTCAGCTCTCTCGCAGGTACCCACAACTGCCTCGG-
G
CAGTTGCCACTGGAAGAGTCTATGACATGAACACTGGTACACTGCGCAATTATGATCCGCGCATAAACCTAGTA-
C
CTGTAAACAGAAGACTGCCTCATGCTTTAGTCCTCCACCATAATGAACACCCACAGAGTGACTTTTCTTCATTC-
G
TCAGCAAATTGAAGGGCAGAACTGTCCTGGTGGTCGGGGAAAAGTTGTCCGTCCCAGGCAAAATGGTTGACTGG-
T
TGTCAGACCGGCCTGAGGCTACCTTCAGAGCTCGGCTGGATTTAGGCATCCCAGGTGATGTGCCCAAATATGAC-
A
TAATATTTGTTAATGTGAGGACCCCATATAAATACCATCACTATCAGCAGTGTGAAGACCATGCCATTAAGCTT-
A
GCATGTTGACCAAGAAAGCTTGTCTGCATCTGAATCCCGGCGGAACCTGTGTCAGCATAGGTTATGGTTACGCT-
G
ACAGGGCCAGCGAAAGCATCATTGGTGCTATAGCGCGGCAGTTCAAGTTTTCCCGGGTATGCAAACCGAAATCC-
T
CACTTGAAGAGACGGAAGTTCTGTTTGTATTCATTGGGTACGATCGCAAGGCCCGTACGCACAATCCTTACAAG-
C
TTTCATCAACCTTGACCAACATTTATACAGGTTCCAGACTCCACGAAGCCGGATGTGCACCCTCATATCATGTG-
G
TGCGAGGGGATATTGCCACGGCCACCGAAGGAGTGATTATAAATGCTGCTAACAGCAAAGGACAACCTGGCGGA-
G
GGGTGTGCGGAGCGCTGTATAAGAAATTCCCGGAAAGCTTCGATTTACAGCCGATCGAAGTAGGAAAAGCGCGA-
C
TGGTCAAAGGTGCAGCTAAACATATCATTCATGCCGTAGGACCAAACTTCAACAAAGTTTCGGAGGTTGAAGGT-
G
ACAAACAGTTGGCAGAGGCTTATGAGTCCATCGCTAAGATTGTCAACGATAACAATTACAAGTCAGTAGCGATT-
C
CACTGTTGTCCACCGGCATCTTTTCCGGGAACAAAGATCGACTAACCCAATCATTGAACCATTTGCTGACAGCT-
T
TAGACACCACTGATGCAGATGTAGCCATATACTGCAGGGACAAGAAATGGGAAATGACTCTCAAGGAAGCAGTG-
G
CTAGGAGAGAAGCAGTGGAGGAGATATGCATATCCGACGACTCTTCAGTGACAGAACCTGATGCAGAGCTGGTG-
A
GGGTGCATCCGAAGAGTTCTTTGGCTGGAAGGAAGGGCTACAGCACAAGCGATGGCAAAACTTTCTCATATTTG-
G
AAGGGACCAAGTTTCACCAGGCGGCCAAGGATATAGCAGAAATTAATGCCATGTGGCCCGTTGCAACGGAGGCC-
A
ATGAGCAGGTATGCATGTATATCCTCGGAGAAAGCATGAGCAGTATTAGGTCGAAATGCCCCGTCGAAGAGTCG-
G
AAGCCTCCACACCACCTAGCACGCTGCCTTGCTTGTGCATCCATGCCATGACTCCAGAAAGAGTACAGCGCCTA-
A
AAGCCTCACGTCCAGAACAAATTACTGTGTGCTCATCCTTTCCATTGCCGAAGTATAGAATCACTGGTGTGCAG-
A
AGATCCAATGCTCCCAGCCTATATTGTTCTCACCGAAAGTGCCTGCGTATATTCATCCAAGGAAGTATCTCGTG-
G
AAACACCACCGGTAGACGAGACTCCGGAGCCATCGGCAGAGAACCAATCCACAGAGGGGACACCTGAACAACCA-
C
CACTTATAACCGAGGATGAGACCAGGACTAGAACGCCTGAGCCGATCATCATCGAAGAGGAAGAAGAGGATAGC-
A
TAAGTTTGCTGTCAGATGGCCCGACCCACCAGGTGCTGCAAGTCGAGGCAGACATTCACGGGCCGCCCTCTGTA-
T
CTAGCTCATCCTGGTCCATTCCTCATGCATCCGACTTTGATGTGGACAGTTTATCCATACTTGACACCCTGGAG-
G
GAGCTAGCGTGACCAGCGGGGCAACGTCAGCCGAGACTAACTCTTACTTCGCAAAGAGTATGGAGTTTCTGGCG-
C
GACCGGTGCCTGCGCCTCGAACAGTATTCAGGAACCCTCCACATCCCGCTCCGCGCACAAGAACACCGTCACTT-
G
CACCCAGCAGGGCCTGCTCGAGAACCAGCCTAGTTTCCACCCCGCCAGGCGTGAATAGGGTGATCACTAGAGAG-
G
AGCTCGAGGCGCTTACCCCGTCACGCACTCCTAGCAGGTCGGTCTCGAGAACCAGCCTGGTCTCCAACCCGCCA-
G
GCGTAAATAGGGTGATTACAAGAGAGGAGTTTGAGGCGTTCGTAGCACAACAACAATGACGGTTTGATGCGGGT-
G
CATACATCTTTTCCTCCGACACCGGTCAAGGGCATTTACAACAAAAATCAGTAAGGCAAACGGTGCTATCCGAA-
G
TGGTGTTGGAGAGGACCGAATTGGAGATTTCGTATGCCCCGCGCCTCGACCAAGAAAAAGAAGAATTACTACGC-
A
AGAAATTACAGTTAAATCCCACACCTGCTAACAGAAGCAGATACCAGTCCAGGAAGGTGGAGAACATGAAAGCC-
A
TAACAGCTAGACGTATTCTGCAAGGCCTAGGGCATTATTTGAAGGCAGAAGGAAAAGTGGAGTGCTACCGAACC-
C
TGCATCCTGTTCCTTTGTATTCATCTAGTGTGAACCGTGCCTTTTCAAGCCCCAAGGTCGCAGTGGAAGCCTGT-
A
ACGCCATGTTGAAAGAGAACTTTCCGACTGTGGCTTCTTACTGTATTATTCCAGAGTACGATGCCTATTTGGAC-
A
TGGTTGACGGAGCTTCATGCTGCTTAGACACTGCCAGTTTTTGCCCTGCAAAGCTGCGCAGCTTTCCAAAGAAA-
C
ACTCCTATTTGGAACCCACAATACGATCGGCAGTGCCTTCAGCGATCCAGAACACGCTCCAGAACGTCCTGGCA-
G
CTGCCACAAAAAGAAATTGCAATGTCACGCAAATGAGAGAATTGCCCGTATTGGATTCGGCGGCCTTTAATGTG-
G
AATGCTTCAAGAAATATGCGTGTAATAATGAATATTGGGAAACGTTTAAAGAAAACCCCATCAGGCTTACTGAA-
G
AAAACGTGGTAAATTACATTACCAAATTAAAAGGACCAAAAGCTGCTGCTCTTTTTGCGAAGACACATAATTTG-
A
ATATGTTGCAGGACATACCAATGGACAGGTTTGTAATGGACTTAAAGAGAGACGTGAAAGTGACTCCAGGAACA-
A
AACATACTGAAGAACGGCCCAAGGTACAGGTGATCCAGGCTGCCGATCCGCTAGCAACAGCGTATCTGTGCGGA-
A
TCCACCGAGAGCTGGTTAGGAGATTAAATGCGGTCCTGCTTCCGAACATTCATACACTGTTTGATATGTCGGCT-
G
AAGACTTTGACGCTATTATAGCCGAGCACTTCCAGCCTGGGGATTGTGTTCTGGAAACTGACATCGCGTCGTTT-
G
ATAAAAGTGAGGACGACGCCATGGCTCTGACCGCGTTAATGATTCTGGAAGACTTAGGTGTGGACGCAGAGCTG-
T
TGACGCTGATTGAGGCGGCTTTCGGCGAAATTTCATCAATACATTTGCCCACTAAAACTAAATTTAAATTCGGA-
G
CCATGATGAAATCTGGAATGTTCCTCACACTGTTTGTGAACACAGTCATTAACATTGTAATCGCAAGCAGAGTG-
T
TGAGAGAACGGCTAACCGGATCACCATGTGCAGCATTCATTGGAGATGACAATATCGTGAAAGGAGTCAAATCG-
G
ACAAATTAATGGCAGACAGGTGCGCCACCTGGTTGAATATGGAAGTCAAGATTATAGATGCTGTGGTGGGCGAG-
A
AAGCGCCTTATTTCTGTGGAGGGTTTATTTTGTGTGACTCCGTGACCGGCACAGCGTGCCGTGTGGCAGACCCC-
C
TAAAAAGGCTGTTTAAGCTTGGCAAACCTCTGGCAGCAGACGATGAACATGATGATGACAGGAGAAGGGCATTG-
C
ATGAAGAGTCAACACGCTGGAACCGAGTGGGTATTCTTTCAGAGCTGTGCAAGGCAGTAGAATCAAGGTATGAA-
A
CCGTAGGAACTTCCATCATAGTTATGGCCATGACTACTCTAGCTAGCAGTGTTAAATCATTCAGCTACCTGAGA-
G
GGGCCCCTATAACTCTCTACGGCTAACCTGAATGGACTACGACATAGTCTAGTCCGCCAAGCTATTCCAGAAGT-
A
GTGAGGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTTGTATATCCATTTTCGGATCTGATCAAGAGAC-
A
GGATGAGGATCGTTTCGCATGATTGAATAAGATGGATTGCACGTAGGTTCTCCGGCCGCTTGGGTGGAGAGGCT-
A
TTCGGCTATGACTGGGCACAACTGACAATCGGCTGCTCTGATGCCGCCGTGATCCGGTTGTCAGCGCAGGGGCG-
C
CCGGTTCTTTTTGTCAAGACCGACCTGTCCGGTGCCCTGAATGAACTGAAGGACGAGGCAGCGCGGCTATCGTG-
G
CTGGCCACGACGGGCGTTCCTTGCGCAGTCTAGACTGGCGCGCCAAACCTGCAGGTTAAAACAGCTGTGGGTTG-
T
TCCCACCCACAGGGCCCACTGGGCGCTAGCACTCTGATTTTACGAAATCCTTGTGCGCCTGTTTTATATCCCTT-
C
CCTAATTCGAAACGTAGAAGCAATGCGCACCACTGATCAATAGTAGGCGTAACGCGCCAGTTACGTCATGATCA-
A
GCATATCTGTTCCCCCGGACTGAGTATCAATAGACTGCTTACGCGGTTGAAGGAGAAAACGTTCGTTATCCGGC-
T
AACTACTTCGAGAAGCCCAGTAACACCATGGAAGCTGCAGGGTGTTTCGCTCAGCACTTCCCCCGTGTAGATCA-
G
GTCGATGAGCCACTGCAATCCCCACAGGTGACTGTGGCAGTGGCTGCGTTGGCGGCCTGCCTATGGGGAGACCC-
A
TAGGACGCTCTAATGTGGACATGGTGCGAAGAGCCTATTGAGCTAGTTAGTAGTCCTCCGGCCCCTGAATGCGG-
C
TAATCCTAACTGCGGAGCACATGCCTTCAACCCAGAGGGTAGTGTGTCGTAATGGGCAACTCTGCAGCGGAACC-
G
ACTACTTTGGGTGTCCGTGTTTCTTTTTATTCTTATATTGGCTGCTTATGGTGACAATTACAGAATTGTTACCA-
T
ATAGCTATTGGATTGGCCATCCGGTGTGTAATAGAGCTGTTATATACCTATTTGTTGGCTTTGTACCACTAACT-
T ##STR00037## ##STR00038##
CCCCCCCTAACGTTACTGGCCGAAGCCGCTTGGAATAAGGCCGGTGTGCGTTTGTCTATATGTTATTTTCCACC-
A
TATTGCCGTCTTTTGGCAATGTGAGGGCCCGGAAACCTGGCCCTGTCTTCTTGACGAGCATTCCTAGGGGTCTT-
T
CCCCTCTCGCCAAAGGAATGCAAGGTCTGTTGAATGTCGTGAAGGAAGCAGTTCCTCTGGAAGCTTCTTGAAGA-
C
AAACAACGTCTGTAGCGACCCTTTGCAGGCAGCGGAACCCCCCACCTGGCGACAGGTGCCTCTGCGGCCAAAAG-
C
CACGTGTATAAGATACACCTGCAAAGGCGGCACAACCCCAGTGCCACGTTGTGAGTTGGATAGTTGTGGAAAGA-
G
TCAAATGGCTCTCCTCAAGCGTATTCAACAAGGGGCTGAAGGATGCCCAGAAGGTACCCCATTGTATGGGATCT-
G
ATCTGGGGCCTCGGTGCACATGCTTTACATGTGTTTAGTCGAGGTTAAAAAAACGTCTAGGCCCCCCGAACCAC-
G ##STR00039##
CCTTAAAATTTTTATTTTATTTTTCTTTTCTTTTCCGAATCGGATTTTGTTTTTAATATTTCAAAAAAAAAAAA-
A
AAAAAAAAAAAAAAAAAAAAAAGGGTCGGCATGGCATCTCCACCTCCTCGCGGTCCGACCTGGGCATCCGAAGG-
A
GGACGCACGTCCACTCGGATGGCTAAGGGAGAGCCACGTTTAAACACGTGATATCTGGCCTCATGGGCCTTCCT-
T
TCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAACATGGTCATAGCTGTTTCCTTGCGTA-
T
TGGGCGCTCTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGGTAAAGCCTGGGGTGCCTAATGA-
G
CAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCT-
G
ACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTT-
C
CCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCT-
T
CGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTG-
G
GCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCG-
G
TAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCT-
A
CAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCTGCGCTCTGCTGAAG-
C
CAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTT-
G
TTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGAC-
G
CTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTT-
T
TAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTATTAGAAAAAT-
T
CATCCAGCAGACGATAAAACGCAATACGCTGGCTATCCGGTGCCGCAATGCCATACAGCACCAGAAAACGATCC-
G
CCCATTCGCCGCCCAGTTCTTCCGCAATATCACGGGTGGCCAGCGCAATATCCTGATAACGATCCGCCACGCCC-
A
GACGGCCGCAATCAATAAAGCCGCTAAAACGGCCATTTTCCACCATAATGTTCGGCAGGCACGCATCACCATGG-
G
TCACCACCAGATCTTCGCCATCCGGCATGCTCGCTTTCAGACGCGCAAACAGCTCTGCCGGTGCCAGGCCCTGA-
T
GTTCTTCATCCAGATCATCCTGATCCACCAGGCCCGCTTCCATACGGGTACGCGCACGTTCAATACGATGTTTC-
G
CCTGATGATCAAACGGACAGGTCGCCGGGTCCAGGGTATGCAGACGACGCATGGCATCCGCCATAATGCTCACT-
T
TTTCTGCCGGCGCCAGATGGCTAGACAGCAGATCCTGACCCGGCACTTCGCCCAGCAGCAGCCAATCACGGCCC-
G
CTTCGGTCACCACATCCAGCACCGCCGCACACGGAACACCGGTGGTGGCCAGCCAGCTCAGACGCGCCGCTTCA-
T
CCTGCAGCTCGTTCAGCGCACCGCTCAGATCGGTTTTCACAAACAGCACCGGACGACCCTGCGCGCTCAGACGA-
A
ACACCGCCGCATCAGAGCAGCCAATGGTCTGCTGCGCCCAATCATAGCCAAACAGACGTTCCACCCACGCTGCC-
G
GGCTACCCGCATGCAGGCCATCCTGTTCAATCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGT-
T
ATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCC-
C
GAAAAGTGCCACCTAAATTGTAAGCGTTAATATTTTGTTAAAATTCGCGTTAAATTTTTGTTAAATCAGCTCAT-
T
TTTTAACCAATAGGCCGAAATCGGCAAAATCCCTTATAAATCAAAAGAATAGACCGAGATAGGGTTGAGTGGCC-
G
CTACAGGGCGCTCCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGTTTCGGTGCGGGCCTCTTCGCT-
A
TTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACA-
C GCGTAATACGACTCACTATAG
TABLE-US-00050 A554 Vector:
SGP-gH-SGP-gL-SGP-UL128-SGP-UL130-SGP-UL131
ATAGGCGGCGCATGAGAGAAGCCCAGACCAATTACCTACCCAAAATGGAGAAAGTTCACGTTGACATCGAGGAA-
G
ACAGCCCATTCCTCAGAGCTTTGCAGCGGAGCTTCCCGCAGTTTGAGGTAGAAGCCAAGCAGGTCACTGATAAT-
G
ACCATGCTAATGCCAGAGCGTTTTCGCATCTGGCTTCAAAACTGATCGAAACGGAGGTGGACCCATCCGACACG-
A
TCCTTGACATTGGAAGTGCGCCCGCCCGCAGAATGTATTCTAAGCACAAGTATCATTGTATCTGTCCGATGAGA-
T
GTGCGGAAGATCCGGACAGATTGTATAAGTATGCAACTAAGCTGAAGAAAAACTGTAAGGAAATAACTGATAAG-
G
AATTGGACAAGAAAATGAAGGAGCTCGCCGCCGTCATGAGCGACCCTGACCTGGAAACTGAGACTATGTGCCTC-
C
ACGACGACGAGTCGTGTCGCTACGAAGGGCAAGTCGCTGTTTACCAGGATGTATACGCGGTTGACGGACCGACA-
A
GTCTCTATCACCAAGCCAATAAGGGAGTTAGAGTCGCCTACTGGATAGGCTTTGACACCACCCCTTTTATGTTT-
A
AGAACTTGGCTGGAGCATATCCATCATACTCTACCAACTGGGCCGACGAAACCGTGTTAACGGCTCGTAACATA-
G
GCCTATGCAGCTCTGACGTTATGGAGCGGTCACGTAGAGGGATGTCCATTCTTAGAAAGAAGTATTTGAAACCA-
T
CCAACAATGTTCTATTCTCTGTTGGCTCGACCATCTACCACGAGAAGAGGGACTTACTGAGGAGCTGGCACCTG-
C
CGTCTGTATTTCACTTACGTGGCAAGCAAAATTACACATGTCGGTGTGAGACTATAGTTAGTTGCGACGGGTAC-
G
TCGTTAAAAGAATAGCTATCAGTCCAGGCCTGTATGGGAAGCCTTCAGGCTATGCTGCTACGATGCACCGCGAG-
G
GATTCTTGTGCTGCAAAGTGACAGACACATTGAACGGGGAGAGGGTCTCTTTTCCCGTGTGCACGTATGTGCCA-
G
CTACATTGTGTGACCAAATGACTGGCATACTGGCAACAGATGTCAGTGCGGACGACGCGCAAAAACTGCTGGTT-
G
GGCTCAACCAGCGTATAGTCGTCAACGGTCGCACCCAGAGAAACACCAATACCATGAAAAATTACCTTTTGCCC-
G
TAGTGGCCCAGGCATTTGCTAGGTGGGCAAAGGAATATAAGGAAGATCAAGAAGATGAAAGGCCACTAGGACTA-
C
GAGATAGACAGTTAGTCATGGGGTGTTGTTGGGCTTTTAGAAGGCACAAGATAACATCTATTTATAAGCGCCCG-
G
ATACCCAAACCATCATCAAAGTGAACAGCGATTTCCACTCATTCGTGCTGCCCAGGATAGGCAGTAACACATTG-
G
AGATCGGGCTGAGAACAAGAATCAGGAAAATGTTAGAGGAGCACAAGGAGCCGTCACCTCTCATTACCGCCGAG-
G
ACGTACAAGAAGCTAAGTGCGCAGCCGATGAGGCTAAGGAGGTGCGTGAAGCCGAGGAGTTGCGCGCAGCTCTA-
C
CACCTTTGGCAGCTGATGTTGAGGAGCCCACTCTGGAAGCCGATGTAGACTTGATGTTACAAGAGGCTGGGGCC-
G
GCTCAGTGGAGACACCTCGTGGCTTGATAAAGGTTACCAGCTACGATGGCGAGGACAAGATCGGCTCTTACGCT-
G
TGCTTTCTCCGCAGGCTGTACTCAAGAGTGAAAAATTATCTTGCATCCACCCTCTCGCTGAACAAGTCATAGTG-
A
TAACACACTCTGGCCGAAAAGGGCGTTATGCCGTGGAACCATACCATGGTAAAGTAGTGGTGCCAGAGGGACAT-
G
CAATACCCGTCCAGGACTTTCAAGCTCTGAGTGAAAGTGCCACCATTGTGTACAACGAACGTGAGTTCGTAAAC-
A
GGTACCTGCACCATATTGCCACACATGGAGGAGCGCTGAACACTGATGAAGAATATTACAAAACTGTCAAGCCC-
A
GCGAGCACGACGGCGAATACCTGTACGACATCGACAGGAAACAGTGCGTCAAGAAAGAACTAGTCACTGGGCTA-
G
GGCTCACAGGCGAGCTGGTGGATCCTCCCTTCCATGAATTCGCCTACGAGAGTCTGAGAACACGACCAGCCGCT-
C
CTTACCAAGTACCAACCATAGGGGTGTATGGCGTGCCAGGATCAGGCAAGTCTGGCATCATTAAAAGCGCAGTC-
A
CCAAAAAAGATCTAGTGGTGAGCGCCAAGAAAGAAAACTGTGCAGAAATTATAAGGGACGTCAAGAAAATGAAA-
G
GGCTGGACGTCAATGCCAGAACTGTGGACTCAGTGCTCTTGAATGGATGCAAACACCCCGTAGAGACCCTGTAT-
A
TTGACGAAGCTTTTGCTTGTCATGCAGGTACTCTCAGAGCGCTCATAGCCATTATAAGACCTAAAAAGGCAGTG-
C
TCTGCGGGGATCCCAAACAGTGCGGTTTTTTTAACATGATGTGCCTGAAAGTGCATTTTAACCACGAGATTTGC-
A
CACAAGTCTTCCACAAAAGCATCTCTCGCCGTTGCACTAAATCTGTGACTTCGGTCGTCTCAACCTTGTTTTAC-
G
ACAAAAAAATGAGAACGACGAATCCGAAAGAGACTAAGATTGTGATTGACACTACCGGCAGTACCAAACCTAAG-
C
AGGACGATCTCATTCTCACTTGTTTCAGAGGGTGGGTGAAGCAGTTGCAAATAGATTACAAAGGCAACGAAATA-
A
TGACGGCAGCTGCCTCTCAAGGGCTGACCCGTAAAGGTGTGTATGCCGTTCGGTACAAGGTGAATGAAAATCCT-
C
TGTACGCACCCACCTCAGAACATGTGAACGTCCTACTGACCCGCACGGAGGACCGCATCGTGTGGAAAACACTA-
G
CCGGCGACCCATGGATAAAAACACTGACTGCCAAGTACCCTGGGAATTTCACTGCCACGATAGAGGAGTGGCAA-
G
CAGAGCATGATGCCATCATGAGGCACATCTTGGAGAGACCGGACCCTACCGACGTCTTCCAGAATAAGGCAAAC-
G
TGTGTTGGGCCAAGGCTTTAGTGCCGGTGCTGAAGACCGCTGGCATAGACATGACCACTGAACAATGGAACACT-
G
TGGATTATTTTGAAACGGACAAAGCTCACTCAGCAGAGATAGTATTGAACCAACTATGCGTGAGGTTCTTTGGA-
C
TCGATCTGGACTCCGGTCTATTTTCTGCACCCACTGTTCCGTTATCCATTAGGAATAATCACTGGGATAACTCC-
C
CGTCGCCTAACATGTACGGGCTGAATAAAGAAGTGGTCCGTCAGCTCTCTCGCAGGTACCCACAACTGCCTCGG-
G
CAGTTGCCACTGGAAGAGTCTATGACATGAACACTGGTACACTGCGCAATTATGATCCGCGCATAAACCTAGTA-
C
CTGTAAACAGAAGACTGCCTCATGCTTTAGTCCTCCACCATAATGAACACCCACAGAGTGACTTTTCTTCATTC-
G
TCAGCAAATTGAAGGGCAGAACTGTCCTGGTGGTCGGGGAAAAGTTGTCCGTCCCAGGCAAAATGGTTGACTGG-
T
TGTCAGACCGGCCTGAGGCTACCTTCAGAGCTCGGCTGGATTTAGGCATCCCAGGTGATGTGCCCAAATATGAC-
A
TAATATTTGTTAATGTGAGGACCCCATATAAATACCATCACTATCAGCAGTGTGAAGACCATGCCATTAAGCTT-
A
GCATGTTGACCAAGAAAGCTTGTCTGCATCTGAATCCCGGCGGAACCTGTGTCAGCATAGGTTATGGTTACGCT-
G
ACAGGGCCAGCGAAAGCATCATTGGTGCTATAGCGCGGCAGTTCAAGTTTTCCCGGGTATGCAAACCGAAATCC-
T
CACTTGAAGAGACGGAAGTTCTGTTTGTATTCATTGGGTACGATCGCAAGGCCCGTACGCACAATCCTTACAAG-
C
TTTCATCAACCTTGACCAACATTTATACAGGTTCCAGACTCCACGAAGCCGGATGTGCACCCTCATATCATGTG-
G
TGCGAGGGGATATTGCCACGGCCACCGAAGGAGTGATTATAAATGCTGCTAACAGCAAAGGACAACCTGGCGGA-
G
GGGTGTGCGGAGCGCTGTATAAGAAATTCCCGGAAAGCTTCGATTTACAGCCGATCGAAGTAGGAAAAGCGCGA-
C
TGGTCAAAGGTGCAGCTAAACATATCATTCATGCCGTAGGACCAAACTTCAACAAAGTTTCGGAGGTTGAAGGT-
G
ACAAACAGTTGGCAGAGGCTTATGAGTCCATCGCTAAGATTGTCAACGATAACAATTACAAGTCAGTAGCGATT-
C
CACTGTTGTCCACCGGCATCTTTTCCGGGAACAAAGATCGACTAACCCAATCATTGAACCATTTGCTGACAGCT-
T
TAGACACCACTGATGCAGATGTAGCCATATACTGCAGGGACAAGAAATGGGAAATGACTCTCAAGGAAGCAGTG-
G
CTAGGAGAGAAGCAGTGGAGGAGATATGCATATCCGACGACTCTTCAGTGACAGAACCTGATGCAGAGCTGGTG-
A
GGGTGCATCCGAAGAGTTCTTTGGCTGGAAGGAAGGGCTACAGCACAAGCGATGGCAAAACTTTCTCATATTTG-
G
AAGGGACCAAGTTTCACCAGGCGGCCAAGGATATAGCAGAAATTAATGCCATGTGGCCCGTTGCAACGGAGGCC-
A
ATGAGCAGGTATGCATGTATATCCTCGGAGAAAGCATGAGCAGTATTAGGTCGAAATGCCCCGTCGAAGAGTCG-
G
AAGCCTCCACACCACCTAGCACGCTGCCTTGCTTGTGCATCCATGCCATGACTCCAGAAAGAGTACAGCGCCTA-
A
AAGCCTCACGTCCAGAACAAATTACTGTGTGCTCATCCTTTCCATTGCCGAAGTATAGAATCACTGGTGTGCAG-
A
AGATCCAATGCTCCCAGCCTATATTGTTCTCACCGAAAGTGCCTGCGTATATTCATCCAAGGAAGTATCTCGTG-
G
AAACACCACCGGTAGACGAGACTCCGGAGCCATCGGCAGAGAACCAATCCACAGAGGGGACACCTGAACAACCA-
C
CACTTATAACCGAGGATGAGACCAGGACTAGAACGCCTGAGCCGATCATCATCGAAGAGGAAGAAGAGGATAGC-
A
TAAGTTTGCTGTCAGATGGCCCGACCCACCAGGTGCTGCAAGTCGAGGCAGACATTCACGGGCCGCCCTCTGTA-
T
CTAGCTCATCCTGGTCCATTCCTCATGCATCCGACTTTGATGTGGACAGTTTATCCATACTTGACACCCTGGAG-
G
GAGCTAGCGTGACCAGCGGGGCAACGTCAGCCGAGACTAACTCTTACTTCGCAAAGAGTATGGAGTTTCTGGCG-
C
GACCGGTGCCTGCGCCTCGAACAGTATTCAGGAACCCTCCACATCCCGCTCCGCGCACAAGAACACCGTCACTT-
G
CACCCAGCAGGGCCTGCTCGAGAACCAGCCTAGTTTCCACCCCGCCAGGCGTGAATAGGGTGATCACTAGAGAG-
G
AGCTCGAGGCGCTTACCCCGTCACGCACTCCTAGCAGGTCGGTCTCGAGAACCAGCCTGGTCTCCAACCCGCCA-
G
GCGTAAATAGGGTGATTACAAGAGAGGAGTTTGAGGCGTTCGTAGCACAACAACAATGACGGTTTGATGCGGGT-
G
CATACATCTTTTCCTCCGACACCGGTCAAGGGCATTTACAACAAAAATCAGTAAGGCAAACGGTGCTATCCGAA-
G
TGGTGTTGGAGAGGACCGAATTGGAGATTTCGTATGCCCCGCGCCTCGACCAAGAAAAAGAAGAATTACTACGC-
A
AGAAATTACAGTTAAATCCCACACCTGCTAACAGAAGCAGATACCAGTCCAGGAAGGTGGAGAACATGAAAGCC-
A
TAACAGCTAGACGTATTCTGCAAGGCCTAGGGCATTATTTGAAGGCAGAAGGAAAAGTGGAGTGCTACCGAACC-
C
TGCATCCTGTTCCTTTGTATTCATCTAGTGTGAACCGTGCCTTTTCAAGCCCCAAGGTCGCAGTGGAAGCCTGT-
A
ACGCCATGTTGAAAGAGAACTTTCCGACTGTGGCTTCTTACTGTATTATTCCAGAGTACGATGCCTATTTGGAC-
A
TGGTTGACGGAGCTTCATGCTGCTTAGACACTGCCAGTTTTTGCCCTGCAAAGCTGCGCAGCTTTCCAAAGAAA-
C
ACTCCTATTTGGAACCCACAATACGATCGGCAGTGCCTTCAGCGATCCAGAACACGCTCCAGAACGTCCTGGCA-
G
CTGCCACAAAAAGAAATTGCAATGTCACGCAAATGAGAGAATTGCCCGTATTGGATTCGGCGGCCTTTAATGTG-
G
AATGCTTCAAGAAATATGCGTGTAATAATGAATATTGGGAAACGTTTAAAGAAAACCCCATCAGGCTTACTGAA-
G
AAAACGTGGTAAATTACATTACCAAATTAAAAGGACCAAAAGCTGCTGCTCTTTTTGCGAAGACACATAATTTG-
A
ATATGTTGCAGGACATACCAATGGACAGGTTTGTAATGGACTTAAAGAGAGACGTGAAAGTGACTCCAGGAACA-
A
AACATACTGAAGAACGGCCCAAGGTACAGGTGATCCAGGCTGCCGATCCGCTAGCAACAGCGTATCTGTGCGGA-
A
TCCACCGAGAGCTGGTTAGGAGATTAAATGCGGTCCTGCTTCCGAACATTCATACACTGTTTGATATGTCGGCT-
G
AAGACTTTGACGCTATTATAGCCGAGCACTTCCAGCCTGGGGATTGTGTTCTGGAAACTGACATCGCGTCGTTT-
G
ATAAAAGTGAGGACGACGCCATGGCTCTGACCGCGTTAATGATTCTGGAAGACTTAGGTGTGGACGCAGAGCTG-
T
TGACGCTGATTGAGGCGGCTTTCGGCGAAATTTCATCAATACATTTGCCCACTAAAACTAAATTTAAATTCGGA-
G
CCATGATGAAATCTGGAATGTTCCTCACACTGTTTGTGAACACAGTCATTAACATTGTAATCGCAAGCAGAGTG-
T
TGAGAGAACGGCTAACCGGATCACCATGTGCAGCATTCATTGGAGATGACAATATCGTGAAAGGAGTCAAATCG-
G
ACAAATTAATGGCAGACAGGTGCGCCACCTGGTTGAATATGGAAGTCAAGATTATAGATGCTGTGGTGGGCGAG-
A
AAGCGCCTTATTTCTGTGGAGGGTTTATTTTGTGTGACTCCGTGACCGGCACAGCGTGCCGTGTGGCAGACCCC-
C
TAAAAAGGCTGTTTAAGCTTGGCAAACCTCTGGCAGCAGACGATGAACATGATGATGACAGGAGAAGGGCATTG-
C
ATGAAGAGTCAACACGCTGGAACCGAGTGGGTATTCTTTCAGAGCTGTGCAAGGCAGTAGAATCAAGGTATGAA-
A
CCGTAGGAACTTCCATCATAGTTATGGCCATGACTACTCTAGCTAGCAGTGTTAAATCATTCAGCTACCTGAGA-
G ##STR00040## ##STR00041## ##STR00042## ##STR00043##
ATGCCGCCTTAAAATTTTTATTTTATTTTTCTTTTCTTTTCCGAATCGGATTTTGTTTTTAATATTTCAAAAAA-
A
AAAAAAAAAAAAAAAAAAAAAAAAAAAAGGGTCGGCATGGCATCTCCACCTCCTCGCGGTCCGACCTGGGCATC-
C
GAAGGAGGACGCACGTCCACTCGGATGGCTAAGGGAGAGCCACGTTTAAACGCTAGAGCAAGACGTTTCCCGTT-
G
AATATGGCTCATAACACCCCTTGTATTACTGTTTATGTAAGCAGACAGTTTTATTGTTCATGATGATATATTTT-
T
ATCTTGTGCAATGTAACATCAGAGATTTTGAGACACAACGTGGCTTTGTTGAATAAATCGAACTTTTGCTGAGT-
T
GAAGGATCAGATCACGCATCTTCCCGACAACGCAGACCGTTCCGTGGCAAAGCAAAAGTTCAAAATCACCAACT-
G
GTCCACCTACAACAAAGCTCTCATCAACCGTGGCTCCCTCACTTTCTGGCTGGATGATGGGGCGATTCAGGCCT-
G
GTATGAGTCAGCAACACCTTCTTCACGAGGCAGACCTCAGCGCTAGCGGAGTGTATACTGGCTTACTATGTTGG-
C
ACTGATGAGGGTGTCAGTGAAGTGCTTCATGTGGCAGGAGAAAAAAGGCTGCACCGGTGCGTCAGCAGAATATG-
T
GATACAGGATATATTCCGCTTCCTCGCTCACTGACTCGCTACGCTCGGTCGTTCGACTGCGGCGAGCGGAAATG-
G
CTTACGAACGGGGCGGAGATTTCCTGGAAGATGCCAGGAAGATACTTAACAGGGAAGTGAGAGGGCCGCGGCAA-
A
GCCGTTTTTCCATAGGCTCCGCCCCCCTGACAAGCATCACGAAATCTGACGCTCAAATCAGTGGTGGCGAAACC-
C
GACAGGACTATAAAGATACCAGGCGTTTCCCCTGGCGGCTCCCTCGTGCGCTCTCCTGTTCCTGCCTTTCGGTT-
T
ACCGGTGTCATTCCGCTGTTATGGCCGCGTTTGTCTCATTCCACGCCTGACACTCAGTTCCGGGTAGGCAGTTC-
G
CTCCAAGCTGGACTGTATGCACGAACCCCCCGTTCAGTCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTG-
A
GTCCAACCCGGAAAGACATGCAAAAGCACCACTGGCAGCAGCCACTGGTAATTGATTTAGAGGAGTTAGTCTTG-
A
AGTCATGCGCCGGTTAAGGCTAAACTGAAAGGACAAGTTTTGGTGACTGCGCTCCTCCAAGCCAGTTACCTCGG-
T
TCAAAGAGTTGGTAGCTCAGAGAACCTTCGAAAAACCGCCCTGCAAGGCGGTTTTTTCGTTTTCAGAGCAAGAG-
A
TTACGCGCAGACCAAAACGATCTCAAGAAGATCATCTTATTAAGGGGTCTGACGCTCAGTGGAACGAAAACTCA-
C
GTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTT-
A
AATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTATTAGAAAAATTCATCCAGCAGACGATAAAAC-
G
CAATACGCTGGCTATCCGGTGCCGCAATGCCATACAGCACCAGAAAACGATCCGCCCATTCGCCGCCCAGTTCT-
T
CCGCAATATCACGGGTGGCCAGCGCAATATCCTGATAACGATCCGCCACGCCCAGACGGCCGCAATCAATAAAG-
C
CGCTAAAACGGCCATTTTCCACCATAATGTTCGGCAGGCACGCATCACCATGGGTCACCACCAGATCTTCGCCA-
T
CCGGCATGCTCGCTTTCAGACGCGCAAACAGCTCTGCCGGTGCCAGGCCCTGATGTTCTTCATCCAGATCATCC-
T
GATCCACCAGGCCCGCTTCCATACGGGTACGCGCACGTTCAATACGATGTTTCGCCTGATGATCAAACGGACAG-
G
TCGCCGGGTCCAGGGTATGCAGACGACGCATGGCATCCGCCATAATGCTCACTTTTTCTGCCGGCGCCAGATGG-
C
TAGACAGCAGATCCTGACCCGGCACTTCGCCCAGCAGCAGCCAATCACGGCCCGCTTCGGTCACCACATCCAGC-
A
CCGCCGCACACGGAACACCGGTGGTGGCCAGCCAGCTCAGACGCGCCGCTTCATCCTGCAGCTCGTTCAGCGCA-
C
CGCTCAGATCGGTTTTCACAAACAGCACCGGACGACCCTGCGCGCTCAGACGAAACACCGCCGCATCAGAGCAG-
C
CAATGGTCTGCTGCGCCCAATCATAGCCAAACAGACGTTCCACCCACGCTGCCGGGCTACCCGCATGCAGGCCA-
T
CCTGTTCAATCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATAC-
A
TATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTAAATTG-
T
AAGCGTTAATATTTTGTTAAAATTCGCGTTAAATTTTTGTTAAATCAGCTCATTTTTTAACCAATAGGCCGAAA-
T
CGGCAAAATCCCTTATAAATCAAAAGAATAGACCGAGATAGGGTTGAGTGGCCGCTACAGGGCGCTCCCATTCG-
C
CATTCAGGCTGCGCAACTGTTGGGAAGGGCGTTTCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGG-
G
GGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACACGCGTAATACGACTCACTATA-
G
TABLE-US-00051 A555 Vector:
SGP-gHsol-SGP-gL-SGP-UL128-SGP-UL130-SGP-UL131
ATAGGCGGCGCATGAGAGAAGCCCAGACCAATTACCTACCCAAAATGGAGAAAGTTCACGTTGACATCGAGGAA-
G
ACAGCCCATTCCTCAGAGCTTTGCAGCGGAGCTTCCCGCAGTTTGAGGTAGAAGCCAAGCAGGTCACTGATAAT-
G
ACCATGCTAATGCCAGAGCGTTTTCGCATCTGGCTTCAAAACTGATCGAAACGGAGGTGGACCCATCCGACACG-
A
TCCTTGACATTGGAAGTGCGCCCGCCCGCAGAATGTATTCTAAGCACAAGTATCATTGTATCTGTCCGATGAGA-
T
GTGCGGAAGATCCGGACAGATTGTATAAGTATGCAACTAAGCTGAAGAAAAACTGTAAGGAAATAACTGATAAG-
G
AATTGGACAAGAAAATGAAGGAGCTCGCCGCCGTCATGAGCGACCCTGACCTGGAAACTGAGACTATGTGCCTC-
C
ACGACGACGAGTCGTGTCGCTACGAAGGGCAAGTCGCTGTTTACCAGGATGTATACGCGGTTGACGGACCGACA-
A
GTCTCTATCACCAAGCCAATAAGGGAGTTAGAGTCGCCTACTGGATAGGCTTTGACACCACCCCTTTTATGTTT-
A
AGAACTTGGCTGGAGCATATCCATCATACTCTACCAACTGGGCCGACGAAACCGTGTTAACGGCTCGTAACATA-
G
GCCTATGCAGCTCTGACGTTATGGAGCGGTCACGTAGAGGGATGTCCATTCTTAGAAAGAAGTATTTGAAACCA-
T
CCAACAATGTTCTATTCTCTGTTGGCTCGACCATCTACCACGAGAAGAGGGACTTACTGAGGAGCTGGCACCTG-
C
CGTCTGTATTTCACTTACGTGGCAAGCAAAATTACACATGTCGGTGTGAGACTATAGTTAGTTGCGACGGGTAC-
G
TCGTTAAAAGAATAGCTATCAGTCCAGGCCTGTATGGGAAGCCTTCAGGCTATGCTGCTACGATGCACCGCGAG-
G
GATTCTTGTGCTGCAAAGTGACAGACACATTGAACGGGGAGAGGGTCTCTTTTCCCGTGTGCACGTATGTGCCA-
G
CTACATTGTGTGACCAAATGACTGGCATACTGGCAACAGATGTCAGTGCGGACGACGCGCAAAAACTGCTGGTT-
G
GGCTCAACCAGCGTATAGTCGTCAACGGTCGCACCCAGAGAAACACCAATACCATGAAAAATTACCTTTTGCCC-
G
TAGTGGCCCAGGCATTTGCTAGGTGGGCAAAGGAATATAAGGAAGATCAAGAAGATGAAAGGCCACTAGGACTA-
C
GAGATAGACAGTTAGTCATGGGGTGTTGTTGGGCTTTTAGAAGGCACAAGATAACATCTATTTATAAGCGCCCG-
G
ATACCCAAACCATCATCAAAGTGAACAGCGATTTCCACTCATTCGTGCTGCCCAGGATAGGCAGTAACACATTG-
G
AGATCGGGCTGAGAACAAGAATCAGGAAAATGTTAGAGGAGCACAAGGAGCCGTCACCTCTCATTACCGCCGAG-
G
ACGTACAAGAAGCTAAGTGCGCAGCCGATGAGGCTAAGGAGGTGCGTGAAGCCGAGGAGTTGCGCGCAGCTCTA-
C
CACCTTTGGCAGCTGATGTTGAGGAGCCCACTCTGGAAGCCGATGTAGACTTGATGTTACAAGAGGCTGGGGCC-
G
GCTCAGTGGAGACACCTCGTGGCTTGATAAAGGTTACCAGCTACGATGGCGAGGACAAGATCGGCTCTTACGCT-
G
TGCTTTCTCCGCAGGCTGTACTCAAGAGTGAAAAATTATCTTGCATCCACCCTCTCGCTGAACAAGTCATAGTG-
A
TAACACACTCTGGCCGAAAAGGGCGTTATGCCGTGGAACCATACCATGGTAAAGTAGTGGTGCCAGAGGGACAT-
G
CAATACCCGTCCAGGACTTTCAAGCTCTGAGTGAAAGTGCCACCATTGTGTACAACGAACGTGAGTTCGTAAAC-
A
GGTACCTGCACCATATTGCCACACATGGAGGAGCGCTGAACACTGATGAAGAATATTACAAAACTGTCAAGCCC-
A
GCGAGCACGACGGCGAATACCTGTACGACATCGACAGGAAACAGTGCGTCAAGAAAGAACTAGTCACTGGGCTA-
G
GGCTCACAGGCGAGCTGGTGGATCCTCCCTTCCATGAATTCGCCTACGAGAGTCTGAGAACACGACCAGCCGCT-
C
CTTACCAAGTACCAACCATAGGGGTGTATGGCGTGCCAGGATCAGGCAAGTCTGGCATCATTAAAAGCGCAGTC-
A
CCAAAAAAGATCTAGTGGTGAGCGCCAAGAAAGAAAACTGTGCAGAAATTATAAGGGACGTCAAGAAAATGAAA-
G
GGCTGGACGTCAATGCCAGAACTGTGGACTCAGTGCTCTTGAATGGATGCAAACACCCCGTAGAGACCCTGTAT-
A
TTGACGAAGCTTTTGCTTGTCATGCAGGTACTCTCAGAGCGCTCATAGCCATTATAAGACCTAAAAAGGCAGTG-
C
TCTGCGGGGATCCCAAACAGTGCGGTTTTTTTAACATGATGTGCCTGAAAGTGCATTTTAACCACGAGATTTGC-
A
CACAAGTCTTCCACAAAAGCATCTCTCGCCGTTGCACTAAATCTGTGACTTCGGTCGTCTCAACCTTGTTTTAC-
G
ACAAAAAAATGAGAACGACGAATCCGAAAGAGACTAAGATTGTGATTGACACTACCGGCAGTACCAAACCTAAG-
C
AGGACGATCTCATTCTCACTTGTTTCAGAGGGTGGGTGAAGCAGTTGCAAATAGATTACAAAGGCAACGAAATA-
A
TGACGGCAGCTGCCTCTCAAGGGCTGACCCGTAAAGGTGTGTATGCCGTTCGGTACAAGGTGAATGAAAATCCT-
C
