U.S. patent application number 15/767600 was filed with the patent office on 2018-10-11 for sexually transmitted disease vaccines.
This patent application is currently assigned to ModernaTX. Inc.. The applicant listed for this patent is ModernaTX. Inc.. Invention is credited to Giuseppe Ciaramella, Sunny Himansu.
Application Number | 20180289792 15/767600 |
Document ID | / |
Family ID | 58558174 |
Filed Date | 2018-10-11 |
United States Patent
Application |
20180289792 |
Kind Code |
A1 |
Ciaramella; Giuseppe ; et
al. |
October 11, 2018 |
SEXUALLY TRANSMITTED DISEASE VACCINES
Abstract
The disclosure relates to sexually transmitted disease
ribonucleic acid vaccines and combination vaccines, as well as
methods of using the vaccines and compositions comprising the
vaccines.
Inventors: |
Ciaramella; Giuseppe;
(Sudbury, MA) ; Himansu; Sunny; (Winchester,
MA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
ModernaTX. Inc. |
Cambridge |
MA |
US |
|
|
Assignee: |
ModernaTX. Inc.
Cambridge
MA
|
Family ID: |
58558174 |
Appl. No.: |
15/767600 |
Filed: |
October 21, 2016 |
PCT Filed: |
October 21, 2016 |
PCT NO: |
PCT/US2016/058314 |
371 Date: |
April 11, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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62247374 |
Oct 28, 2015 |
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62247418 |
Oct 28, 2015 |
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62244822 |
Oct 22, 2015 |
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62244884 |
Oct 22, 2015 |
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62245031 |
Oct 22, 2015 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 39/118 20130101;
A61P 31/20 20180101; A61P 31/14 20180101; C12N 2710/20071 20130101;
A61K 9/5123 20130101; C12N 7/00 20130101; A61K 2039/70 20130101;
A61K 39/245 20130101; B82Y 5/00 20130101; A61K 9/0019 20130101;
A61K 39/12 20130101; Y02A 50/39 20180101; A61P 31/22 20180101; A61K
2039/545 20130101; A61K 2039/55555 20130101; A61P 31/12 20180101;
C12N 2710/20034 20130101; Y02A 50/30 20180101; A61K 2039/53
20130101 |
International
Class: |
A61K 39/118 20060101
A61K039/118; A61K 9/00 20060101 A61K009/00; A61K 39/245 20060101
A61K039/245 |
Claims
1. A sexually transmitted disease (STD) vaccine, comprising: at
least one RNA polynucleotide having an open reading frame encoding
at least one STD antigenic polypeptide, formulated in a cationic
lipid nanoparticle.
2. The STD vaccine of claim 1, wherein the antigenic polypeptide is
selected from human papillomavirus (HPV), herpes simplex virus
(HSV) and Chlamydia trachomatis antigenic polypeptides.
3. A human papillomavirus (HPV) vaccine, comprising: at least one
ribonucleic acid (RNA) polynucleotide having an open reading frame
encoding at least one HPV antigenic polypeptide or an immunogenic
fragment thereof.
4. The vaccine of claim 3, wherein the at least one antigenic
polypeptide is selected from HPV E1 protein, HPV E2 protein, HPV E4
protein, HPV E5 protein, HPV E6 protein, HPV E7 protein, HPV L1
protein, and HPV L2 protein, optionally wherein the HPV serotype is
selected from HPV serotypes 6, 11, 16, 18, 31, 33, 35, 39, 45, 51,
52, 56, 58, 59, 68, 73 and 82.
5. The vaccine of claim 3 or 4, wherein the vaccine comprises at
least one RNA polynucleotide having an open reading frame encoding
at least two antigenic polypeptides or immunogenic fragments
thereof selected from HPV E1 protein, HPV E2 protein, HPV E4
protein, HPV E5 protein, HPV E6 protein, HPV E7 protein, HPV L1
protein, and HPV L2 protein.
6. The vaccine of any one of claims 3-5, wherein the vaccine
comprises at least two RNA polynucleotides, each having an open
reading frame encoding at least one antigenic polypeptide or an
immunogenic fragment thereof selected from HPV E1 protein, HPV E2
protein, HPV E4 protein, HPV E5 protein, HPV E6 protein, HPV E7
protein, HPV L1 protein, and HPV L2 protein, wherein the HPV
antigenic polypeptide encoded by one of the open reading frames
differs from the HPV antigenic polypeptide encoded by another of
the open reading frames.
7. The vaccine of any one of claims 3-6, wherein the at least one
antigenic polypeptide comprises an amino acid sequence identified
by any one of SEQ ID NO: 31-61.
8. The vaccine of any one of claims 3-7, wherein the at least one
RNA polypeptide is encoded by a nucleic acid sequence identified by
any one of SEQ ID NO: 1-30, and/or wherein the at least one RNA
polypeptide comprises a nucleic acid sequence identified by any one
of SEQ ID NO: 431-461.
9. The vaccine of any one of claims 3-8, wherein the at least one
antigenic polypeptide has an amino acid sequence that has at least
95% identity to an amino acid sequence identified by any one of SEQ
ID NO: 31-61.
10. The vaccine of any one of claims 3-9, wherein the at least one
antigenic polypeptide has an amino acid sequence that has 95%-99%
identity to an amino acid sequence identified by any one of SEQ ID
NO: 31-61.
11. The vaccine of any one of claims 3-10, wherein the at least one
antigenic polypeptide has an amino acid sequence that has at least
90% identity to an amino acid sequence of SEQ ID NO: 31-61 and
wherein the antigenic polypeptide or immunogenic fragment thereof
has membrane fusion activity, attaches to cell receptors, causes
fusion of viral and cellular membranes, and/or is responsible for
binding of the virus to a cell being infected.
12. The vaccine of any one of claims 3-11, wherein the at least one
antigenic polypeptide has an amino acid sequence that has 90%-99%
identity to an amino acid sequence of SEQ ID NO: 31-61 and wherein
the antigenic polypeptide or immunogenic fragment thereof has
membrane fusion activity, attaches to cell receptors, causes fusion
of viral and cellular membranes, and/or is responsible for binding
of the virus to a cell being infected.
13. A Chlamydia vaccine, comprising: at least one ribonucleic acid
(RNA) polynucleotide having an open reading frame encoding at least
one Chlamydia trachomatis antigenic polypeptide or an immunogenic
fragment thereof.
14. The vaccine of claim 13, wherein the at least one antigenic
polypeptide is a major outer membrane protein (MOMP) or an
immunogenic fragment thereof, optionally having a Chlamydia
trachomatis serovar selected serovar H, F, E, D, I, G, J and K.
15. The vaccine of claim 13 or 14, wherein the vaccine comprises at
least one RNA polynucleotide having an open reading frame encoding
at least two antigenic polypeptides or immunogenic fragments
thereof selected from a MOMP of serovar H, a MOMP of serovar F, a
MOMP of serovar E, a MOMP of serovar D, a MOMP of serovar I, a MOMP
of serovar G, a MOMP of serovar J, and a MOMP of serovar K.
16. The vaccine of any one of claims 13-15, wherein the vaccine
comprises at least two RNA polynucleotides, each having an open
reading frame encoding at least one antigenic polypeptide or an
immunogenic fragment thereof selected from a MOMP of serovar H, a
MOMP of serovar F, a MOMP of serovar E, a MOMP of serovar D, a MOMP
of serovar I, a MOMP of serovar G, a MOMP of serovar J, and a MOMP
of serovar K, wherein the antigenic polypeptide encoded by one of
the open reading frames differs from the antigenic polypeptide
encoded by another of the open reading frames.