TGTACGCACCCACCTCAGAACATGTGAACGTCCTACTGACCCGCACGGAGGACCGCATCGTGTGGAAAACACTA-
G
CCGGCGACCCATGGATAAAAACACTGACTGCCAAGTACCCTGGGAATTTCACTGCCACGATAGAGGAGTGGCAA-
G
CAGAGCATGATGCCATCATGAGGCACATCTTGGAGAGACCGGACCCTACCGACGTCTTCCAGAATAAGGCAAAC-
G
TGTGTTGGGCCAAGGCTTTAGTGCCGGTGCTGAAGACCGCTGGCATAGACATGACCACTGAACAATGGAACACT-
G
TGGATTATTTTGAAACGGACAAAGCTCACTCAGCAGAGATAGTATTGAACCAACTATGCGTGAGGTTCTTTGGA-
C
TCGATCTGGACTCCGGTCTATTTTCTGCACCCACTGTTCCGTTATCCATTAGGAATAATCACTGGGATAACTCC-
C
CGTCGCCTAACATGTACGGGCTGAATAAAGAAGTGGTCCGTCAGCTCTCTCGCAGGTACCCACAACTGCCTCGG-
G
CAGTTGCCACTGGAAGAGTCTATGACATGAACACTGGTACACTGCGCAATTATGATCCGCGCATAAACCTAGTA-
C
CTGTAAACAGAAGACTGCCTCATGCTTTAGTCCTCCACCATAATGAACACCCACAGAGTGACTTTTCTTCATTC-
G
TCAGCAAATTGAAGGGCAGAACTGTCCTGGTGGTCGGGGAAAAGTTGTCCGTCCCAGGCAAAATGGTTGACTGG-
T
TGTCAGACCGGCCTGAGGCTACCTTCAGAGCTCGGCTGGATTTAGGCATCCCAGGTGATGTGCCCAAATATGAC-
A
TAATATTTGTTAATGTGAGGACCCCATATAAATACCATCACTATCAGCAGTGTGAAGACCATGCCATTAAGCTT-
A
GCATGTTGACCAAGAAAGCTTGTCTGCATCTGAATCCCGGCGGAACCTGTGTCAGCATAGGTTATGGTTACGCT-
G
ACAGGGCCAGCGAAAGCATCATTGGTGCTATAGCGCGGCAGTTCAAGTTTTCCCGGGTATGCAAACCGAAATCC-
T
CACTTGAAGAGACGGAAGTTCTGTTTGTATTCATTGGGTACGATCGCAAGGCCCGTACGCACAATCCTTACAAG-
C
TTTCATCAACCTTGACCAACATTTATACAGGTTCCAGACTCCACGAAGCCGGATGTGCACCCTCATATCATGTG-
G
TGCGAGGGGATATTGCCACGGCCACCGAAGGAGTGATTATAAATGCTGCTAACAGCAAAGGACAACCTGGCGGA-
G
GGGTGTGCGGAGCGCTGTATAAGAAATTCCCGGAAAGCTTCGATTTACAGCCGATCGAAGTAGGAAAAGCGCGA-
C
TGGTCAAAGGTGCAGCTAAACATATCATTCATGCCGTAGGACCAAACTTCAACAAAGTTTCGGAGGTTGAAGGT-
G
ACAAACAGTTGGCAGAGGCTTATGAGTCCATCGCTAAGATTGTCAACGATAACAATTACAAGTCAGTAGCGATT-
C
CACTGTTGTCCACCGGCATCTTTTCCGGGAACAAAGATCGACTAACCCAATCATTGAACCATTTGCTGACAGCT-
T
TAGACACCACTGATGCAGATGTAGCCATATACTGCAGGGACAAGAAATGGGAAATGACTCTCAAGGAAGCAGTG-
G
CTAGGAGAGAAGCAGTGGAGGAGATATGCATATCCGACGACTCTTCAGTGACAGAACCTGATGCAGAGCTGGTG-
A
GGGTGCATCCGAAGAGTTCTTTGGCTGGAAGGAAGGGCTACAGCACAAGCGATGGCAAAACTTTCTCATATTTG-
G
AAGGGACCAAGTTTCACCAGGCGGCCAAGGATATAGCAGAAATTAATGCCATGTGGCCCGTTGCAACGGAGGCC-
A
ATGAGCAGGTATGCATGTATATCCTCGGAGAAAGCATGAGCAGTATTAGGTCGAAATGCCCCGTCGAAGAGTCG-
G
AAGCCTCCACACCACCTAGCACGCTGCCTTGCTTGTGCATCCATGCCATGACTCCAGAAAGAGTACAGCGCCTA-
A
AAGCCTCACGTCCAGAACAAATTACTGTGTGCTCATCCTTTCCATTGCCGAAGTATAGAATCACTGGTGTGCAG-
A
AGATCCAATGCTCCCAGCCTATATTGTTCTCACCGAAAGTGCCTGCGTATATTCATCCAAGGAAGTATCTCGTG-
G
AAACACCACCGGTAGACGAGACTCCGGAGCCATCGGCAGAGAACCAATCCACAGAGGGGACACCTGAACAACCA-
C
CACTTATAACCGAGGATGAGACCAGGACTAGAACGCCTGAGCCGATCATCATCGAAGAGGAAGAAGAGGATAGC-
A
TAAGTTTGCTGTCAGATGGCCCGACCCACCAGGTGCTGCAAGTCGAGGCAGACATTCACGGGCCGCCCTCTGTA-
T
CTAGCTCATCCTGGTCCATTCCTCATGCATCCGACTTTGATGTGGACAGTTTATCCATACTTGACACCCTGGAG-
G
GAGCTAGCGTGACCAGCGGGGCAACGTCAGCCGAGACTAACTCTTACTTCGCAAAGAGTATGGAGTTTCTGGCG-
C
GACCGGTGCCTGCGCCTCGAACAGTATTCAGGAACCCTCCACATCCCGCTCCGCGCACAAGAACACCGTCACTT-
G
CACCCAGCAGGGCCTGCTCGAGAACCAGCCTAGTTTCCACCCCGCCAGGCGTGAATAGGGTGATCACTAGAGAG-
G
AGCTCGAGGCGCTTACCCCGTCACGCACTCCTAGCAGGTCGGTCTCGAGAACCAGCCTGGTCTCCAACCCGCCA-
G
GCGTAAATAGGGTGATTACAAGAGAGGAGTTTGAGGCGTTCGTAGCACAACAACAATGACGGTTTGATGCGGGT-
G
CATACATCTTTTCCTCCGACACCGGTCAAGGGCATTTACAACAAAAATCAGTAAGGCAAACGGTGCTATCCGAA-
G
TGGTGTTGGAGAGGACCGAATTGGAGATTTCGTATGCCCCGCGCCTCGACCAAGAAAAAGAAGAATTACTACGC-
A
AGAAATTACAGTTAAATCCCACACCTGCTAACAGAAGCAGATACCAGTCCAGGAAGGTGGAGAACATGAAAGCC-
A
TAACAGCTAGACGTATTCTGCAAGGCCTAGGGCATTATTTGAAGGCAGAAGGAAAAGTGGAGTGCTACCGAACC-
C
TGCATCCTGTTCCTTTGTATTCATCTAGTGTGAACCGTGCCTTTTCAAGCCCCAAGGTCGCAGTGGAAGCCTGT-
A
ACGCCATGTTGAAAGAGAACTTTCCGACTGTGGCTTCTTACTGTATTATTCCAGAGTACGATGCCTATTTGGAC-
A
TGGTTGACGGAGCTTCATGCTGCTTAGACACTGCCAGTTTTTGCCCTGCAAAGCTGCGCAGCTTTCCAAAGAAA-
C
ACTCCTATTTGGAACCCACAATACGATCGGCAGTGCCTTCAGCGATCCAGAACACGCTCCAGAACGTCCTGGCA-
G
CTGCCACAAAAAGAAATTGCAATGTCACGCAAATGAGAGAATTGCCCGTATTGGATTCGGCGGCCTTTAATGTG-
G
AATGCTTCAAGAAATATGCGTGTAATAATGAATATTGGGAAACGTTTAAAGAAAACCCCATCAGGCTTACTGAA-
G
AAAACGTGGTAAATTACATTACCAAATTAAAAGGACCAAAAGCTGCTGCTCTTTTTGCGAAGACACATAATTTG-
A
ATATGTTGCAGGACATACCAATGGACAGGTTTGTAATGGACTTAAAGAGAGACGTGAAAGTGACTCCAGGAACA-
A
AACATACTGAAGAACGGCCCAAGGTACAGGTGATCCAGGCTGCCGATCCGCTAGCAACAGCGTATCTGTGCGGA-
A
TCCACCGAGAGCTGGTTAGGAGATTAAATGCGGTCCTGCTTCCGAACATTCATACACTGTTTGATATGTCGGCT-
G
AAGACTTTGACGCTATTATAGCCGAGCACTTCCAGCCTGGGGATTGTGTTCTGGAAACTGACATCGCGTCGTTT-
G
ATAAAAGTGAGGACGACGCCATGGCTCTGACCGCGTTAATGATTCTGGAAGACTTAGGTGTGGACGCAGAGCTG-
T
TGACGCTGATTGAGGCGGCTTTCGGCGAAATTTCATCAATACATTTGCCCACTAAAACTAAATTTAAATTCGGA-
G
CCATGATGAAATCTGGAATGTTCCTCACACTGTTTGTGAACACAGTCATTAACATTGTAATCGCAAGCAGAGTG-
T
TGAGAGAACGGCTAACCGGATCACCATGTGCAGCATTCATTGGAGATGACAATATCGTGAAAGGAGTCAAATCG-
G
ACAAATTAATGGCAGACAGGTGCGCCACCTGGTTGAATATGGAAGTCAAGATTATAGATGCTGTGGTGGGCGAG-
A
AAGCGCCTTATTTCTGTGGAGGGTTTATTTTGTGTGACTCCGTGACCGGCACAGCGTGCCGTGTGGCAGACCCC-
C
TAAAAAGGCTGTTTAAGCTTGGCAAACCTCTGGCAGCAGACGATGAACATGATGATGACAGGAGAAGGGCATTG-
C
ATGAAGAGTCAACACGCTGGAACCGAGTGGGTATTCTTTCAGAGCTGTGCAAGGCAGTAGAATCAAGGTATGAA-
A
CCGTAGGAACTTCCATCATAGTTATGGCCATGACTACTCTAGCTAGCAGTGTTAAATCATTCAGCTACCTGAGA-
G ##STR00044## ##STR00045## ##STR00046##
TGCGTTTGTCTATATGTTATTTTCCACCATATTGCCGTCTTTTGGCAATGTGAGGGCCCGGAAACCTGGCCCTG-
T
CTTCTTGACGAGCATTCCTAGGGGTCTTTCCCCTCTCGCCAAAGGAATGCAAGGTCTGTTGAATGTCGTGAAGG-
A
AGCAGTTCCTCTGGAAGCTTCTTGAAGACAAACAACGTCTGTAGCGACCCTTTGCAGGCAGCGGAACCCCCCAC-
C
TGGCGACAGGTGCCTCTGCGGCCAAAAGCCACGTGTATAAGATACACCTGCAAAGGCGGCACAACCCCAGTGCC-
A
CGTTGTGAGTTGGATAGTTGTGGAAAGAGTCAAATGGCTCTCCTCAAGCGTATTCAACAAGGGGCTGAAGGATG-
C
CCAGAAGGTACCCCATTGTATGGGATCTGATCTGGGGCCTCGGTGCACATGCTTTACATGTGTTTAGTCGAGGT-
T ##STR00047##
CAACTTAGAAGCAACGCAAACCAGATCAATAGTAGGTGTGACATACCAGTCGCATCTTGATCAAGCACTTCTGT-
A
TCCCCGGACCGAGTATCAATAGACTGTGCACACGGTTGAAGGAGAAAACGTCCGTTACCCGGCTAACTACTTCG-
A
GAAGCCTAGTAACGCCATTGAAGTTGCAGAGTGTTTCGCTCAGCACTCCCCCCGTGTAGATCAGGTCGATGAGT-
C
ACCGCATTCCCCACGGGCGACCGTGGCGGTGGCTGCGTTGGCGGCCTGCCTATGGGGTAACCCATAGGACGCTC-
T
AATACGGACATGGCGTGAAGAGTCTATTGAGCTAGTTAGTAGTCCTCCGGCCCCTGAATGCGGCTAATCCTAAC-
T
GCGGAGCACATACCCTTAATCCAAAGGGCAGTGTGTCGTAACGGGCAACTCTGCAGCGGAACCGACTACTTTGG-
G
TGTCCGTGTTTCTTTTTATTCTTGTATTGGCTGCTTATGGTGACAATTAAAGAATTGTTACCATATAGCTATTG-
G
ATTGGCCATCCAGTGTCAAACAGAGCTATTGTATATCTCTTTGTTGGATTCACACCTCTCACTCTTGAAACGTT-
A ##STR00048##
ATACAGCAGCAATTGGCAAGCTGCTTACATAGAACTCGCGGCGATTGGCATGCCGCCTTAAAATTTTTATTTTA-
T
TTTTCTTTTCTTTTCCGAATCGGATTTTGTTTTTAATATTTCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA-
A
AAGGGTCGGCATGGCATCTCCACCTCCTCGCGGTCCGACCTGGGCATCCGAAGGAGGACGCACGTCCACTCGGA-
T
GGCTAAGGGAGAGCCACGTTTAAACGCTAGAGCAAGACGTTTCCCGTTGAATATGGCTCATAACACCCCTTGTA-
T
TACTGTTTATGTAAGCAGACAGTTTTATTGTTCATGATGATATATTTTTATCTTGTGCAATGTAACATCAGAGA-
T
TTTGAGACACAACGTGGCTTTGTTGAATAAATCGAACTTTTGCTGAGTTGAAGGATCAGATCACGCATCTTCCC-
G
ACAACGCAGACCGTTCCGTGGCAAAGCAAAAGTTCAAAATCACCAACTGGTCCACCTACAACAAAGCTCTCATC-
A
ACCGTGGCTCCCTCACTTTCTGGCTGGATGATGGGGCGATTCAGGCCTGGTATGAGTCAGCAACACCTTCTTCA-
C
GAGGCAGACCTCAGCGCTAGCGGAGTGTATACTGGCTTACTATGTTGGCACTGATGAGGGTGTCAGTGAAGTGC-
T
TCATGTGGCAGGAGAAAAAAGGCTGCACCGGTGCGTCAGCAGAATATGTGATACAGGATATATTCCGCTTCCTC-
G
CTCACTGACTCGCTACGCTCGGTCGTTCGACTGCGGCGAGCGGAAATGGCTTACGAACGGGGCGGAGATTTCCT-
G
GAAGATGCCAGGAAGATACTTAACAGGGAAGTGAGAGGGCCGCGGCAAAGCCGTTTTTCCATAGGCTCCGCCCC-
C
CTGACAAGCATCACGAAATCTGACGCTCAAATCAGTGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCG-
T
TTCCCCTGGCGGCTCCCTCGTGCGCTCTCCTGTTCCTGCCTTTCGGTTTACCGGTGTCATTCCGCTGTTATGGC-
C
GCGTTTGTCTCATTCCACGCCTGACACTCAGTTCCGGGTAGGCAGTTCGCTCCAAGCTGGACTGTATGCACGAA-
C
CCCCCGTTCAGTCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGAAAGACATGCAAAA-
G
CACCACTGGCAGCAGCCACTGGTAATTGATTTAGAGGAGTTAGTCTTGAAGTCATGCGCCGGTTAAGGCTAAAC-
T
GAAAGGACAAGTTTTGGTGACTGCGCTCCTCCAAGCCAGTTACCTCGGTTCAAAGAGTTGGTAGCTCAGAGAAC-
C
TTCGAAAAACCGCCCTGCAAGGCGGTTTTTTCGTTTTCAGAGCAAGAGATTACGCGCAGACCAAAACGATCTCA-
A
GAAGATCATCTTATTAAGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATT-
A
TCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTA-
A
ACTTGGTCTGACAGTTATTAGAAAAATTCATCCAGCAGACGATAAAACGCAATACGCTGGCTATCCGGTGCCGC-
A
ATGCCATACAGCACCAGAAAACGATCCGCCCATTCGCCGCCCAGTTCTTCCGCAATATCACGGGTGGCCAGCGC-
A
ATATCCTGATAACGATCCGCCACGCCCAGACGGCCGCAATCAATAAAGCCGCTAAAACGGCCATTTTCCACCAT-
A
ATGTTCGGCAGGCACGCATCACCATGGGTCACCACCAGATCTTCGCCATCCGGCATGCTCGCTTTCAGACGCGC-
A
AACAGCTCTGCCGGTGCCAGGCCCTGATGTTCTTCATCCAGATCATCCTGATCCACCAGGCCCGCTTCCATACG-
G
GTACGCGCACGTTCAATACGATGTTTCGCCTGATGATCAAACGGACAGGTCGCCGGGTCCAGGGTATGCAGACG-
A
CGCATGGCATCCGCCATAATGCTCACTTTTTCTGCCGGCGCCAGATGGCTAGACAGCAGATCCTGACCCGGCAC-
T
TCGCCCAGCAGCAGCCAATCACGGCCCGCTTCGGTCACCACATCCAGCACCGCCGCACACGGAACACCGGTGGT-
G
GCCAGCCAGCTCAGACGCGCCGCTTCATCCTGCAGCTCGTTCAGCGCACCGCTCAGATCGGTTTTCACAAACAG-
C
ACCGGACGACCCTGCGCGCTCAGACGAAACACCGCCGCATCAGAGCAGCCAATGGTCTGCTGCGCCCAATCATA-
G
CCAAACAGACGTTCCACCCACGCTGCCGGGCTACCCGCATGCAGGCCATCCTGTTCAATCATACTCTTCCTTTT-
T
CAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAA-
A
CAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTAAATTGTAAGCGTTAATATTTTGTTAAAATTC-
G
CGTTAAATTTTTGTTAAATCAGCTCATTTTTTAACCAATAGGCCGAAATCGGCAAAATCCCTTATAAATCAAAA-
G
AATAGACCGAGATAGGGTTGAGTGGCCGCTACAGGGCGCTCCCATTCGCCATTCAGGCTGCGCAACTGTTGGGA-
A
GGGCGTTTCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTT-
G GGTAACGCCAGGGTTTTCCCAGTCACACGCGTAATACGACTCACTATAG
TABLE-US-00052 A556 Vector:
SGP-gHsol6His-SGP-gL-SGP-UL128-SGP-UL130-SGP-UL131
ATAGGCGGCGCATGAGAGAAGCCCAGACCAATTACCTACCCAAAATGGAGAAAGTTCACGTTGACATCGAGGAA-
G
ACAGCCCATTCCTCAGAGCTTTGCAGCGGAGCTTCCCGCAGTTTGAGGTAGAAGCCAAGCAGGTCACTGATAAT-
G
ACCATGCTAATGCCAGAGCGTTTTCGCATCTGGCTTCAAAACTGATCGAAACGGAGGTGGACCCATCCGACACG-
A
TCCTTGACATTGGAAGTGCGCCCGCCCGCAGAATGTATTCTAAGCACAAGTATCATTGTATCTGTCCGATGAGA-
T
GTGCGGAAGATCCGGACAGATTGTATAAGTATGCAACTAAGCTGAAGAAAAACTGTAAGGAAATAACTGATAAG-
G
AATTGGACAAGAAAATGAAGGAGCTCGCCGCCGTCATGAGCGACCCTGACCTGGAAACTGAGACTATGTGCCTC-
C
ACGACGACGAGTCGTGTCGCTACGAAGGGCAAGTCGCTGTTTACCAGGATGTATACGCGGTTGACGGACCGACA-
A
GTCTCTATCACCAAGCCAATAAGGGAGTTAGAGTCGCCTACTGGATAGGCTTTGACACCACCCCTTTTATGTTT-
A
AGAACTTGGCTGGAGCATATCCATCATACTCTACCAACTGGGCCGACGAAACCGTGTTAACGGCTCGTAACATA-
G
GCCTATGCAGCTCTGACGTTATGGAGCGGTCACGTAGAGGGATGTCCATTCTTAGAAAGAAGTATTTGAAACCA-
T
CCAACAATGTTCTATTCTCTGTTGGCTCGACCATCTACCACGAGAAGAGGGACTTACTGAGGAGCTGGCACCTG-
C
CGTCTGTATTTCACTTACGTGGCAAGCAAAATTACACATGTCGGTGTGAGACTATAGTTAGTTGCGACGGGTAC-
G
TCGTTAAAAGAATAGCTATCAGTCCAGGCCTGTATGGGAAGCCTTCAGGCTATGCTGCTACGATGCACCGCGAG-
G
GATTCTTGTGCTGCAAAGTGACAGACACATTGAACGGGGAGAGGGTCTCTTTTCCCGTGTGCACGTATGTGCCA-
G
CTACATTGTGTGACCAAATGACTGGCATACTGGCAACAGATGTCAGTGCGGACGACGCGCAAAAACTGCTGGTT-
G
GGCTCAACCAGCGTATAGTCGTCAACGGTCGCACCCAGAGAAACACCAATACCATGAAAAATTACCTTTTGCCC-
G
TAGTGGCCCAGGCATTTGCTAGGTGGGCAAAGGAATATAAGGAAGATCAAGAAGATGAAAGGCCACTAGGACTA-
C
GAGATAGACAGTTAGTCATGGGGTGTTGTTGGGCTTTTAGAAGGCACAAGATAACATCTATTTATAAGCGCCCG-
G
ATACCCAAACCATCATCAAAGTGAACAGCGATTTCCACTCATTCGTGCTGCCCAGGATAGGCAGTAACACATTG-
G
AGATCGGGCTGAGAACAAGAATCAGGAAAATGTTAGAGGAGCACAAGGAGCCGTCACCTCTCATTACCGCCGAG-
G
ACGTACAAGAAGCTAAGTGCGCAGCCGATGAGGCTAAGGAGGTGCGTGAAGCCGAGGAGTTGCGCGCAGCTCTA-
C
CACCTTTGGCAGCTGATGTTGAGGAGCCCACTCTGGAAGCCGATGTAGACTTGATGTTACAAGAGGCTGGGGCC-
G
GCTCAGTGGAGACACCTCGTGGCTTGATAAAGGTTACCAGCTACGATGGCGAGGACAAGATCGGCTCTTACGCT-
G
TGCTTTCTCCGCAGGCTGTACTCAAGAGTGAAAAATTATCTTGCATCCACCCTCTCGCTGAACAAGTCATAGTG-
A
TAACACACTCTGGCCGAAAAGGGCGTTATGCCGTGGAACCATACCATGGTAAAGTAGTGGTGCCAGAGGGACAT-
G
CAATACCCGTCCAGGACTTTCAAGCTCTGAGTGAAAGTGCCACCATTGTGTACAACGAACGTGAGTTCGTAAAC-
A
GGTACCTGCACCATATTGCCACACATGGAGGAGCGCTGAACACTGATGAAGAATATTACAAAACTGTCAAGCCC-
A
GCGAGCACGACGGCGAATACCTGTACGACATCGACAGGAAACAGTGCGTCAAGAAAGAACTAGTCACTGGGCTA-
G
GGCTCACAGGCGAGCTGGTGGATCCTCCCTTCCATGAATTCGCCTACGAGAGTCTGAGAACACGACCAGCCGCT-
C
CTTACCAAGTACCAACCATAGGGGTGTATGGCGTGCCAGGATCAGGCAAGTCTGGCATCATTAAAAGCGCAGTC-
A
CCAAAAAAGATCTAGTGGTGAGCGCCAAGAAAGAAAACTGTGCAGAAATTATAAGGGACGTCAAGAAAATGAAA-
G
GGCTGGACGTCAATGCCAGAACTGTGGACTCAGTGCTCTTGAATGGATGCAAACACCCCGTAGAGACCCTGTAT-
A
TTGACGAAGCTTTTGCTTGTCATGCAGGTACTCTCAGAGCGCTCATAGCCATTATAAGACCTAAAAAGGCAGTG-
C
TCTGCGGGGATCCCAAACAGTGCGGTTTTTTTAACATGATGTGCCTGAAAGTGCATTTTAACCACGAGATTTGC-
A
CACAAGTCTTCCACAAAAGCATCTCTCGCCGTTGCACTAAATCTGTGACTTCGGTCGTCTCAACCTTGTTTTAC-
G
ACAAAAAAATGAGAACGACGAATCCGAAAGAGACTAAGATTGTGATTGACACTACCGGCAGTACCAAACCTAAG-
C
AGGACGATCTCATTCTCACTTGTTTCAGAGGGTGGGTGAAGCAGTTGCAAATAGATTACAAAGGCAACGAAATA-
A
TGACGGCAGCTGCCTCTCAAGGGCTGACCCGTAAAGGTGTGTATGCCGTTCGGTACAAGGTGAATGAAAATCCT-
C
TGTACGCACCCACCTCAGAACATGTGAACGTCCTACTGACCCGCACGGAGGACCGCATCGTGTGGAAAACACTA-
G
CCGGCGACCCATGGATAAAAACACTGACTGCCAAGTACCCTGGGAATTTCACTGCCACGATAGAGGAGTGGCAA-
G
CAGAGCATGATGCCATCATGAGGCACATCTTGGAGAGACCGGACCCTACCGACGTCTTCCAGAATAAGGCAAAC-
G
TGTGTTGGGCCAAGGCTTTAGTGCCGGTGCTGAAGACCGCTGGCATAGACATGACCACTGAACAATGGAACACT-
G
TGGATTATTTTGAAACGGACAAAGCTCACTCAGCAGAGATAGTATTGAACCAACTATGCGTGAGGTTCTTTGGA-
C
TCGATCTGGACTCCGGTCTATTTTCTGCACCCACTGTTCCGTTATCCATTAGGAATAATCACTGGGATAACTCC-
C
CGTCGCCTAACATGTACGGGCTGAATAAAGAAGTGGTCCGTCAGCTCTCTCGCAGGTACCCACAACTGCCTCGG-
G
CAGTTGCCACTGGAAGAGTCTATGACATGAACACTGGTACACTGCGCAATTATGATCCGCGCATAAACCTAGTA-
C
CTGTAAACAGAAGACTGCCTCATGCTTTAGTCCTCCACCATAATGAACACCCACAGAGTGACTTTTCTTCATTC-
G
TCAGCAAATTGAAGGGCAGAACTGTCCTGGTGGTCGGGGAAAAGTTGTCCGTCCCAGGCAAAATGGTTGACTGG-
T
TGTCAGACCGGCCTGAGGCTACCTTCAGAGCTCGGCTGGATTTAGGCATCCCAGGTGATGTGCCCAAATATGAC-
A
TAATATTTGTTAATGTGAGGACCCCATATAAATACCATCACTATCAGCAGTGTGAAGACCATGCCATTAAGCTT-
A
GCATGTTGACCAAGAAAGCTTGTCTGCATCTGAATCCCGGCGGAACCTGTGTCAGCATAGGTTATGGTTACGCT-
G
ACAGGGCCAGCGAAAGCATCATTGGTGCTATAGCGCGGCAGTTCAAGTTTTCCCGGGTATGCAAACCGAAATCC-
T
CACTTGAAGAGACGGAAGTTCTGTTTGTATTCATTGGGTACGATCGCAAGGCCCGTACGCACAATCCTTACAAG-
C
TTTCATCAACCTTGACCAACATTTATACAGGTTCCAGACTCCACGAAGCCGGATGTGCACCCTCATATCATGTG-
G
TGCGAGGGGATATTGCCACGGCCACCGAAGGAGTGATTATAAATGCTGCTAACAGCAAAGGACAACCTGGCGGA-
G
GGGTGTGCGGAGCGCTGTATAAGAAATTCCCGGAAAGCTTCGATTTACAGCCGATCGAAGTAGGAAAAGCGCGA-
C
TGGTCAAAGGTGCAGCTAAACATATCATTCATGCCGTAGGACCAAACTTCAACAAAGTTTCGGAGGTTGAAGGT-
G
ACAAACAGTTGGCAGAGGCTTATGAGTCCATCGCTAAGATTGTCAACGATAACAATTACAAGTCAGTAGCGATT-
C
CACTGTTGTCCACCGGCATCTTTTCCGGGAACAAAGATCGACTAACCCAATCATTGAACCATTTGCTGACAGCT-
T
TAGACACCACTGATGCAGATGTAGCCATATACTGCAGGGACAAGAAATGGGAAATGACTCTCAAGGAAGCAGTG-
G
CTAGGAGAGAAGCAGTGGAGGAGATATGCATATCCGACGACTCTTCAGTGACAGAACCTGATGCAGAGCTGGTG-
A
GGGTGCATCCGAAGAGTTCTTTGGCTGGAAGGAAGGGCTACAGCACAAGCGATGGCAAAACTTTCTCATATTTG-
G
AAGGGACCAAGTTTCACCAGGCGGCCAAGGATATAGCAGAAATTAATGCCATGTGGCCCGTTGCAACGGAGGCC-
A
ATGAGCAGGTATGCATGTATATCCTCGGAGAAAGCATGAGCAGTATTAGGTCGAAATGCCCCGTCGAAGAGTCG-
G
AAGCCTCCACACCACCTAGCACGCTGCCTTGCTTGTGCATCCATGCCATGACTCCAGAAAGAGTACAGCGCCTA-
A
AAGCCTCACGTCCAGAACAAATTACTGTGTGCTCATCCTTTCCATTGCCGAAGTATAGAATCACTGGTGTGCAG-
A
AGATCCAATGCTCCCAGCCTATATTGTTCTCACCGAAAGTGCCTGCGTATATTCATCCAAGGAAGTATCTCGTG-
G
AAACACCACCGGTAGACGAGACTCCGGAGCCATCGGCAGAGAACCAATCCACAGAGGGGACACCTGAACAACCA-
C
CACTTATAACCGAGGATGAGACCAGGACTAGAACGCCTGAGCCGATCATCATCGAAGAGGAAGAAGAGGATAGC-
A
TAAGTTTGCTGTCAGATGGCCCGACCCACCAGGTGCTGCAAGTCGAGGCAGACATTCACGGGCCGCCCTCTGTA-
T
CTAGCTCATCCTGGTCCATTCCTCATGCATCCGACTTTGATGTGGACAGTTTATCCATACTTGACACCCTGGAG-
G
GAGCTAGCGTGACCAGCGGGGCAACGTCAGCCGAGACTAACTCTTACTTCGCAAAGAGTATGGAGTTTCTGGCG-
C
GACCGGTGCCTGCGCCTCGAACAGTATTCAGGAACCCTCCACATCCCGCTCCGCGCACAAGAACACCGTCACTT-
G
CACCCAGCAGGGCCTGCTCGAGAACCAGCCTAGTTTCCACCCCGCCAGGCGTGAATAGGGTGATCACTAGAGAG-
G
AGCTCGAGGCGCTTACCCCGTCACGCACTCCTAGCAGGTCGGTCTCGAGAACCAGCCTGGTCTCCAACCCGCCA-
G
GCGTAAATAGGGTGATTACAAGAGAGGAGTTTGAGGCGTTCGTAGCACAACAACAATGACGGTTTGATGCGGGT-
G
CATACATCTTTTCCTCCGACACCGGTCAAGGGCATTTACAACAAAAATCAGTAAGGCAAACGGTGCTATCCGAA-
G
TGGTGTTGGAGAGGACCGAATTGGAGATTTCGTATGCCCCGCGCCTCGACCAAGAAAAAGAAGAATTACTACGC-
A
AGAAATTACAGTTAAATCCCACACCTGCTAACAGAAGCAGATACCAGTCCAGGAAGGTGGAGAACATGAAAGCC-
A
TAACAGCTAGACGTATTCTGCAAGGCCTAGGGCATTATTTGAAGGCAGAAGGAAAAGTGGAGTGCTACCGAACC-
C
TGCATCCTGTTCCTTTGTATTCATCTAGTGTGAACCGTGCCTTTTCAAGCCCCAAGGTCGCAGTGGAAGCCTGT-
A
ACGCCATGTTGAAAGAGAACTTTCCGACTGTGGCTTCTTACTGTATTATTCCAGAGTACGATGCCTATTTGGAC-
A
TGGTTGACGGAGCTTCATGCTGCTTAGACACTGCCAGTTTTTGCCCTGCAAAGCTGCGCAGCTTTCCAAAGAAA-
C
ACTCCTATTTGGAACCCACAATACGATCGGCAGTGCCTTCAGCGATCCAGAACACGCTCCAGAACGTCCTGGCA-
G
CTGCCACAAAAAGAAATTGCAATGTCACGCAAATGAGAGAATTGCCCGTATTGGATTCGGCGGCCTTTAATGTG-
G
AATGCTTCAAGAAATATGCGTGTAATAATGAATATTGGGAAACGTTTAAAGAAAACCCCATCAGGCTTACTGAA-
G
AAAACGTGGTAAATTACATTACCAAATTAAAAGGACCAAAAGCTGCTGCTCTTTTTGCGAAGACACATAATTTG-
A
ATATGTTGCAGGACATACCAATGGACAGGTTTGTAATGGACTTAAAGAGAGACGTGAAAGTGACTCCAGGAACA-
A
AACATACTGAAGAACGGCCCAAGGTACAGGTGATCCAGGCTGCCGATCCGCTAGCAACAGCGTATCTGTGCGGA-
A
TCCACCGAGAGCTGGTTAGGAGATTAAATGCGGTCCTGCTTCCGAACATTCATACACTGTTTGATATGTCGGCT-
G
AAGACTTTGACGCTATTATAGCCGAGCACTTCCAGCCTGGGGATTGTGTTCTGGAAACTGACATCGCGTCGTTT-
G
ATAAAAGTGAGGACGACGCCATGGCTCTGACCGCGTTAATGATTCTGGAAGACTTAGGTGTGGACGCAGAGCTG-
T
TGACGCTGATTGAGGCGGCTTTCGGCGAAATTTCATCAATACATTTGCCCACTAAAACTAAATTTAAATTCGGA-
G
CCATGATGAAATCTGGAATGTTCCTCACACTGTTTGTGAACACAGTCATTAACATTGTAATCGCAAGCAGAGTG-
T
TGAGAGAACGGCTAACCGGATCACCATGTGCAGCATTCATTGGAGATGACAATATCGTGAAAGGAGTCAAATCG-
G
ACAAATTAATGGCAGACAGGTGCGCCACCTGGTTGAATATGGAAGTCAAGATTATAGATGCTGTGGTGGGCGAG-
A
AAGCGCCTTATTTCTGTGGAGGGTTTATTTTGTGTGACTCCGTGACCGGCACAGCGTGCCGTGTGGCAGACCCC-
C
TAAAAAGGCTGTTTAAGCTTGGCAAACCTCTGGCAGCAGACGATGAACATGATGATGACAGGAGAAGGGCATTG-
C
ATGAAGAGTCAACACGCTGGAACCGAGTGGGTATTCTTTCAGAGCTGTGCAAGGCAGTAGAATCAAGGTATGAA-
A
CCGTAGGAACTTCCATCATAGTTATGGCCATGACTACTCTAGCTAGCAGTGTTAAATCATTCAGCTACCTGAGA-
G ##STR00049## ##STR00050## ##STR00051##
CGTTACTGGCCGAAGCCGCTTGGAATAAGGCCGGTGTGCGTTTGTCTATATGTTATTTTCCACCATATTGCCGT-
C
TTTTGGCAATGTGAGGGCCCGGAAACCTGGCCCTGTCTTCTTGACGAGCATTCCTAGGGGTCTTTCCCCTCTCG-
C
CAAAGGAATGCAAGGTCTGTTGAATGTCGTGAAGGAAGCAGTTCCTCTGGAAGCTTCTTGAAGACAAACAACGT-
C
TGTAGCGACCCTTTGCAGGCAGCGGAACCCCCCACCTGGCGACAGGTGCCTCTGCGGCCAAAAGCCACGTGTAT-
A
AGATACACCTGCAAAGGCGGCACAACCCCAGTGCCACGTTGTGAGTTGGATAGTTGTGGAAAGAGTCAAATGGC-
T
CTCCTCAAGCGTATTCAACAAGGGGCTGAAGGATGCCCAGAAGGTACCCCATTGTATGGGATCTGATCTGGGGC-
C
TCGGTGCACATGCTTTACATGTGTTTAGTCGAGGTTAAAAAAACGTCTAGGCCCCCCGAACCACGGGGACGTGG-
T ##STR00052##
CTTTGTACGCCTGTTTTATACCCCCTCCCTGATTTGCAACTTAGAAGCAACGCAAACCAGATCAATAGTAGGTG-
T
GACATACCAGTCGCATCTTGATCAAGCACTTCTGTATCCCCGGACCGAGTATCAATAGACTGTGCACACGGTTG-
A
AGGAGAAAACGTCCGTTACCCGGCTAACTACTTCGAGAAGCCTAGTAACGCCATTGAAGTTGCAGAGTGTTTCG-
C
TCAGCACTCCCCCCGTGTAGATCAGGTCGATGAGTCACCGCATTCCCCACGGGCGACCGTGGCGGTGGCTGCGT-
T
GGCGGCCTGCCTATGGGGTAACCCATAGGACGCTCTAATACGGACATGGCGTGAAGAGTCTATTGAGCTAGTTA-
G
TAGTCCTCCGGCCCCTGAATGCGGCTAATCCTAACTGCGGAGCACATACCCTTAATCCAAAGGGCAGTGTGTCG-
T
AACGGGCAACTCTGCAGCGGAACCGACTACTTTGGGTGTCCGTGTTTCTTTTTATTCTTGTATTGGCTGCTTAT-
G
GTGACAATTAAAGAATTGTTACCATATAGCTATTGGATTGGCCATCCAGTGTCAAACAGAGCTATTGTATATCT-
C
TTTGTTGGATTCACACCTCTCACTCTTGAAACGTTACACACCCTCAATTACATTATACTGCTGAACACGAAGCG-
C ##STR00053##
GGCGATTGGCATGCCGCCTTAAAATTTTTATTTTATTTTTCTTTTCTTTTCCGAATCGGATTTTGTTTTTAATA-
T
TTCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGGGTCGGCATGGCATCTCCACCTCCTCGCGGTCCGA-
C
CTGGGCATCCGAAGGAGGACGCACGTCCACTCGGATGGCTAAGGGAGAGCCACGTTTAAACGCTAGAGCAAGAC-
G
TTTCCCGTTGAATATGGCTCATAACACCCCTTGTATTACTGTTTATGTAAGCAGACAGTTTTATTGTTCATGAT-
G
ATATATTTTTATCTTGTGCAATGTAACATCAGAGATTTTGAGACACAACGTGGCTTTGTTGAATAAATCGAACT-
T
TTGCTGAGTTGAAGGATCAGATCACGCATCTTCCCGACAACGCAGACCGTTCCGTGGCAAAGCAAAAGTTCAAA-
A
TCACCAACTGGTCCACCTACAACAAAGCTCTCATCAACCGTGGCTCCCTCACTTTCTGGCTGGATGATGGGGCG-
A
TTCAGGCCTGGTATGAGTCAGCAACACCTTCTTCACGAGGCAGACCTCAGCGCTAGCGGAGTGTATACTGGCTT-
A
CTATGTTGGCACTGATGAGGGTGTCAGTGAAGTGCTTCATGTGGCAGGAGAAAAAAGGCTGCACCGGTGCGTCA-
G
CAGAATATGTGATACAGGATATATTCCGCTTCCTCGCTCACTGACTCGCTACGCTCGGTCGTTCGACTGCGGCG-
A
GCGGAAATGGCTTACGAACGGGGCGGAGATTTCCTGGAAGATGCCAGGAAGATACTTAACAGGGAAGTGAGAGG-
G
CCGCGGCAAAGCCGTTTTTCCATAGGCTCCGCCCCCCTGACAAGCATCACGAAATCTGACGCTCAAATCAGTGG-
T
GGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCTGGCGGCTCCCTCGTGCGCTCTCCTGTTCCTG-
C
CTTTCGGTTTACCGGTGTCATTCCGCTGTTATGGCCGCGTTTGTCTCATTCCACGCCTGACACTCAGTTCCGGG-
T
AGGCAGTTCGCTCCAAGCTGGACTGTATGCACGAACCCCCCGTTCAGTCCGACCGCTGCGCCTTATCCGGTAAC-
T
ATCGTCTTGAGTCCAACCCGGAAAGACATGCAAAAGCACCACTGGCAGCAGCCACTGGTAATTGATTTAGAGGA-
G
TTAGTCTTGAAGTCATGCGCCGGTTAAGGCTAAACTGAAAGGACAAGTTTTGGTGACTGCGCTCCTCCAAGCCA-
G
TTACCTCGGTTCAAAGAGTTGGTAGCTCAGAGAACCTTCGAAAAACCGCCCTGCAAGGCGGTTTTTTCGTTTTC-
A
GAGCAAGAGATTACGCGCAGACCAAAACGATCTCAAGAAGATCATCTTATTAAGGGGTCTGACGCTCAGTGGAA-
C
GAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAA-
A
TGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTATTAGAAAAATTCATCCAGCAG-
A
CGATAAAACGCAATACGCTGGCTATCCGGTGCCGCAATGCCATACAGCACCAGAAAACGATCCGCCCATTCGCC-
G
CCCAGTTCTTCCGCAATATCACGGGTGGCCAGCGCAATATCCTGATAACGATCCGCCACGCCCAGACGGCCGCA-
A
TCAATAAAGCCGCTAAAACGGCCATTTTCCACCATAATGTTCGGCAGGCACGCATCACCATGGGTCACCACCAG-
A
TCTTCGCCATCCGGCATGCTCGCTTTCAGACGCGCAAACAGCTCTGCCGGTGCCAGGCCCTGATGTTCTTCATC-
C
AGATCATCCTGATCCACCAGGCCCGCTTCCATACGGGTACGCGCACGTTCAATACGATGTTTCGCCTGATGATC-
A
AACGGACAGGTCGCCGGGTCCAGGGTATGCAGACGACGCATGGCATCCGCCATAATGCTCACTTTTTCTGCCGG-
C
GCCAGATGGCTAGACAGCAGATCCTGACCCGGCACTTCGCCCAGCAGCAGCCAATCACGGCCCGCTTCGGTCAC-
C
ACATCCAGCACCGCCGCACACGGAACACCGGTGGTGGCCAGCCAGCTCAGACGCGCCGCTTCATCCTGCAGCTC-
G
TTCAGCGCACCGCTCAGATCGGTTTTCACAAACAGCACCGGACGACCCTGCGCGCTCAGACGAAACACCGCCGC-
A
TCAGAGCAGCCAATGGTCTGCTGCGCCCAATCATAGCCAAACAGACGTTCCACCCACGCTGCCGGGCTACCCGC-
A
TGCAGGCCATCCTGTTCAATCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCAT-
G
AGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCC-
A
CCTAAATTGTAAGCGTTAATATTTTGTTAAAATTCGCGTTAAATTTTTGTTAAATCAGCTCATTTTTTAACCAA-
T
AGGCCGAAATCGGCAAAATCCCTTATAAATCAAAAGAATAGACCGAGATAGGGTTGAGTGGCCGCTACAGGGCG-
C
TCCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGTTTCGGTGCGGGCCTCTTCGCTATTACGCCAGC-
T
GGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACACGCGTAATACG-
A CTCACTATAG
TABLE-US-00053 VZV gB
MFVTAWSVSPSSFYESLQVEPTQSEDITRSAHLGDGDEIREAIHKSQDAETKPTFYVCPPP
TGSTIVRLEPPRTCPDYHLGKNFTEGIAWYKENIAAYKFKATVYYKDVIVSTAWAGSSYTQ
ITNRYADRVPIPVSEITDTIDKFGKCSSKATYVRNNHKVEAFNEDKNPQDMPLIASKYNSVG
SKAWHTTNDTYMVAGTPGTYRTGTSVNCIIEEVEARSIFPYDSFGLSTGDIIYMSPFFGLRD
GAYREHSNYAMDRFHQFEGYRQRDLDTRALLEPAARNFLVTPHLTVGWNWKPKRTEVCSLVK
WREVEDWRDEYAHNFRFTMKTLSTTFISETNEFNLNQIHLSQCVKEEARAIINRIYTTRYN
SSHVRTGDIQTYLARGGFVVVFQPLLSNSLARLYLQELVRENTNHSPQKHPTRNTRSRRSVP
VELRANRTITTTSSVEFAMLQFTYDHIQEHVNEMLARISSSWCQLQNRERALWSGLFPINPS
ALASTILDQRVKARILGDVISVSNCPELGSDTRIILQNSMRVSGSTTRCYSRPLISIVSLNG
SGTVEGQLGTDNELIMSRDLLEPCVANHKRYFLFGHHYVYYEDYRYVREIAVHDVGMISTYV
DLNLTLLKDREFMPLQVYTRDELRDTGLLDYSEIQRRNQMHSLRFYDIDKWQYDSGTAIMQ
GMAQFFQGLGTAGQAVGHWLGATGALLSTVHGFTTFLSNPFGALAVGLLVLAGLVAAFFAY
RYVLKLKTSPMKALYPLTTKGLKQLPEGMDPFAEKPNATDTPIEEIGDSQNTEPSVNSGFDP
DKFREAQEMIKYMTLVSAAERQESKARKKNKTSALLTSRLTGLALRNRRGYSRVRTENVTGV
TABLE-US-00054 VZV gH
MFALVLAWILPLWTTANKSYVTPTPATRSIGHMSALLREYSDRNMSLKLEAFYPTGFDEEL
IKSLHWGNDRKHVFLVIVKVNPTTHEGDVGLVIFPKYLLSPYHFKAEHRAPFPAGRFGFLSH
PVTPDVSFFDSSFAPYLTTQHLVAFTTFPPNPLVWHLERAETAATAERPFGVSLLPARPTVP
KNTILEHKAHFATWDALARHTFFSAEAIITNSTLRIHVPLFGSVWPIRYWATGSVLLTSDSG
RVEVNIGVGFMSSLISLSSGLPIELIWPHTVKLNAVTSDTTWFQLNPPGPDPGPSYRVYLL
GRGLDMNFSKHATVDICAYPEESLDYRYHLSMAHTEALRMTTKADQHDINEESYYHIAARIA
TSIFALSEMGRTTEYFLLDEIVDVQYQLKFLNYILMRIGAGAHPNTISGTSDLIFADPSQLH