17. The vaccine of any one of claims 13-16, wherein the at least
one antigenic polypeptide comprises an amino acid sequence
identified by any one of SEQ ID NO: 65-183.
18. The vaccine of any one of claims 13-17, wherein the at least
one RNA polypeptide is encoded by a nucleic acid sequence
identified by any one of SEQ ID NO: 62-64 or 184-294, and/or
wherein the at least one RNA polypeptide comprises a nucleic acid
sequence identified by any one of SEQ ID NO: 317-430.
19. The vaccine of any one of claims 13-18, wherein the at least
one antigenic polypeptide has an amino acid sequence that has at
least 95% identity to an amino acid sequence identified by any one
of SEQ ID NO: 65-183.
20. The vaccine of any one of claims 13-19, wherein the at least
one antigenic polypeptide has an amino acid sequence that has
95%-99% identity to an amino acid sequence identified by any one of
SEQ ID NO: 65-183.
21. The vaccine of any one of claims 13-20, wherein the at least
one antigenic polypeptide has an amino acid sequence that has at
least 90% identity to an amino acid sequence of SEQ ID NO: 65-183
and wherein the antigenic polypeptide or immunogenic fragment
thereof has membrane fusion activity, attaches to cell receptors,
causes fusion of viral and cellular membranes, and/or is
responsible for binding of the virus to a cell being infected.
22. The vaccine of any one of claims 13-21, wherein the at least
one antigenic polypeptide has an amino acid sequence that has
90%-99% identity to an amino acid sequence of SEQ ID NO: 65-183 and
wherein the antigenic polypeptide or immunogenic fragment thereof
has membrane fusion activity, attaches to cell receptors, causes
fusion of viral and cellular membranes, and/or is responsible for
binding of the virus to a cell being infected.
23. A sexually transmitted disease (STD) vaccine, comprising: at
least one ribonucleic acid (RNA) polynucleotide having an open
reading frame encoding at least two antigenic polypeptides selected
from human papillomavirus (HPV) antigenic polypeptides or
immunogenic fragments thereof, herpes simplex virus (HSV) antigenic
polypeptides or immunogenic fragments thereof, and Chlamydia
trachomatis antigenic polypeptides or immunogenic fragments
thereof.
24. The vaccine of claim 23, wherein at least one HPV antigenic
polypeptide is selected from HPV E1 protein, HPV E2 protein, HPV E4
protein, HPV E5 protein, HPV E6 protein, HPV E7 protein, HPV L1
protein, and HPV L2 protein; and/or wherein at least one HSV
antigenic polypeptide is selected from glycoprotein B, HSV
glycoprotein C, HSV glycoprotein D, HSV glycoprotein E, and HSV
(glycoprotein I); and/or wherein at least one Chlamydia trachomatis
antigenic polypeptide is a MOMP antigenic polypeptide.
25. The vaccine of claim 23, wherein the vaccine comprises at least
one RNA polynucleotide having an open reading frame encoding at
least two antigenic polypeptides or immunogenic fragments thereof
selected from HPV antigenic polypeptides or immunogenic fragments
thereof, HSV antigenic polypeptides or immunogenic fragments
thereof, and Chlamydia trachomatis antigenic polypeptides or
immunogenic fragments thereof.
26. The vaccine of any one of claims 23-25, wherein the vaccine
comprises at least two RNA polynucleotides, each having an open
reading frame encoding at least one antigenic polypeptide or an
immunogenic fragment thereof selected from HPV antigenic
polypeptides or immunogenic fragments thereof, HSV antigenic
polypeptides or immunogenic fragments thereof, and Chlamydia
trachomatis antigenic polypeptides or immunogenic fragments
thereof, wherein the antigenic polypeptide encoded by one of the
open reading frames differs from the antigenic polypeptide encoded
by another of the open reading frames.
27. The vaccine of any one of claims 23-26, wherein the at least
one antigenic polypeptide comprises an amino acid sequence
identified by any one of SEQ ID NO: 31-61 or 65-183.
28. The vaccine of any one of claims 23-27, wherein the at least
one RNA polypeptide is encoded by a nucleic acid sequence
identified by any one of SEQ ID NO: 1-28, 62-64 or 184-294, and/or
wherein the at least one RNA polypeptide comprises a nucleic acid
sequence identified by any one of SEQ ID NO: 317-319 or
320-461.
29. The vaccine of any one of claims 23-25, wherein the at least
one antigenic polypeptide has an amino acid sequence that has at
least 95% identity to an amino acid sequence identified by any one
of SEQ ID NO: 31-61 or 65-183.
30. The vaccine of any one of claims 23-25, wherein the at least
one antigenic polypeptide has an amino acid sequence that has
95%-99% identity to an amino acid sequence identified by any one of
SEQ ID NO: 31-61 or 65-183.
31. The vaccine of any one of claims 23-25, wherein the at least
one antigenic polypeptide has an amino acid sequence that has at
least 90% identity to an amino acid sequence of SEQ ID NO: 31-61 or
65-183 and wherein the antigenic polypeptide or immunogenic
fragment thereof has membrane fusion activity, attaches to cell
receptors, causes fusion of viral and cellular membranes, and/or is
responsible for binding of the virus to a cell being infected.
32. The vaccine of any one of claims 23-25, wherein the at least
one antigenic polypeptide has an amino acid sequence that has
90%-99% identity to an amino acid sequence of SEQ ID NO: 31-61 or
65-183 and wherein the antigenic polypeptide or immunogenic
fragment thereof has membrane fusion activity, attaches to cell
receptors, causes fusion of viral and cellular membranes, and/or is
responsible for binding of the virus to a cell being infected.
33. The vaccine of any one of claims 1-32, wherein the at least one
RNA polynucleotide has less than 80% identity to wild-type mRNA
sequence.
34. The vaccine of any one of claims 1-32, wherein at least one RNA
polynucleotide has at least 80% identity to wild-type mRNA
sequence, but does not include wild-type mRNA sequence.
35. The vaccine of any one of claims 1-34, wherein the at least one
antigenic polypeptide has membrane fusion activity, attaches to
cell receptors, causes fusion of viral and cellular membranes,
and/or is responsible for binding of the virus to a cell being
infected.
36. The vaccine of any one of claims 1-35, wherein the at least one
RNA polynucleotide comprises at least one chemical
modification.
37. The vaccine of claim 36, wherein the chemical modification is
selected from pseudouridine, N1-methylpseudouridine,
N1-ethylpseudouridine, 2-thiouridine, 4'-thiouridine,
5-methylcytosine, 5-methyluridine,
2-thio-1-methyl-1-deaza-pseudouridine,
2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine,
2-thio-dihydropseudouridine, 2-thio-dihydrouridine,
2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine,
4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine,
4-thio-pseudouridine, 5-aza-uridine, dihydropseudouridine,
5-methoxyuridine and 2'-O-methyl uridine.
38. The vaccine of claim 36 or 37, wherein the chemical
modification is in the 5-position of the uracil.
39. The vaccine of any one of claims 36-38, wherein the chemical
modification is a N1-methylpseudouridine or
N1-ethylpseudouridine.
40. The vaccine of any one of claims 36-39, wherein at least 80% of
the uracil in the open reading frame have a chemical
modification.
41. The vaccine of claim 40, wherein at least 90% of the uracil in
the open reading frame have a chemical modification.