DELSLLFGQVKPANVDYFISYDEARDQLKTAYALSRGQDHVNALSLARRVIMSIYKGLLVKQ
NLNATERQALFFASMILLNFREGLENSSRVLDGRTTLLLMTSMCTAAHATQAALNIQEGLAY
LNPSKHMFTIPNVYSPCMGSLRTDLTEEIHVMNLLSAIPTRPGLNEVLHTQLDESEIFDAAF
KTMMIFTTWTAKDLHILHTHVPEVFTCQDAAARNGEYVLILPAVQGHSYVITRNKPQRGLVY
SLADVDVYNPISWYLSKDTCVSEHGVIETVALPHPDNLKECLYCGSVFLRYLTTGAIMDII
IIDSKDTERQLAAMGNSTIPPFNPDMHGDDSKAVLLFPNGTWTLLGFERRQAIRMSGQYLG
ASLGGAFLAWGFGIIGWMLCGNSRLREYNKIPLT
TABLE-US-00055 VZV gL
MASHKWLLQMIVFLKTITIAYCLHLQDDTPLFFGAKPLSDVSLIITEPCV
SSVYEAWDYAAPPVSNLSEALSGIWKTKCPVPEVILWFKDKQMAYWTNPY
VTLKGLTQSVGEEHKSGDIRDALLDALSGVWVDSTPSSTNIPENGCVWGA DRLFQRVCQ
TABLE-US-00056 VZV gI
MFLIQCLISAVIFYIQVTNALIFKGDHVSLQVNSSLTSILIPMQNDNYTE
IKGQLVFIGEQLPTGTNYSGTLELLYADTVAFCFRSVQVIRYDGCPRIRT
SAFISCRYKHSWHYGNSTDRISTEPDAGVMLKITKPGINDAGVYVLLVRL
DHSRSTDGFILGVNVYTAGSHHNIHGVIYTSPSLQNGYSTRALFQQARLC
DLPATPKGSGTSLFQHMLDLRAGKSLEDNPWLHEDWTTETKSWKEGIENH
VYPTDMSTLPEKSLNDPPENLLIIIPIVASVMILTAMVIVIVISVKRRRI
KKHPIYRPNTKTRRGIQNATPESDVMLEAAIAQLATIREESPPHSWNPFV K
TABLE-US-00057 VZV gE
MGTVNKPWGVLMGFGIITGTLRITNPVRASVLRYDDFHIDEDKLDTNSVYEPYYHSDHAES
SWVNRGESSRKAYDHNSPYIWPRNDYDGFLENAHEHHGVYNQGRGIDSGERLMQPTQMSAQE
DLGDDTGIHVIPTLNGDDRHKIVNVDQRQYGDVFKGDLNPKPQGQRLIEVSVEENHPFTLRA
PIQRIYGVRYTETWSFLPSLTCTGDAAPAIQHICLKHTTCFQDVWDVDCAENTKEDQLAEI
SYRFQGKKEADQPWIWNTSTLFDELELDPPEIEPGVLKVLRTEKQYLGVYIWNMRGSDGTS
TYATFLVTWKGDEKTRNPTPAVTPQPRGAEFHMWNYHSHVFSVGDTFSLAMHLQYKIHEAPF
DLLLEWLYVPIDPTCQPMRLYSTCLYHPNAPQCLSHMNSGCTFTSPHLAQRVASTVYQNCEH
ADNYTAYCLGISHMEPSFGLILHDGGTTLKFVDTPESLSGLYVFWYFNGHVEAVAYTWST
VDHFVNAIEERGFPPTAGQPPATTKPKEITPVNPGTSPLLRYAAWTGGLAAWLLCLVIFLI
CTAKRMRVKAYRVDKSPYNQSMYYAGLPVDDFEDSESTDTEEEFGNAIGGSHGGSSYTVYID
KTR
TABLE-US-00058 VZV VEERep.SGPgB 1.sub.--
ataggcggcgcatgagagaagcccagaccaattacctacccaaaatggagaaagttcacgttgacatc
gaggaagacagcccattcctcagagctttgcagcggagcttcccgcagtttgaggtagaagccaagca
ggtcactgataatgaccatgctaatgccagagcgttttcgcatctggcttcaaaactgatcgaaacgg
aggtggacccatccgacacgatccttgacattggaagtgcgcccgcccgcagaatgtattctaagcac
aagtatcattgtatctgtccgatgagatgtgcggaagatccggacagattgtataagtatgcaactaa
gctgaagaaaaactgtaaggaaataactgataaggaattggacaagaaaatgaaggagctcgccgccg
tcatgagcgaccctgacctggaaactgagactatgtgcctccacgacgacgagtcgtgtcgctacgaa
gggcaagtcgctgtttaccaggatgtatacgcggttgacggaccgacaagtctctatcaccaagccaa
taagggagttagagtcgcctactggataggctttgacaccaccccttttatgtttaagaacttggctg
gagcatatccatcatactctaccaactgggccgacgaaaccgtgttaacggctcgtaacataggccta
tgcagctctgacgttatggagcggtcacgtagagggatgtccattcttagaaagaagtatttgaaacc
atccaacaatgttctattctctgttggctcgaccatctaccacgagaagagggacttactgaggagct
ggcacctgccgtctgtatttcacttacgtggcaagcaaaattacacatgtcggtgtgagactatagtt
agttgcgacgggtacgtcgttaaaagaatagctatcagtccaggcctgtatgggaagccttcaggcta
tgctgctacgatgcaccgcgagggattcttgtgctgcaaagtgacagacacattgaacggggagaggg
tctcttttcccgtgtgcacgtatgtgccagctacattgtgtgaccaaatgactggcatactggcaaca
gatgtcagtgcggacgacgcgcaaaaactgctggttgggctcaaccagcgtatagtcgtcaacggtcg
cacccagagaaacaccaataccatgaaaaattaccttttgcccgtagtggcccaggcatttgctaggt
gggcaaaggaatataaggaagatcaagaagatgaaaggccactaggactacgagatagacagttagtc
atggggtgttgttgggcttttagaaggcacaagataacatctatttataagcgcccggatacccaaac
catcatcaaagtgaacagcgatttccactcattcgtgctgcccaggataggcagtaacacattggaga
tcgggctgagaacaagaatcaggaaaatgttagaggagcacaaggagccgtcacctctcattaccgcc
gaggacgtacaagaagctaagtgcgcagccgatgaggctaaggaggtgcgtgaagccgaggagttgcg
cgcagctctaccacctttggcagctgatgttgaggagcccactctggaagccgatgtagacttgatgt
tacaagaggctggggccggctcagtggagacacctcgtggcttgataaaggttaccagctacgatggc
gaggacaagatcggctcttacgctgtgctttctccgcaggctgtactcaagagtgaaaaattatcttg
catccaccctctcgctgaacaagtcatagtgataacacactctggccgaaaagggcgttatgccgtgg
aaccataccatggtaaagtagtggtgccagagggacatgcaatacccgtccaggactttcaagctctg
agtgaaagtgccaccattgtgtacaacgaacgtgagttcgtaaacaggtacctgcaccatattgccac
acatggaggagcgctgaacactgatgaagaatattacaaaactgtcaagcccagcgagcacgacggcg
aatacctgtacgacatcgacaggaaacagtgcgtcaagaaagaactagtcactgggctagggctcaca
ggcgagctggtggatcctcccttccatgaattcgcctacgagagtctgagaacacgaccagccgctcc
ttaccaagtaccaaccataggggtgtatggcgtgccaggatcaggcaagtctggcatcattaaaagcg
cagtcaccaaaaaagatctagtggtgagcgccaagaaagaaaactgtgcagaaattataagggacgtc
aagaaaatgaaagggctggacgtcaatgccagaactgtggactcagtgctcttgaatggatgcaaaca
ccccgtagagaccctgtatattgacgaagcttttgcttgtcatgcaggtactctcagagcgctcatag
ccattataagacctaaaaaggcagtgctctgcggggatcccaaacagtgcggtttttttaacatgatg
tgcctgaaagtgcattttaaccacgagatttgcacacaagtcttccacaaaagcatctctcgccgttg
cactaaatctgtgacttcggtcgtctcaaccttgttttacgacaaaaaaatgagaacgacgaatccga
aagagactaagattgtgattgacactaccggcagtaccaaacctaagcaggacgatctcattctcact
tgtttcagagggtgggtgaagcagttgcaaatagattacaaaggcaacgaaataatgacggcagctgc
ctctcaagggctgacccgtaaaggtgtgtatgccgttcggtacaaggtgaatgaaaatcctctgtacg
cacccacctcagaacatgtgaacgtcctactgacccgcacggaggaccgcatcgtgtggaaaacacta
gccggcgacccatggataaaaacactgactgccaagtaccctgggaatttcactgccacgatagagga
gtggcaagcagagcatgatgccatcatgaggcacatcttggagagaccggaccctaccgacgtcttcc
agaataaggcaaacgtgtgttgggccaaggctttagtgccggtgctgaagaccgctggcatagacatg
accactgaacaatggaacactgtggattattttgaaacggacaaagctcactcagcagagatagtatt
gaaccaactatgcgtgaggttctttggactcgatctggactccggtctattttctgcacccactgttc
cgttatccattaggaataatcactgggataactccccgtcgcctaacatgtacgggctgaataaagaa
gtggtccgtcagctctctcgcaggtacccacaactgcctcgggcagttgccactggaagagtctatga
catgaacactggtacactgcgcaattatgatccgcgcataaacctagtacctgtaaacagaagactgc
ctcatgctttagtcctccaccataatgaacacccacagagtgacttttcttcattcgtcagcaaattg
aagggcagaactgtcctggtggtcggggaaaagttgtccgtcccaggcaaaatggttgactggttgtc
agaccggcctgaggctaccttcagagctcggctggatttaggcatcccaggtgatgtgcccaaatatg
acataatatttgttaatgtgaggaccccatataaataccatcactatcagcagtgtgaagaccatgcc
attaagcttagcatgttgaccaagaaagcttgtctgcatctgaatcccggcggaacctgtgtcagcat
aggttatggttacgctgacagggccagcgaaagcatcattggtgctatagcgcggcagttcaagtttt
cccgggtatgcaaaccgaaatcctcacttgaagagacggaagttctgtttgtattcattgggtacgat
cgcaaggcccgtacgcacaatccttacaagctttcatcaaccttgaccaacatttatacaggttccag
actccacgaagccggatgtgcaccctcatatcatgtggtgcgaggggatattgccacggccaccgaag
gagtgattataaatgctgctaacagcaaaggacaacctggcggaggggtgtgcggagcgctgtataag
aaattcccggaaagcttcgatttacagccgatcgaagtaggaaaagcgcgactggtcaaaggtgcagc
taaacatatcattcatgccgtaggaccaaacttcaacaaagtttcggaggttgaaggtgacaaacagt
tggcagaggcttatgagtccatcgctaagattgtcaacgataacaattacaagtcagtagcgattcca
ctgttgtccaccggcatcttttccgggaacaaagatcgactaacccaatcattgaaccatttgctgac
agctttagacaccactgatgcagatgtagccatatactgcagggacaagaaatgggaaatgactctca
aggaagcagtggctaggagagaagcagtggaggagatatgcatatccgacgactcttcagtgacagaa
cctgatgcagagctggtgagggtgcatccgaagagttctttggctggaaggaagggctacagcacaag
cgatggcaaaactttctcatatttggaagggaccaagtttcaccaggcggccaaggatatagcagaaa
ttaatgccatgtggcccgttgcaacggaggccaatgagcaggtatgcatgtatatcctcggagaaagc
atgagcagtattaggtcgaaatgccccgtcgaagagtcggaagcctccacaccacctagcacgctgcc
ttgcttgtgcatccatgccatgactccagaaagagtacagcgcctaaaagcctcacgtccagaacaaa
ttactgtgtgctcatcctttccattgccgaagtatagaatcactggtgtgcagaagatccaatgctcc
cagcctatattgttctcaccgaaagtgcctgcgtatattcatccaaggaagtatctcgtggaaacacc
accggtagacgagactccggagccatcggcagagaaccaatccacagaggggacacctgaacaaccac
cacttataaccgaggatgagaccaggactagaacgcctgagccgatcatcatcgaagaggaagaagag
gatagcataagtttgctgtcagatggcccgacccaccaggtgctgcaagtcgaggcagacattcacgg
gccgccctctgtatctagctcatcctggtccattcctcatgcatccgactttgatgtggacagtttat
ccatacttgacaccctggagggagctagcgtgaccagcggggcaacgtcagccgagactaactcttac
ttcgcaaagagtatggagtttctggcgcgaccggtgcctgcgcctcgaacagtattcaggaaccctcc
acatcccgctccgcgcacaagaacaccgtcacttgcacccagcagggcctgctcgagaaccagcctag
tttccaccccgccaggcgtgaatagggtgatcactagagaggagctcgaggcgcttaccccgtcacgc
actcctagcaggtcggtctcgagaaccagcctggtctccaacccgccaggcgtaaatagggtgattac
aagagaggagtttgaggcgttcgtagcacaacaacaatgacggtttgatgcgggtgcatacatctttt
cctccgacaccggtcaagggcatttacaacaaaaatcagtaaggcaaacggtgctatccgaagtggtg
ttggagaggaccgaattggagatttcgtatgccccgcgcctcgaccaagaaaaagaagaattactacg
caagaaattacagttaaatcccacacctgctaacagaagcagataccagtccaggaaggtggagaaca
tgaaagccataacagctagacgtattctgcaaggcctagggcattatttgaaggcagaaggaaaagtg
gagtgctaccgaaccctgcatcctgttcctttgtattcatctagtgtgaaccgtgccttttcaagccc
caaggtcgcagtggaagcctgtaacgccatgttgaaagagaactttccgactgtggcttcttactgta
ttattccagagtacgatgcctatttggacatggttgacggagcttcatgctgcttagacactgccagt
ttttgccctgcaaagctgcgcagctttccaaagaaacactcctatttggaacccacaatacgatcggc
agtgccttcagcgatccagaacacgctccagaacgtcctggcagctgccacaaaaagaaattgcaatg
tcacgcaaatgagagaattgcccgtattggattcggcggcctttaatgtggaatgcttcaagaaatat
gcgtgtaataatgaatattgggaaacgtttaaagaaaaccccatcaggcttactgaagaaaacgtggt
aaattacattaccaaattaaaaggaccaaaagctgctgctctttttgcgaagacacataatttgaata
tgttgcaggacataccaatggacaggtttgtaatggacttaaagagagacgtgaaagtgactccagga
acaaaacatactgaagaacggcccaaggtacaggtgatccaggctgccgatccgctagcaacagcgta
tctgtgcggaatccaccgagagctggttaggagattaaatgcggtcctgcttccgaacattcatacac
tgtttgatatgtcggctgaagactttgacgctattatagccgagcacttccagcctggggattgtgtt
ctggaaactgacatcgcgtcgtttgataaaagtgaggacgacgccatggctctgaccgcgttaatgat
tctggaagacttaggtgtggacgcagagctgttgacgctgattgaggcggctttcggcgaaatttcat
caatacatttgcccactaaaactaaatttaaattcggagccatgatgaaatctggaatgttcctcaca
ctgtttgtgaacacagtcattaacattgtaatcgcaagcagagtgttgagagaacggctaaccggatc
accatgtgcagcattcattggagatgacaatatcgtgaaaggagtcaaatcggacaaattaatggcag
acaggtgcgccacctggttgaatatggaagtcaagattatagatgctgtggtgggcgagaaagcgcct
tatttctgtggagggtttattttgtgtgactccgtgaccggcacagcgtgccgtgtggcagaccccct
aaaaaggctgtttaagcttggcaaacctctggcagcagacgatgaacatgatgatgacaggagaaggg
cattgcatgaagagtcaacacgctggaaccgagtgggtattctttcagagctgtgcaaggcagtagaa
tcaaggtatgaaaccgtaggaacttccatcatagttatggccatgactactctagctagcagtgttaa
atcattcagctacctgagaggggcccctataactctctacggctaacctgaatggactacgacatagt
ctagtcgagtctagtcgacgccaccatgttcgtgaccgccgtggtgtccgtgtcccccagcagctttt
acgagagcctgcaggtcgagcccacccagagcgaggacatcacaagatctgcccacctgggcgacggc
gacgagatcagagaggccatccacaagagccaggacgccgagacaaagcccaccttctacgtgtgccc
cccacctaccggctctacaattgtgcggctggaaccccccagaacctgccctgattaccacctgggca
agaacttcaccgagggaattgccgtggtgtacaaagagaatatcgccgcctacaagttcaaggccacc
gtgtactacaaggacgtgatcgtgtccaccgcctgggccggcagcagctacacccagatcaccaacag
atacgccgaccgggtgcccatccccgtgtctgagatcaccgacaccatcgacaagttcggcaagtgca
gcagcaaggccacctacgtgcggaacaaccacaaggtggaagccttcaacgaggacaagaacccccag
gacatgcccctgatcgccagcaagtacaacagcgtgggctccaaggcctggcacaccaccaacgacac
ctacatggtggccggcacccccggcacatacagaacaggcaccagcgtgaactgcatcatcgaggaag
tggaagcccggtccatcttcccatacgacagcttcggcctgagcaccggcgacattatctacatgagc
cctttcttcggcctgcgggacggcgcctacagagagcacagcaactacgccatggaccggttccacca
gttcgagggctacagacagcgggacctggacacaagagccctgctggaacctgccgccagaaacttcc
tggtcacccctcacctgaccgtgggctggaactggaagcccaagcggaccgaagtgtgcagcctggtc
aagtggcgcgaggtggaagatgtcgtgcgggatgagtacgcccacaacttccggttcaccatgaagac
cctgagcaccaccttcatcagcgagacaaacgagttcaacctgaaccagatccacctgagccagtgcg
tgaaagaggaagccagagccatcatcaaccggatctacaccacccggtacaacagcagccacgtgcgg
accggcgatatccagacctatctggctagaggcggcttcgtggtggtgtttcagcccctgctgagcaa
cagcctggctagactgtacctgcaggaactcgtcagagagaacaccaaccacagcccccagaagcacc
ccacccggaataccagatccagacgcagcgtgcccgtggaactgagagccaaccggaccatcaccacc
accagcagcgtggaattcgccatgctgcagttcacctacgaccacatccaggaacacgtgaacgagat
gctggcccggatcagcagcagttggtgccagctgcagaatcgggaaagggccctgtggtccggcctgt
tccccatcaatccaagcgccctggccagcaccatcctggaccagagagtgaaggccagaatcctgggg
gacgtgatcagcgtgtccaactgtcctgagctgggcagcgacacccggatcatcctgcagaacagcat
gcgggtgtccggcagcaccaccagatgctacagcagacccctgatcagcatcgtgtccctgaacggca
gcggcacagtggaaggccagctgggcaccgataacgagctgatcatgagccgggacctgctcgaaccc
tgcgtggccaatcacaagcggtactttctgttcggccaccactacgtgtactatgaggactacagata
cgtgcgcgagatcgccgtgcacgacgtgggcatgatcagcacctacgtggacctgaacctgaccctgc
tgaaggaccgcgagttcatgccactgcaggtctacacccgggacgagctgagagataccggcctgctg
gactacagcgagatccagcggcggaaccagatgcactccctgcggttctacgacatcgacaaggtggt
gcagtacgacagcggcaccgccatcatgcagggcatggcccagttctttcagggcctgggaacagccg
gacaggccgtgggacatgtggtgctgggagctacaggcgccctgctgtctaccgtgcacggcttcacc
acctttctgagcaaccccttcggagccctggctgtgggactgctggtcctggctggactggtggccgc
cttctttgcctaccgctacgtgctgaagctgaaaaccagccccatgaaggccctgtaccccctgacca
ccaagggcctgaagcagctgcctgagggcatggaccccttcgccgagaagcccaatgccaccgacacc
cccatcgaggaaatcggcgacagccagaacaccgagccctccgtgaacagcggcttcgaccccgacaa
gtttcgcgaggcccaggaaatgatcaagtacatgaccctggtgtctgctgccgagcggcaggaaagca
aggcccggaagaagaacaagacctccgccctgctgaccagcagactgacaggactggccctgcggaac
agacggggctatagcagagtgcggaccgagaatgtgaccggcgtgtaatctagacgcggccgcataca
gcagcaattggcaagctgcttacatagaactcgcggcgattggcatgccgccttaaaatttttatttt
atttttcttttcttttccgaatcggattttgtttttaatatttcaaaaaaaaaaaaaaaaaaaaaaaa
aaaaaaaaaaagggtcggcatggcatctccacctcctcgcggtccgacctgggcatccgaaggaggac
gcacgtccactcggatggctaagggagagccacgtttaaaccagctccaattcgccctatagtgagtc
gtattacgcgcgctcactggccgtcgttttacaacgtcgtgactgggaaaaccctggcgttacccaac
ttaatcgccttgcagcacatccccctttcgccagctggcgtaatagcgaagaggcccgcaccgatcgc
ccttcccaacagttgcgcagcctgaatggcgaatgggacgcgccctgtagcggcgcattaagcgcggc
gggtgtggtggttacgcgcagcgtgaccgctacacttgccagcgccctagcgcccgctcctttcgctt
tcttcccttcctttctcgccacgttcgccggctttccccgtcaagctctaaatcgggggctcccttta
gggttccgatttagtgctttacggcacctcgaccccaaaaaacttgattagggtgatggttcacgtag
tgggccatcgccctgatagacggtttttcgccctttgacgttggagtccacgttctttaatagtggac
tcttgttccaaactggaacaacactcaaccctatctcggtctattcttttgatttataagggattttg
ccgatttcggcctattggttaaaaaatgagctgatttaacaaaaatttaacgcgaattttaacaaaat
attaacgcttacaatttaggtggcacttttcggggaaatgtgcgcggaacccctatttgtttattttt
ctaaatacattcaaatatgtatccgctcatgagacaataaccctgataaatgcttcaataatattgaa
aaaggaagagtatgagtattcaacatttccgtgtcgcccttattcccttttttgcggcattttgcctt
cctgtttttgctcacccagaaacgctggtgaaagtaaaagatgctgaagatcagttgggtgcacgagt
gggttacatcgaactggatctcaacagcggtaagatccttgagagttttcgccccgaagaacgttttc
caatgatgagcacttttaaagttctgctatgtggcgcggtattatcccgtattgacgccgggcaagag
caactcggtcgccgcatacactattctcagaatgacttggttgagtactcaccagtcacagaaaagca
tcttacggatggcatgacagtaagagaattatgcagtgctgccataaccatgagtgataacactgcgg
ccaacttacttctgacaacgatcggaggaccgaaggagctaaccgcttttttgcacaacatgggggat
catgtaactcgccttgatcgttgggaaccggagctgaatgaagccataccaaacgacgagcgtgacac
cacgatgcctgtagcaatggcaacaacgttgcgcaaactattaactggcgaactacttactctagctt
cccggcaacaattaatagactggatggaggcggataaagttgcaggaccacttctgcgctcggccctt
ccggctggctggtttattgctgataaatctggagccggtgagcgtgggtctcgcggtatcattgcagc
actggggccagatggtaagccctcccgtatcgtagttatctacacgacggggagtcaggcaactatgg
atgaacgaaatagacagatcgctgagataggtgcctcactgattaagcattggtaactgtcagaccaa
gtttactcatatatactttagattgatttaaaacttcatttttaatttaaaaggatctaggtgaagat
cctttttgataatctcatgaccaaaatcccttaacgtgagttttcgttccactgagcgtcagaccccg
tagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaatctgctgcttgcaaacaaaa
aaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctttttccgaaggtaac
tggcttcagcagagcgcagataccaaatactgttcttctagtgtagccgtagttaggccaccacttca
agaactctgtagcaccgcctacatacctcgctctgctaatcctgttaccagtggctgctgccagtggc
gataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcagcggtcgggctg
aacggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactgagatacctacagc
gtgagctatgagaaagcgccacgcttcccgaagggagaaaggcggacaggtatccggtaagcggcagg
gtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatctttatagtcctgtcgg
gtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtcaggggggcggagcctatggaaaa
acgccagcaacgcggcctttttacggttcctggccttttgctggccttttgctcacatgttctttcct
gcgttatcccctgattctgtggataaccgtattaccgcctttgagtgagctgataccgctcgccgcag
ccgaacgaccgagcgcagcgagtcagtgagcgaggaagcggaagagcgcccaatacgcaaaccgcctc
tccccgcgcgttggccgattcattaatgcagctggcacgacaggtttcccgactggaaagcgggcagt
gagcgcaacgcaattaatgtgagttagctcactcattaggcaccccaggctttacactttatgctccc
ggctcgtatgttgtgtggaattgtgagcggataacaatttcacacaggaaacagctatgaccatgatt
acgccaagcgcgcaattaaccctcactaaagggaacaaaagctgggtaccgggcccacgcgtaatacg
actcactatag_13339
TABLE-US-00059 VZV VEERep.SGPgH 1.sub.--
ataggcggcgcatgagagaagcccagaccaattacctacccaaaatggagaaagttcacgttgacatc
gaggaagacagcccattcctcagagctttgcagcggagcttcccgcagtttgaggtagaagccaagca
ggtcactgataatgaccatgctaatgccagagcgttttcgcatctggcttcaaaactgatcgaaacgg
aggtggacccatccgacacgatccttgacattggaagtgcgcccgcccgcagaatgtattctaagcac
aagtatcattgtatctgtccgatgagatgtgcggaagatccggacagattgtataagtatgcaactaa
gctgaagaaaaactgtaaggaaataactgataaggaattggacaagaaaatgaaggagctcgccgccg
tcatgagcgaccctgacctggaaactgagactatgtgcctccacgacgacgagtcgtgtcgctacgaa
gggcaagtcgctgtttaccaggatgtatacgcggttgacggaccgacaagtctctatcaccaagccaa
taagggagttagagtcgcctactggataggctttgacaccaccccttttatgtttaagaacttggctg
gagcatatccatcatactctaccaactgggccgacgaaaccgtgttaacggctcgtaacataggccta
tgcagctctgacgttatggagcggtcacgtagagggatgtccattcttagaaagaagtatttgaaacc
atccaacaatgttctattctctgttggctcgaccatctaccacgagaagagggacttactgaggagct
ggcacctgccgtctgtatttcacttacgtggcaagcaaaattacacatgtcggtgtgagactatagtt
agttgcgacgggtacgtcgttaaaagaatagctatcagtccaggcctgtatgggaagccttcaggcta
tgctgctacgatgcaccgcgagggattcttgtgctgcaaagtgacagacacattgaacggggagaggg
tctcttttcccgtgtgcacgtatgtgccagctacattgtgtgaccaaatgactggcatactggcaaca
gatgtcagtgcggacgacgcgcaaaaactgctggttgggctcaaccagcgtatagtcgtcaacggtcg
cacccagagaaacaccaataccatgaaaaattaccttttgcccgtagtggcccaggcatttgctaggt
gggcaaaggaatataaggaagatcaagaagatgaaaggccactaggactacgagatagacagttagtc
atggggtgttgttgggcttttagaaggcacaagataacatctatttataagcgcccggatacccaaac
catcatcaaagtgaacagcgatttccactcattcgtgctgcccaggataggcagtaacacattggaga
tcgggctgagaacaagaatcaggaaaatgttagaggagcacaaggagccgtcacctctcattaccgcc
gaggacgtacaagaagctaagtgcgcagccgatgaggctaaggaggtgcgtgaagccgaggagttgcg
cgcagctctaccacctttggcagctgatgttgaggagcccactctggaagccgatgtagacttgatgt
tacaagaggctggggccggctcagtggagacacctcgtggcttgataaaggttaccagctacgatggc
gaggacaagatcggctcttacgctgtgctttctccgcaggctgtactcaagagtgaaaaattatcttg
catccaccctctcgctgaacaagtcatagtgataacacactctggccgaaaagggcgttatgccgtgg
aaccataccatggtaaagtagtggtgccagagggacatgcaatacccgtccaggactttcaagctctg
agtgaaagtgccaccattgtgtacaacgaacgtgagttcgtaaacaggtacctgcaccatattgccac
acatggaggagcgctgaacactgatgaagaatattacaaaactgtcaagcccagcgagcacgacggcg
aatacctgtacgacatcgacaggaaacagtgcgtcaagaaagaactagtcactgggctagggctcaca
ggcgagctggtggatcctcccttccatgaattcgcctacgagagtctgagaacacgaccagccgctcc
ttaccaagtaccaaccataggggtgtatggcgtgccaggatcaggcaagtctggcatcattaaaagcg
cagtcaccaaaaaagatctagtggtgagcgccaagaaagaaaactgtgcagaaattataagggacgtc
aagaaaatgaaagggctggacgtcaatgccagaactgtggactcagtgctcttgaatggatgcaaaca
ccccgtagagaccctgtatattgacgaagcttttgcttgtcatgcaggtactctcagagcgctcatag
ccattataagacctaaaaaggcagtgctctgcggggatcccaaacagtgcggtttttttaacatgatg
tgcctgaaagtgcattttaaccacgagatttgcacacaagtcttccacaaaagcatctctcgccgttg
cactaaatctgtgacttcggtcgtctcaaccttgttttacgacaaaaaaatgagaacgacgaatccga
aagagactaagattgtgattgacactaccggcagtaccaaacctaagcaggacgatctcattctcact
tgtttcagagggtgggtgaagcagttgcaaatagattacaaaggcaacgaaataatgacggcagctgc
ctctcaagggctgacccgtaaaggtgtgtatgccgttcggtacaaggtgaatgaaaatcctctgtacg
cacccacctcagaacatgtgaacgtcctactgacccgcacggaggaccgcatcgtgtggaaaacacta
gccggcgacccatggataaaaacactgactgccaagtaccctgggaatttcactgccacgatagagga
gtggcaagcagagcatgatgccatcatgaggcacatcttggagagaccggaccctaccgacgtcttcc
agaataaggcaaacgtgtgttgggccaaggctttagtgccggtgctgaagaccgctggcatagacatg
accactgaacaatggaacactgtggattattttgaaacggacaaagctcactcagcagagatagtatt
gaaccaactatgcgtgaggttctttggactcgatctggactccggtctattttctgcacccactgttc
cgttatccattaggaataatcactgggataactccccgtcgcctaacatgtacgggctgaataaagaa
gtggtccgtcagctctctcgcaggtacccacaactgcctcgggcagttgccactggaagagtctatga
catgaacactggtacactgcgcaattatgatccgcgcataaacctagtacctgtaaacagaagactgc
ctcatgctttagtcctccaccataatgaacacccacagagtgacttttcttcattcgtcagcaaattg
aagggcagaactgtcctggtggtcggggaaaagttgtccgtcccaggcaaaatggttgactggttgtc
agaccggcctgaggctaccttcagagctcggctggatttaggcatcccaggtgatgtgcccaaatatg
acataatatttgttaatgtgaggaccccatataaataccatcactatcagcagtgtgaagaccatgcc
attaagcttagcatgttgaccaagaaagcttgtctgcatctgaatcccggcggaacctgtgtcagcat
aggttatggttacgctgacagggccagcgaaagcatcattggtgctatagcgcggcagttcaagtttt
cccgggtatgcaaaccgaaatcctcacttgaagagacggaagttctgtttgtattcattgggtacgat
cgcaaggcccgtacgcacaatccttacaagctttcatcaaccttgaccaacatttatacaggttccag
actccacgaagccggatgtgcaccctcatatcatgtggtgcgaggggatattgccacggccaccgaag
gagtgattataaatgctgctaacagcaaaggacaacctggcggaggggtgtgcggagcgctgtataag
aaattcccggaaagcttcgatttacagccgatcgaagtaggaaaagcgcgactggtcaaaggtgcagc
taaacatatcattcatgccgtaggaccaaacttcaacaaagtttcggaggttgaaggtgacaaacagt
tggcagaggcttatgagtccatcgctaagattgtcaacgataacaattacaagtcagtagcgattcca
ctgttgtccaccggcatcttttccgggaacaaagatcgactaacccaatcattgaaccatttgctgac
agctttagacaccactgatgcagatgtagccatatactgcagggacaagaaatgggaaatgactctca
aggaagcagtggctaggagagaagcagtggaggagatatgcatatccgacgactcttcagtgacagaa
cctgatgcagagctggtgagggtgcatccgaagagttctttggctggaaggaagggctacagcacaag
cgatggcaaaactttctcatatttggaagggaccaagtttcaccaggcggccaaggatatagcagaaa
ttaatgccatgtggcccgttgcaacggaggccaatgagcaggtatgcatgtatatcctcggagaaagc
atgagcagtattaggtcgaaatgccccgtcgaagagtcggaagcctccacaccacctagcacgctgcc
ttgcttgtgcatccatgccatgactccagaaagagtacagcgcctaaaagcctcacgtccagaacaaa
ttactgtgtgctcatcctttccattgccgaagtatagaatcactggtgtgcagaagatccaatgctcc
cagcctatattgttctcaccgaaagtgcctgcgtatattcatccaaggaagtatctcgtggaaacacc
accggtagacgagactccggagccatcggcagagaaccaatccacagaggggacacctgaacaaccac
cacttataaccgaggatgagaccaggactagaacgcctgagccgatcatcatcgaagaggaagaagag
gatagcataagtttgctgtcagatggcccgacccaccaggtgctgcaagtcgaggcagacattcacgg
gccgccctctgtatctagctcatcctggtccattcctcatgcatccgactttgatgtggacagtttat
ccatacttgacaccctggagggagctagcgtgaccagcggggcaacgtcagccgagactaactcttac
ttcgcaaagagtatggagtttctggcgcgaccggtgcctgcgcctcgaacagtattcaggaaccctcc
acatcccgctccgcgcacaagaacaccgtcacttgcacccagcagggcctgctcgagaaccagcctag
tttccaccccgccaggcgtgaatagggtgatcactagagaggagctcgaggcgcttaccccgtcacgc
actcctagcaggtcggtctcgagaaccagcctggtctccaacccgccaggcgtaaatagggtgattac
aagagaggagtttgaggcgttcgtagcacaacaacaatgacggtttgatgcgggtgcatacatctttt
cctccgacaccggtcaagggcatttacaacaaaaatcagtaaggcaaacggtgctatccgaagtggtg
ttggagaggaccgaattggagatttcgtatgccccgcgcctcgaccaagaaaaagaagaattactacg
caagaaattacagttaaatcccacacctgctaacagaagcagataccagtccaggaaggtggagaaca
tgaaagccataacagctagacgtattctgcaaggcctagggcattatttgaaggcagaaggaaaagtg
gagtgctaccgaaccctgcatcctgttcctttgtattcatctagtgtgaaccgtgccttttcaagccc
caaggtcgcagtggaagcctgtaacgccatgttgaaagagaactttccgactgtggcttcttactgta
ttattccagagtacgatgcctatttggacatggttgacggagcttcatgctgcttagacactgccagt
ttttgccctgcaaagctgcgcagctttccaaagaaacactcctatttggaacccacaatacgatcggc
agtgccttcagcgatccagaacacgctccagaacgtcctggcagctgccacaaaaagaaattgcaatg
tcacgcaaatgagagaattgcccgtattggattcggcggcctttaatgtggaatgcttcaagaaatat
gcgtgtaataatgaatattgggaaacgtttaaagaaaaccccatcaggcttactgaagaaaacgtggt
aaattacattaccaaattaaaaggaccaaaagctgctgctctttttgcgaagacacataatttgaata
tgttgcaggacataccaatggacaggtttgtaatggacttaaagagagacgtgaaagtgactccagga
acaaaacatactgaagaacggcccaaggtacaggtgatccaggctgccgatccgctagcaacagcgta
tctgtgcggaatccaccgagagctggttaggagattaaatgcggtcctgcttccgaacattcatacac
tgtttgatatgtcggctgaagactttgacgctattatagccgagcacttccagcctggggattgtgtt
ctggaaactgacatcgcgtcgtttgataaaagtgaggacgacgccatggctctgaccgcgttaatgat
tctggaagacttaggtgtggacgcagagctgttgacgctgattgaggcggctttcggcgaaatttcat
caatacatttgcccactaaaactaaatttaaattcggagccatgatgaaatctggaatgttcctcaca