42. The vaccine of claim 41, wherein 100% of the uracil in the open
reading frame have a chemical modification.
43. The vaccine of any one of claims 1-42, wherein at least one RNA
polynucleotide further encodes at least one 5' terminal cap.
44. The vaccine of claim 43, wherein the 5' terminal cap is
7mG(5')ppp(5')NlmpNp.
45. The vaccine of any one of claims 1-44, wherein at least one
antigenic polypeptide or immunogenic fragment thereof is fused to a
signal peptide selected from: a HuIgGk signal peptide
(METPAQLLFLLLLWLPDTTG; SEQ ID NO: 304); IgE heavy chain epsilon-1
signal peptide (MDWTWILFLVAAATRVHS; SEQ ID NO: 305); Japanese
encephalitis PRM signal sequence (MLGSNSGQRVVFTILLLLVAPAYS; SEQ ID
NO: 306), VSVg protein signal sequence (MKCLLYLAFLFIGVNCA; SEQ ID
NO: 307) and Japanese encephalitis JEV signal sequence
(MWLVSLAIVTACAGA; SEQ ID NO: 308).
46. The vaccine of claim 45, wherein the signal peptide is fused to
the N-terminus of at least one antigenic polypeptide.
47. The vaccine of claim 45, wherein the signal peptide is fused to
the C-terminus of at least one antigenic polypeptide.
48. The vaccine of any one of claims 1-47, wherein the antigenic
polypeptide or immunogenic fragment thereof comprises a mutated
N-linked glycosylation site.
49. The vaccine of any one of claims 3-48 formulated in a
nanoparticle.
50. The vaccine of claim 49, wherein the nanoparticle is a lipid
nanoparticle.
51. The vaccine of claim 1, 2, 50 or 51, wherein the nanoparticle
has a mean diameter of 50-200 nm.
52. The vaccine of claim 1, 2, 50 or 51, wherein the lipid
nanoparticle comprises a cationic lipid, a PEG-modified lipid, a
sterol and a non-cationic lipid.
53. The vaccine of claim 52, wherein the lipid nanoparticle carrier
comprises a molar ratio of about 20-60% cationic lipid, 0.5-15%
PEG-modified lipid, 25-55% sterol, and 25% non-cationic lipid.
54. The vaccine of claim 52 or 53, wherein the cationic lipid is an
ionizable cationic lipid and the non-cationic lipid is a neutral
lipid, and the sterol is a cholesterol.
55. The vaccine of any one of claim 53 or 54, wherein the cationic
lipid is selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319).
56. The vaccine of any one of claims 1, 2, 50-55, wherein the lipid
nanoparticle comprises a compound of Formula (I), optionally
Compound 3, 18, 20, 25, 26, 29, 30, 60, 108-112, or 122.
57. The vaccine of any one of claims 1, 2, 50-55, wherein the lipid
nanoparticle comprises a compound of Formula (II).
58. The vaccine of any one of claims 1-57, wherein the nanoparticle
has a polydispersity value of less than 0.4.
59. The vaccine of any one of claims 1-58, wherein the nanoparticle
has a net neutral charge at a neutral pH value.
60. The vaccine of any one of claims 1-59 further comprising an
adjuvant.
61. The vaccine of claim 60, wherein the adjuvant is a flagellin
protein or peptide.
62. The vaccine of claim 61, wherein the flagellin protein or
peptide comprises an amino acid sequence identified by any one of
SEQ ID NO: 301-303.
63. The vaccine of any one of claims 1-62, wherein the open reading
frame is codon-optimized.
64. The vaccine of any one of claims 1-63, wherein the vaccine is
multivalent.
65. The vaccine of any one of claims 1-64 formulated in an
effective amount to produce an antigen-specific immune
response.
66. A method of inducing an immune response in a subject, the
method comprising administering to the subject the vaccine of any
one of claims 1-65 in an amount effective to produce an
antigen-specific immune response in the subject.
67. The method of claim 66, wherein the antigen specific immune
response comprises a T cell response or a B cell response.
68. The method of claim 66 or 67, wherein the subject is
administered a single dose of the vaccine.
69. The method of claim 66 or 67, wherein the subject is
administered a booster dose of the vaccine.
70. The method of any one of claims 66-69, wherein the vaccine is
administered to the subject by intradermal injection or
intramuscular injection.
71. The method of any one of claims 66-70, wherein an
anti-antigenic polypeptide antibody titer produced in the subject
is increased by at least 1 log relative to a control.
72. The method of any one of claims 66-71, wherein an
anti-antigenic polypeptide antibody titer produced in the subject
is increased by 1-3 log relative to a control.
73. The method of any one of claims 66-72, wherein the
anti-antigenic polypeptide antibody titer produced in the subject
is increased at least 2 times relative to a control.
74. The method of any one of claims 66-73, wherein the
anti-antigenic polypeptide antibody titer produced in the subject
is increased 2-10 times relative to a control.
75. The method of any one of claims 71-74, wherein the control is
an anti-antigenic polypeptide antibody titer produced in a subject
who has not been administered a vaccine against the virus.
76. The method of any one of claims 71-74, wherein the control is
an anti-antigenic polypeptide antibody titer produced in a subject
who has been administered a live attenuated vaccine or an
inactivated vaccine against the virus.
77. The method of any one of claims 71-74, wherein the control is
an anti-antigenic polypeptide antibody titer produced in a subject
who has been administered a recombinant protein vaccine or purified
protein vaccine against the virus.
78. The method of any one of claims 71-74, wherein the control is
an anti-antigenic polypeptide antibody titer produced in a subject
who has been administered a VLP vaccine against the virus.
79. The method of any one of claims 66-78, wherein the effective
amount is a dose equivalent to an at least 2-fold reduction in the
standard of care dose of a recombinant protein vaccine or a
purified protein vaccine against the virus, and wherein an
anti-antigenic polypeptide antibody titer produced in the subject
is equivalent to an anti-antigenic polypeptide antibody titer
produced in a control subject administered the standard of care
dose of a recombinant protein vaccine or a purified protein vaccine
against the virus, respectively.
80. The method of any one of claims 66-78, wherein the effective
amount is a dose equivalent to an at least 2-fold reduction in the
standard of care dose of a live attenuated vaccine or an
inactivated vaccine against the virus, and wherein an
anti-antigenic polypeptide antibody titer produced in the subject
is equivalent to an anti-antigenic polypeptide antibody titer
produced in a control subject administered the standard of care
dose of a live attenuated vaccine or an inactivated vaccine against
the virus, respectively.
81. The method of any one of claims 66-78, wherein the effective
amount is a dose equivalent to an at least 2-fold reduction in the
standard of care dose of a VLP vaccine against the virus, and
wherein an anti-antigenic polypeptide antibody titer produced in
the subject is equivalent to an anti-antigenic polypeptide antibody
titer produced in a control subject administered the standard of
care dose of a VLP vaccine against the virus.
82. The method of any one of claims 66-81, wherein the effective
amount is a total dose of 50 .mu.g-1000 .mu.g.
83. The method of claim 82, wherein the effective amount is a dose
of 25 .mu.g, 100 .mu.g, 400 .mu.g, or 500 .mu.g administered to the
subject a total of two times.
84. The method of any one of claims 66-83, wherein the efficacy of
the vaccine against the virus is greater than 65%.
85. The method of any one of claims 66-84, wherein the vaccine
immunizes the subject against the virus for up to 2 years.