ctgtttgtgaacacagtcattaacattgtaatcgcaagcagagtgttgagagaacggctaaccggatc
accatgtgcagcattcattggagatgacaatatcgtgaaaggagtcaaatcggacaaattaatggcag
acaggtgcgccacctggttgaatatggaagtcaagattatagatgctgtggtgggcgagaaagcgcct
tatttctgtggagggtttattttgtgtgactccgtgaccggcacagcgtgccgtgtggcagaccccct
aaaaaggctgtttaagcttggcaaacctctggcagcagacgatgaacatgatgatgacaggagaaggg
cattgcatgaagagtcaacacgctggaaccgagtgggtattctttcagagctgtgcaaggcagtagaa
tcaaggtatgaaaccgtaggaacttccatcatagttatggccatgactactctagctagcagtgttaa
atcattcagctacctgagaggggcccctataactctctacggctaacctgaatggactacgacatagt
ctagtcgagtctagtcgacgccaccatgttcgccctggtgctggccgtggtcatcctgcctctgtgga
ccaccgccaacaagagctacgtgacccccacacccgccaccagatccatcggacacatgagcgccctg
ctgagagagtacagcgaccggaacatgagcctgaagctggaagccttctaccccaccggcttcgacga
ggaactgatcaagagcctgcactggggcaacgaccggaagcacgtgttcctcgtgatcgtgaaagtga
accccaccacccacgagggcgacgtcggcctggtcatcttccccaagtacctgctgagcccctaccac
ttcaaggccgagcacagagcccccttccctgctggccgctttggctttctgagccaccctgtgacccc
cgacgtgtcattcttcgacagcagcttcgccccctacctgaccacacagcacctggtggccttcacca
ccttcccccccaatcctctcgtgtggcacctggaaagagccgagacagccgccaccgccgaaagacct
tttggcgtgtccctgctgcccgccagacctaccgtgcccaagaacaccatcctggaacacaaggccca
cttcgccacctgggatgccctggccagacacaccttctttagcgccgaggccatcatcaccaacagca
ccctgagaatccacgtgcccctgttcggcagcgtgtggcccatcagatactgggccacaggcagcgtg
ctgctgaccagcgatagcggcagagtggaagtgaacatcggcgtgggcttcatgagcagcctgatcag
cctgagcagcggcctgcccatcgagctgattgtggtgccccacaccgtgaagctgaacgccgtgacca
gcgacaccacctggttccagctgaacccccctggccctgatcctggccctagttacagagtgtacctg
ctgggcagaggcctggacatgaacttcagcaagcacgccaccgtggacatctgcgcctaccctgagga
aagcctggactacagataccacctgagcatggcccacaccgaggccctgagaatgaccaccaaggccg
accagcacgacatcaacgaggaaagctactaccacattgccgccagaatcgccaccagcatcttcgcc
ctgagcgagatgggccggaccaccgagtactttctgctggacgagatcgtggacgtgcagtaccagct
gaagttcctgaactacatcctgatgcggatcggcgctggcgcccaccctaataccatcagcggcacca
gcgacctgatcttcgccgatcctagccagctgcacgacgagctgagcctgctgttcggccaggtcaaa
cccgccaacgtggactacttcatcagctacgacgaggcccgggaccagctgaaaacagcctacgccct
gtccagaggccaggatcatgtgaacgccctgtccctggccaggcgcgtgatcatgagcatctacaagg
gcctgctggtcaagcagaacctgaacgccaccgagcggcaggccctgttcttcgccagcatgatcctg
ctgaacttcagagagggcctggaaaacagcagccgggtgctggatggcagaaccaccctgctgctgat
gaccagcatgtgcacagccgcccatgccacacaggccgccctgaatatccaggaaggcctggcttacc
tgaaccccagcaagcacatgttcaccatccccaacgtgtacagcccctgcatgggcagcctgagaacc
gacctgaccgaagagatccacgtgatgaacctgctgtccgccatccccaccagacccggactgaatga
ggtgctgcacacccagctggacgagtccgagatcttcgacgccgccttcaagaccatgatgatcttta
ccacctggaccgccaaggacctgcacatcctgcacacacacgtgcccgaggtgttcacatgccaagat
gccgccgctcggaacggcgagtatgtgctgattctgcctgccgtgcagggccacagctacgtgatcac
ccggaacaagccccagcggggcctggtgtatagcctggctgacgtggacgtgtacaaccccatcagcg
tggtgtacctgagcaaggatacctgcgtgtccgagcacggcgtgatcgaaacagtggccctgccccac
cccgacaacctgaaagagtgcctgtactgcggctccgtgttcctgcggtatctgaccaccggcgccat
catggacatcatcatcatcgacagcaaggacaccgagagacagctggccgccatgggcaacagcacca
tcccccccttcaaccccgacatgcacggcgacgatagcaaggccgtgctgctgttccccaacggcacc
gtggtcacactgctgggcttcgagcggagacaggccatcagaatgagcggccagtacctgggcgcctc
tctgggtggtgcctttctggccgtcgtgggctttggcatcatcggctggatgctgtgcggcaacagca
gactgcgcgagtacaacaagatccccctgacctaatctagacgcggccgcatacagcagcaattggca
agctgcttacatagaactcgcggcgattggcatgccgccttaaaatttttattttatttttcttttct
tttccgaatcggattttgtttttaatatttcaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaagg
gtcggcatggcatctccacctcctcgcggtccgacctgggcatccgaaggaggacgcacgtccactcg
gatggctaagggagagccacgtttaaaccagctccaattcgccctatagtgagtcgtattacgcgcgc
tcactggccgtcgttttacaacgtcgtgactgggaaaaccctggcgttacccaacttaatcgccttgc
agcacatccccctttcgccagctggcgtaatagcgaagaggcccgcaccgatcgcccttcccaacagt
tgcgcagcctgaatggcgaatgggacgcgccctgtagcggcgcattaagcgcggcgggtgtggtggtt
acgcgcagcgtgaccgctacacttgccagcgccctagcgcccgctcctttcgctttcttcccttcctt
tctcgccacgttcgccggctttccccgtcaagctctaaatcgggggctccctttagggttccgattta
gtgctttacggcacctcgaccccaaaaaacttgattagggtgatggttcacgtagtgggccatcgccc
tgatagacggtttttcgccctttgacgttggagtccacgttctttaatagtggactcttgttccaaac
tggaacaacactcaaccctatctcggtctattcttttgatttataagggattttgccgatttcggcct
attggttaaaaaatgagctgatttaacaaaaatttaacgcgaattttaacaaaatattaacgcttaca
atttaggtggcacttttcggggaaatgtgcgcggaacccctatttgtttatttttctaaatacattca
aatatgtatccgctcatgagacaataaccctgataaatgcttcaataatattgaaaaaggaagagtat
gagtattcaacatttccgtgtcgcccttattcccttttttgcggcattttgccttcctgtttttgctc
acccagaaacgctggtgaaagtaaaagatgctgaagatcagttgggtgcacgagtgggttacatcgaa
ctggatctcaacagcggtaagatccttgagagttttcgccccgaagaacgttttccaatgatgagcac
ttttaaagttctgctatgtggcgcggtattatcccgtattgacgccgggcaagagcaactcggtcgcc
gcatacactattctcagaatgacttggttgagtactcaccagtcacagaaaagcatcttacggatggc
atgacagtaagagaattatgcagtgctgccataaccatgagtgataacactgcggccaacttacttct
gacaacgatcggaggaccgaaggagctaaccgcttttttgcacaacatgggggatcatgtaactcgcc
ttgatcgttgggaaccggagctgaatgaagccataccaaacgacgagcgtgacaccacgatgcctgta
gcaatggcaacaacgttgcgcaaactattaactggcgaactacttactctagcttcccggcaacaatt
aatagactggatggaggcggataaagttgcaggaccacttctgcgctcggcccttccggctggctggt
ttattgctgataaatctggagccggtgagcgtgggtctcgcggtatcattgcagcactggggccagat
ggtaagccctcccgtatcgtagttatctacacgacggggagtcaggcaactatggatgaacgaaatag
acagatcgctgagataggtgcctcactgattaagcattggtaactgtcagaccaagtttactcatata
tactttagattgatttaaaactteatttttaatttaaaaggatctaggtgaagatcctttttgataat
ctcatgaccaaaatcccttaacgtgagttttcgttccactgagcgtcagaccccgtagaaaagatcaa
aggatcttcttgagatcctttttttctgcgcgtaatctgctgcttgcaaacaaaaaaaccaccgctac
cagcggtggtttgtttgccggatcaagagctaccaactctttttccgaaggtaactggcttcagcaga
gcgcagataccaaatactgttcttctagtgtagccgtagttaggccaccacttcaagaactctgtagc
accgcctacatacctcgctctgctaatcctgttaccagtggctgctgccagtggcgataagtcgtgtc
ttaccgggttggactcaagacgatagttaccggataaggcgcagcggtcgggctgaacggggggttcg
tgcacacagcccagcttggagcgaacgacctacaccgaactgagatacctacagcgtgagctatgaga
aagcgccacgcttcccgaagggagaaaggcggacaggtatccggtaagcggcagggtcggaacaggag
agcgcacgagggagcttccagggggaaacgcctggtatctttatagtcctgtcgggtttcgccacctc
tgacttgagcgtcgatttttgtgatgctcgtcaggggggcggagcctatggaaaaacgccagcaacgc
ggcctttttacggttcctggccttttgctggccttttgctcacatgttctttcctgcgttatcccctg
attctgtggataaccgtattaccgcctttgagtgagctgataccgctcgccgcagccgaacgaccgag
cgcagcgagtcagtgagcgaggaagcggaagagcgcccaatacgcaaaccgcctctccccgcgcgttg
gccgattcattaatgcagctggcacgacaggtttcccgactggaaagcgggcagtgagcgcaacgcaa
ttaatgtgagttagctcactcattaggcaccccaggctttacactttatgctcccggctcgtatgttg
tgtggaattgtgagcggataacaatttcacacaggaaacagctatgaccatgattacgccaagcgcgc
aattaaccctcactaaagggaacaaaagctgggtaccgggcccacgcgtaatacgactcactatag_13258
TABLE-US-00060 VZV VEERep.SGPgL 1.sub.--
ataggcggcgcatgagagaagcccagaccaattacctacccaaaatggagaaagttcacgttgacatc
gaggaagacagcccattcctcagagctttgcagcggagcttcccgcagtttgaggtagaagccaagca
ggtcactgataatgaccatgctaatgccagagcgttttcgcatctggcttcaaaactgatcgaaacgg
aggtggacccatccgacacgatccttgacattggaagtgcgcccgcccgcagaatgtattctaagcac
aagtatcattgtatctgtccgatgagatgtgcggaagatccggacagattgtataagtatgcaactaa
gctgaagaaaaactgtaaggaaataactgataaggaattggacaagaaaatgaaggagctcgccgccg
tcatgagcgaccctgacctggaaactgagactatgtgcctccacgacgacgagtcgtgtcgctacgaa
gggcaagtcgctgtttaccaggatgtatacgcggttgacggaccgacaagtctctatcaccaagccaa
taagggagttagagtcgcctactggataggctttgacaccaccccttttatgtttaagaacttggctg
gagcatatccatcatactctaccaactgggccgacgaaaccgtgttaacggctcgtaacataggccta
tgcagctctgacgttatggagcggtcacgtagagggatgtccattcttagaaagaagtatttgaaacc
atccaacaatgttctattctctgttggctcgaccatctaccacgagaagagggacttactgaggagct
ggcacctgccgtctgtatttcacttacgtggcaagcaaaattacacatgtcggtgtgagactatagtt
agttgcgacgggtacgtcgttaaaagaatagctatcagtccaggcctgtatgggaagccttcaggcta
tgctgctacgatgcaccgcgagggattcttgtgctgcaaagtgacagacacattgaacggggagaggg
tctcttttcccgtgtgcacgtatgtgccagctacattgtgtgaccaaatgactggcatactggcaaca
gatgtcagtgcggacgacgcgcaaaaactgctggttgggctcaaccagcgtatagtcgtcaacggtcg
cacccagagaaacaccaataccatgaaaaattaccttttgcccgtagtggcccaggcatttgctaggt
gggcaaaggaatataaggaagatcaagaagatgaaaggccactaggactacgagatagacagttagtc
atggggtgttgttgggcttttagaaggcacaagataacatctatttataagcgcccggatacccaaac
catcatcaaagtgaacagcgatttccactcattcgtgctgcccaggataggcagtaacacattggaga
tcgggctgagaacaagaatcaggaaaatgttagaggagcacaaggagccgtcacctctcattaccgcc
gaggacgtacaagaagctaagtgcgcagccgatgaggctaaggaggtgcgtgaagccgaggagttgcg
cgcagctctaccacctttggcagctgatgttgaggagcccactctggaagccgatgtagacttgatgt
tacaagaggctggggccggctcagtggagacacctcgtggcttgataaaggttaccagctacgatggc
gaggacaagatcggctcttacgctgtgctttctccgcaggctgtactcaagagtgaaaaattatcttg
catccaccctctcgctgaacaagtcatagtgataacacactctggccgaaaagggcgttatgccgtgg
aaccataccatggtaaagtagtggtgccagagggacatgcaatacccgtccaggactttcaagctctg
agtgaaagtgccaccattgtgtacaacgaacgtgagttcgtaaacaggtacctgcaccatattgccac
acatggaggagcgctgaacactgatgaagaatattacaaaactgtcaagcccagcgagcacgacggcg
aatacctgtacgacatcgacaggaaacagtgcgtcaagaaagaactagtcactgggctagggctcaca
ggcgagctggtggatcctcccttccatgaattcgcctacgagagtctgagaacacgaccagccgctcc
ttaccaagtaccaaccataggggtgtatggcgtgccaggatcaggcaagtctggcatcattaaaagcg
cagtcaccaaaaaagatctagtggtgagcgccaagaaagaaaactgtgcagaaattataagggacgtc
aagaaaatgaaagggctggacgtcaatgccagaactgtggactcagtgctcttgaatggatgcaaaca
ccccgtagagaccctgtatattgacgaagcttttgcttgtcatgcaggtactctcagagcgctcatag
ccattataagacctaaaaaggcagtgctctgcggggatcccaaacagtgcggtttttttaacatgatg
tgcctgaaagtgcattttaaccacgagatttgcacacaagtcttccacaaaagcatctctcgccgttg
cactaaatctgtgacttcggtcgtctcaaccttgttttacgacaaaaaaatgagaacgacgaatccga
aagagactaagattgtgattgacactaccggcagtaccaaacctaagcaggacgatctcattctcact
tgtttcagagggtgggtgaagcagttgcaaatagattacaaaggcaacgaaataatgacggcagctgc
ctctcaagggctgacccgtaaaggtgtgtatgccgttcggtacaaggtgaatgaaaatcctctgtacg
cacccacctcagaacatgtgaacgtcctactgacccgcacggaggaccgcatcgtgtggaaaacacta
gccggcgacccatggataaaaacactgactgccaagtaccctgggaatttcactgccacgatagagga
gtggcaagcagagcatgatgccatcatgaggcacatcttggagagaccggaccctaccgacgtcttcc
agaataaggcaaacgtgtgttgggccaaggctttagtgccggtgctgaagaccgctggcatagacatg
accactgaacaatggaacactgtggattattttgaaacggacaaagctcactcagcagagatagtatt
gaaccaactatgcgtgaggttctttggactcgatctggactccggtctattttctgcacccactgttc
cgttatccattaggaataatcactgggataactccccgtcgcctaacatgtacgggctgaataaagaa
gtggtccgtcagctctctcgcaggtacccacaactgcctcgggcagttgccactggaagagtctatga
catgaacactggtacactgcgcaattatgatccgcgcataaacctagtacctgtaaacagaagactgc
ctcatgctttagtcctccaccataatgaacacccacagagtgacttttcttcattcgtcagcaaattg
aagggcagaactgtcctggtggtcggggaaaagttgtccgtcccaggcaaaatggttgactggttgtc
agaccggcctgaggctaccttcagagctcggctggatttaggcatcccaggtgatgtgcccaaatatg
acataatatttgttaatgtgaggaccccatataaataccatcactatcagcagtgtgaagaccatgcc
attaagcttagcatgttgaccaagaaagcttgtctgcatctgaatcccggcggaacctgtgtcagcat
aggttatggttacgctgacagggccagcgaaagcatcattggtgctatagcgcggcagttcaagtttt
cccgggtatgcaaaccgaaatcctcacttgaagagacggaagttctgtttgtattcattgggtacgat
cgcaaggcccgtacgcacaatccttacaagctttcatcaaccttgaccaacatttatacaggttccag
actccacgaagccggatgtgcaccctcatatcatgtggtgcgaggggatattgccacggccaccgaag
gagtgattataaatgctgctaacagcaaaggacaacctggcggaggggtgtgcggagcgctgtataag
aaattcccggaaagcttcgatttacagccgatcgaagtaggaaaagcgcgactggtcaaaggtgcagc
taaacatatcattcatgccgtaggaccaaacttcaacaaagtttcggaggttgaaggtgacaaacagt
tggcagaggcttatgagtccatcgctaagattgtcaacgataacaattacaagtcagtagcgattcca
ctgttgtccaccggcatcttttccgggaacaaagatcgactaacccaatcattgaaccatttgctgac
agctttagacaccactgatgcagatgtagccatatactgcagggacaagaaatgggaaatgactctca
aggaagcagtggctaggagagaagcagtggaggagatatgcatatccgacgactcttcagtgacagaa
cctgatgcagagctggtgagggtgcatccgaagagttctttggctggaaggaagggctacagcacaag
cgatggcaaaactttctcatatttggaagggaccaagtttcaccaggcggccaaggatatagcagaaa
ttaatgccatgtggcccgttgcaacggaggccaatgagcaggtatgcatgtatatcctcggagaaagc
atgagcagtattaggtcgaaatgccccgtcgaagagtcggaagcctccacaccacctagcacgctgcc
ttgcttgtgcatccatgccatgactccagaaagagtacagcgcctaaaagcctcacgtccagaacaaa
ttactgtgtgctcatcctttccattgccgaagtatagaatcactggtgtgcagaagatccaatgctcc
cagcctatattgttctcaccgaaagtgcctgcgtatattcatccaaggaagtatctcgtggaaacacc
accggtagacgagactccggagccatcggcagagaaccaatccacagaggggacacctgaacaaccac
cacttataaccgaggatgagaccaggactagaacgcctgagccgatcatcatcgaagaggaagaagag
gatagcataagtttgctgtcagatggcccgacccaccaggtgctgcaagtcgaggcagacattcacgg
gccgccctctgtatctagctcatcctggtccattcctcatgcatccgactttgatgtggacagtttat
ccatacttgacaccctggagggagctagcgtgaccagcggggcaacgtcagccgagactaactcttac
ttcgcaaagagtatggagtttctggcgcgaccggtgcctgcgcctcgaacagtattcaggaaccctcc
acatcccgctccgcgcacaagaacaccgtcacttgcacccagcagggcctgctcgagaaccagcctag
tttccaccccgccaggcgtgaatagggtgatcactagagaggagctcgaggcgcttaccccgtcacgc
actcctagcaggtcggtctcgagaaccagcctggtctccaacccgccaggcgtaaatagggtgattac
aagagaggagtttgaggcgttcgtagcacaacaacaatgacggtttgatgcgggtgcatacatctttt
cctccgacaccggtcaagggcatttacaacaaaaatcagtaaggcaaacggtgctatccgaagtggtg
ttggagaggaccgaattggagatttcgtatgccccgcgcctcgaccaagaaaaagaagaattactacg
caagaaattacagttaaatcccacacctgctaacagaagcagataccagtccaggaaggtggagaaca
tgaaagccataacagctagacgtattctgcaaggcctagggcattatttgaaggcagaaggaaaagtg
gagtgctaccgaaccctgcatcctgttcctttgtattcatctagtgtgaaccgtgccttttcaagccc
caaggtcgcagtggaagcctgtaacgccatgttgaaagagaactttccgactgtggcttcttactgta
ttattccagagtacgatgcctatttggacatggttgacggagcttcatgctgcttagacactgccagt
ttttgccctgcaaagctgcgcagctttccaaagaaacactcctatttggaacccacaatacgatcggc
agtgccttcagcgatccagaacacgctccagaacgtcctggcagctgccacaaaaagaaattgcaatg
tcacgcaaatgagagaattgcccgtattggattcggcggcctttaatgtggaatgcttcaagaaatat
gcgtgtaataatgaatattgggaaacgtttaaagaaaaccccatcaggcttactgaagaaaacgtggt
aaattacattaccaaattaaaaggaccaaaagctgctgctctttttgcgaagacacataatttgaata
tgttgcaggacataccaatggacaggtttgtaatggacttaaagagagacgtgaaagtgactccagga
acaaaacatactgaagaacggcccaaggtacaggtgatccaggctgccgatccgctagcaacagcgta
tctgtgcggaatccaccgagagctggttaggagattaaatgcggtcctgcttccgaacattcatacac
tgtttgatatgtcggctgaagactttgacgctattatagccgagcacttccagcctggggattgtgtt
ctggaaactgacatcgcgtcgtttgataaaagtgaggacgacgccatggctctgaccgcgttaatgat
tctggaagacttaggtgtggacgcagagctgttgacgctgattgaggcggctttcggcgaaatttcat
caatacatttgcccactaaaactaaatttaaattcggagccatgatgaaatctggaatgttcctcaca
ctgtttgtgaacacagtcattaacattgtaatcgcaagcagagtgttgagagaacggctaaccggatc
accatgtgcagcattcattggagatgacaatatcgtgaaaggagtcaaatcggacaaattaatggcag
acaggtgcgccacctggttgaatatggaagtcaagattatagatgctgtggtgggcgagaaagcgcct
tatttctgtggagggtttattttgtgtgactccgtgaccggcacagcgtgccgtgtggcagaccccct
aaaaaggctgtttaagcttggcaaacctctggcagcagacgatgaacatgatgatgacaggagaaggg
cattgcatgaagagtcaacacgctggaaccgagtgggtattctttcagagctgtgcaaggcagtagaa
tcaaggtatgaaaccgtaggaacttccatcatagttatggccatgactactctagctagcagtgttaa
atcattcagctacctgagaggggcccctataactctctacggctaacctgaatggactacgacatagt
ctagtcgagtctagtcgacgccaccatggccagccacaagtggctgctgcagatgatcgtgttcctga
aaaccatcacaatcgcctactgcctgcatctgcaggacgacacccctctgttcttcggcgccaagcct
ctgagcgacgtgtccctgatcatcaccgagccttgcgtgtccagcgtgtacgaggcctgggattatgc
cgcccctcccgtgtccaatctgagcgaagccctgagcggcatcgtggtcaagaccaagtgccccgtgc
ccgaagtgatcctgtggttcaaggacaagcagatggcctactggaccaacccttacgtgaccctgaag
ggcctgacccagagcgtgggcgaggaacacaagagcggcgacatcagagatgccctgctggatgccct
gtccggtgtctgggtggacagcacaccctccagcaccaacatccccgagaacggctgtgtgtggggag
ccgaccggctgttccagagagtgtgtcagtaatctagacgcggccgcatacagcagcaattggcaagc
tgcttacatagaactcgcggcgattggcatgccgccttaaaatttttattttatttttcttttctttt
ccgaatcggattttgtttttaatatttcaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaagggtc
ggcatggcatctccacctcctcgcggtccgacctgggcatccgaaggaggacgcacgtccactcggat
ggctaagggagagccacgtttaaaccagctccaattcgccctatagtgagtcgtattacgcgcgctca
ctggccgtcgttttacaacgtcgtgactgggaaaaccctggcgttacccaacttaatcgccttgcagc
acatccccctttcgccagctggcgtaatagcgaagaggcccgcaccgatcgcccttcccaacagttgc
gcagcctgaatggcgaatgggacgcgccctgtagcggcgcattaagcgcggcgggtgtggtggttacg
cgcagcgtgaccgctacacttgccagcgccctagcgcccgctcctttcgctttcttcccttcctttct
cgccacgttcgccggctttccccgtcaagctctaaatcgggggctccctttagggttccgatttagtg
ctttacggcacctcgaccccaaaaaacttgattagggtgatggttcacgtagtgggccatcgccctga
tagacggtttttcgccctttgacgttggagtccacgttctttaatagtggactcttgttccaaactgg
aacaacactcaaccctatctcggtctattcttttgatttataagggattttgccgatttcggcctatt
ggttaaaaaatgagctgatttaacaaaaatttaacgcgaattttaacaaaatattaacgcttacaatt
taggtggcacttttcggggaaatgtgcgcggaacccctatttgtttatttttctaaatacattcaaat
atgtatccgctcatgagacaataaccctgataaatgcttcaataatattgaaaaaggaagagtatgag
tattcaacatttccgtgtcgcccttattcccttttttgcggcattttgccttcctgtttttgctcacc
cagaaacgctggtgaaagtaaaagatgctgaagatcagttgggtgcacgagtgggttacatcgaactg
gatctcaacagcggtaagatccttgagagttttcgccccgaagaacgttttccaatgatgagcacttt
taaagttctgctatgtggcgcggtattatcccgtattgacgccgggcaagagcaactcggtcgccgca
tacactattctcagaatgacttggttgagtactcaccagtcacagaaaagcatcttacggatggcatg
acagtaagagaattatgcagtgctgccataaccatgagtgataacactgcggccaacttacttctgac
aacgatcggaggaccgaaggagctaaccgcttttttgcacaacatgggggatcatgtaactcgccttg
atcgttgggaaccggagctgaatgaagccataccaaacgacgagcgtgacaccacgatgcctgtagca
atggcaacaacgttgcgcaaactattaactggcgaactacttactctagcttcccggcaacaattaat
agactggatggaggcggataaagttgcaggaccacttctgcgctcggcccttccggctggctggttta
ttgctgataaatctggagccggtgagcgtgggtctcgcggtatcattgcagcactggggccagatggt
aagccctcccgtatcgtagttatctacacgacggggagtcaggcaactatggatgaacgaaatagaca
gatcgctgagataggtgcctcactgattaagcattggtaactgtcagaccaagtttactcatatatac
tttagattgatttaaaacttcatttttaatttaaaaggatctaggtgaagatcctttttgataatctc
atgaccaaaatcccttaacgtgagttttcgttccactgagcgtcagaccccgtagaaaagatcaaagg
atcttcttgagatcctttttttctgcgcgtaatctgctgcttgcaaacaaaaaaaccaccgctaccag
cggtggtttgtttgccggatcaagagctaccaactctttttccgaaggtaactggcttcagcagagcg
cagataccaaatactgttcttctagtgtagccgtagttaggccaccacttcaagaactctgtagcacc
gcctacatacctcgctctgctaatcctgttaccagtggctgctgccagtggcgataagtcgtgtctta
ccgggttggactcaagacgatagttaccggataaggcgcagcggtcgggctgaacggggggttcgtgc
acacagcccagcttggagcgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaag
cgccacgcttcccgaagggagaaaggcggacaggtatccggtaagcggcagggtcggaacaggagagc
gcacgagggagcttccagggggaaacgcctggtatctttatagtcctgtcgggtttcgccacctctga
cttgagcgtcgatttttgtgatgctcgtcaggggggcggagcctatggaaaaacgccagcaacgcggc
ctttttacggttcctggccttttgctggccttttgctcacatgttctttcctgcgttatcccctgatt
ctgtggataaccgtattaccgcctttgagtgagctgataccgctcgccgcagccgaacgaccgagcgc
agcgagtcagtgagcgaggaagcggaagagcgcccaatacgcaaaccgcctctccccgcgcgttggcc
gattcattaatgcagctggcacgacaggtttcccgactggaaagcgggcagtgagcgcaacgcaatta
atgtgagttagctcactcattaggcaccccaggctttacactttatgctcccggctcgtatgttgtgt
ggaattgtgagcggataacaatttcacacaggaaacagctatgaccatgattacgccaagcgcgcaat
taaccctcactaaagggaacaaaagctgggtaccgggcccacgcgtaatacgactcactatag_11215
TABLE-US-00061 VZV VEERep.SGPgH-SGPgL 1.sub.--
ataggcggcgcatgagagaagcccagaccaattacctacccaaaatggagaaagttcacgttgacatc
gaggaagacagcccattcctcagagctttgcagcggagcttcccgcagtttgaggtagaagccaagca
ggtcactgataatgaccatgctaatgccagagcgttttcgcatctggcttcaaaactgatcgaaacgg
aggtggacccatccgacacgatccttgacattggaagtgcgcccgcccgcagaatgtattctaagcac
aagtatcattgtatctgtccgatgagatgtgcggaagatccggacagattgtataagtatgcaactaa
gctgaagaaaaactgtaaggaaataactgataaggaattggacaagaaaatgaaggagctcgccgccg
tcatgagcgaccctgacctggaaactgagactatgtgcctccacgacgacgagtcgtgtcgctacgaa
gggcaagtcgctgtttaccaggatgtatacgcggttgacggaccgacaagtctctatcaccaagccaa
taagggagttagagtcgcctactggataggctttgacaccaccccttttatgtttaagaacttggctg
gagcatatccatcatactctaccaactgggccgacgaaaccgtgttaacggctcgtaacataggccta
tgcagctctgacgttatggagcggtcacgtagagggatgtccattcttagaaagaagtatttgaaacc
atccaacaatgttctattctctgttggctcgaccatctaccacgagaagagggacttactgaggagct
ggcacctgccgtctgtatttcacttacgtggcaagcaaaattacacatgtcggtgtgagactatagtt
agttgcgacgggtacgtcgttaaaagaatagctatcagtccaggcctgtatgggaagccttcaggcta
tgctgctacgatgcaccgcgagggattcttgtgctgcaaagtgacagacacattgaacggggagaggg
tctcttttcccgtgtgcacgtatgtgccagctacattgtgtgaccaaatgactggcatactggcaaca
gatgtcagtgcggacgacgcgcaaaaactgctggttgggctcaaccagcgtatagtcgtcaacggtcg
cacccagagaaacaccaataccatgaaaaattaccttttgcccgtagtggcccaggcatttgctaggt
gggcaaaggaatataaggaagatcaagaagatgaaaggccactaggactacgagatagacagttagtc
atggggtgttgttgggcttttagaaggcacaagataacatctatttataagcgcccggatacccaaac
catcatcaaagtgaacagcgatttccactcattcgtgctgcccaggataggcagtaacacattggaga
tcgggctgagaacaagaatcaggaaaatgttagaggagcacaaggagccgtcacctctcattaccgcc
gaggacgtacaagaagctaagtgcgcagccgatgaggctaaggaggtgcgtgaagccgaggagttgcg
cgcagctctaccacctttggcagctgatgttgaggagcccactctggaagccgatgtagacttgatgt
tacaagaggctggggccggctcagtggagacacctcgtggcttgataaaggttaccagctacgatggc
gaggacaagatcggctcttacgctgtgctttctccgcaggctgtactcaagagtgaaaaattatcttg
catccaccctctcgctgaacaagtcatagtgataacacactctggccgaaaagggcgttatgccgtgg
aaccataccatggtaaagtagtggtgccagagggacatgcaatacccgtccaggactttcaagctctg
agtgaaagtgccaccattgtgtacaacgaacgtgagttcgtaaacaggtacctgcaccatattgccac
acatggaggagcgctgaacactgatgaagaatattacaaaactgtcaagcccagcgagcacgacggcg
aatacctgtacgacatcgacaggaaacagtgcgtcaagaaagaactagtcactgggctagggctcaca
ggcgagctggtggatcctcccttccatgaattcgcctacgagagtctgagaacacgaccagccgctcc
ttaccaagtaccaaccataggggtgtatggcgtgccaggatcaggcaagtctggcatcattaaaagcg
cagtcaccaaaaaagatctagtggtgagcgccaagaaagaaaactgtgcagaaattataagggacgtc
aagaaaatgaaagggctggacgtcaatgccagaactgtggactcagtgctcttgaatggatgcaaaca
ccccgtagagaccctgtatattgacgaagcttttgcttgtcatgcaggtactctcagagcgctcatag
ccattataagacctaaaaaggcagtgctctgcggggatcccaaacagtgcggtttttttaacatgatg
tgcctgaaagtgcattttaaccacgagatttgcacacaagtcttccacaaaagcatctctcgccgttg
cactaaatctgtgacttcggtcgtctcaaccttgttttacgacaaaaaaatgagaacgacgaatccga
aagagactaagattgtgattgacactaccggcagtaccaaacctaagcaggacgatctcattctcact
tgtttcagagggtgggtgaagcagttgcaaatagattacaaaggcaacgaaataatgacggcagctgc
ctctcaagggctgacccgtaaaggtgtgtatgccgttcggtacaaggtgaatgaaaatcctctgtacg
cacccacctcagaacatgtgaacgtcctactgacccgcacggaggaccgcatcgtgtggaaaacacta
gccggcgacccatggataaaaacactgactgccaagtaccctgggaatttcactgccacgatagagga
gtggcaagcagagcatgatgccatcatgaggcacatcttggagagaccggaccctaccgacgtcttcc
agaataaggcaaacgtgtgttgggccaaggctttagtgccggtgctgaagaccgctggcatagacatg
accactgaacaatggaacactgtggattattttgaaacggacaaagctcactcagcagagatagtatt
gaaccaactatgcgtgaggttctttggactcgatctggactccggtctattttctgcacccactgttc
cgttatccattaggaataatcactgggataactccccgtcgcctaacatgtacgggctgaataaagaa
gtggtccgtcagctctctcgcaggtacccacaactgcctcgggcagttgccactggaagagtctatga
catgaacactggtacactgcgcaattatgatccgcgcataaacctagtacctgtaaacagaagactgc
ctcatgctttagtcctccaccataatgaacacccacagagtgacttttcttcattcgtcagcaaattg
aagggcagaactgtcctggtggtcggggaaaagttgtccgtcccaggcaaaatggttgactggttgtc
agaccggcctgaggctaccttcagagctcggctggatttaggcatcccaggtgatgtgcccaaatatg
acataatatttgttaatgtgaggaccccatataaataccatcactatcagcagtgtgaagaccatgcc
attaagcttagcatgttgaccaagaaagcttgtctgcatctgaatcccggcggaacctgtgtcagcat
aggttatggttacgctgacagggccagcgaaagcatcattggtgctatagcgcggcagttcaagtttt
cccgggtatgcaaaccgaaatcctcacttgaagagacggaagttctgtttgtattcattgggtacgat
cgcaaggcccgtacgcacaatccttacaagctttcatcaaccttgaccaacatttatacaggttccag
actccacgaagccggatgtgcaccctcatatcatgtggtgcgaggggatattgccacggccaccgaag
gagtgattataaatgctgctaacagcaaaggacaacctggcggaggggtgtgcggagcgctgtataag
aaattcccggaaagcttcgatttacagccgatcgaagtaggaaaagcgcgactggtcaaaggtgcagc
taaacatatcattcatgccgtaggaccaaacttcaacaaagtttcggaggttgaaggtgacaaacagt
tggcagaggcttatgagtccatcgctaagattgtcaacgataacaattacaagtcagtagcgattcca
ctgttgtccaccggcatcttttccgggaacaaagatcgactaacccaatcattgaaccatttgctgac
agctttagacaccactgatgcagatgtagccatatactgcagggacaagaaatgggaaatgactctca
aggaagcagtggctaggagagaagcagtggaggagatatgcatatccgacgactcttcagtgacagaa
cctgatgcagagctggtgagggtgcatccgaagagttctttggctggaaggaagggctacagcacaag
cgatggcaaaactttctcatatttggaagggaccaagtttcaccaggcggccaaggatatagcagaaa
ttaatgccatgtggcccgttgcaacggaggccaatgagcaggtatgcatgtatatcctcggagaaagc
atgagcagtattaggtcgaaatgccccgtcgaagagtcggaagcctccacaccacctagcacgctgcc
ttgcttgtgcatccatgccatgactccagaaagagtacagcgcctaaaagcctcacgtccagaacaaa
ttactgtgtgctcatcctttccattgccgaagtatagaatcactggtgtgcagaagatccaatgctcc
cagcctatattgttctcaccgaaagtgcctgcgtatattcatccaaggaagtatctcgtggaaacacc
accggtagacgagactccggagccatcggcagagaaccaatccacagaggggacacctgaacaaccac
cacttataaccgaggatgagaccaggactagaacgcctgagccgatcatcatcgaagaggaagaagag
gatagcataagtttgctgtcagatggcccgacccaccaggtgctgcaagtcgaggcagacattcacgg
gccgccctctgtatctagctcatcctggtccattcctcatgcatccgactttgatgtggacagtttat
ccatacttgacaccctggagggagctagcgtgaccagcggggcaacgtcagccgagactaactcttac
ttcgcaaagagtatggagtttctggcgcgaccggtgcctgcgcctcgaacagtattcaggaaccctcc
acatcccgctccgcgcacaagaacaccgtcacttgcacccagcagggcctgctcgagaaccagcctag
tttccaccccgccaggcgtgaatagggtgatcactagagaggagctcgaggcgcttaccccgtcacgc
actcctagcaggtcggtctcgagaaccagcctggtctccaacccgccaggcgtaaatagggtgattac
aagagaggagtttgaggcgttcgtagcacaacaacaatgacggtttgatgcgggtgcatacatctttt
cctccgacaccggtcaagggcatttacaacaaaaatcagtaaggcaaacggtgctatccgaagtggtg
ttggagaggaccgaattggagatttcgtatgccccgcgcctcgaccaagaaaaagaagaattactacg
caagaaattacagttaaatcccacacctgctaacagaagcagataccagtccaggaaggtggagaaca
tgaaagccataacagctagacgtattctgcaaggcctagggcattatttgaaggcagaaggaaaagtg
gagtgctaccgaaccctgcatcctgttcctttgtattcatctagtgtgaaccgtgccttttcaagccc
caaggtcgcagtggaagcctgtaacgccatgttgaaagagaactttccgactgtggcttcttactgta
ttattccagagtacgatgcctatttggacatggttgacggagcttcatgctgcttagacactgccagt
ttttgccctgcaaagctgcgcagctttccaaagaaacactcctatttggaacccacaatacgatcggc
agtgccttcagcgatccagaacacgctccagaacgtcctggcagctgccacaaaaagaaattgcaatg
tcacgcaaatgagagaattgcccgtattggattcggcggcctttaatgtggaatgcttcaagaaatat
gcgtgtaataatgaatattgggaaacgtttaaagaaaaccccatcaggcttactgaagaaaacgtggt
aaattacattaccaaattaaaaggaccaaaagctgctgctctttttgcgaagacacataatttgaata
tgttgcaggacataccaatggacaggtttgtaatggacttaaagagagacgtgaaagtgactccagga
acaaaacatactgaagaacggcccaaggtacaggtgatccaggctgccgatccgctagcaacagcgta
tctgtgcggaatccaccgagagctggttaggagattaaatgcggtcctgcttccgaacattcatacac
tgtttgatatgtcggctgaagactttgacgctattatagccgagcacttccagcctggggattgtgtt
ctggaaactgacatcgcgtcgtttgataaaagtgaggacgacgccatggctctgaccgcgttaatgat
tctggaagacttaggtgtggacgcagagctgttgacgctgattgaggcggctttcggcgaaatttcat
caatacatttgcccactaaaactaaatttaaattcggagccatgatgaaatctggaatgttcctcaca
ctgtttgtgaacacagtcattaacattgtaatcgcaagcagagtgttgagagaacggctaaccggatc
accatgtgcagcattcattggagatgacaatatcgtgaaaggagtcaaatcggacaaattaatggcag
acaggtgcgccacctggttgaatatggaagtcaagattatagatgctgtggtgggcgagaaagcgcct
tatttctgtggagggtttattttgtgtgactccgtgaccggcacagcgtgccgtgtggcagaccccct
aaaaaggctgtttaagcttggcaaacctctggcagcagacgatgaacatgatgatgacaggagaaggg
cattgcatgaagagtcaacacgctggaaccgagtgggtattctttcagagctgtgcaaggcagtagaa
tcaaggtatgaaaccgtaggaacttccatcatagttatggccatgactactctagctagcagtgttaa
atcattcagctacctgagaggggcccctataactctctacggctaacctgaatggactacgacatagt
ctagtcgagtctagtcgacgccaccatgttcgccctggtgctggccgtggtcatcctgcctctgtgga
ccaccgccaacaagagctacgtgacccccacacccgccaccagatccatcggacacatgagcgccctg
ctgagagagtacagcgaccggaacatgagcctgaagctggaagccttctaccccaccggcttcgacga
ggaactgatcaagagcctgcactggggcaacgaccggaagcacgtgttcctcgtgatcgtgaaagtga
accccaccacccacgagggcgacgtcggcctggtcatcttccccaagtacctgctgagcccctaccac
ttcaaggccgagcacagagcccccttccctgctggccgctttggctttctgagccaccctgtgacccc
cgacgtgtcattcttcgacagcagcttcgccccctacctgaccacacagcacctggtggccttcacca
ccttcccccccaatcctctcgtgtggcacctggaaagagccgagacagccgccaccgccgaaagacct
tttggcgtgtccctgctgcccgccagacctaccgtgcccaagaacaccatcctggaacacaaggccca
cttcgccacctgggatgccctggccagacacaccttctttagcgccgaggccatcatcaccaacagca
ccctgagaatccacgtgcccctgttcggcagcgtgtggcccatcagatactgggccacaggcagcgtg
ctgctgaccagcgatagcggcagagtggaagtgaacatcggcgtgggcttcatgagcagcctgatcag
cctgagcagcggcctgcccatcgagctgattgtggtgccccacaccgtgaagctgaacgccgtgacca
gcgacaccacctggttccagctgaacccccctggccctgatcctggccctagttacagagtgtacctg
ctgggcagaggcctggacatgaacttcagcaagcacgccaccgtggacatctgcgcctaccctgagga
aagcctggactacagataccacctgagcatggcccacaccgaggccctgagaatgaccaccaaggccg
accagcacgacatcaacgaggaaagctactaccacattgccgccagaatcgccaccagcatcttcgcc
ctgagcgagatgggccggaccaccgagtactttctgctggacgagatcgtggacgtgcagtaccagct
gaagttcctgaactacatcctgatgcggatcggcgctggcgcccaccctaataccatcagcggcacca
gcgacctgatcttcgccgatcctagccagctgcacgacgagctgagcctgctgttcggccaggtcaaa
cccgccaacgtggactacttcatcagctacgacgaggcccgggaccagctgaaaacagcctacgccct
gtccagaggccaggatcatgtgaacgccctgtccctggccaggcgcgtgatcatgagcatctacaagg
gcctgctggtcaagcagaacctgaacgccaccgagcggcaggccctgttcttcgccagcatgatcctg
ctgaacttcagagagggcctggaaaacagcagccgggtgctggatggcagaaccaccctgctgctgat
gaccagcatgtgcacagccgcccatgccacacaggccgccctgaatatccaggaaggcctggcttacc
tgaaccccagcaagcacatgttcaccatccccaacgtgtacagcccctgcatgggcagcctgagaacc
gacctgaccgaagagatccacgtgatgaacctgctgtccgccatccccaccagacccggactgaatga
ggtgctgcacacccagctggacgagtccgagatcttcgacgccgccttcaagaccatgatgatcttta
ccacctggaccgccaaggacctgcacatcctgcacacacacgtgcccgaggtgttcacatgccaagat
gccgccgctcggaacggcgagtatgtgctgattctgcctgccgtgcagggccacagctacgtgatcac
ccggaacaagccccagcggggcctggtgtatagcctggctgacgtggacgtgtacaaccccatcagcg
tggtgtacctgagcaaggatacctgcgtgtccgagcacggcgtgatcgaaacagtggccctgccccac
cccgacaacctgaaagagtgcctgtactgcggctccgtgttcctgcggtatctgaccaccggcgccat
catggacatcatcatcatcgacagcaaggacaccgagagacagctggccgccatgggcaacagcacca
tcccccccttcaaccccgacatgcacggcgacgatagcaaggccgtgctgctgttccccaacggcacc
gtggtcacactgctgggcttcgagcggagacaggccatcagaatgagcggccagtacctgggcgcctc
tctgggtggtgcctttctggccgtcgtgggctttggcatcatcggctggatgctgtgcggcaacagca
gactgcgcgagtacaacaagatccccctgacctaatctagacgtcgcgaccacccaggatccgcctat
aactctctacggctaacctgaatggactacgacatagtctagtcgacgccaccatggccagccacaag
tggctgctgcagatgatcgtgttcctgaaaaccatcacaatcgcctactgcctgcatctgcaggacga
cacccctctgttcttcggcgccaagcctctgagcgacgtgtccctgatcatcaccgagccttgcgtgt
ccagcgtgtacgaggcctgggattatgccgcccctcccgtgtccaatctgagcgaagccctgagcggc
atcgtggtcaagaccaagtgccccgtgcccgaagtgatcctgtggttcaaggacaagcagatggccta
ctggaccaacccttacgtgaccctgaagggcctgacccagagcgtgggcgaggaacacaagagcggcg
acatcagagatgccctgctggatgccctgtccggtgtctgggtggacagcacaccctccagcaccaac
atccccgagaacggctgtgtgtggggagccgaccggctgttccagagagtgtgtcagtaatctagacg
cggccgcatacagcagcaattggcaagctgcttacatagaactcgcggcgattggcatgccgccttaa
aatttttattttatttttcttttcttttccgaatcggattttgtttttaatatttcaaaaaaaaaaaa
aaaaaaaaaaaaaaaaaaaaaaagggtcggcatggcatctccacctcctcgcggtccgacctgggcat
ccgaaggaggacgcacgtccactcggatggctaagggagagccacgtttaaaccagctccaattcgcc
ctatagtgagtcgtattacgcgcgctcactggccgtcgttttacaacgtcgtgactgggaaaaccctg
gcgttacccaacttaatcgccttgcagcacatccccctttcgccagctggcgtaatagcgaagaggcc
cgcaccgatcgcccttcccaacagttgcgcagcctgaatggcgaatgggacgcgccctgtagcggcgc
attaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacacttgccagcgccctagcgcccg
ctcctttcgctttcttcccttcctttctcgccacgttcgccggctttccccgtcaagctctaaatcgg
gggctccctttagggttccgatttagtgctttacggcacctcgaccccaaaaaacttgattagggtga
tggttcacgtagtgggccatcgccctgatagacggtttttcgccctttgacgttggagtccacgttct
ttaatagtggactcttgttccaaactggaacaacactcaaccctatctcggtctattcttttgattta
taagggattttgccgatttcggcctattggttaaaaaatgagctgatttaacaaaaatttaacgcgaa
ttttaacaaaatattaacgcttacaatttaggtggcacttttcggggaaatgtgcgcggaacccctat
ttgtttatttttctaaatacattcaaatatgtatccgctcatgagacaataaccctgataaatgcttc
aataatattgaaaaaggaagagtatgagtattcaacatttccgtgtcgcccttattcccttttttgcg
gcattttgccttcctgtttttgctcacccagaaacgctggtgaaagtaaaagatgctgaagatcagtt
gggtgcacgagtgggttacatcgaactggatctcaacagcggtaagatccttgagagttttcgccccg
aagaacgttttccaatgatgagcacttttaaagttctgctatgtggcgcggtattatcccgtattgac
gccgggcaagagcaactcggtcgccgcatacactattctcagaatgacttggttgagtactcaccagt
cacagaaaagcatcttacggatggcatgacagtaagagaattatgcagtgctgccataaccatgagtg
ataacactgcggccaacttacttctgacaacgatcggaggaccgaaggagctaaccgcttttttgcac
aacatgggggatcatgtaactcgccttgatcgttgggaaccggagctgaatgaagccataccaaacga
cgagcgtgacaccacgatgcctgtagcaatggcaacaacgttgcgcaaactattaactggcgaactac
ttactctagcttcccggcaacaattaatagactggatggaggcggataaagttgcaggaccacttctg
cgctcggcccttccggctggctggtttattgctgataaatctggagccggtgagcgtgggtctcgcgg
tatcattgcagcactggggccagatggtaagccctcccgtatcgtagttatctacacgacggggagtc
aggcaactatggatgaacgaaatagacagatcgctgagataggtgcctcactgattaagcattggtaa
ctgtcagaccaagtttactcatatatactttagattgatttaaaacttcatttttaatttaaaaggat
ctaggtgaagatcctttttgataatctcatgaccaaaatcccttaacgtgagttttcgttccactgag
cgtcagaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaatctgctgc
ttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctttt
tccgaaggtaactggcttcagcagagcgcagataccaaatactgttcttctagtgtagccgtagttag
gccaccacttcaagaactctgtagcaccgcctacatacctcgctctgctaatcctgttaccagtggct
gctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgca
gcggtcgggctgaacggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactga
gatacctacagcgtgagctatgagaaagcgccacgcttcccgaagggagaaaggcggacaggtatccg
gtaagcggcagggtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatcttta
tagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtcaggggggcgga
gcctatggaaaaacgccagcaacgcggcctttttacggttcctggccttttgctggccttttgctcac
atgttctttcctgcgttatcccctgattctgtggataaccgtattaccgcctttgagtgagctgatac
cgctcgccgcagccgaacgaccgagcgcagcgagtcagtgagcgaggaagcggaagagcgcccaatac
gcaaaccgcctctccccgcgcgttggccgattcattaatgcagctggcacgacaggtttcccgactgg
aaagcgggcagtgagcgcaacgcaattaatgtgagttagctcactcattaggcaccccaggctttaca
ctttatgctcccggctcgtatgttgtgtggaattgtgagcggataacaatttcacacaggaaacagct
atgaccatgattacgccaagcgcgcaattaaccctcactaaagggaacaaaagctgggtaccgggccc
acgcgtaatacgactcactatag_13827
TABLE-US-00062 VZV VEERep.SGPgE 1.sub.--
ataggcggcgcatgagagaagcccagaccaattacctacccaaaatggagaaagttcacgttgacatc
gaggaagacagcccattcctcagagctttgcagcggagcttcccgcagtttgaggtagaagccaagca
ggtcactgataatgaccatgctaatgccagagcgttttcgcatctggcttcaaaactgatcgaaacgg
aggtggacccatccgacacgatccttgacattggaagtgcgcccgcccgcagaatgtattctaagcac
aagtatcattgtatctgtccgatgagatgtgcggaagatccggacagattgtataagtatgcaactaa
gctgaagaaaaactgtaaggaaataactgataaggaattggacaagaaaatgaaggagctcgccgccg
tcatgagcgaccctgacctggaaactgagactatgtgcctccacgacgacgagtcgtgtcgctacgaa
gggcaagtcgctgtttaccaggatgtatacgcggttgacggaccgacaagtctctatcaccaagccaa
taagggagttagagtcgcctactggataggctttgacaccaccccttttatgtttaagaacttggctg
gagcatatccatcatactctaccaactgggccgacgaaaccgtgttaacggctcgtaacataggccta
tgcagctctgacgttatggagcggtcacgtagagggatgtccattcttagaaagaagtatttgaaacc
atccaacaatgttctattctctgttggctcgaccatctaccacgagaagagggacttactgaggagct
ggcacctgccgtctgtatttcacttacgtggcaagcaaaattacacatgtcggtgtgagactatagtt
agttgcgacgggtacgtcgttaaaagaatagctatcagtccaggcctgtatgggaagccttcaggcta
tgctgctacgatgcaccgcgagggattcttgtgctgcaaagtgacagacacattgaacggggagaggg
tctcttttcccgtgtgcacgtatgtgccagctacattgtgtgaccaaatgactggcatactggcaaca
gatgtcagtgcggacgacgcgcaaaaactgctggttgggctcaaccagcgtatagtcgtcaacggtcg
cacccagagaaacaccaataccatgaaaaattaccttttgcccgtagtggcccaggcatttgctaggt
gggcaaaggaatataaggaagatcaagaagatgaaaggccactaggactacgagatagacagttagtc
atggggtgttgttgggcttttagaaggcacaagataacatctatttataagcgcccggatacccaaac
catcatcaaagtgaacagcgatttccactcattcgtgctgcccaggataggcagtaacacattggaga
tcgggctgagaacaagaatcaggaaaatgttagaggagcacaaggagccgtcacctctcattaccgcc
gaggacgtacaagaagctaagtgcgcagccgatgaggctaaggaggtgcgtgaagccgaggagttgcg
cgcagctctaccacctttggcagctgatgttgaggagcccactctggaagccgatgtagacttgatgt
tacaagaggctggggccggctcagtggagacacctcgtggcttgataaaggttaccagctacgatggc
gaggacaagatcggctcttacgctgtgctttctccgcaggctgtactcaagagtgaaaaattatcttg
catccaccctctcgctgaacaagtcatagtgataacacactctggccgaaaagggcgttatgccgtgg
aaccataccatggtaaagtagtggtgccagagggacatgcaatacccgtccaggactttcaagctctg
agtgaaagtgccaccattgtgtacaacgaacgtgagttcgtaaacaggtacctgcaccatattgccac
acatggaggagcgctgaacactgatgaagaatattacaaaactgtcaagcccagcgagcacgacggcg
aatacctgtacgacatcgacaggaaacagtgcgtcaagaaagaactagtcactgggctagggctcaca
ggcgagctggtggatcctcccttccatgaattcgcctacgagagtctgagaacacgaccagccgctcc
ttaccaagtaccaaccataggggtgtatggcgtgccaggatcaggcaagtctggcatcattaaaagcg
cagtcaccaaaaaagatctagtggtgagcgccaagaaagaaaactgtgcagaaattataagggacgtc
aagaaaatgaaagggctggacgtcaatgccagaactgtggactcagtgctcttgaatggatgcaaaca
ccccgtagagaccctgtatattgacgaagcttttgcttgtcatgcaggtactctcagagcgctcatag
ccattataagacctaaaaaggcagtgctctgcggggatcccaaacagtgcggtttttttaacatgatg
tgcctgaaagtgcattttaaccacgagatttgcacacaagtcttccacaaaagcatctctcgccgttg
cactaaatctgtgacttcggtcgtctcaaccttgttttacgacaaaaaaatgagaacgacgaatccga
aagagactaagattgtgattgacactaccggcagtaccaaacctaagcaggacgatctcattctcact
tgtttcagagggtgggtgaagcagttgcaaatagattacaaaggcaacgaaataatgacggcagctgc
ctctcaagggctgacccgtaaaggtgtgtatgccgttcggtacaaggtgaatgaaaatcctctgtacg
cacccacctcagaacatgtgaacgtcctactgacccgcacggaggaccgcatcgtgtggaaaacacta
gccggcgacccatggataaaaacactgactgccaagtaccctgggaatttcactgccacgatagagga
gtggcaagcagagcatgatgccatcatgaggcacatcttggagagaccggaccctaccgacgtcttcc
agaataaggcaaacgtgtgttgggccaaggctttagtgccggtgctgaagaccgctggcatagacatg
accactgaacaatggaacactgtggattattttgaaacggacaaagctcactcagcagagatagtatt
gaaccaactatgcgtgaggttctttggactcgatctggactccggtctattttctgcacccactgttc
cgttatccattaggaataatcactgggataactccccgtcgcctaacatgtacgggctgaataaagaa
gtggtccgtcagctctctcgcaggtacccacaactgcctcgggcagttgccactggaagagtctatga
catgaacactggtacactgcgcaattatgatccgcgcataaacctagtacctgtaaacagaagactgc
ctcatgctttagtcctccaccataatgaacacccacagagtgacttttcttcattcgtcagcaaattg
aagggcagaactgtcctggtggtcggggaaaagttgtccgtcccaggcaaaatggttgactggttgtc
agaccggcctgaggctaccttcagagctcggctggatttaggcatcccaggtgatgtgcccaaatatg
acataatatttgttaatgtgaggaccccatataaataccatcactatcagcagtgtgaagaccatgcc
attaagcttagcatgttgaccaagaaagcttgtctgcatctgaatcccggcggaacctgtgtcagcat
aggttatggttacgctgacagggccagcgaaagcatcattggtgctatagcgcggcagttcaagtttt
cccgggtatgcaaaccgaaatcctcacttgaagagacggaagttctgtttgtattcattgggtacgat
cgcaaggcccgtacgcacaatccttacaagctttcatcaaccttgaccaacatttatacaggttccag
actccacgaagccggatgtgcaccctcatatcatgtggtgcgaggggatattgccacggccaccgaag
gagtgattataaatgctgctaacagcaaaggacaacctggcggaggggtgtgcggagcgctgtataag
aaattcccggaaagcttcgatttacagccgatcgaagtaggaaaagcgcgactggtcaaaggtgcagc
taaacatatcattcatgccgtaggaccaaacttcaacaaagtttcggaggttgaaggtgacaaacagt
tggcagaggcttatgagtccatcgctaagattgtcaacgataacaattacaagtcagtagcgattcca
ctgttgtccaccggcatcttttccgggaacaaagatcgactaacccaatcattgaaccatttgctgac
agctttagacaccactgatgcagatgtagccatatactgcagggacaagaaatgggaaatgactctca
aggaagcagtggctaggagagaagcagtggaggagatatgcatatccgacgactcttcagtgacagaa
cctgatgcagagctggtgagggtgcatccgaagagttctttggctggaaggaagggctacagcacaag
cgatggcaaaactttctcatatttggaagggaccaagtttcaccaggcggccaaggatatagcagaaa
ttaatgccatgtggcccgttgcaacggaggccaatgagcaggtatgcatgtatatcctcggagaaagc
atgagcagtattaggtcgaaatgccccgtcgaagagtcggaagcctccacaccacctagcacgctgcc
ttgcttgtgcatccatgccatgactccagaaagagtacagcgcctaaaagcctcacgtccagaacaaa
ttactgtgtgctcatcctttccattgccgaagtatagaatcactggtgtgcagaagatccaatgctcc
cagcctatattgttctcaccgaaagtgcctgcgtatattcatccaaggaagtatctcgtggaaacacc
accggtagacgagactccggagccatcggcagagaaccaatccacagaggggacacctgaacaaccac
cacttataaccgaggatgagaccaggactagaacgcctgagccgatcatcatcgaagaggaagaagag
gatagcataagtttgctgtcagatggcccgacccaccaggtgctgcaagtcgaggcagacattcacgg
gccgccctctgtatctagctcatcctggtccattcctcatgcatccgactttgatgtggacagtttat
ccatacttgacaccctggagggagctagcgtgaccagcggggcaacgtcagccgagactaactcttac
ttcgcaaagagtatggagtttctggcgcgaccggtgcctgcgcctcgaacagtattcaggaaccctcc
acatcccgctccgcgcacaagaacaccgtcacttgcacccagcagggcctgctcgagaaccagcctag
tttccaccccgccaggcgtgaatagggtgatcactagagaggagctcgaggcgcttaccccgtcacgc
actcctagcaggtcggtctcgagaaccagcctggtctccaacccgccaggcgtaaatagggtgattac
aagagaggagtttgaggcgttcgtagcacaacaacaatgacggtttgatgcgggtgcatacatctttt
cctccgacaccggtcaagggcatttacaacaaaaatcagtaaggcaaacggtgctatccgaagtggtg
ttggagaggaccgaattggagatttcgtatgccccgcgcctcgaccaagaaaaagaagaattactacg
caagaaattacagttaaatcccacacctgctaacagaagcagataccagtccaggaaggtggagaaca
tgaaagccataacagctagacgtattctgcaaggcctagggcattatttgaaggcagaaggaaaagtg
gagtgctaccgaaccctgcatcctgttcctttgtattcatctagtgtgaaccgtgccttttcaagccc
caaggtcgcagtggaagcctgtaacgccatgttgaaagagaactttccgactgtggcttcttactgta
ttattccagagtacgatgcctatttggacatggttgacggagcttcatgctgcttagacactgccagt
ttttgccctgcaaagctgcgcagctttccaaagaaacactcctatttggaacccacaatacgatcggc
agtgccttcagcgatccagaacacgctccagaacgtcctggcagctgccacaaaaagaaattgcaatg
tcacgcaaatgagagaattgcccgtattggattcggcggcctttaatgtggaatgcttcaagaaatat
gcgtgtaataatgaatattgggaaacgtttaaagaaaaccccatcaggcttactgaagaaaacgtggt
aaattacattaccaaattaaaaggaccaaaagctgctgctctttttgcgaagacacataatttgaata
tgttgcaggacataccaatggacaggtttgtaatggacttaaagagagacgtgaaagtgactccagga
acaaaacatactgaagaacggcccaaggtacaggtgatccaggctgccgatccgctagcaacagcgta
tctgtgcggaatccaccgagagctggttaggagattaaatgcggtcctgcttccgaacattcatacac
tgtttgatatgtcggctgaagactttgacgctattatagccgagcacttccagcctggggattgtgtt
ctggaaactgacatcgcgtcgtttgataaaagtgaggacgacgccatggctctgaccgcgttaatgat
tctggaagacttaggtgtggacgcagagctgttgacgctgattgaggcggctttcggcgaaatttcat
caatacatttgcccactaaaactaaatttaaattcggagccatgatgaaatctggaatgttcctcaca
ctgtttgtgaacacagtcattaacattgtaatcgcaagcagagtgttgagagaacggctaaccggatc
accatgtgcagcattcattggagatgacaatatcgtgaaaggagtcaaatcggacaaattaatggcag
acaggtgcgccacctggttgaatatggaagtcaagattatagatgctgtggtgggcgagaaagcgcct
tatttctgtggagggtttattttgtgtgactccgtgaccggcacagcgtgccgtgtggcagaccccct
aaaaaggctgtttaagcttggcaaacctctggcagcagacgatgaacatgatgatgacaggagaaggg
cattgcatgaagagtcaacacgctggaaccgagtgggtattctttcagagctgtgcaaggcagtagaa
tcaaggtatgaaaccgtaggaacttccatcatagttatggccatgactactctagctagcagtgttaa
atcattcagctacctgagaggggcccctataactctctacggctaacctgaatggactacgacatagt
ctagtcgagtctagtcgacgccaccatgggcaccgtgaacaagcctgtcgtgggcgtgctgatgggct
tcggcatcatcaccggcaccctgagaatcaccaaccctgtgcgggccagcgtgctgagatacgacgac
ttccacatcgacgaggacaagctggacaccaacagcgtgtacgagccctactaccacagcgaccacgc
cgagagcagctgggtcaacagaggcgagagcagccggaaggcctacgaccacaacagcccctacatct
ggccccggaacgactacgacggcttcctggaaaacgcccacgagcaccacggcgtgtacaatcagggc
agaggcatcgacagcggcgagagactgatgcagcccacacagatgagcgcccaggaagatctgggcga
cgacacaggcatccacgtgatccccaccctgaacggcgacgaccggcacaagatcgtgaacgtggacc
agcggcagtacggcgacgtgttcaagggcgacctgaaccctaagccccagggccagagactgatcgag
gtgtccgtggaagagaaccaccccttcaccctgagagcccccatccagagaatctacggcgtgcggta
taccgagacttggagcttcctgcccagcctgacctgtacaggcgacgccgctcctgccatccagcaca
tctgcctgaagcacaccacctgtttccaggacgtggtggtggacgtggactgcgccgagaacaccaaa
gaggaccagctggccgagatcagctaccggttccagggcaagaaagaggccgaccagccctggatcgt
ggtcaataccagcaccctgttcgacgagctggaactggacccccccgagattgaacccggcgtgctga
aggtgctgcggaccgagaagcagtacctgggcgtgtacatctggaacatgcggggctccgacggcacc
tctacctacgccaccttcctggtcacatggaagggcgacgagaaaacccggaaccctacccctgccgt
gacccctcagcctagaggcgccgagttccatatgtggaattaccactcccacgtgttcagcgtgggcg
acaccttcagcctggccatgcatctgcagtacaagatccacgaggcccccttcgacctgctgctggaa
tggctgtacgtgcccatcgaccctacctgccagcccatgcggctgtacagcacctgtctgtaccaccc
caacgcccctcagtgcctgagccacatgaacagcggctgcaccttcaccagccctcacctggctcaga
gggtggccagcaccgtgtaccagaattgcgagcacgccgacaactacaccgcctactgcctgggcatc
agccacatggaacccagcttcggcctgatcctgcacgatggcggcaccaccctgaagttcgtggacac
acccgagagcctgagcggcctgtacgtgttcgtggtgtacttcaacggccacgtggaagccgtggcct
acaccgtggtgtccaccgtggaccacttcgtgaacgccatcgaggaaagaggcttcccacccacagcc
ggacagcctccagccaccaccaagcccaaagaaatcacccccgtgaaccccggcaccagccccctgct
gagatatgctgcttggacaggcggactggccgctgtggtgctgctgtgcctggtcatcttcctgatct
gcaccgccaagcggatgagagtgaaggcctaccgggtggacaagtccccctacaaccagagcatgtac
tacgccggcctgcccgtggacgatttcgaggatagcgagagcaccgacaccgaggaagagttcggcaa
cgccatcggcggatctcacggcggcagcagctacaccgtgtacatcgacaagaccagataatctagac
gcggccgcatacagcagcaattggcaagctgcttacatagaactcgcggcgattggcatgccgcctta
aaatttttattttatttttcttttcttttccgaatcggattttgtttttaatatttcaaaaaaaaaaa
aaaaaaaaaaaaaaaaaaaaaaaagggtcggcatggcatctccacctcctcgcggtccgacctgggca
tccgaaggaggacgcacgtccactcggatggctaagggagagccacgtttaaaccagctccaattcgc
cctatagtgagtcgtattacgcgcgctcactggccgtcgttttacaacgtcgtgactgggaaaaccct
ggcgttacccaacttaatcgccttgcagcacatccccctttcgccagctggcgtaatagcgaagaggc
ccgcaccgatcgcccttcccaacagttgcgcagcctgaatggcgaatgggacgcgccctgtagcggcg
cattaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacacttgccagcgccctagcgccc
gctcctttcgctttcttcccttcctttctcgccacgttcgccggctttccccgtcaagctctaaatcg
ggggctccctttagggttccgatttagtgctttacggcacctcgaccccaaaaaacttgattagggtg
atggttcacgtagtgggccatcgccctgatagacggtttttcgccctttgacgttggagtccacgttc
tttaatagtggactcttgttccaaactggaacaacactcaaccctatctcggtctattcttttgattt
ataagggattttgccgatttcggcctattggttaaaaaatgagctgatttaacaaaaatttaacgcga
attttaacaaaatattaacgcttacaatttaggtggcacttttcggggaaatgtgcgcggaaccccta
tttgtttatttttctaaatacattcaaatatgtatccgctcatgagacaataaccctgataaatgctt
caataatattgaaaaaggaagagtatgagtattcaacatttccgtgtcgcccttattcccttttttgc
ggcattttgccttcctgtttttgctcacccagaaacgctggtgaaagtaaaagatgctgaagatcagt
tgggtgcacgagtgggttacatcgaactggatctcaacagcggtaagatccttgagagttttcgcccc
gaagaacgttttccaatgatgagcacttttaaagttctgctatgtggcgcggtattatcccgtattga
cgccgggcaagagcaactcggtcgccgcatacactattctcagaatgacttggttgagtactcaccag
tcacagaaaagcatcttacggatggcatgacagtaagagaattatgcagtgctgccataaccatgagt
gataacactgcggccaacttacttctgacaacgatcggaggaccgaaggagctaaccgcttttttgca
caacatgggggatcatgtaactcgccttgatcgttgggaaccggagctgaatgaagccataccaaacg
acgagcgtgacaccacgatgcctgtagcaatggcaacaacgttgcgcaaactattaactggcgaacta
cttactctagcttcccggcaacaattaatagactggatggaggcggataaagttgcaggaccacttct
gcgctcggcccttccggctggctggtttattgctgataaatctggagccggtgagcgtgggtctcgcg
gtatcattgcagcactggggccagatggtaagccctcccgtatcgtagttatctacacgacggggagt
caggcaactatggatgaacgaaatagacagatcgctgagataggtgcctcactgattaagcattggta
actgtcagaccaagtttactcatatatactttagattgatttaaaactteatttttaatttaaaagga
tctaggtgaagatcctttttgataatctcatgaccaaaatcccttaacgtgagttttcgttccactga
gcgtcagaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaatctgctg
cttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactcttt
ttccgaaggtaactggcttcagcagagcgcagataccaaatactgttcttctagtgtagccgtagtta
ggccaccacttcaagaactctgtagcaccgcctacatacctcgctctgctaatcctgttaccagtggc
tgctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgc
agcggtcgggctgaacggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactg
agatacctacagcgtgagctatgagaaagcgccacgcttcccgaagggagaaaggcggacaggtatcc
ggtaagcggcagggtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatcttt
atagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtcaggggggcgg
agcctatggaaaaacgccagcaacgcggcctttttacggttcctggccttttgctggccttttgctca
catgttctttcctgcgttatcccctgattctgtggataaccgtattaccgcctttgagtgagctgata
ccgctcgccgcagccgaacgaccgagcgcagcgagtcagtgagcgaggaagcggaagagcgcccaata
cgcaaaccgcctctccccgcgcgttggccgattcattaatgcagctggcacgacaggtttcccgactg
gaaagcgggcagtgagcgcaacgcaattaatgtgagttagctcactcattaggcaccccaggctttac
actttatgctcccggctcgtatgttgtgtggaattgtgagcggataacaatttcacacaggaaacagc
tatgaccatgattacgccaagcgcgcaattaaccctcactaaagggaacaaaagctgggtaccgggcc