86. The method of any one of claims 66-84, wherein the vaccine
immunizes the subject against the virus for more than 2 years.
87. The method of any one of claims 66-86, wherein the subject has
an age of about 12 to about 50 years old.
88. The method of any one of claims 66-87, wherein the subject has
been exposed to the virus, wherein the subject is infected with the
virus, or wherein the subject is at risk of infection by the
virus.
89. The method of any one of claims 66-88, wherein the subject is
immunocompromised.
90. The vaccine of any one of claims 1-65 for use in a method of
inducing an antigen specific immune response in a subject, the
method comprising administering to the subject the vaccine in an
amount effective to produce an antigen specific immune response in
the subject.
91. Use of the vaccine of any one of claims 1-65 in the manufacture
of a medicament for use in a method of inducing an antigen specific
immune response in a subject, the method comprising administering
to the subject the vaccine in an amount effective to produce an
antigen specific immune response in the subject.
92. An engineered nucleic acid encoding at least one RNA
polynucleotide of a vaccine of any one of claims 1-65.
93. A pharmaceutical composition for use in vaccination of a
subject comprising an effective dose of mRNA encoding a sexually
transmitted disease antigen, wherein the effective dose is
sufficient to produce detectable levels of antigen as measured in
serum of the subject at 1-72 hours post administration.
94. The composition of claim 93, wherein the cut off index of the
antigen is 1-2.
95. A pharmaceutical composition for use in vaccination of a
subject comprising an effective dose of mRNA encoding a sexually
transmitted disease antigen, wherein the effective dose is
sufficient to produce a 1,000-10,000 neutralization titer produced
by neutralizing antibody against said antigen as measured in serum
of the subject at 1-72 hours post administration.
96. A vaccine comprising an mRNA encoding a sexually transmitted
disease antigen formulated in a lipid nanoparticle comprising
compounds of Formula (I): ##STR00055## or a salt or isomer thereof,
wherein: R.sub.1 is selected from the group consisting of
C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'', --YR'', and
--R''M'R'; R.sub.2 and R.sub.3 are independently selected from the
group consisting of H, C.sub.1-14 alkyl, C.sub.2-14 alkenyl,
--R*YR'', --YR'', and --R*OR'', or R.sub.2 and R.sub.3, together
with the atom to which they are attached, form a heterocycle or
carbocycle; R.sub.4 is selected from the group consisting of a
C.sub.3-6 carbocycle, --(CH.sub.2).sub.nQ, --(CH.sub.2).sub.nCHQR,
--CHQR, --CQ(R).sub.2, and unsubstituted C.sub.1-6 alkyl, where Q
is selected from a carbocycle, heterocycle, --OR,
--O(CH.sub.2).sub.nN(R).sub.2, --C(O)OR, --OC(O)R, --CX.sub.3,
--CX.sub.2H, --CXH.sub.2, --CN, --N(R).sub.2, --C(O)N(R).sub.2,
--N(R)C(O)R, --N(R)S(O).sub.2R, --N(R)C(O)N(R).sub.2,
--N(R)C(S)N(R).sub.2, --N(R)R.sub.8, --O(CH.sub.2).sub.nOR,
--N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)N(R).sub.2,
--C(.dbd.NR.sub.9)R, --C(O)N(R)O R, and --C(R)N(R).sub.2C(O)OR, and
each n is independently selected from 1, 2, 3, 4, and 5; each
R.sub.5 is independently selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each R.sub.6 is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; M and M' are independently
selected from --C(O)O--, --OC(O)--, --C(O)N(R')--, --N(R')C(O)--,
--C(O)--, --C(S)--, --C(S)S--, --SC(S)--, --CH(OH)--,
--P(O)(OR')O--, --S(O).sub.2--, --S--S--, an aryl group, and a
heteroaryl group; R.sub.7 is selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; R.sub.8 is selected from
the group consisting of C.sub.3-6 carbocycle and heterocycle;
R.sub.9 is selected from the group consisting of H, CN, NO.sub.2,
C.sub.1-6 alkyl, --OR, --S(O).sub.2R, --S(O).sub.2N(R).sub.2,
C.sub.2-6 alkenyl, C.sub.3-6 carbocycle and heterocycle; each R is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; each R' is independently selected
from the group consisting of C.sub.1-18 alkyl, C.sub.2-18 alkenyl,
--R*YR'', --YR'', and H; each R'' is independently selected from
the group consisting of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
each R* is independently selected from the group consisting of
C.sub.1-12 alkyl and C.sub.2-12 alkenyl; each Y is independently a
C.sub.3-6 carbocycle; each X is independently selected from the
group consisting of F, Cl, Br, and I; and m is selected from 5, 6,
7, 8, 9, 10, 11, 12, and 13.
97. The vaccine of claim 96, wherein a subset of compounds of
Formula (I) includes those in which when R.sub.4 is
--(CH.sub.2).sub.nQ, --(CH.sub.2).sub.nCHQR, --CHQR, or
-CQ(R).sub.2, then (i) Q is not --N(R).sub.2 when n is 1, 2, 3, 4
or 5, or (ii) Q is not 5, 6, or 7-membered heterocycloalkyl when n
is 1 or 2.
98. The vaccine of claim 96, wherein a subset of compounds of
Formula (I) includes those in which R.sub.1 is selected from the
group consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; R.sub.2 and R.sub.3 are independently
selected from the group consisting of H, C.sub.1-14 alkyl,
C.sub.2-14 alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and
R.sub.3, together with the atom to which they are attached, form a
heterocycle or carbocycle; R.sub.4 is selected from the group
consisting of a C.sub.3-6 carbocycle, --(CH.sub.2).sub.nQ,
--(CH.sub.2).sub.nCHQR, --CHQR, --CQ(R).sub.2, and unsubstituted
C.sub.1-6 alkyl, where Q is selected from a C.sub.3-6 carbocycle, a
5- to 14-membered heteroaryl having one or more heteroatoms
selected from N, O, and S, --OR, --O(CH.sub.2)--N(R).sub.2,
--C(O)OR, --OC(O)R, --CX.sub.3, --CX.sub.2H, --CXH.sub.2, --CN,
--C(O)N(R).sub.2, --N(R)C(O)R, --N(R)S(O).sub.2R,
--N(R)C(O)N(R).sub.2, --N(R)C(S)N(R).sub.2, --CRN(R).sub.2C(O)OR,
--N(R)R.sub.8, --O(CH.sub.2).sub.nOR,
--N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)N(R).sub.2,
--C(.dbd.NR.sub.9)R, --C(O)N(R)O R, and a 5- to 14-membered
heterocycloalkyl having one or more heteroatoms selected from N, O,
and S which is substituted with one or more substituents selected
from oxo (.dbd.O), OH, amino, mono- or di-alkylamino, and C.sub.1-3
alkyl, and each n is independently selected from 1, 2, 3, 4, and 5;
each R.sub.5 is independently selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each R.sub.6 is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; M and M' are independently
selected from --C(O)O--, --OC(O)--, --C(O)N(R')--, --N(R')C(O)--,
--C(O)--, --C(S)--, --C(S)S--, --SC(S)--, --CH(OH)--,
--P(O)(OR')O--, --S(O).sub.2--, --S--S--, an aryl group, and a
heteroaryl group; R.sub.7 is selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; R.sub.8 is selected from
the group consisting of C.sub.3-6 carbocycle and heterocycle;
R.sub.9 is selected from the group consisting of H, CN, NO.sub.2,
C.sub.1-6 alkyl, --OR, --S(O).sub.2R, --S(O).sub.2N(R).sub.2,
C.sub.2-6 alkenyl, C.sub.3-6 carbocycle and heterocycle; each R is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; each R' is independently selected
from the group consisting of C.sub.1-18 alkyl, C.sub.2-18 alkenyl,
--R*YR'', --YR'', and H; each R'' is independently selected from
the group consisting of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
each R* is independently selected from the group consisting of
C.sub.1-12 alkyl and C.sub.2-12 alkenyl; each Y is independently a
C.sub.3-6 carbocycle; each X is independently selected from the
group consisting of F, Cl, Br, and I; and m is selected from 5, 6,
7, 8, 9, 10, 11, 12, and 13, or salts or isomers thereof.