cacgcgtaatacgactcactatag_12604
TABLE-US-00063 VZV VEERep.SGPgI 1.sub.--
ataggcggcgcatgagagaagcccagaccaattacctacccaaaatggagaaagttcacgttgacatc
gaggaagacagcccattcctcagagctttgcagcggagcttcccgcagtttgaggtagaagccaagca
ggtcactgataatgaccatgctaatgccagagcgttttcgcatctggcttcaaaactgatcgaaacgg
aggtggacccatccgacacgatccttgacattggaagtgcgcccgcccgcagaatgtattctaagcac
aagtatcattgtatctgtccgatgagatgtgcggaagatccggacagattgtataagtatgcaactaa
gctgaagaaaaactgtaaggaaataactgataaggaattggacaagaaaatgaaggagctcgccgccg
tcatgagcgaccctgacctggaaactgagactatgtgcctccacgacgacgagtcgtgtcgctacgaa
gggcaagtcgctgtttaccaggatgtatacgcggttgacggaccgacaagtctctatcaccaagccaa
taagggagttagagtcgcctactggataggctttgacaccaccccttttatgtttaagaacttggctg
gagcatatccatcatactctaccaactgggccgacgaaaccgtgttaacggctcgtaacataggccta
tgcagctctgacgttatggagcggtcacgtagagggatgtccattcttagaaagaagtatttgaaacc
atccaacaatgttctattctctgttggctcgaccatctaccacgagaagagggacttactgaggagct
ggcacctgccgtctgtatttcacttacgtggcaagcaaaattacacatgtcggtgtgagactatagtt
agttgcgacgggtacgtcgttaaaagaatagctatcagtccaggcctgtatgggaagccttcaggcta
tgctgctacgatgcaccgcgagggattcttgtgctgcaaagtgacagacacattgaacggggagaggg
tctcttttcccgtgtgcacgtatgtgccagctacattgtgtgaccaaatgactggcatactggcaaca
gatgtcagtgcggacgacgcgcaaaaactgctggttgggctcaaccagcgtatagtcgtcaacggtcg
cacccagagaaacaccaataccatgaaaaattaccttttgcccgtagtggcccaggcatttgctaggt
gggcaaaggaatataaggaagatcaagaagatgaaaggccactaggactacgagatagacagttagtc
atggggtgttgttgggcttttagaaggcacaagataacatctatttataagcgcccggatacccaaac
catcatcaaagtgaacagcgatttccactcattcgtgctgcccaggataggcagtaacacattggaga
tcgggctgagaacaagaatcaggaaaatgttagaggagcacaaggagccgtcacctctcattaccgcc
gaggacgtacaagaagctaagtgcgcagccgatgaggctaaggaggtgcgtgaagccgaggagttgcg
cgcagctctaccacctttggcagctgatgttgaggagcccactctggaagccgatgtagacttgatgt
tacaagaggctggggccggctcagtggagacacctcgtggcttgataaaggttaccagctacgatggc
gaggacaagatcggctcttacgctgtgctttctccgcaggctgtactcaagagtgaaaaattatcttg
catccaccctctcgctgaacaagtcatagtgataacacactctggccgaaaagggcgttatgccgtgg
aaccataccatggtaaagtagtggtgccagagggacatgcaatacccgtccaggactttcaagctctg
agtgaaagtgccaccattgtgtacaacgaacgtgagttcgtaaacaggtacctgcaccatattgccac
acatggaggagcgctgaacactgatgaagaatattacaaaactgtcaagcccagcgagcacgacggcg
aatacctgtacgacatcgacaggaaacagtgcgtcaagaaagaactagtcactgggctagggctcaca
ggcgagctggtggatcctcccttccatgaattcgcctacgagagtctgagaacacgaccagccgctcc
ttaccaagtaccaaccataggggtgtatggcgtgccaggatcaggcaagtctggcatcattaaaagcg
cagtcaccaaaaaagatctagtggtgagcgccaagaaagaaaactgtgcagaaattataagggacgtc
aagaaaatgaaagggctggacgtcaatgccagaactgtggactcagtgctcttgaatggatgcaaaca
ccccgtagagaccctgtatattgacgaagcttttgcttgtcatgcaggtactctcagagcgctcatag
ccattataagacctaaaaaggcagtgctctgcggggatcccaaacagtgcggtttttttaacatgatg
tgcctgaaagtgcattttaaccacgagatttgcacacaagtcttccacaaaagcatctctcgccgttg
cactaaatctgtgacttcggtcgtctcaaccttgttttacgacaaaaaaatgagaacgacgaatccga
aagagactaagattgtgattgacactaccggcagtaccaaacctaagcaggacgatctcattctcact
tgtttcagagggtgggtgaagcagttgcaaatagattacaaaggcaacgaaataatgacggcagctgc
ctctcaagggctgacccgtaaaggtgtgtatgccgttcggtacaaggtgaatgaaaatcctctgtacg
cacccacctcagaacatgtgaacgtcctactgacccgcacggaggaccgcatcgtgtggaaaacacta
gccggcgacccatggataaaaacactgactgccaagtaccctgggaatttcactgccacgatagagga
gtggcaagcagagcatgatgccatcatgaggcacatcttggagagaccggaccctaccgacgtcttcc
agaataaggcaaacgtgtgttgggccaaggctttagtgccggtgctgaagaccgctggcatagacatg
accactgaacaatggaacactgtggattattttgaaacggacaaagctcactcagcagagatagtatt
gaaccaactatgcgtgaggttctttggactcgatctggactccggtctattttctgcacccactgttc
cgttatccattaggaataatcactgggataactccccgtcgcctaacatgtacgggctgaataaagaa
gtggtccgtcagctctctcgcaggtacccacaactgcctcgggcagttgccactggaagagtctatga
catgaacactggtacactgcgcaattatgatccgcgcataaacctagtacctgtaaacagaagactgc
ctcatgctttagtcctccaccataatgaacacccacagagtgacttttcttcattcgtcagcaaattg
aagggcagaactgtcctggtggtcggggaaaagttgtccgtcccaggcaaaatggttgactggttgtc
agaccggcctgaggctaccttcagagctcggctggatttaggcatcccaggtgatgtgcccaaatatg
acataatatttgttaatgtgaggaccccatataaataccatcactatcagcagtgtgaagaccatgcc
attaagcttagcatgttgaccaagaaagcttgtctgcatctgaatcccggcggaacctgtgtcagcat
aggttatggttacgctgacagggccagcgaaagcatcattggtgctatagcgcggcagttcaagtttt
cccgggtatgcaaaccgaaatcctcacttgaagagacggaagttctgtttgtattcattgggtacgat
cgcaaggcccgtacgcacaatccttacaagctttcatcaaccttgaccaacatttatacaggttccag
actccacgaagccggatgtgcaccctcatatcatgtggtgcgaggggatattgccacggccaccgaag
gagtgattataaatgctgctaacagcaaaggacaacctggcggaggggtgtgcggagcgctgtataag
aaattcccggaaagcttcgatttacagccgatcgaagtaggaaaagcgcgactggtcaaaggtgcagc
taaacatatcattcatgccgtaggaccaaacttcaacaaagtttcggaggttgaaggtgacaaacagt
tggcagaggcttatgagtccatcgctaagattgtcaacgataacaattacaagtcagtagcgattcca
ctgttgtccaccggcatcttttccgggaacaaagatcgactaacccaatcattgaaccatttgctgac
agctttagacaccactgatgcagatgtagccatatactgcagggacaagaaatgggaaatgactctca
aggaagcagtggctaggagagaagcagtggaggagatatgcatatccgacgactcttcagtgacagaa
cctgatgcagagctggtgagggtgcatccgaagagttctttggctggaaggaagggctacagcacaag
cgatggcaaaactttctcatatttggaagggaccaagtttcaccaggcggccaaggatatagcagaaa
ttaatgccatgtggcccgttgcaacggaggccaatgagcaggtatgcatgtatatcctcggagaaagc
atgagcagtattaggtcgaaatgccccgtcgaagagtcggaagcctccacaccacctagcacgctgcc
ttgcttgtgcatccatgccatgactccagaaagagtacagcgcctaaaagcctcacgtccagaacaaa
ttactgtgtgctcatcctttccattgccgaagtatagaatcactggtgtgcagaagatccaatgctcc
cagcctatattgttctcaccgaaagtgcctgcgtatattcatccaaggaagtatctcgtggaaacacc
accggtagacgagactccggagccatcggcagagaaccaatccacagaggggacacctgaacaaccac
cacttataaccgaggatgagaccaggactagaacgcctgagccgatcatcatcgaagaggaagaagag
gatagcataagtttgctgtcagatggcccgacccaccaggtgctgcaagtcgaggcagacattcacgg
gccgccctctgtatctagctcatcctggtccattcctcatgcatccgactttgatgtggacagtttat
ccatacttgacaccctggagggagctagcgtgaccagcggggcaacgtcagccgagactaactcttac
ttcgcaaagagtatggagtttctggcgcgaccggtgcctgcgcctcgaacagtattcaggaaccctcc
acatcccgctccgcgcacaagaacaccgtcacttgcacccagcagggcctgctcgagaaccagcctag
tttccaccccgccaggcgtgaatagggtgatcactagagaggagctcgaggcgcttaccccgtcacgc
actcctagcaggtcggtctcgagaaccagcctggtctccaacccgccaggcgtaaatagggtgattac
aagagaggagtttgaggcgttcgtagcacaacaacaatgacggtttgatgcgggtgcatacatctttt
cctccgacaccggtcaagggcatttacaacaaaaatcagtaaggcaaacggtgctatccgaagtggtg
ttggagaggaccgaattggagatttcgtatgccccgcgcctcgaccaagaaaaagaagaattactacg
caagaaattacagttaaatcccacacctgctaacagaagcagataccagtccaggaaggtggagaaca
tgaaagccataacagctagacgtattctgcaaggcctagggcattatttgaaggcagaaggaaaagtg
gagtgctaccgaaccctgcatcctgttcctttgtattcatctagtgtgaaccgtgccttttcaagccc
caaggtcgcagtggaagcctgtaacgccatgttgaaagagaactttccgactgtggcttcttactgta
ttattccagagtacgatgcctatttggacatggttgacggagcttcatgctgcttagacactgccagt
ttttgccctgcaaagctgcgcagctttccaaagaaacactcctatttggaacccacaatacgatcggc
agtgccttcagcgatccagaacacgctccagaacgtcctggcagctgccacaaaaagaaattgcaatg
tcacgcaaatgagagaattgcccgtattggattcggcggcctttaatgtggaatgcttcaagaaatat
gcgtgtaataatgaatattgggaaacgtttaaagaaaaccccatcaggcttactgaagaaaacgtggt
aaattacattaccaaattaaaaggaccaaaagctgctgctctttttgcgaagacacataatttgaata
tgttgcaggacataccaatggacaggtttgtaatggacttaaagagagacgtgaaagtgactccagga
acaaaacatactgaagaacggcccaaggtacaggtgatccaggctgccgatccgctagcaacagcgta
tctgtgcggaatccaccgagagctggttaggagattaaatgcggtcctgcttccgaacattcatacac
tgtttgatatgtcggctgaagactttgacgctattatagccgagcacttccagcctggggattgtgtt
ctggaaactgacatcgcgtcgtttgataaaagtgaggacgacgccatggctctgaccgcgttaatgat
tctggaagacttaggtgtggacgcagagctgttgacgctgattgaggcggctttcggcgaaatttcat
caatacatttgcccactaaaactaaatttaaattcggagccatgatgaaatctggaatgttcctcaca
ctgtttgtgaacacagtcattaacattgtaatcgcaagcagagtgttgagagaacggctaaccggatc
accatgtgcagcattcattggagatgacaatatcgtgaaaggagtcaaatcggacaaattaatggcag
acaggtgcgccacctggttgaatatggaagtcaagattatagatgctgtggtgggcgagaaagcgcct
tatttctgtggagggtttattttgtgtgactccgtgaccggcacagcgtgccgtgtggcagaccccct
aaaaaggctgtttaagcttggcaaacctctggcagcagacgatgaacatgatgatgacaggagaaggg
cattgcatgaagagtcaacacgctggaaccgagtgggtattctttcagagctgtgcaaggcagtagaa
tcaaggtatgaaaccgtaggaacttccatcatagttatggccatgactactctagctagcagtgttaa
atcattcagctacctgagaggggcccctataactctctacggctaacctgaatggactacgacatagt
ctagtcgagtctagtcgacgccaccatgtttctgatccagtgcctgatcagcgccgtgatcttctata
ttcaagtcacaaacgccctgatctttaagggcgaccacgtgtcactgcaggtcaacagcagcctgacc
agcatcctgatccccatgcagaacgacaattacaccgagatcaagggccagctggtgttcatcggcga
gcagctgcccaccggcaccaattacagcggcaccctggaactgctgtacgccgataccgtggccttct
gcttcagaagcgtgcaggtcatcagatacgacggctgcccccggatcagaaccagcgcctteatcage
tgccggtacaagcacagctggcactacggcaacagcaccgaccggatcagcaccgaacctgatgccgg
cgtgatgctgaagatcaccaagcccggcatcaacgacgccggcgtgtacgtgctgctcgtgcggctgg
atcacagcagaagcaccgacggcttcatcctgggcgtgaacgtgtacaccgccggcagccaccacaac
atccacggcgtgatctacaccagccccagcctgcagaacggctacagcaccagagccctgttccagca
ggccagactgtgcgatctgcccgccacacctaagggcagcggcacaagcctgtttcagcacatgctgg
acctgagagccggcaagagcctggaagataacccctggctgcacgaggacgtggtcaccaccgagaca
aagagcgtggtcaaagagggcatcgagaaccacgtgtaccccaccgacatgagcaccctgcccgagaa
gtccctgaacgacccccctgagaacctgctgatcatcatccccatcgtggccagcgtgatgatcctga
ccgccatggtcatcgtgatcgtgatcagcgtgaagcggcggagaatcaagaagcaccccatctaccgg
cccaacaccaagaccagacggggcatccagaacgccacccctgagtccgacgtgatgctggaagccgc
cattgcccagctggccaccatcagagaggaaagcccccctcacagcgtcgtgaaccccttcgtgaagt
aatctagacgcggccgcatacagcagcaattggcaagctgcttacatagaactcgcggcgattggcat
gccgccttaaaatttttattttatttttcttttcttttccgaatcggattttgtttttaatatttcaa
aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaagggtcggcatggcatctccacctcctcgcggtccg
acctgggcatccgaaggaggacgcacgtccactcggatggctaagggagagccacgtttaaaccagct
ccaattcgccctatagtgagtcgtattacgcgcgctcactggccgtcgttttacaacgtcgtgactgg
gaaaaccctggcgttacccaacttaatcgccttgcagcacatccccctttcgccagctggcgtaatag
cgaagaggcccgcaccgatcgcccttcccaacagttgcgcagcctgaatggcgaatgggacgcgccct
gtagcggcgcattaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacacttgccagcgcc
ctagcgcccgctcctttcgctttcttcccttcctttctcgccacgttcgccggctttccccgtcaagc
tctaaatcgggggctccctttagggttccgatttagtgctttacggcacctcgaccccaaaaaacttg
attagggtgatggttcacgtagtgggccatcgccctgatagacggtttttcgccctttgacgttggag
tccacgttctttaatagtggactcttgttccaaactggaacaacactcaaccctatctcggtctattc
ttttgatttataagggattttgccgatttcggcctattggttaaaaaatgagctgatttaacaaaaat
ttaacgcgaattttaacaaaatattaacgcttacaatttaggtggcacttttcggggaaatgtgcgcg
gaacccctatttgtttatttttctaaatacattcaaatatgtatccgctcatgagacaataaccctga
taaatgcttcaataatattgaaaaaggaagagtatgagtattcaacatttccgtgtcgcccttattcc
cttttttgcggcattttgccttcctgtttttgctcacccagaaacgctggtgaaagtaaaagatgctg
aagatcagttgggtgcacgagtgggttacatcgaactggatctcaacagcggtaagatccttgagagt
tttcgccccgaagaacgttttccaatgatgagcacttttaaagttctgctatgtggcgcggtattatc
ccgtattgacgccgggcaagagcaactcggtcgccgcatacactattctcagaatgacttggttgagt
actcaccagtcacagaaaagcatcttacggatggcatgacagtaagagaattatgcagtgctgccata
accatgagtgataacactgcggccaacttacttctgacaacgatcggaggaccgaaggagctaaccgc
ttttttgcacaacatgggggatcatgtaactcgccttgatcgttgggaaccggagctgaatgaagcca
taccaaacgacgagcgtgacaccacgatgcctgtagcaatggcaacaacgttgcgcaaactattaact
ggcgaactacttactctagcttcccggcaacaattaatagactggatggaggcggataaagttgcagg
accacttctgcgctcggcccttccggctggctggtttattgctgataaatctggagccggtgagcgtg
ggtctcgcggtatcattgcagcactggggccagatggtaagccctcccgtatcgtagttatctacacg
acggggagtcaggcaactatggatgaacgaaatagacagatcgctgagataggtgcctcactgattaa
gcattggtaactgtcagaccaagtttactcatatatactttagattgatttaaaacttcatttttaat
ttaaaaggatctaggtgaagatcctttttgataatctcatgaccaaaatcccttaacgtgagttttcg
ttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgt
aatctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctac
caactctttttccgaaggtaactggcttcagcagagcgcagataccaaatactgttcttctagtgtag
ccgtagttaggccaccacttcaagaactctgtagcaccgcctacatacctcgctctgctaatcctgtt
accagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccgg
ataaggcgcagcggtcgggctgaacggggggttcgtgcacacagcccagcttggagcgaacgacctac
accgaactgagatacctacagcgtgagctatgagaaagcgccacgcttcccgaagggagaaaggcgga
caggtatccggtaagcggcagggtcggaacaggagagcgcacgagggagcttccagggggaaacgcct
ggtatctttatagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtca
ggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggccttttgctggcc
ttttgctcacatgttctttcctgcgttatcccctgattctgtggataaccgtattaccgcctttgagt
gagctgataccgctcgccgcagccgaacgaccgagcgcagcgagtcagtgagcgaggaagcggaagag
cgcccaatacgcaaaccgcctctccccgcgcgttggccgattcattaatgcagctggcacgacaggtt
tcccgactggaaagcgggcagtgagcgcaacgcaattaatgtgagttagctcactcattaggcacccc
aggctttacactttatgctcccggctcgtatgttgtgtggaattgtgagcggataacaatttcacaca
ggaaacagctatgaccatgattacgccaagcgcgcaattaaccctcactaaagggaacaaaagctggg
taccgggcccacgcgtaatacgactcactatag_11797
TABLE-US-00064 VZV VEErep.SGPgE-SGPgI 1.sub.--
ataggcggcgcatgagagaagcccagaccaattacctacccaaaatggagaaagttcacgttgacatc
gaggaagacagcccattcctcagagctttgcagcggagcttcccgcagtttgaggtagaagccaagca
ggtcactgataatgaccatgctaatgccagagcgttttcgcatctggcttcaaaactgatcgaaacgg
aggtggacccatccgacacgatccttgacattggaagtgcgcccgcccgcagaatgtattctaagcac
aagtatcattgtatctgtccgatgagatgtgcggaagatccggacagattgtataagtatgcaactaa
gctgaagaaaaactgtaaggaaataactgataaggaattggacaagaaaatgaaggagctcgccgccg
tcatgagcgaccctgacctggaaactgagactatgtgcctccacgacgacgagtcgtgtcgctacgaa
gggcaagtcgctgtttaccaggatgtatacgcggttgacggaccgacaagtctctatcaccaagccaa
taagggagttagagtcgcctactggataggctttgacaccaccccttttatgtttaagaacttggctg
gagcatatccatcatactctaccaactgggccgacgaaaccgtgttaacggctcgtaacataggccta
tgcagctctgacgttatggagcggtcacgtagagggatgtccattcttagaaagaagtatttgaaacc
atccaacaatgttctattctctgttggctcgaccatctaccacgagaagagggacttactgaggagct
ggcacctgccgtctgtatttcacttacgtggcaagcaaaattacacatgtcggtgtgagactatagtt
agttgcgacgggtacgtcgttaaaagaatagctatcagtccaggcctgtatgggaagccttcaggcta
tgctgctacgatgcaccgcgagggattcttgtgctgcaaagtgacagacacattgaacggggagaggg
tctcttttcccgtgtgcacgtatgtgccagctacattgtgtgaccaaatgactggcatactggcaaca
gatgtcagtgcggacgacgcgcaaaaactgctggttgggctcaaccagcgtatagtcgtcaacggtcg
cacccagagaaacaccaataccatgaaaaattaccttttgcccgtagtggcccaggcatttgctaggt
gggcaaaggaatataaggaagatcaagaagatgaaaggccactaggactacgagatagacagttagtc
atggggtgttgttgggcttttagaaggcacaagataacatctatttataagcgcccggatacccaaac
catcatcaaagtgaacagcgatttccactcattcgtgctgcccaggataggcagtaacacattggaga
tcgggctgagaacaagaatcaggaaaatgttagaggagcacaaggagccgtcacctctcattaccgcc
gaggacgtacaagaagctaagtgcgcagccgatgaggctaaggaggtgcgtgaagccgaggagttgcg
cgcagctctaccacctttggcagctgatgttgaggagcccactctggaagccgatgtagacttgatgt
tacaagaggctggggccggctcagtggagacacctcgtggcttgataaaggttaccagctacgatggc
gaggacaagatcggctcttacgctgtgctttctccgcaggctgtactcaagagtgaaaaattatcttg
catccaccctctcgctgaacaagtcatagtgataacacactctggccgaaaagggcgttatgccgtgg
aaccataccatggtaaagtagtggtgccagagggacatgcaatacccgtccaggactttcaagctctg
agtgaaagtgccaccattgtgtacaacgaacgtgagttcgtaaacaggtacctgcaccatattgccac
acatggaggagcgctgaacactgatgaagaatattacaaaactgtcaagcccagcgagcacgacggcg
aatacctgtacgacatcgacaggaaacagtgcgtcaagaaagaactagtcactgggctagggctcaca
ggcgagctggtggatcctcccttccatgaattcgcctacgagagtctgagaacacgaccagccgctcc
ttaccaagtaccaaccataggggtgtatggcgtgccaggatcaggcaagtctggcatcattaaaagcg
cagtcaccaaaaaagatctagtggtgagcgccaagaaagaaaactgtgcagaaattataagggacgtc
aagaaaatgaaagggctggacgtcaatgccagaactgtggactcagtgctcttgaatggatgcaaaca
ccccgtagagaccctgtatattgacgaagcttttgcttgtcatgcaggtactctcagagcgctcatag
ccattataagacctaaaaaggcagtgctctgcggggatcccaaacagtgcggtttttttaacatgatg
tgcctgaaagtgcattttaaccacgagatttgcacacaagtcttccacaaaagcatctctcgccgttg
cactaaatctgtgacttcggtcgtctcaaccttgttttacgacaaaaaaatgagaacgacgaatccga
aagagactaagattgtgattgacactaccggcagtaccaaacctaagcaggacgatctcattctcact
tgtttcagagggtgggtgaagcagttgcaaatagattacaaaggcaacgaaataatgacggcagctgc
ctctcaagggctgacccgtaaaggtgtgtatgccgttcggtacaaggtgaatgaaaatcctctgtacg
cacccacctcagaacatgtgaacgtcctactgacccgcacggaggaccgcatcgtgtggaaaacacta
gccggcgacccatggataaaaacactgactgccaagtaccctgggaatttcactgccacgatagagga
gtggcaagcagagcatgatgccatcatgaggcacatcttggagagaccggaccctaccgacgtcttcc
agaataaggcaaacgtgtgttgggccaaggctttagtgccggtgctgaagaccgctggcatagacatg
accactgaacaatggaacactgtggattattttgaaacggacaaagctcactcagcagagatagtatt
gaaccaactatgcgtgaggttctttggactcgatctggactccggtctattttctgcacccactgttc
cgttatccattaggaataatcactgggataactccccgtcgcctaacatgtacgggctgaataaagaa
gtggtccgtcagctctctcgcaggtacccacaactgcctcgggcagttgccactggaagagtctatga
catgaacactggtacactgcgcaattatgatccgcgcataaacctagtacctgtaaacagaagactgc
ctcatgctttagtcctccaccataatgaacacccacagagtgacttttcttcattcgtcagcaaattg
aagggcagaactgtcctggtggtcggggaaaagttgtccgtcccaggcaaaatggttgactggttgtc
agaccggcctgaggctaccttcagagctcggctggatttaggcatcccaggtgatgtgcccaaatatg
acataatatttgttaatgtgaggaccccatataaataccatcactatcagcagtgtgaagaccatgcc
attaagcttagcatgttgaccaagaaagcttgtctgcatctgaatcccggcggaacctgtgtcagcat
aggttatggttacgctgacagggccagcgaaagcatcattggtgctatagcgcggcagttcaagtttt
cccgggtatgcaaaccgaaatcctcacttgaagagacggaagttctgtttgtattcattgggtacgat
cgcaaggcccgtacgcacaatccttacaagctttcatcaaccttgaccaacatttatacaggttccag
actccacgaagccggatgtgcaccctcatatcatgtggtgcgaggggatattgccacggccaccgaag
gagtgattataaatgctgctaacagcaaaggacaacctggcggaggggtgtgcggagcgctgtataag
aaattcccggaaagcttcgatttacagccgatcgaagtaggaaaagcgcgactggtcaaaggtgcagc
taaacatatcattcatgccgtaggaccaaacttcaacaaagtttcggaggttgaaggtgacaaacagt
tggcagaggcttatgagtccatcgctaagattgtcaacgataacaattacaagtcagtagcgattcca
ctgttgtccaccggcatcttttccgggaacaaagatcgactaacccaatcattgaaccatttgctgac
agctttagacaccactgatgcagatgtagccatatactgcagggacaagaaatgggaaatgactctca
aggaagcagtggctaggagagaagcagtggaggagatatgcatatccgacgactcttcagtgacagaa
cctgatgcagagctggtgagggtgcatccgaagagttctttggctggaaggaagggctacagcacaag
cgatggcaaaactttctcatatttggaagggaccaagtttcaccaggcggccaaggatatagcagaaa
ttaatgccatgtggcccgttgcaacggaggccaatgagcaggtatgcatgtatatcctcggagaaagc
atgagcagtattaggtcgaaatgccccgtcgaagagtcggaagcctccacaccacctagcacgctgcc
ttgcttgtgcatccatgccatgactccagaaagagtacagcgcctaaaagcctcacgtccagaacaaa
ttactgtgtgctcatcctttccattgccgaagtatagaatcactggtgtgcagaagatccaatgctcc
cagcctatattgttctcaccgaaagtgcctgcgtatattcatccaaggaagtatctcgtggaaacacc
accggtagacgagactccggagccatcggcagagaaccaatccacagaggggacacctgaacaaccac
cacttataaccgaggatgagaccaggactagaacgcctgagccgatcatcatcgaagaggaagaagag
gatagcataagtttgctgtcagatggcccgacccaccaggtgctgcaagtcgaggcagacattcacgg
gccgccctctgtatctagctcatcctggtccattcctcatgcatccgactttgatgtggacagtttat
ccatacttgacaccctggagggagctagcgtgaccagcggggcaacgtcagccgagactaactcttac
ttcgcaaagagtatggagtttctggcgcgaccggtgcctgcgcctcgaacagtattcaggaaccctcc
acatcccgctccgcgcacaagaacaccgtcacttgcacccagcagggcctgctcgagaaccagcctag
tttccaccccgccaggcgtgaatagggtgatcactagagaggagctcgaggcgcttaccccgtcacgc
actcctagcaggtcggtctcgagaaccagcctggtctccaacccgccaggcgtaaatagggtgattac
aagagaggagtttgaggcgttcgtagcacaacaacaatgacggtttgatgcgggtgcatacatctttt
cctccgacaccggtcaagggcatttacaacaaaaatcagtaaggcaaacggtgctatccgaagtggtg
ttggagaggaccgaattggagatttcgtatgccccgcgcctcgaccaagaaaaagaagaattactacg
caagaaattacagttaaatcccacacctgctaacagaagcagataccagtccaggaaggtggagaaca
tgaaagccataacagctagacgtattctgcaaggcctagggcattatttgaaggcagaaggaaaagtg
gagtgctaccgaaccctgcatcctgttcctttgtattcatctagtgtgaaccgtgccttttcaagccc
caaggtcgcagtggaagcctgtaacgccatgttgaaagagaactttccgactgtggcttcttactgta
ttattccagagtacgatgcctatttggacatggttgacggagcttcatgctgcttagacactgccagt
ttttgccctgcaaagctgcgcagctttccaaagaaacactcctatttggaacccacaatacgatcggc
agtgccttcagcgatccagaacacgctccagaacgtcctggcagctgccacaaaaagaaattgcaatg
tcacgcaaatgagagaattgcccgtattggattcggcggcctttaatgtggaatgcttcaagaaatat
gcgtgtaataatgaatattgggaaacgtttaaagaaaaccccatcaggcttactgaagaaaacgtggt
aaattacattaccaaattaaaaggaccaaaagctgctgctctttttgcgaagacacataatttgaata
tgttgcaggacataccaatggacaggtttgtaatggacttaaagagagacgtgaaagtgactccagga
acaaaacatactgaagaacggcccaaggtacaggtgatccaggctgccgatccgctagcaacagcgta
tctgtgcggaatccaccgagagctggttaggagattaaatgcggtcctgcttccgaacattcatacac
tgtttgatatgtcggctgaagactttgacgctattatagccgagcacttccagcctggggattgtgtt
ctggaaactgacatcgcgtcgtttgataaaagtgaggacgacgccatggctctgaccgcgttaatgat
tctggaagacttaggtgtggacgcagagctgttgacgctgattgaggcggctttcggcgaaatttcat
caatacatttgcccactaaaactaaatttaaattcggagccatgatgaaatctggaatgttcctcaca
ctgtttgtgaacacagtcattaacattgtaatcgcaagcagagtgttgagagaacggctaaccggatc
accatgtgcagcattcattggagatgacaatatcgtgaaaggagtcaaatcggacaaattaatggcag
acaggtgcgccacctggttgaatatggaagtcaagattatagatgctgtggtgggcgagaaagcgcct
tatttctgtggagggtttattttgtgtgactccgtgaccggcacagcgtgccgtgtggcagaccccct
aaaaaggctgtttaagcttggcaaacctctggcagcagacgatgaacatgatgatgacaggagaaggg
cattgcatgaagagtcaacacgctggaaccgagtgggtattctttcagagctgtgcaaggcagtagaa
tcaaggtatgaaaccgtaggaacttccatcatagttatggccatgactactctagctagcagtgttaa
atcattcagctacctgagaggggcccctataactctctacggctaacctgaatggactacgacatagt
ctagtcgagtctagtcgacgccaccatgggcaccgtgaacaagcctgtcgtgggcgtgctgatgggct
tcggcatcatcaccggcaccctgagaatcaccaaccctgtgcgggccagcgtgctgagatacgacgac
ttccacatcgacgaggacaagctggacaccaacagcgtgtacgagccctactaccacagcgaccacgc
cgagagcagctgggtcaacagaggcgagagcagccggaaggcctacgaccacaacagcccctacatct
ggccccggaacgactacgacggcttcctggaaaacgcccacgagcaccacggcgtgtacaatcagggc
agaggcatcgacagcggcgagagactgatgcagcccacacagatgagcgcccaggaagatctgggcga
cgacacaggcatccacgtgatccccaccctgaacggcgacgaccggcacaagatcgtgaacgtggacc
agcggcagtacggcgacgtgttcaagggcgacctgaaccctaagccccagggccagagactgatcgag
gtgtccgtggaagagaaccaccccttcaccctgagagcccccatccagagaatctacggcgtgcggta
taccgagacttggagcttcctgcccagcctgacctgtacaggcgacgccgctcctgccatccagcaca
tctgcctgaagcacaccacctgtttccaggacgtggtggtggacgtggactgcgccgagaacaccaaa
gaggaccagctggccgagatcagctaccggttccagggcaagaaagaggccgaccagccctggatcgt
ggtcaataccagcaccctgttcgacgagctggaactggacccccccgagattgaacccggcgtgctga
aggtgctgcggaccgagaagcagtacctgggcgtgtacatctggaacatgcggggctccgacggcacc
tctacctacgccaccttcctggtcacatggaagggcgacgagaaaacccggaaccctacccctgccgt
gacccctcagcctagaggcgccgagttccatatgtggaattaccactcccacgtgttcagcgtgggcg
acaccttcagcctggccatgcatctgcagtacaagatccacgaggcccccttcgacctgctgctggaa
tggctgtacgtgcccatcgaccctacctgccagcccatgcggctgtacagcacctgtctgtaccaccc
caacgcccctcagtgcctgagccacatgaacagcggctgcaccttcaccagccctcacctggctcaga
gggtggccagcaccgtgtaccagaattgcgagcacgccgacaactacaccgcctactgcctgggcatc
agccacatggaacccagcttcggcctgatcctgcacgatggcggcaccaccctgaagttcgtggacac
acccgagagcctgagcggcctgtacgtgttcgtggtgtacttcaacggccacgtggaagccgtggcct
acaccgtggtgtccaccgtggaccacttcgtgaacgccatcgaggaaagaggcttcccacccacagcc
ggacagcctccagccaccaccaagcccaaagaaatcacccccgtgaaccccggcaccagccccctgct
gagatatgctgcttggacaggcggactggccgctgtggtgctgctgtgcctggtcatcttcctgatct
gcaccgccaagcggatgagagtgaaggcctaccgggtggacaagtccccctacaaccagagcatgtac
tacgccggcctgcccgtggacgatttcgaggatagcgagagcaccgacaccgaggaagagttcggcaa
cgccatcggcggatctcacggcggcagcagctacaccgtgtacatcgacaagaccagataatctagac
gtcgcgaccacccaggatccgcctataactctctacggctaacctgaatggactacgacatagtctag
tcgacgccaccatgtttctgatccagtgcctgatcagcgccgtgatcttctatattcaagtcacaaac
gccctgatctttaagggcgaccacgtgtcactgcaggtcaacagcagcctgaccagcatcctgatccc
catgcagaacgacaattacaccgagatcaagggccagctggtgttcatcggcgagcagctgcccaccg
gcaccaattacagcggcaccctggaactgctgtacgccgataccgtggccttctgcttcagaagcgtg
caggtcatcagatacgacggctgcccccggatcagaaccagcgcctteatcagetgccggtacaagca
cagctggcactacggcaacagcaccgaccggatcagcaccgaacctgatgccggcgtgatgctgaaga
tcaccaagcccggcatcaacgacgccggcgtgtacgtgctgctcgtgcggctggatcacagcagaagc
accgacggcttcatcctgggcgtgaacgtgtacaccgccggcagccaccacaacatccacggcgtgat
ctacaccagccccagcctgcagaacggctacagcaccagagccctgttccagcaggccagactgtgcg
atctgcccgccacacctaagggcagcggcacaagcctgtttcagcacatgctggacctgagagccggc
aagagcctggaagataacccctggctgcacgaggacgtggtcaccaccgagacaaagagcgtggtcaa
agagggcatcgagaaccacgtgtaccccaccgacatgagcaccctgcccgagaagtccctgaacgacc
cccctgagaacctgctgatcatcatccccatcgtggccagcgtgatgatcctgaccgccatggtcatc
gtgatcgtgatcagcgtgaagcggcggagaatcaagaagcaccccatctaccggcccaacaccaagac
cagacggggcatccagaacgccacccctgagtccgacgtgatgctggaagccgccattgcccagctgg
ccaccatcagagaggaaagcccccctcacagcgtcgtgaaccccttcgtgaagtaatctagacgcggc
cgcatacagcagcaattggcaagctgcttacatagaactcgcggcgattggcatgccgccttaaaatt
tttattttatttttcttttcttttccgaatcggattttgtttttaatatttcaaaaaaaaaaaaaaaa
aaaaaaaaaaaaaaaaaaagggtcggcatggcatctccacctcctcgcggtccgacctgggcatccga
aggaggacgcacgtccactcggatggctaagggagagccacgtttaaaccagctccaattcgccctat
agtgagtcgtattacgcgcgctcactggccgtcgttttacaacgtcgtgactgggaaaaccctggcgt
tacccaacttaatcgccttgcagcacatccccctttcgccagctggcgtaatagcgaagaggcccgca
ccgatcgcccttcccaacagttgcgcagcctgaatggcgaatgggacgcgccctgtagcggcgcatta
agcgcggcgggtgtggtggttacgcgcagcgtgaccgctacacttgccagcgccctagcgcccgctcc
tttcgctttcttcccttcctttctcgccacgttcgccggctttccccgtcaagctctaaatcgggggc
tccctttagggttccgatttagtgctttacggcacctcgaccccaaaaaacttgattagggtgatggt
tcacgtagtgggccatcgccctgatagacggtttttcgccctttgacgttggagtccacgttctttaa
tagtggactcttgttccaaactggaacaacactcaaccctatctcggtctattcttttgatttataag
ggattttgccgatttcggcctattggttaaaaaatgagctgatttaacaaaaatttaacgcgaatttt
aacaaaatattaacgcttacaatttaggtggcacttttcggggaaatgtgcgcggaacccctatttgt
ttatttttctaaatacattcaaatatgtatccgctcatgagacaataaccctgataaatgcttcaata
atattgaaaaaggaagagtatgagtattcaacatttccgtgtcgcccttattcccttttttgcggcat
tttgccttcctgtttttgctcacccagaaacgctggtgaaagtaaaagatgctgaagatcagttgggt
gcacgagtgggttacatcgaactggatctcaacagcggtaagatccttgagagttttcgccccgaaga
acgttttccaatgatgagcacttttaaagttctgctatgtggcgcggtattatcccgtattgacgccg
ggcaagagcaactcggtcgccgcatacactattctcagaatgacttggttgagtactcaccagtcaca
gaaaagcatcttacggatggcatgacagtaagagaattatgcagtgctgccataaccatgagtgataa
cactgcggccaacttacttctgacaacgatcggaggaccgaaggagctaaccgcttttttgcacaaca
tgggggatcatgtaactcgccttgatcgttgggaaccggagctgaatgaagccataccaaacgacgag
cgtgacaccacgatgcctgtagcaatggcaacaacgttgcgcaaactattaactggcgaactacttac
tctagcttcccggcaacaattaatagactggatggaggcggataaagttgcaggaccacttctgcgct
cggcccttccggctggctggtttattgctgataaatctggagccggtgagcgtgggtctcgcggtatc
attgcagcactggggccagatggtaagccctcccgtatcgtagttatctacacgacggggagtcaggc
aactatggatgaacgaaatagacagatcgctgagataggtgcctcactgattaagcattggtaactgt
cagaccaagtttactcatatatactttagattgatttaaaacttcatttttaatttaaaaggatctag
gtgaagatcctttttgataatctcatgaccaaaatcccttaacgtgagttttcgttccactgagcgtc
agaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaatctgctgcttgc
aaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctttttccg
aaggtaactggcttcagcagagcgcagataccaaatactgttcttctagtgtagccgtagttaggcca
ccacttcaagaactctgtagcaccgcctacatacctcgctctgctaatcctgttaccagtggctgctg
ccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcagcgg
tcgggctgaacggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactgagata
cctacagcgtgagctatgagaaagcgccacgcttcccgaagggagaaaggcggacaggtatccggtaa
gcggcagggtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatctttatagt
cctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtcaggggggcggagcct
atggaaaaacgccagcaacgcggcctttttacggttcctggccttttgctggccttttgctcacatgt
tctttcctgcgttatcccctgattctgtggataaccgtattaccgcctttgagtgagctgataccgct
cgccgcagccgaacgaccgagcgcagcgagtcagtgagcgaggaagcggaagagcgcccaatacgcaa
accgcctctccccgcgcgttggccgattcattaatgcagctggcacgacaggtttcccgactggaaag
cgggcagtgagcgcaacgcaattaatgtgagttagctcactcattaggcaccccaggctttacacttt
atgctcccggctcgtatgttgtgtggaattgtgagcggataacaatttcacacaggaaacagctatga
ccatgattacgccaagcgcgcaattaaccctcactaaagggaacaaaagctgggtaccgggcccacgc
gtaatacgactcactatag_13775
TABLE-US-00065 VEE-based replicon encoding eGFP nsP1
~~~~~~~~~~~~~~~~~ 1 ATAGGCGGCG CATGAGAGAA GCCCAGACCA ATTACCTACC
CAAAATGGAG AAAGTTCACG nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
61 TTGACATCGA GGAAGACAGC CCATTCCTCA GAGCTTTGCA GCGGAGCTTC
CCGCAGTTTG nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
121 AGGTAGAAGC CAAGCAGGTC ACTGATAATG ACCATGCTAA TGCCAGAGCG
TTTTCGCATC nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
181 TGGCTTCAAA ACTGATCGAA ACGGAGGTGG ACCCATCCGA CACGATCCTT
GACATTGGAA nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
241 GTGCGCCCGC CCGCAGAATG TATTCTAAGC ACAAGTATCA TTGTATCTGT
CCGATGAGAT nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
301 GTGCGGAAGA TCCGGACAGA TTGTATAAGT ATGCAACTAA GCTGAAGAAA
AACTGTAAGG nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
361 AAATAACTGA TAAGGAATTG GACAAGAAAA TGAAGGAGCT CGCCGCCGTC
ATGAGCGACC nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
421 CTGACCTGGA AACTGAGACT ATGTGCCTCC ACGACGACGA GTCGTGTCGC
TACGAAGGGC nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
481 AAGTCGCTGT TTACCAGGAT GTATACGCGG TTGACGGACC GACAAGTCTC
TATCACCAAG nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
541 CCAATAAGGG AGTTAGAGTC GCCTACTGGA TAGGCTTTGA CACCACCCCT
TTTATGTTTA nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
601 AGAACTTGGC TGGAGCATAT CCATCATACT CTACCAACTG GGCCGACGAA
ACCGTGTTAA nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
661 CGGCTCGTAA CATAGGCCTA TGCAGCTCTG ACGTTATGGA GCGGTCACGT
AGAGGGATGT nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
721 CCATTCTTAG AAAGAAGTAT TTGAAACCAT CCAACAATGT TCTATTCTCT
GTTGGCTCGA nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
781 CCATCTACCA CGAGAAGAGG GACTTACTGA GGAGCTGGCA CCTGCCGTCT
GTATTTCACT nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
841 TACGTGGCAA GCAAAATTAC ACATGTCGGT GTGAGACTAT AGTTAGTTGC
GACGGGTACG nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
901 TCGTTAAAAG AATAGCTATC AGTCCAGGCC TGTATGGGAA GCCTTCAGGC
TATGCTGCTA nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
961 CGATGCACCG CGAGGGATTC TTGTGCTGCA AAGTGACAGA CACATTGAAC
GGGGAGAGGG nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1021 TCTCTTTTCC CGTGTGCACG TATGTGCCAG CTACATTGTG TGACCAAATG
ACTGGCATAC nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1081 TGGCAACAGA TGTCAGTGCG GACGACGCGC AAAAACTGCT GGTTGGGCTC
AACCAGCGTA nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1141 TAGTCGTCAA CGGTCGCACC CAGAGAAACA CCAATACCAT GAAAAATTAC
CTTTTGCCCG nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1201 TAGTGGCCCA GGCATTTGCT AGGTGGGCAA AGGAATATAA GGAAGATCAA
GAAGATGAAA nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1261 GGCCACTAGG ACTACGAGAT AGACAGTTAG TCATGGGGTG TTGTTGGGCT
TTTAGAAGGC nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1321 ACAAGATAAC ATCTATTTAT AAGCGCCCGG ATACCCAAAC CATCATCAAA
GTGAACAGCG nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1381 ATTTCCACTC ATTCGTGCTG CCCAGGATAG GCAGTAACAC ATTGGAGATC
GGGCTGAGAA nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1441 CAAGAATCAG GAAAATGTTA GAGGAGCACA AGGAGCCGTC ACCTCTCATT
ACCGCCGAGG nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1501 ACGTACAAGA AGCTAAGTGC GCAGCCGATG AGGCTAAGGA GGTGCGTGAA
GCCGAGGAGT nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1561 TGCGCGCAGC TCTACCACCT TTGGCAGCTG ATGTTGAGGA GCCCACTCTG
GAAGCCGATG nsP2 ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 1621 TAGACTTGAT GTTACAAGAG
GCTGGGGCCG GCTCAGTGGA GACACCTCGT GGCTTGATAA nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1681 AGGTTACCAG CTACGATGGC GAGGACAAGA TCGGCTCTTA CGCTGTGCTT
TCTCCGCAGG nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1741 CTGTACTCAA GAGTGAAAAA TTATCTTGCA TCCACCCTCT CGCTGAACAA
GTCATAGTGA nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1801 TAACACACTC TGGCCGAAAA GGGCGTTATG CCGTGGAACC ATACCATGGT
AAAGTAGTGG nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1861 TGCCAGAGGG ACATGCAATA CCCGTCCAGG ACTTTCAAGC TCTGAGTGAA
AGTGCCACCA nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1921 TTGTGTACAA CGAACGTGAG TTCGTAAACA GGTACCTGCA CCATATTGCC
ACACATGGAG nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1981 GAGCGCTGAA CACTGATGAA GAATATTACA AAACTGTCAA GCCCAGCGAG
CACGACGGCG nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2041 AATACCTGTA CGACATCGAC AGGAAACAGT GCGTCAAGAA AGAACTAGTC
ACTGGGCTAG nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2101 GGCTCACAGG CGAGCTGGTG GATCCTCCCT TCCATGAATT CGCCTACGAG
AGTCTGAGAA nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2161 CACGACCAGC CGCTCCTTAC CAAGTACCAA CCATAGGGGT GTATGGCGTG
CCAGGATCAG nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2221 GCAAGTCTGG CATCATTAAA AGCGCAGTCA CCAAAAAAGA TCTAGTGGTG
AGCGCCAAGA nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2281 AAGAAAACTG TGCAGAAATT ATAAGGGACG TCAAGAAAAT GAAAGGGCTG
GACGTCAATG nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2341 CCAGAACTGT GGACTCAGTG CTCTTGAATG GATGCAAACA CCCCGTAGAG
ACCCTGTATA nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2401 TTGACGAAGC TTTTGCTTGT CATGCAGGTA CTCTCAGAGC GCTCATAGCC
ATTATAAGAC nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2461 CTAAAAAGGC AGTGCTCTGC GGGGATCCCA AACAGTGCGG TTTTTTTAAC
ATGATGTGCC nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2521 TGAAAGTGCA TTTTAACCAC GAGATTTGCA CACAAGTCTT CCACAAAAGC
ATCTCTCGCC nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2581 GTTGCACTAA ATCTGTGACT TCGGTCGTCT CAACCTTGTT TTACGACAAA
AAAATGAGAA nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2641 CGACGAATCC GAAAGAGACT AAGATTGTGA TTGACACTAC CGGCAGTACC
AAACCTAAGC nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2701 AGGACGATCT CATTCTCACT TGTTTCAGAG GGTGGGTGAA GCAGTTGCAA
ATAGATTACA nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2761 AAGGCAACGA AATAATGACG GCAGCTGCCT CTCAAGGGCT GACCCGTAAA
GGTGTGTATG nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2821 CCGTTCGGTA CAAGGTGAAT GAAAATCCTC TGTACGCACC CACCTCAGAA
CATGTGAACG nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2881 TCCTACTGAC CCGCACGGAG GACCGCATCG TGTGGAAAAC ACTAGCCGGC
GACCCATGGA nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2941 TAAAAACACT GACTGCCAAG TACCCTGGGA ATTTCACTGC CACGATAGAG
GAGTGGCAAG nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3001 CAGAGCATGA TGCCATCATG AGGCACATCT TGGAGAGACC GGACCCTACC
GACGTCTTCC nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3061 AGAATAAGGC AAACGTGTGT TGGGCCAAGG CTTTAGTGCC GGTGCTGAAG
ACCGCTGGCA nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3121 TAGACATGAC CACTGAACAA TGGAACACTG TGGATTATTT TGAAACGGAC
AAAGCTCACT nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3181 CAGCAGAGAT AGTATTGAAC CAACTATGCG TGAGGTTCTT TGGACTCGAT
CTGGACTCCG nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3241 GTCTATTTTC TGCACCCACT GTTCCGTTAT CCATTAGGAA TAATCACTGG
GATAACTCCC nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3301 CGTCGCCTAA CATGTACGGG CTGAATAAAG AAGTGGTCCG TCAGCTCTCT
CGCAGGTACC nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3361 CACAACTGCC TCGGGCAGTT GCCACTGGAA GAGTCTATGA CATGAACACT
GGTACACTGC nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3421 GCAATTATGA TCCGCGCATA AACCTAGTAC CTGTAAACAG AAGACTGCCT
CATGCTTTAG nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3481 TCCTCCACCA TAATGAACAC CCACAGAGTG ACTTTTCTTC ATTCGTCAGC
AAATTGAAGG nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3541 GCAGAACTGT CCTGGTGGTC GGGGAAAAGT TGTCCGTCCC AGGCAAAATG
GTTGACTGGT nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3601 TGTCAGACCG GCCTGAGGCT ACCTTCAGAG CTCGGCTGGA TTTAGGCATC
CCAGGTGATG nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3661 TGCCCAAATA TGACATAATA TTTGTTAATG TGAGGACCCC ATATAAATAC
CATCACTATC
nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3721 AGCAGTGTGA AGACCATGCC ATTAAGCTTA GCATGTTGAC CAAGAAAGCT
TGTCTGCATC nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3781 TGAATCCCGG CGGAACCTGT GTCAGCATAG GTTATGGTTA CGCTGACAGG
GCCAGCGAAA nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3841 GCATCATTGG TGCTATAGCG CGGCAGTTCA AGTTTTCCCG GGTATGCAAA
CCGAAATCCT nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3901 CACTTGAAGA GACGGAAGTT CTGTTTGTAT TCATTGGGTA CGATCGCAAG
GCCCGTACGC nsP2
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3961 ACAATCCTTA CAAGCTTTCA TCAACCTTGA CCAACATTTA TACAGGTTCC
AGACTCCACG nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ nsP2
~~~~~~~~~~~~ 4021 AAGCCGGATG TGCACCCTCA TATCATGTGG TGCGAGGGGA
TATTGCCACG GCCACCGAAG nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
4081 GAGTGATTAT AAATGCTGCT AACAGCAAAG GACAACCTGG CGGAGGGGTG
TGCGGAGCGC nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
4141 TGTATAAGAA ATTCCCGGAA AGCTTCGATT TACAGCCGAT CGAAGTAGGA
AAAGCGCGAC nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
4201 TGGTCAAAGG TGCAGCTAAA CATATCATTC ATGCCGTAGG ACCAAACTTC
AACAAAGTTT nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
4261 CGGAGGTTGA AGGTGACAAA CAGTTGGCAG AGGCTTATGA GTCCATCGCT
AAGATTGTCA nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
4321 ACGATAACAA TTACAAGTCA GTAGCGATTC CACTGTTGTC CACCGGCATC
TTTTCCGGGA nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
4381 ACAAAGATCG ACTAACCCAA TCATTGAACC ATTTGCTGAC AGCTTTAGAC
ACCACTGATG nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
4441 CAGATGTAGC CATATACTGC AGGGACAAGA AATGGGAAAT GACTCTCAAG
GAAGCAGTGG nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
4501 CTAGGAGAGA AGCAGTGGAG GAGATATGCA TATCCGACGA CTCTTCAGTG
ACAGAACCTG nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
4561 ATGCAGAGCT GGTGAGGGTG CATCCGAAGA GTTCTTTGGC TGGAAGGAAG
GGCTACAGCA nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
4621 CAAGCGATGG CAAAACTTTC TCATATTTGG AAGGGACCAA GTTTCACCAG
GCGGCCAAGG nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
4681 ATATAGCAGA AATTAATGCC ATGTGGCCCG TTGCAACGGA GGCCAATGAG
CAGGTATGCA nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
4741 TGTATATCCT CGGAGAAAGC ATGAGCAGTA TTAGGTCGAA ATGCCCCGTC
GAAGAGTCGG nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
4801 AAGCCTCCAC ACCACCTAGC ACGCTGCCTT GCTTGTGCAT CCATGCCATG
ACTCCAGAAA nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
4861 GAGTACAGCG CCTAAAAGCC TCACGTCCAG AACAAATTAC TGTGTGCTCA
TCCTTTCCAT nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
4921 TGCCGAAGTA TAGAATCACT GGTGTGCAGA AGATCCAATG CTCCCAGCCT
ATATTGTTCT nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
4981 CACCGAAAGT GCCTGCGTAT ATTCATCCAA GGAAGTATCT CGTGGAAACA
CCACCGGTAG nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
5041 ACGAGACTCC GGAGCCATCG GCAGAGAACC AATCCACAGA GGGGACACCT
GAACAACCAC nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
5101 CACTTATAAC CGAGGATGAG ACCAGGACTA GAACGCCTGA GCCGATCATC
ATCGAAGAGG nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
5161 AAGAAGAGGA TAGCATAAGT TTGCTGTCAG ATGGCCCGAC CCACCAGGTG
CTGCAAGTCG nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
5221 AGGCAGACAT TCACGGGCCG CCCTCTGTAT CTAGCTCATC CTGGTCCATT
CCTCATGCAT nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
5281 CCGACTTTGA TGTGGACAGT TTATCCATAC TTGACACCCT GGAGGGAGCT
AGCGTGACCA nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
5341 GCGGGGCAAC GTCAGCCGAG ACTAACTCTT ACTTCGCAAA GAGTATGGAG
TTTCTGGCGC nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
5401 GACCGGTGCC TGCGCCTCGA ACAGTATTCA GGAACCCTCC ACATCCCGCT
CCGCGCACAA nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
5461 GAACACCGTC ACTTGCACCC AGCAGGGCCT GCTCGAGAAC CAGCCTAGTT
TCCACCCCGC nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
5521 CAGGCGTGAA TAGGGTGATC ACTAGAGAGG AGCTCGAGGC GCTTACCCCG
TCACGCACTC nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
5581 CTAGCAGGTC GGTCTCGAGA ACCAGCCTGG TCTCCAACCC GCCAGGCGTA
AATAGGGTGA nsP4 ~~~~~~~~~~~~~~~~~~~~ nsP3
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 5641 TTACAAGAGA
GGAGTTTGAG GCGTTCGTAG CACAACAACA ATGACGGTTT GATGCGGGTG nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
5701 CATACATCTT TTCCTCCGAC ACCGGTCAAG GGCATTTACA ACAAAAATCA
GTAAGGCAAA nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
5761 CGGTGCTATC CGAAGTGGTG TTGGAGAGGA CCGAATTGGA GATTTCGTAT
GCCCCGCGCC nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
5821 TCGACCAAGA AAAAGAAGAA TTACTACGCA AGAAATTACA GTTAAATCCC
ACACCTGCTA nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
5881 ACAGAAGCAG ATACCAGTCC AGGAAGGTGG AGAACATGAA AGCCATAACA
GCTAGACGTA nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
5941 TTCTGCAAGG CCTAGGGCAT TATTTGAAGG CAGAAGGAAA AGTGGAGTGC
TACCGAACCC nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
6001 TGCATCCTGT TCCTTTGTAT TCATCTAGTG TGAACCGTGC CTTTTCAAGC
CCCAAGGTCG nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
6061 CAGTGGAAGC CTGTAACGCC ATGTTGAAAG AGAACTTTCC GACTGTGGCT
TCTTACTGTA nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
6121 TTATTCCAGA GTACGATGCC TATTTGGACA TGGTTGACGG AGCTTCATGC
TGCTTAGACA nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
6181 CTGCCAGTTT TTGCCCTGCA AAGCTGCGCA GCTTTCCAAA GAAACACTCC
TATTTGGAAC nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
6241 CCACAATACG ATCGGCAGTG CCTTCAGCGA TCCAGAACAC GCTCCAGAAC
GTCCTGGCAG nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
6301 CTGCCACAAA AAGAAATTGC AATGTCACGC AAATGAGAGA ATTGCCCGTA
TTGGATTCGG nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
6361 CGGCCTTTAA TGTGGAATGC TTCAAGAAAT ATGCGTGTAA TAATGAATAT
TGGGAAACGT nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
6421 TTAAAGAAAA CCCCATCAGG CTTACTGAAG AAAACGTGGT AAATTACATT
ACCAAATTAA nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
6481 AAGGACCAAA AGCTGCTGCT CTTTTTGCGA AGACACATAA TTTGAATATG
TTGCAGGACA nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
6541 TACCAATGGA CAGGTTTGTA ATGGACTTAA AGAGAGACGT GAAAGTGACT
CCAGGAACAA nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
6601 AACATACTGA AGAACGGCCC AAGGTACAGG TGATCCAGGC TGCCGATCCG
CTAGCAACAG nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
6661 CGTATCTGTG CGGAATCCAC CGAGAGCTGG TTAGGAGATT AAATGCGGTC
CTGCTTCCGA nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
6721 ACATTCATAC ACTGTTTGAT ATGTCGGCTG AAGACTTTGA CGCTATTATA
GCCGAGCACT nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
6781 TCCAGCCTGG GGATTGTGTT CTGGAAACTG ACATCGCGTC GTTTGATAAA
AGTGAGGACG nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
6841 ACGCCATGGC TCTGACCGCG TTAATGATTC TGGAAGACTT AGGTGTGGAC
GCAGAGCTGT nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
6901 TGACGCTGAT TGAGGCGGCT TTCGGCGAAA TTTCATCAAT ACATTTGCCC
ACTAAAACTA nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
6961 AATTTAAATT CGGAGCCATG ATGAAATCTG GAATGTTCCT CACACTGTTT
GTGAACACAG nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
7021 TCATTAACAT TGTAATCGCA AGCAGAGTGT TGAGAGAACG GCTAACCGGA
TCACCATGTG nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
7081 CAGCATTCAT TGGAGATGAC AATATCGTGA AAGGAGTCAA ATCGGACAAA
TTAATGGCAG nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
7141 ACAGGTGCGC CACCTGGTTG AATATGGAAG TCAAGATTAT AGATGCTGTG
GTGGGCGAGA nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
7201 AAGCGCCTTA TTTCTGTGGA GGGTTTATTT TGTGTGACTC CGTGACCGGC
ACAGCGTGCC nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
7261 GTGTGGCAGA CCCCCTAAAA AGGCTGTTTA AGCTTGGCAA ACCTCTGGCA
GCAGACGATG nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
7321 AACATGATGA TGACAGGAGA AGGGCATTGC ATGAAGAGTC AACACGCTGG
AACCGAGTGG nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
7381 GTATTCTTTC AGAGCTGTGC AAGGCAGTAG AATCAAGGTA TGAAACCGTA
GGAACTTCCA nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
7441 TCATAGTTAT GGCCATGACT ACTCTAGCTA GCAGTGTTAA ATCATTCAGC
TACCTGAGAG subgenomic promoter ~~~~~~~~~~~~~~~~~~~~~~~~~~ nsP4
~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 7501 GGGCCCCTAT AACTCTCTAC GGCTAACCTG
AATGGACTAC GACATAGTCT AGTCGACGCC eGFP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 7561
ACCATGGTGA GCAAGGGCGA GGAGCTGTTC ACCGGGGTGG TGCCCATCCT GGTCGAGCTG
eGFP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
7621 GACGGCGACG TAAACGGCCA CAAGTTCAGC GTGTCCGGCG AGGGCGAGGG
CGATGCCACC eGFP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
7681 TACGGCAAGC TGACCCTGAA GTTCATCTGC ACCACCGGCA AGCTGCCCGT
GCCCTGGCCC eGFP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
7741 ACCCTCGTGA CCACCCTGAC CTACGGCGTG CAGTGCTTCA GCCGCTACCC
CGACCACATG eGFP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
7801 AAGCAGCACG ACTTCTTCAA GTCCGCCATG CCCGAAGGCT ACGTCCAGGA
GCGCACCATC eGFP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
7861 TTCTTCAAGG ACGACGGCAA CTACAAGACC CGCGCCGAGG TGAAGTTCGA
GGGCGACACC eGFP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
7921 CTGGTGAACC GCATCGAGCT GAAGGGCATC GACTTCAAGG AGGACGGCAA
CATCCTGGGG eGFP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
7981 CACAAGCTGG AGTACAACTA CAACAGCCAC AACGTCTATA TCATGGCCGA
CAAGCAGAAG eGFP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
8041 AACGGCATCA AGGTGAACTT CAAGATCCGC CACAACATCG AGGACGGCAG
CGTGCAGCTC eGFP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
8101 GCCGACCACT ACCAGCAGAA CACCCCCATC GGCGACGGCC CCGTGCTGCT
GCCCGACAAC eGFP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
8161 CACTACCTGA GCACCCAGTC CGCCCTGAGC AAAGACCCCA ACGAGAAGCG
CGATCACATG eGFP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
8221 GTCCTGCTGG AGTTCGTGAC CGCCGCCGGG ATCACTCTCG GCATGGACGA
GCTGTACAAG eGFP 3'UTR ~~~~~~ ~~~~~~~~~~~~~~~~~~~~~~~~~~~ 8281
TGATAATCTA GACGGCGCGC CCACCCAGCG GCCGCATACA GCAGCAATTG GCAAGCTGCT
3'UTR
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
8341 TACATAGAAC TCGCGGCGAT TGGCATGCCG CCTTAAAATT TTTATTTTAT
TTTTCTTTTC 3'UTR ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 8401
TTTTCCGAAT CGGATTTTGT TTTTAATATT TCAAAAAAAA AAAAAAAAAA AAAAAAAAAA
HDV ribozyme
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 8461
AAAAAAAGGG TCGGCATGGC ATCTCCACCT CCTCGCGGTC CGACCTGGGC ATCCGAAGGA
HDV ribozyme ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 8521
GGACGCACGT CCACTCGGAT GGCTAAGGGA GAGCCACGTT TAAACCAGCT CCAATTCGCC
8581 CTATAGTGAG TCGTATTACG CGCGCTCACT GGCCGTCGTT TTACAACGTC
GTGACTGGGA 8641 AAACCCTGGC GTTACCCAAC TTAATCGCCT TGCAGCACAT
CCCCCTTTCG CCAGCTGGCG 8701 TAATAGCGAA GAGGCCCGCA CCGATCGCCC
TTCCCAACAG TTGCGCAGCC TGAATGGCGA 8761 ATGGGACGCG CCCTGTAGCG
GCGCATTAAG CGCGGCGGGT GTGGTGGTTA CGCGCAGCGT 8821 GACCGCTACA
CTTGCCAGCG CCCTAGCGCC CGCTCCTTTC GCTTTCTTCC CTTCCTTTCT 8881
CGCCACGTTC GCCGGCTTTC CCCGTCAAGC TCTAAATCGG GGGCTCCCTT TAGGGTTCCG
8941 ATTTAGTGCT TTACGGCACC TCGACCCCAA AAAACTTGAT TAGGGTGATG