99. The vaccine of claim 96, wherein a subset of compounds of
Formula (I) includes those in which R.sub.1 is selected from the
group consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; R.sub.2 and R.sub.3 are independently
selected from the group consisting of H, C.sub.1-14 alkyl,
C.sub.2-14 alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and
R.sub.3, together with the atom to which they are attached, form a
heterocycle or carbocycle; R.sub.4 is selected from the group
consisting of a C.sub.3-6 carbocycle, --(CH.sub.2).sub.nQ,
--(CH.sub.2).sub.nCHQR, --CHQR, --CQ(R).sub.2, and unsubstituted
C.sub.1-6 alkyl, where Q is selected from a C.sub.3-6 carbocycle, a
5- to 14-membered heterocycle having one or more heteroatoms
selected from N, O, and S, --OR, --O(CH.sub.2)--N(R).sub.2,
--C(O)OR, --OC(O)R, --CX.sub.3, --CX.sub.2H, --CXH.sub.2, --CN,
--C(O)N(R).sub.2, --N(R)C(O)R, --N(R)S(O).sub.2R,
--N(R)C(O)N(R).sub.2, --N(R)C(S)N(R).sub.2, --CRN(R).sub.2C(O)OR,
--N(R)R.sub.8, --O(CH.sub.2).sub.nOR,
--N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)R,
--C(O)N(R)OR, and --C(.dbd.NR.sub.9) N(R).sub.2, and each n is
independently selected from 1, 2, 3, 4, and 5; and when Q is a 5-
to 14-membered heterocycle and (i) R.sub.4 is --(CH.sub.2).sub.nQ
in which n is 1 or 2, or (ii) R.sub.4 is --(CH.sub.2).sub.nCHQR in
which n is 1, or (iii) R.sub.4 is --CHQR, and --CQ(R).sub.2, then Q
is either a 5- to 14-membered heteroaryl or 8- to 14-membered
heterocycloalkyl; each R.sub.5 is independently selected from the
group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each
R.sub.6 is independently selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; M and M' are
independently selected from --C(O)O--, --OC(O)--, --C(O)N(R')--,
--N(R')C(O)--, --C(O)--, --C(S)--, --C(S)S--, --SC(S)--,
--CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--, --S--S--, an aryl
group, and a heteroaryl group; R.sub.7 is selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; R.sub.8 is
selected from the group consisting of C.sub.3-6 carbocycle and
heterocycle; R.sub.9 is selected from the group consisting of H,
CN, NO.sub.2, C.sub.1-6 alkyl, --OR, --S(O).sub.2R,
--S(O).sub.2N(R).sub.2, C.sub.2-6 alkenyl, C.sub.3-6 carbocycle and
heterocycle; each R is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each R' is
independently selected from the group consisting of C.sub.1-18
alkyl, C.sub.2-18 alkenyl, --R*YR'', --YR'', and H; each R'' is
independently selected from the group consisting of C.sub.3-14
alkyl and C.sub.3-14 alkenyl; each R* is independently selected
from the group consisting of C.sub.1-12 alkyl and C.sub.2-12
alkenyl; each Y is independently a C.sub.3-6 carbocycle; each X is
independently selected from the group consisting of F, Cl, Br, and
I; and m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13, or
salts or isomers thereof.
100. The vaccine of claim 96, wherein a subset of compounds of
Formula (I) includes those in which R.sub.1 is selected from the
group consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; R.sub.2 and R.sub.3 are independently
selected from the group consisting of H, C.sub.1-14 alkyl,
C.sub.2-14 alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and
R.sub.3, together with the atom to which they are attached, form a
heterocycle or carbocycle; R.sub.4 is selected from the group
consisting of a C.sub.3-6 carbocycle, --(CH.sub.2).sub.nQ,
--(CH.sub.2).sub.nCHQR, --CHQR, --CQ(R).sub.2, and unsubstituted
C.sub.1-6 alkyl, where Q is selected from a C.sub.3-6 carbocycle, a
5- to 14-membered heteroaryl having one or more heteroatoms
selected from N, O, and S, --OR, --O(CH.sub.2).sub.nN(R).sub.2,
--C(O)OR, --OC(O)R, --CX.sub.3, --CX.sub.2H, --CXH.sub.2, --CN,
--C(O)N(R).sub.2, --N(R)C(O)R, --N(R)S(O).sub.2R,
--N(R)C(O)N(R).sub.2, --N(R)C(S)N(R).sub.2, --CRN(R).sub.2C(O)OR,
--N(R)R.sub.8, --O(CH.sub.2).sub.nOR,
--N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)R,
--C(O)N(R)OR, and --C(.dbd.NR.sub.9) N(R).sub.2, and each n is
independently selected from 1, 2, 3, 4, and 5; each R.sub.5 is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; each R.sub.6 is independently
selected from the group consisting of C.sub.1-3 alkyl, C.sub.2-3
alkenyl, and H; M and M' are independently selected from --C(O)O--,
--OC(O)--, --C(O)N(R')--, --N(R')C(O)--, --C(O)--, --C(S)--,
--C(S)S--, --SC(S)--, --CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--,
--S--S--, an aryl group, and a heteroaryl group; R.sub.7 is
selected from the group consisting of C.sub.1-3 alkyl, C.sub.2-3
alkenyl, and H; R.sub.8 is selected from the group consisting of
C.sub.3-6 carbocycle and heterocycle; R.sub.9 is selected from the
group consisting of H, CN, NO.sub.2, C.sub.1-6 alkyl, --OR,
--S(O).sub.2R, --S(O).sub.2N(R).sub.2, C.sub.2-6 alkenyl, C.sub.3-6
carbocycle and heterocycle; each R is independently selected from
the group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
each R' is independently selected from the group consisting of
C.sub.1-18 alkyl, C.sub.2-18 alkenyl, --R*YR'', --YR'', and H; each
R'' is independently selected from the group consisting of
C.sub.3-14 alkyl and C.sub.3-14 alkenyl; each R* is independently
selected from the group consisting of C.sub.1-12 alkyl and
C.sub.2-12 alkenyl; each Y is independently a C.sub.3-6 carbocycle;
each X is independently selected from the group consisting of F,
Cl, Br, and I; and m is selected from 5, 6, 7, 8, 9, 10, 11, 12,
and 13, or salts or isomers thereof.