GTTCACGTAG 9001 TGGGCCATCG CCCTGATAGA CGGTTTTTCG CCCTTTGACG
TTGGAGTCCA CGTTCTTTAA 9061 TAGTGGACTC TTGTTCCAAA CTGGAACAAC
ACTCAACCCT ATCTCGGTCT ATTCTTTTGA 9121 TTTATAAGGG ATTTTGCCGA
TTTCGGCCTA TTGGTTAAAA AATGAGCTGA TTTAACAAAA 9181 ATTTAACGCG
AATTTTAACA AAATATTAAC GCTTACAATT TAGGTGGCAC TTTTCGGGGA 9241
AATGTGCGCG GAACCCCTAT TTGTTTATTT TTCTAAATAC ATTCAAATAT GTATCCGCTC
bla ~~~~~~~~~ 9301 ATGAGACAAT AACCCTGATA AATGCTTCAA TAATATTGAA
AAAGGAAGAG TATGAGTATT bla
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
9361 CAACATTTCC GTGTCGCCCT TATTCCCTTT TTTGCGGCAT TTTGCCTTCC
TGTTTTTGCT bla
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
9421 CACCCAGAAA CGCTGGTGAA AGTAAAAGAT GCTGAAGATC AGTTGGGTGC
ACGAGTGGGT bla
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
9481 TACATCGAAC TGGATCTCAA CAGCGGTAAG ATCCTTGAGA GTTTTCGCCC
CGAAGAACGT bla
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
9541 TTTCCAATGA TGAGCACTTT TAAAGTTCTG CTATGTGGCG CGGTATTATC
CCGTATTGAC bla
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
9601 GCCGGGCAAG AGCAACTCGG TCGCCGCATA CACTATTCTC AGAATGACTT
GGTTGAGTAC bla
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
9661 TCACCAGTCA CAGAAAAGCA TCTTACGGAT GGCATGACAG TAAGAGAATT
ATGCAGTGCT bla
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
9721 GCCATAACCA TGAGTGATAA CACTGCGGCC AACTTACTTC TGACAACGAT
CGGAGGACCG bla
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
9781 AAGGAGCTAA CCGCTTTTTT GCACAACATG GGGGATCATG TAACTCGCCT
TGATCGTTGG bla
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
9841 GAACCGGAGC TGAATGAAGC CATACCAAAC GACGAGCGTG ACACCACGAT
GCCTGTAGCA bla
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
9901 ATGGCAACAA CGTTGCGCAA ACTATTAACT GGCGAACTAC TTACTCTAGC
TTCCCGGCAA bla
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
9961 CAATTAATAG ACTGGATGGA GGCGGATAAA GTTGCAGGAC CACTTCTGCG
CTCGGCCCTT bla
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
10021 CCGGCTGGCT GGTTTATTGC TGATAAATCT GGAGCCGGTG AGCGTGGGTC
TCGCGGTATC bla
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
10081 ATTGCAGCAC TGGGGCCAGA TGGTAAGCCC TCCCGTATCG TAGTTATCTA
CACGACGGGG bla
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
10141 AGTCAGGCAA CTATGGATGA ACGAAATAGA CAGATCGCTG AGATAGGTGC
CTCACTGATT bla
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
10201 AAGCATTGGT AACTGTCAGA CCAAGTTTAC TCATATATAC TTTAGATTGA
TTTAAAACTT 10261 CATTTTTAAT TTAAAAGGAT CTAGGTGAAG ATCCTTTTTG
ATAATCTCAT GACCAAAATC 10321 CCTTAACGTG AGTTTTCGTT CCACTGAGCG
TCAGACCCCG TAGAAAAGAT CAAAGGATCT 10381 TCTTGAGATC CTTTTTTTCT
GCGCGTAATC TGCTGCTTGC AAACAAAAAA ACCACCGCTA 10441 CCAGCGGTGG
TTTGTTTGCC GGATCAAGAG CTACCAACTC TTTTTCCGAA GGTAACTGGC 10501
TTCAGCAGAG CGCAGATACC AAATACTGTT CTTCTAGTGT AGCCGTAGTT AGGCCACCAC
10561 TTCAAGAACT CTGTAGCACC GCCTACATAC CTCGCTCTGC TAATCCTGTT
ACCAGTGGCT 10621 GCTGCCAGTG GCGATAAGTC GTGTCTTACC GGGTTGGACT
CAAGACGATA GTTACCGGAT 10681 AAGGCGCAGC GGTCGGGCTG AACGGGGGGT
TCGTGCACAC AGCCCAGCTT GGAGCGAACG 10741 ACCTACACCG AACTGAGATA
CCTACAGCGT GAGCTATGAG AAAGCGCCAC GCTTCCCGAA 10801 GGGAGAAAGG
CGGACAGGTA TCCGGTAAGC GGCAGGGTCG GAACAGGAGA GCGCACGAGG 10861
GAGCTTCCAG GGGGAAACGC CTGGTATCTT TATAGTCCTG TCGGGTTTCG CCACCTCTGA
10921 CTTGAGCGTC GATTTTTGTG ATGCTCGTCA GGGGGGCGGA GCCTATGGAA
AAACGCCAGC 10981 AACGCGGCCT TTTTACGGTT CCTGGCCTTT TGCTGGCCTT
TTGCTCACAT GTTCTTTCCT 11041 GCGTTATCCC CTGATTCTGT GGATAACCGT
ATTACCGCCT TTGAGTGAGC TGATACCGCT 11101 CGCCGCAGCC GAACGACCGA
GCGCAGCGAG TCAGTGAGCG AGGAAGCGGA AGAGCGCCCA 11161 ATACGCAAAC
CGCCTCTCCC CGCGCGTTGG CCGATTCATT AATGCAGCTG GCACGACAGG 11221
TTTCCCGACT GGAAAGCGGG CAGTGAGCGC AACGCAATTA ATGTGAGTTA GCTCACTCAT
11281 TAGGCACCCC AGGCTTTACA CTTTATGCTC CCGGCTCGTA TGTTGTGTGG
AATTGTGAGC 11341 GGATAACAAT TTCACACAGG AAACAGCTAT GACCATGATT
ACGCCAAGCG CGCAATTAAC 11401 CCTCACTAAA GGGAACAAAA GCTGGGTACC
GGGCCCACGC GTAATACGAC TCACTATAG
TABLE-US-00066 VEE cap helper 5'UTR
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ nsP1
~~~~~~~~~~~~~~~~~ 1 ATAGGCGGCG CATGAGAGAA GCCCAGACCA ATTACCTACC
CAAATAGGAG AAAGTTCACG nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
61 TTGACATCGA GGAAGACAGC CCATTCCTCA GAGCTTTGCA GCGGAGCTTC
CCGCAGTTTG nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
121 AGGTAGAAGC CAAGCAGGTC ACTGATAATG ACCATGCTAA TGCCAGAGCG
TTTTCGCATC nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
181 TGGCTTCAAA ACTGATCGAA ACGGAGGTGG ACCCATCCGA CACGATCCTT
GACATTGGAC VEECAP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 241
GGACCGACCA TGTTCCCGTT CCAGCCAATG TATCCGATGC AGCCAATGCC CTATCGCAAC
VEECAP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
301 CCGTTCGCGG CCCCGCGCAG GCCCTGGTTC CCCAGAACCG ACCCTTTTCT
GGCGATGCAG VEECAP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
361 GTGCAGGAAT TAACCCGCTC GATGGCTAAC CTGACGTTCA AGCAACGCCG
GGACGCGCCA VEECAP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
421 CCTGAGGGGC CATCCGCTAA GAAACCGAAG AAGGAGGCCT CGCAAAAACA
GAAAGGGGGA VEECAP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
481 GGCCAAGGGA AGAAGAAGAA GAACCAAGGG AAGAAGAAGG CTAAGACAGG
GCCGCCTAAT VEECAP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
541 CCGAAGGCAC AGAATGGAAA CAAGAAGAAG ACCAACAAGA AACCAGGCAA
GAGACAGCGC VEECAP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
601 ATGGTCATGA AATTGGAATC TGACAAGACG TTCCCAATCA TGTTGGAAGG
GAAGATAAAC VEECAP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
H152G ~~~ 661 GGCTACGCTT GTGTGGTCGG AGGGAAGTTA TTCAGGCCGA
TGGGTGTGGA AGGCAAGATC VEECAP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
721 GACAACGACG TTCTGGCCGC GCTTAAGACG AAGAAAGCAT CCAAATACGA
TCTTGAGTAT VEECAP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
781 GCAGATGTGC CACAGAACAT GCGGGCCGAT ACATTCAAAT ACACCCATGA
GAAACCCCAA VEECAP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
841 GGCTATTACA GCTGGCATCA TGGAGCAGTC CAATATGAAA ATGGGCGTTT
CACGGTGCCG VEECAP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
901 AAAGGAGTTG GGGCCAAGGG AGACAGCGGA CGACCCATTC TGGATAACCA
GGGACGGGTG VEECAP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
961 GTCGCTATTG TGCTGGGAGG TGTGAATGAA GGATCTAGGA CAGCCCTTTC
AGTCGTCATG VEECAP
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1021 TGGAACGAGA AGGGAGTTAC CGTGAAGTAT ACTCCGGAGA ACTGCGAGCA
ATGGTAATAG VEECAP 3'UTR ~~~
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 1081
TAAGCGGCCG CATACAGCAG CAATTGGCAA GCTGCTTACA TAGAACTCGC GGCGATTGGC
3'UTR
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1141 ATGCCGCCTT AAAATTTTTA TTTTATTTTT CTTTTCTTTT CCGAATCGGA
TTTTGTTTTT 3'UTR HDV ribozyme ~~~~~~~~ ~~~~~~~~~~~~~~~~~~ 1201
AATATTTCAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAGGGTCGG CATGGCATCT
HDV ribozyme
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1261 CCACCTCCTC GCGGTCCGAC CTGGGCATCC GAAGGAGGAC GCACGTCCAC
TCGGATGGCT HDV ribozyme ~~~~~~~~~~~~~~ 1321 AAGGGAGAGC CACGTTTAAA
CACGTGATAT CTGGCCTCAT GGGCCTTCCT TTCACTGCCC 1381 GCTTTCCAGT
CGGGAAACCT GTCGTGCCAG CTGCATTAAC ATGGTCATAG CTGTTTCCTT 1441
GCGTATTGGG CGCTCTCCGC TTCCTCGCTC ACTGACTCGC TGCGCTCGGT CGTTCGGGTA
colE1 ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 1501
AAGCCTGGGG TGCCTAATGA GCAAAAGGCC AGCAAAAGGC CAGGAACCGT AAAAAGGCCG
colE1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1561 CGTTGCTGGC GTTTTTCCAT AGGCTCCGCC CCCCTGACGA GCATCACAAA
AATCGACGCT colE1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1621 CAAGTCAGAG GTGGCGAAAC CCGACAGGAC TATAAAGATA CCAGGCGTTT
CCCCCTGGAA colE1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1681 GCTCCCTCGT GCGCTCTCCT GTTCCGACCC TGCCGCTTAC CGGATACCTG
TCCGCCTTTC colE1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1741 TCCCTTCGGG AAGCGTGGCG CTTTCTCATA GCTCACGCTG TAGGTATCTC
AGTTCGGTGT colE1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1801 AGGTCGTTCG CTCCAAGCTG GGCTGTGTGC ACGAACCCCC CGTTCAGCCC
GACCGCTGCG colE1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1861 CCTTATCCGG TAACTATCGT CTTGAGTCCA ACCCGGTAAG ACACGACTTA
TCGCCACTGG colE1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1921 CAGCAGCCAC TGGTAACAGG ATTAGCAGAG CGAGGTATGT AGGCGGTGCT
ACAGAGTTCT colE1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1981 TGAAGTGGTG GCCTAACTAC GGCTACACTA GAAGAACAGT ATTTGGTATC
TGCGCTCTGC colE1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2041 TGAAGCCAGT TACCTTCGGA AAAAGAGTTG GTAGCTCTTG ATCCGGCAAA
CAAACCACCG colE1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2101 CTGGTAGCGG TGGTTTTTTT GTTTGCAAGC AGCAGATTAC GCGCAGAAAA
AAAGGATCTC colE1 ~~~~~~~~~~~~~~~~~~~~~~~~~~~ 2161 AAGAAGATCC
TTTGATCTTT TCTACGGGGT CTGACGCTCA GTGGAACGAA AACTCACGTT 2221
AAGGGATTTT GGTCATGAGA TTATCAAAAA GGATCTTCAC CTAGATCCTT TTAAATTAAA
2281 AATGAAGTTT TAAATCAATC TAAAGTATAT ATGAGTAAAC TTGGTCTGAC
AGTTATTAGA ~~~ KanR 2341 AAAATTCATC CAGCAGACGA TAAAACGCAA
TACGCTGGCT ATCCGGTGCC GCAATGCCAT
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 2401 ACAGCACCAG AAAACGATCC GCCCATTCGC CGCCCAGTTC TTCCGCAATA
TCACGGGTGG
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 2461 CCAGCGCAAT ATCCTGATAA CGATCCGCCA CGCCCAGACG GCCGCAATCA
ATAAAGCCGC
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 2521 TAAAACGGCC ATTTTCCACC ATAATGTTCG GCAGGCACGC ATCACCATGG
GTCACCACCA
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 2581 GATCTTCGCC ATCCGGCATG CTCGCTTTCA GACGCGCAAA CAGCTCTGCC
GGTGCCAGGC
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 2641 CCTGATGTTC TTCATCCAGA TCATCCTGAT CCACCAGGCC CGCTTCCATA
CGGGTACGCG
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 2701 CACGTTCAAT ACGATGTTTC GCCTGATGAT CAAACGGACA GGTCGCCGGG
TCCAGGGTAT
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 2761 GCAGACGACG CATGGCATCC GCCATAATGC TCACTTTTTC TGCCGGCGCC
AGATGGCTAG
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 2821 ACAGCAGATC CTGACCCGGC ACTTCGCCCA GCAGCAGCCA ATCACGGCCC
GCTTCGGTCA
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 2881 CCACATCCAG CACCGCCGCA CACGGAACAC CGGTGGTGGC CAGCCAGCTC
AGACGCGCCG
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 2941 CTTCATCCTG CAGCTCGTTC AGCGCACCGC TCAGATCGGT TTTCACAAAC
AGCACCGGAC
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 3001 GACCCTGCGC GCTCAGACGA AACACCGCCG CATCAGAGCA GCCAATGGTC
TGCTGCGCCC
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 3061 AATCATAGCC AAACAGACGT TCCACCCACG CTGCCGGGCT ACCCGCATGC
AGGCCATCCT
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 3121 GTTCAATCAT ACTCTTCCTT TTTCAATATT ATTGAAGCAT TTATCAGGGT
TATTGTCTCA ~~~~~~~~~~~ KanR 3181 TGAGCGGATA CATATTTGAA TGTATTTAGA
AAAATAAACA AATAGGGGTT CCGCGCACAT 3241 TTCCCCGAAA AGTGCCACCT
AAATTGTAAG CGTTAATATT TTGTTAAAAT TCGCGTTAAA 3301 TTTTTGTTAA
ATCAGCTCAT TTTTTAACCA ATAGGCCGAA ATCGGCAAAA TCCCTTATAA 3361
ATCAAAAGAA TAGACCGAGA TAGGGTTGAG TGGCCGCTAC AGGGCGCTCC CATTCGCCAT
3421 TCAGGCTGCG CAACTGTTGG GAAGGGCGTT TCGGTGCGGG CCTCTTCGCT
ATTACGCCAG 3481 CTGGCGAAAG GGGGATGTGC TGCAAGGCGA TTAAGTTGGG
TAACGCCAGG GTTTTCCCAG T7 promoter ~~~~~~~~~~~~~~~~~~~~ 3541
TCACACGCGT AATACGACTC ACTATAG
TABLE-US-00067 VEE gly helper 5'UTR
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ nsP1
~~~~~~~~~~~~~~~~~ 1 ATAGGCGGCG CATGAGAGAA GCCCAGACCA ATTACCTACC
CAAATAGGAG AAAGTTCACG nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
61 TTGACATCGA GGAAGACAGC CCATTCCTCA GAGCTTTGCA GCGGAGCTTC
CCGCAGTTTG nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
121 AGGTAGAAGC CAAGCAGGTC ACTGATAATG ACCATGCTAA TGCCAGAGCG
TTTTCGCATC nsP1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
181 TGGCTTCAAA ACTGATCGAA ACGGAGGTGG ACCCATCCGA CACGATCCTT
GACATTGGAC VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 241
GGACCGACCA TGTCACTAGT GACCACCATG TGTCTGCTCG CCAATGTGAC GTTCCCATGT
VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
301 GCTCAACCAC CAATTTGCTA CGACAGAAAA CCAGCAGAGA CTTTGGCCAT
GCTCAGCGTT VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
361 AACGTTGACA ACCCGGGCTA CGATGAGCTG CTGGAAGCAG CTGTTAAGTG
CCCCGGAAGG VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
421 AAAAGGAGAT CCACCGAGGA GCTGTTTAAT GAGTATAAGC TAACGCGCCC
TTACATGGCC VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
481 AGATGCATCA GATGTGCAGT TGGGAGCTGC CATAGTCCAA TAGCAATCGA
GGCAGTAAAG VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
541 AGCGACGGGC ACGACGGTTA TGTTAGACTT CAGACTTCCT CGCAGTATGG
CCTGGATTCC VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
601 TCCGGCAACT TAAAGGGCAG GACCATGCGG TATGACATGC ACGGGACCAT
TAAAGAGATA VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
661 CCACTACATC AAGTGTCACT CTATACATCT CGCCCGTGTC ACATTGTGGA
TGGGCACGGT VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
721 TTTCCTGC TTGCCAGGTG CCCGGCAGGG GACTCCATCA CCATGGAATT TAAGAAAGAT
VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
781 TCCGTCAGAC ACTCCTGCTC GGTGCCGTAT GAAGTGAAAT TTAATCCTGT
AGGCAGAGAA VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
841 CTCTATACTC ATCCCCCAGA ACACGGAGTA GAGCAAGCGT GCCAAGTCTA
CGCACATGAT VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
901 GCACAGAACA GAGGAGCTTA TGTCGAGATG CACCTCCCGG GCTCAGAAGT
GGACAGCAGT VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
961 TTGGTTTCCT TGAGCGGCAG TTCAGTCACC GTGACACCTC CTGATGGGAC
TAGCGCCCTG VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1021 GTGGAATGCG AGTGTGGCGG CACAAAGATC TCCGAGACCA TCAACAAGAC
AAAACAGTTC VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1081 AGCCAGTGCA CAAAGAAGGA GCAGTGCAGA GCATATCGGC TGCAGAACGA
TAAGTGGGTG VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1141 TATAATTCTG ACAAACTGCC CAAAGCAGCG GGAGCCACCT TAAAAGGAAA
ACTGCATGTC VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1201 CCATTCTTGC TGGCAGACGG CAAATGCACC GTGCCTCTAG CACCAGAACC
TATGATAACC VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1261 TTCGGTTTCA GATCAGTGTC ACTGAAACTG CACCCTAAGA ATCCCACATA
TCTAATCACC VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1321 CGCCAACTTG CTGATGAGCC TCACTACACG CACGAGCTCA TATCTGAACC
AGCTGTTAGG VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1381 AATTTTACCG TCACCGAAAA AGGGTGGGAG TTTGTATGGG GAAACCACCC
GCCGAAAAGG VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1441 TTTTGGGCAC AGGAAACAGC ACCCGGAAAT CCACATGGGC TACCGCACGA
GGTGATAACT VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1501 CATTATTACC ACAGATACCC TATGTCCACC ATCCTGGGTT TGTCAATTTG
TGCCGCCATT VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1561 GCAACCGTTT CCGTTGCAGC GTCTACCTGG CTGTTTTGCA GATCTAGAGT
TGCGTGCCTA VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1621 ACTCCTTACC GGCTAACACC TAACGCTAGG ATACCATTTT GTCTGGCTGT
GCTTTGCTGC VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1681 GCCCGCACTG CCCGGGCCGA GACCACCTGG GAGTCCTTGG ATCACCTATG
GAACAATAAC VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1741 CAACAGATGT TCTGGATTCA ATTGCTGATC CCTCTGGCCG CCTTGATCGT
AGTGACTCGC VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1801 CTGCTCAGGT GCGTGTGCTG TGTCGTGCCT TTTTTAGTCA TGGCCGGCGC
CGCAGGCGCC VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1861 GGCGCCTACG AGCACGCGAC CACGATGCCG AGCCAAGCGG GAATCTCGTA
TAACACTATA VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1921 GTCAACAGAG CAGGCTACGC ACCACTCCCT ATCAGCATAA CACCAACAAA
GATCAAGCTG VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
1981 ATACCTACAG TGAACTTGGA GTACGTCACC TGCCACTACA AAACAGGAAT
GGATTCACCA VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2041 GCCATCAAAT GCTGCGGATC TCAGGAATGC ACTCCAACTT ACAGGCCTGA
TGAACAGTGC VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2101 AAAGTCTTCA CAGGGGTTTA CCCGTTCATG TGGGGTGGTG CATATTGCTT
TTGCGACACT VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2161 GAGAACACCC AAGTCAGCAA GGCCTACGTA ATGAAATCTG ACGACTGCCT
TGCGGATCAT VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2221 GCTGAAGCAT ATAAAGCGCA CACAGCCTCA GTGCAGGCGT TCCTCAACAT
CACAGTGGGA VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2281 GAACACTCTA TTGTGACTAC CGTGTATGTG AATGGAGAAA CTCCTGTGAA
TTTCAATGGG VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2341 GTCAAAATAA CTGCAGGTCC GCTTTCCACA GCTTGGACAC CCTTTGATCG
CAAAATCGTG VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2401 CAGTATGCCG GGGAGATCTA TAATTATGAT TTTCCTGAGT ATGGGGCAGG
ACAACCAGGA VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2461 GCATTTGGAG ATATACAATC CAGAACAGTC TCAAGCTCTG ATCTGTATGC
CAATACCAAC VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2521 CTAGTGCTGC AGAGACCCAA AGCAGGAGCG ATCCACGTGC CATACACTCA
GGCACCTTCG VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2581 GGTTTTGAGC AATGGAAGAA AGATAAAGCT CCATCATTGA AATTTACCGC
CCCTTTCGGA VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2641 TGCGAAATAT ATACAAACCC CATTCGCGCC GAAAACTGTG CTGTAGGGTC
AATTCCATTA VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2701 GCCTTTGACA TTCCCGACGC CTTGTTCACC AGGGTGTCAG AAACACCGAC
ACTTTCAGCG VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2761 GCCGAATGCA CTCTTAACGA GTGCGTGTAT TCTTCCGACT TTGGTGGGAT
CGCCACGGTC VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2821 AAGTACTCGG CCAGCAAGTC AGGCAAGTGC GCAGTCCATG TGCCATCAGG
GACTGCTACC VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2881 CTAAAAGAAG CAGCAGTCGA GCTAACCGAG CAAGGGTCGG CGACTATCCA
TTTCTCGACC VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2941 GCAAATATCC ACCCGGAGTT CAGGCTCCAA ATATGCACAT CATATGTTAC
GTGCAAAGGT VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3001 GATTGTCACC CCCCGAAAGA CCATATTGTG ACACACCCTC AGTATCACGC
CCAAACATTT VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3061 ACAGCCGCGG TGTCAAAAAC CGCGTGGACG TGGTTAACAT CCCTGCTGGG
AGGATCAGCC VEE GLY
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3121 GTAATTATTA TAATTGGCTT GGTGCTGGCT ACTATTGTGG CCATGTACGT
GCTGACCAAC VEE GLY 3'UTR ~~~~~~~~~~~~~~~~~~~~~~~
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 3181 CAGAAACATA ATTAATAGTA
AGCGGCCGCA TACAGCAGCA ATTGGCAAGC TGCTTACATA 3'UTR
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3241 GAACTCGCGG CGATTGGCAT GCCGCCTTAA AATTTTTATT TTATTTTTCT
TTTCTTTTCC 3'UTR ~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 3301 GAATCGGATT
TTGTTTTTAA TATTTCAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA HDV ribozyme
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3361 AGGGTCGGCA TGGCATCTCC ACCTCCTCGC GGTCCGACCT GGGCATCCGA
AGGAGGACGC HDV ribozyme ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 3421
ACGTCCACTC GGATGGCTAA GGGAGAGCCA CGTTTAAACA CGTGATATCT GGCCTCATGG
3481 GCCTTCCTTT CACTGCCCGC TTTCCAGTCG GGAAACCTGT CGTGCCAGCT
GCATTAACAT 3541 GGTCATAGCT GTTTCCTTGC GTATTGGGCG CTCTCCGCTT
CCTCGCTCAC TGACTCGCTG colE1 ~~~~~~~~~~~~~~~~~~~~~~~~~~~ 3601
CGCTCGGTCG TTCGGGTAAA GCCTGGGGTG CCTAATGAGC AAAAGGCCAG CAAAAGGCCA
colE1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3661 GGAACCGTAA AAAGGCCGCG TTGCTGGCGT TTTTCCATAG GCTCCGCCCC
CCTGACGAGC colE1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3721 ATCACAAAAA TCGACGCTCA AGTCAGAGGT GGCGAAACCC GACAGGACTA
TAAAGATACC
colE1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3781 AGGCGTTTCC CCCTGGAAGC TCCCTCGTGC GCTCTCCTGT TCCGACCCTG
CCGCTTACCG colE1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3841 GATACCTGTC CGCCTTTCTC CCTTCGGGAA GCGTGGCGCT TTCTCATAGC
TCACGCTGTA colE1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3901 GGTATCTCAG TTCGGTGTAG GTCGTTCGCT CCAAGCTGGG CTGTGTGCAC
GAACCCCCCG colE1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3961 TTCAGCCCGA CCGCTGCGCC TTATCCGGTA ACTATCGTCT TGAGTCCAAC
CCGGTAAGAC colE1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
4021 ACGACTTATC GCCACTGGCA GCAGCCACTG GTAACAGGAT TAGCAGAGCG
AGGTATGTAG colE1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
4081 GCGGTGCTAC AGAGTTCTTG AAGTGGTGGC CTAACTACGG CTACACTAGA
AGAACAGTAT colE1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
4141 TTGGTATCTG CGCTCTGCTG AAGCCAGTTA CCTTCGGAAA AAGAGTTGGT
AGCTCTTGAT colE1
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
4201 CCGGCAAACA AACCACCGCT GGTAGCGGTG GTTTTTTTGT TTGCAAGCAG
CAGATTACGC colE1 ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
4261 GCAGAAAAAA AGGATCTCAA GAAGATCCTT TGATCTTTTC TACGGGGTCT
GACGCTCAGT 4321 GGAACGAAAA CTCACGTTAA GGGATTTTGG TCATGAGATT
ATCAAAAAGG ATCTTCACCT 4381 AGATCCTTTT AAATTAAAAA TGAAGTTTTA
AATCAATCTA AAGTATATAT GAGTAAACTT 4441 GGTCTGACAG TTATTAGAAA
AATTCATCCA GCAGACGATA AAACGCAATA CGCTGGCTAT
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ KanR 4501
CCGGTGCCGC AATGCCATAC AGCACCAGAA AACGATCCGC CCATTCGCCG CCCAGTTCTT
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 4561 CCGCAATATC ACGGGTGGCC AGCGCAATAT CCTGATAACG ATCCGCCACG
CCCAGACGGC
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 4621 CGCAATCAAT AAAGCCGCTA AAACGGCCAT TTTCCACCAT AATGTTCGGC
AGGCACGCAT
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 4681 CACCATGGGT CACCACCAGA TCTTCGCCAT CCGGCATGCT CGCTTTCAGA
CGCGCAAACA
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 4741 GCTCTGCCGG TGCCAGGCCC TGATGTTCTT CATCCAGATC ATCCTGATCC
ACCAGGCCCG
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 4801 CTTCCATACG GGTACGCGCA CGTTCAATAC GATGTTTCGC CTGATGATCA
AACGGACAGG
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 4861 TCGCCGGGTC CAGGGTATGC AGACGACGCA TGGCATCCGC CATAATGCTC
ACTTTTTCTG
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 4921 CCGGCGCCAG ATGGCTAGAC AGCAGATCCT GACCCGGCAC TTCGCCCAGC
AGCAGCCAAT
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 4981 CACGGCCCGC TTCGGTCACC ACATCCAGCA CCGCCGCACA CGGAACACCG
GTGGTGGCCA
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 5041 GCCAGCTCAG ACGCGCCGCT TCATCCTGCA GCTCGTTCAG CGCACCGCTC
AGATCGGTTT
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 5101 TCACAAACAG CACCGGACGA CCCTGCGCGC TCAGACGAAA CACCGCCGCA
TCAGAGCAGC
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 5161 CAATGGTCTG CTGCGCCCAA TCATAGCCAA ACAGACGTTC CACCCACGCT
GCCGGGCTAC
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
KanR 5221 CCGCATGCAG GCCATCCTGT TCAATCATAC TCTTCCTTTT TCAATATTAT
TGAAGCATTT ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ KanR 5281 ATCAGGGTTA
TTGTCTCATG AGCGGATACA TATTTGAATG TATTTAGAAA AATAAACAAA 5341
TAGGGGTTCC GCGCACATTT CCCCGAAAAG TGCCACCTAA ATTGTAAGCG TTAATATTTT
5401 GTTAAAATTC GCGTTAAATT TTTGTTAAAT CAGCTCATTT TTTAACCAAT
AGGCCGAAAT 5461 CGGCAAAATC CCTTATAAAT CAAAAGAATA GACCGAGATA
GGGTTGAGTG GCCGCTACAG 5521 GGCGCTCCCA TTCGCCATTC AGGCTGCGCA
ACTGTTGGGA AGGGCGTTTC GGTGCGGGCC 5581 TCTTCGCTAT TACGCCAGCT
GGCGAAAGGG GGATGTGCTG CAAGGCGATT AAGTTGGGTA T7 promoter
~~~~~~~~~~~~~~~~~~~~ 5641 ACGCCAGGGT TTTCCCAGTC ACACGCGTAA
TACGACTCAC TATAG
* * * * *