101. The vaccine of claim 96, wherein subset of compounds of
Formula (I) includes those in which R.sub.1 is selected from the
group consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; R.sub.2 and R.sub.3 are independently
selected from the group consisting of H, C.sub.2-14 alkyl,
C.sub.2-14 alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and
R.sub.3, together with the atom to which they are attached, form a
heterocycle or carbocycle; R.sub.4 is --(CH.sub.2).sub.nQ or
--(CH.sub.2).sub.nCHQR, where Q is --N(R).sub.2, and n is selected
from 3, 4, and 5; each R.sub.5 is independently selected from the
group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each
R.sub.6 is independently selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; M and M' are
independently selected from --C(O)O--, --OC(O)--, --C(O)N(R')--,
--N(R')C(O)--, --C(O)--, --C(S)--, --C(S)S--, --SC(S)--,
--CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--, --S--S--, an aryl
group, and a heteroaryl group; R.sub.7 is selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each R is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; each R' is independently selected
from the group consisting of C.sub.1-18 alkyl, C.sub.2-18 alkenyl,
--R*YR'', --YR'', and H; each R'' is independently selected from
the group consisting of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
each R* is independently selected from the group consisting of
C.sub.1-12 alkyl and C.sub.1-12 alkenyl; each Y is independently a
C.sub.3-6 carbocycle; each X is independently selected from the
group consisting of F, Cl, Br, and I; and m is selected from 5, 6,
7, 8, 9, 10, 11, 12, and 13, or salts or isomers thereof.
102. The vaccine of claim 96, wherein a subset of compounds of
Formula (I) includes those in which R.sub.1 is selected from the
group consisting of C.sub.5-30 alkyl, C.sub.5-20 alkenyl, --R*YR'',
--YR'', and --R''M'R'; R.sub.2 and R.sub.3 are independently
selected from the group consisting of C.sub.1-14 alkyl, C.sub.2-14
alkenyl, --R*YR'', --YR'', and --R*OR'', or R.sub.2 and R.sub.3,
together with the atom to which they are attached, form a
heterocycle or carbocycle; R.sub.4 is selected from the group
consisting of --(CH.sub.2).sub.nQ, --(CH.sub.2).sub.nCHQR, --CHQR,
and --CQ(R).sub.2, where Q is --N(R).sub.2, and n is selected from
1, 2, 3, 4, and 5; each R.sub.5 is independently selected from the
group consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each
R.sub.6 is independently selected from the group consisting of
C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; M and M' are
independently selected from --C(O)O--, --OC(O)--, --C(O)N(R')--,
--N(R')C(O)--, --C(O)--, --C(S)--, --C(S)S--, --SC(S)--,
--CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--, --S--S--, an aryl
group, and a heteroaryl group; R.sub.7 is selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H; each R is
independently selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H; each R' is independently selected
from the group consisting of C.sub.1-18 alkyl, C.sub.2-18 alkenyl,
--R*YR'', --YR'', and H; each R'' is independently selected from
the group consisting of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
each R* is independently selected from the group consisting of
C.sub.1-12 alkyl and C.sub.1-12 alkenyl; each Y is independently a
C.sub.3-6 carbocycle; each X is independently selected from the
group consisting of F, Cl, Br, and I; and m is selected from 5, 6,
7, 8, 9, 10, 11, 12, and 13, or salts or isomers thereof.
103. The vaccine of claim 96, wherein a subset of compounds of
Formula (I) includes those of Formula (IA): ##STR00056## or a salt
or isomer thereof, wherein 1 is selected from 1, 2, 3, 4, and 5; m
is selected from 5, 6, 7, 8, and 9; M.sub.1 is a bond or M';
R.sub.4 is unsubstituted C.sub.1-3 alkyl, or --(CH.sub.2).sub.nQ,
in which Q is OH, --NHC(S)N(R).sub.2, --NHC(O)N(R).sub.2,
--N(R)C(O)R, --N(R)S(O).sub.2R, --N(R)R.sub.8,
--NHC(.dbd.NR.sub.9)N(R).sub.2, --NHC(.dbd.CHR.sub.9)N(R).sub.2,
--OC(O)N(R).sub.2, --N(R)C(O)OR, heteroaryl or heterocycloalkyl; M
and M' are independently selected from --C(O)O--, --OC(O)--,
--C(O)N(R')--, --P(O)(OR')O--, --S--S--, an aryl group, and a
heteroaryl group; and R.sub.2 and R.sub.3 are independently
selected from the group consisting of H, C.sub.1-14 alkyl, and
C.sub.2-14 alkenyl.
Description
RELATED APPLICATIONS
[0001] This application claims the benefit under 35 U.S.C. .sctn.
119(e) of U.S. provisional application No. 62/244,884, filed Oct.
22, 2015, U.S. provisional application No. 62/247,418, filed Oct.
28, 2015, U.S. provisional application No. 62/244,822, filed Oct.
22, 2015, and U.S. provisional application No. 62/247,374, filed
Oct. 28, 2015, each of which is incorporated by reference herein in
its entirety. This application also claims the benefit under 35
U.S.C. .sctn. 119(e) of U.S. provisional application No.
62/245,031, filed Oct. 22, 2015, which is incorporated by reference
herein in its entirety.
BACKGROUND
[0002] Sexually transmitted diseases (STDs) are a major global
cause of acute illness, infertility, long-term disability, and
death, with severe medical and psychological consequences for
millions of men, women, and children (Hafner L. et al. Mucosal
Immunology (2008) 1, 116-130).
[0003] Human papillomavirus (HPV) is a group of over 170 small DNA
viruses from the papillomavirus family. It is the most commonly
sexually transmitted infection, and while most HPV infections are
subclinical, HPV is an etiological agent for cervical cancer, the
second greatest cause of mortality among cancer-affected women
worldwide. HPV-associated cancers account for over 5% of the total
diagnosed cancer cases internationally, and the incidence is higher
in developing countries, where HPV is estimated to cause about
500,000 cases annually. The high levels of HPV exposure and health
consequences indicate the importance of developing safe vaccine
candidates against HPV.
[0004] Chlamydia infection is caused by the Chlamydia trachomatis
(C. trachomatis) bacterium. It is one of the most commonly sexually
transmitted infections worldwide, affecting approximately 215
million people internationally. In the United States, there are
around 2.8 million new cases of Chlamydia each year. Chlamydia
trachomatis can also cause Chlamydia conjunctivitis or trachoma, a
disease that can result in blindness. Worldwide, approximately 80
million people have active infections, resulting in impaired vision
and blindness for nearly 2.2 million individuals. The international
health consequences associated with Chlamydia exemplify the
importance of developing effective and safe vaccine candidates
against Chlamydia.
[0005] Herpes simplex viruses (HSV) are double-stranded linear DNA
viruses in the Herpesviridae family. Two members of the herpes
simplex virus family infect humans--known as HSV-1 and HSV-2.
Symptoms of HSV infection include the formation of blisters in the
skin or mucous membranes of the mouth, lips, and/or genitals. HSV
is a neuroinvasive virus that can cause sporadic recurring episodes
of viral reactivation in infected individuals. HSV is transmitted
by contact with an infected area of the skin during a period of
viral activation.
[0006] Deoxyribonucleic acid (DNA) vaccination is one technique
used to stimulate humoral and cellular immune responses to foreign
antigens, such as HPV antigens, HSV antigens and/or Chlamydia
antigens. The direct injection of genetically engineered DNA (e.g.,
naked plasmid DNA) into a living host results in a small number of
its cells directly producing an antigen, resulting in a protective
immunological response. With this technique, however, comes
potential problems, including the possibility of insertional
mutagenesis, which could lead to the activation of oncogenes or the
inhibition of tumor suppressor genes.
SUMMARY
[0007] Provided herein are ribonucleic acid (RNA) vaccines that
build on the knowledge that RNA (e.g., messenger RNA (mRNA)) can
safely direct the body's cellular machinery to produce nearly any
protein of interest, from native proteins to antibodies and other
entirely novel protein constructs that can have therapeutic
activity inside and outside of cells. The RNA (e.g., mRNA) vaccines
of the present disclosure may be used to induce a balanced immune
response against HPV, HSV and/or Chlamydia (e.g., C. trachomatis),
comprising both cellular and humoral immunity, without risking the
possibility of insertional mutagenesis, for example. HPV, HSV
and/or Chlamydia are referred to herein as "sexually transmitted
diseases (STDs)." Thus, the term "STD RNA vaccines" and "HPV, HSV
and/or Chlamydia" encompasses HPV RNA vaccines, HSV RNA vaccines,
Chlamydia RNA vaccines, and combination vaccines comprising: at
least one HPV RNA vaccine and at least one HSV RNA vaccine; at
least one HPV RNA vaccine and at least one Chlamydia RNA vaccine,
at least one HSV vaccine and at least one Chlamydia RNA vaccine;
and at least one HPV RNA vaccine, at least one HSV RNA vaccine and
at least one Chlamydia RNA vaccine.
[0008] The RNA (e.g., mRNA) vaccines may be utilized in various
settings depending on the prevalence of the infection or the degree
or level of unmet medical need. The RNA (e.g. mRNA) vaccines may be
utilized to treat and/or prevent HPV, HSV and/or Chlamydia of
various genotypes, strains, and isolates. The RNA (e.g., mRNA)
vaccines have superior properties in that they produce much larger
antibody titers and produce responses earlier than commercially
available anti-viral therapeutic treatments. While not wishing to
be bound by theory, it is believed that the RNA (e.g., mRNA)
vaccines, as mRNA polynucleotides, are better designed to produce
the appropriate protein conformation upon translation as the RNA
(e.g., mRNA) vaccines co-opt natural cellular machinery. Unlike
traditional vaccines, which are manufactured ex vivo and may
trigger unwanted cellular responses, RNA (e.g., mRNA) vaccines are
presented to the cellular system in a more native fashion.
[0009] Surprisingly, it has been shown that efficacy of mRNA
vaccines can be significantly enhanced when combined with a
flagellin adjuvant, in particular, when one or more
antigen-encoding mRNAs is combined with an mRNA encoding flagellin.
RNA (e.g., mRNA) vaccines combined with the flagellin adjuvant
(e.g., mRNA-encoded flagellin adjuvant) have superior properties in
that they may produce much larger antibody titers and produce
responses earlier than commercially available vaccine
formulations.
[0010] Some embodiments of the present disclosure provide RNA
(e.g., mRNA) vaccines that include at least one RNA (e.g., mRNA)
polynucleotide having an open reading frame encoding at least one
antigenic polypeptide or an immunogenic fragment thereof (e.g., an
immunogenic fragment capable of inducing an immune response to the
antigenic polypeptide) and at least one RNA (e.g., mRNA
polynucleotide) having an open reading frame encoding a flagellin
adjuvant.
[0011] In some embodiments, at least one flagellin polypeptide
(e.g., encoded flagellin polypeptide) is a flagellin protein. In
some embodiments, at least one flagellin polypeptide (e.g., encoded
flagellin polypeptide) is an immunogenic flagellin fragment. In
some embodiments, at least one flagellin polypeptide and at least
one antigenic polypeptide are encoded by a single RNA (e.g., mRNA)
polynucleotide. In other embodiments, at least one flagellin
polypeptide and at least one antigenic polypeptide are each encoded
by a different RNA polynucleotide.
[0012] In some embodiments at least one flagellin polypeptide has
at least 80%, at least 85%, at least 90%, or at least 95% identity
to a flagellin polypeptide having a sequence of SEQ ID NO:
301-303.
[0013] Provided herein, in some embodiments, is a ribonucleic acid
(RNA) (e.g., mRNA) vaccine, comprising at least one (e.g., at least
2, 3, 4 or 5) RNA (e.g., mRNA) polynucleotide having an open
reading frame encoding at least one (e.g., at least 2, 3, 4 or 5)
HPV, HSV and/or Chlamydia (e.g., C. trachomatis) antigenic
polypeptide, or any combination of two or more of the foregoing
antigenic polypeptides. Herein, use of the term "antigenic
polypeptide" encompasses immunogenic fragments of the antigenic
polypeptide (an immunogenic fragment that induces (or is capable of
inducing) an immune response to HPV, HSV and/or Chlamydia (e.g., C.
trachomatis), unless otherwise stated.
[0014] Also provided herein, in some embodiments, is a RNA (e.g.,
mRNA) vaccine comprising at least one (e.g., at least 2, 3, 4 or 5)
RNA polynucleotide having an open reading frame encoding at least
one (e.g., at least 2, 3, 4 or 5) HPV, HSV and/or Chlamydia (e.g.,
C. trachomatis) antigenic polypeptide or an immunogenic fragment
thereof, linked to a signal peptide.
[0015] Further provided herein, in some embodiments, is a nucleic
acid (e.g., DNA) encoding at least one (e.g., at least 2, 3, 4 or
5) HPV, HSV and/or Chlamydia (e.g., C. trachomatis) RNA (e.g.,
mRNA) polynucleotide.
[0016] Further still, provided herein, in some embodiments, is a
method of inducing an immune response in a subject, the method
comprising administering to the subject a vaccine comprising at
least one (e.g., at least 2, 3, 4 or 5) RNA (e.g., mRNA)
polynucleotide having an open reading frame encoding at least one
(e.g., at least 2, 3, 4 or 5) HPV, HSV and/or Chlamydia (e.g., C.
trachomatis) antigenic polypeptide, or any combination of two or
more of the foregoing antigenic polypeptides.
[0017] HPV
[0018] In some embodiments, a RNA (e.g., mRNA) vaccine comprises at
least one RNA (e.g., mRNA) polynucleotide having an open reading
frame encoding at least one HPV antigenic polypeptide or an
immunogenic fragment thereof (e.g., an immunogenic fragment capable
of inducing an immune response to HPV). In some embodiments, at
least one antigenic polypeptide is selected from E1, E2, E4, E5,
E6, E7, L1, and L2. In some embodiments, the at least one antigenic
polypeptide is selected from E1, E2, E4, E5, E6, and E7. In some
embodiments, the at least one antigenic polypeptide is E6, E7, or a
combination of E6 and E7. In some embodiments, the at least one
antigenic polypeptide is L1, L2, or a combination of L1 and L2.
[0019] In some embodiments, the at least one antigenic polypeptide
is L1. In some embodiments, the L1 protein is obtained from HPV
serotypes 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59,
68, 73 or 82.
[0020] In some embodiments, the at least one antigenic polypeptide
is L1, L2 or a combination of L1 and L2, and E6, E7, or a
combination of E6 and E7.
[0021] In some embodiments, the at least one antigenic polypeptide
is from HPV strain HPV type 16 (HPV16), HPV type 18 (HPV18), HPV
type 26 (HPV26), HPV type 31 (HPV31), HPV type 33 (HPV33), HPV type
35 (HPV35), HPV type 45 (HPV45), HPV type 51 (HPV51), HPV type 52
(HPV52), HPV type 53 (HPV53), HPV type 56 (HPV56), HPV type 58
(HPV58), HPV type 59 (HPV59), HPV type 66 (HPV66), HPV type 68
(HPV68), HPV type 82 (HPV82), or a combination thereof. In some
embodiments, the at least one antigenic polypeptide is from HPV
strain HPV16, HPV18, or a combination thereof.
[0022] In some embodiments, the at least one antigenic polypeptide
is from HPV strain HPV type 6 (HPV6), HPV type 11 (HPV11), HPV type
13 (HPV13), HPV type 40 (HPV40), HPV type 42 (HPV42), HPV type 43
(HPV43), HPV type 44 (HPV44), HPV type 54 (HPV54), HPV type 61
(HPV61), HPV type 70 (HPV70), HPV type 72 (HPV72), HPV type 81
(HPV81), HPV type 89 (HPV89), or a combination thereof.
[0023] In some embodiments, the at least one antigenic polypeptide
is from HPV strain HPV type 30 (HPV30), HPV type 34 (HPV34), HPV
type 55 (HPV55), HPV type 62 (HPV62), HPV type 64 (HPV64), HPV type
67 (HPV67), HPV type 69 (HPV69), HPV type 71 (HPV71), HPV type 73
(HPV73), HPV type 74 (HPV74), HPV type 83 (HPV83), HPV type 84
(HPV84), HPV type 85 (HPV85), or a combination thereof.
[0024] In some embodiments, a vaccine comprises at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
at least one (e.g., one, two, three, four, five, six, seven, or
eight) of E1, E2, E4, E5, E6, E7, L1, and L2 protein obtained from
HPV, or a combination thereof. In some embodiments, a vaccine
comprises at least one RNA (e.g., mRNA) polynucleotide having an
open reading frame encoding at least one (e.g., one, two, three,
four, five, or six) polypeptide selected from E1, E2, E4, E5, E6,
and E7 protein obtained from HPV, or a combination thereof. In some
embodiments a vaccine comprises at least one RNA (e.g., mRNA)
polynucleotide having an open reading frame encoding at least one
polypeptide selected from E6 and E7 protein obtained from HPV, or a
combination thereof. In some embodiments, a vaccine comprises at
least one RNA (e.g., mRNA) polynucleotide having an open reading
frame encoding a polypeptide selected from L1 or L2 protein
obtained from HPV, or a combination thereof.
[0025] In some embodiments, the at least one RNA polynucleotide
encodes an antigenic polypeptide that structurally modifies an
infected cell.
[0026] In some embodiments, the at least one RNA polynucleotide
encodes an antigenic polypeptide that forms part or all of the HPV
viral capsid.
[0027] In some embodiments, the at least one RNA polynucleotide
encodes an antigenic polypeptide that is capable of self-assembling
into virus-like particles.
[0028] In some embodiments, the at least one RNA polynucleotide
encodes an antigenic polypeptide that is responsible for binding of
the HPV to a cell being infected.
[0029] In some embodiments, the at least one RNA polynucleotide
encodes an antigenic polypeptide that interacts with retinoblastoma
protein (pRb). In some embodiments, the at least one RNA
polynucleotide encodes an antigenic polypeptide that interacts with
p53.
[0030] In some embodiments, at least one HPV antigenic polypeptide
comprises an amino acid sequence of SEQ ID NO: 31-59 (Table 2). In
some embodiments, the amino acid sequence of the HPV antigenic
polypeptide is, or is a fragment of, or is a homolog or variant
having at least 80% (e.g., 85%, 90%, 95%, 98%, 99%) identity to,
the amino acid sequence of SEQ ID NO: 31-59 (Table 2).
[0031] In some embodiments, at least one HPV antigenic polypeptide
is encoded by a nucleic acid sequence identified by any one of SEQ
ID NO: 1-28 (Table 1).
[0032] In some embodiments, at least one HPV RNA (e.g., mRNA)
polynucleotide is encoded by a nucleic acid sequence, or a fragment
of a nucleotide sequence, identified by any one of SEQ ID NO: 1-28
(Table 1).
[0033] In some embodiments, at least one HPV RNA (e.g., mRNA)
polynucleotide comprises a nucleic acid sequence, or a fragment of
a nucleotide sequence, identified by any one of SEQ ID NO: 431-461
(Table 1).
[0034] Chlamydia
[0035] In some embodiments, a RNA (e.g., mRNA) vaccine comprises at
least one RNA (e.g., mRNA) polynucleotide having an open reading
frame encoding at least one Chlamydia (e.g., C. trachomatis)
antigenic polypeptide or an immunogenic fragment thereof (e.g., an
immunogenic fragment capable of inducing an immune response to
Chlamydia, e.g., C. trachomatis).
[0036] In some embodiments, at least one antigenic polypeptide is a
major outer membrane protein (MOMP or OmpA) or an immunogenic
fragment thereof. The MOMP may be from Chlamydia trachomatis
serovar (serotype) H, F, E, D, I, G, J or K.
[0037] In some embodiments, at least one antigenic polypeptide is
from a virulence related outer membrane protein family (such as
OmpA, OmpL, OmpF, OprF) or an immunogenic fragment thereof. The OMP
may be from Chlamydia trachomatis or any Gram negative bacteria
(e.g., Pseudomonas aeruginosa).
[0038] In some embodiments, at least one Chlamydia antigenic
polypeptide comprises an amino acid sequence identified by any one
of SEQ ID NO: 65-72 or 73-183 (Tables 5 or 7). In some embodiments,
the amino acid sequence of the Chlamydia antigenic polypeptide is,
or is a fragment of, or is a homolog or variant having at least 80%
(e.g., 85%, 90%, 95%, 98%, 99%) identity to, the amino acid
sequence of SEQ ID NO: 65-72 or 73-183 (Tables 5 or 7).
[0039] In some embodiments, at least one Chlamydia antigenic
polypeptide is encoded by a nucleic acid sequence identified by any
one of SEQ ID NO: 62-64 or 184-294 (Tables 4 or 8).
[0040] In some embodiments, at least one Chlamydia RNA (e.g., mRNA)
polynucleotide comprises a nucleic acid sequence, or a fragment of
a nucleotide sequence, identified by any one of SEQ ID NO: 317-319
or 320-430 (Tables 4 or 8).
[0041] HSV
[0042] In some embodiments, a RNA (e.g., mRNA) vaccine comprises at
least one RNA (e.g., mRNA) polynucleotide having an open reading
frame encoding at least one herpes simplex virus (HSV) antigenic
polypeptide or an immunogenic fragment thereof (e.g., an
immunogenic fragment capable of inducing an immune response to
HSV).
[0043] In some embodiments, at least one antigenic polypeptide is
HSV (HSV-1 or HSV-2) glycoprotein B, HSV (HSV-1 or HSV-2)
glycoprotein C, HSV (HSV-1 or HSV-2) glycoprotein D, HSV (HSV-1 or
HSV-2) glycoprotein E, HSV (HSV-1 or HSV-2) glycoprotein I. In some
embodiments, at least one antigenic polypeptide has at least 95%,
at least 96%, at least 97%, at least 98% or at least 99% to HSV
(HSV-1 or HSV-2) glycoprotein B, HSV (HSV-1 or HSV-2) glycoprotein
C, HSV (HSV-1 or HSV-2) glycoprotein D, HSV (HSV-1 or HSV-2)
glycoprotein E, HSV (HSV-1 or HSV-2) glycoprotein I or HSV (HSV-1
or HSV-2) ICP4 protein.
[0044] In some embodiments, at least one antigen polypeptide is a
non-glycogenic polypeptide, for example, not limited to, HSV (HSV-1
or HSV-2) ICP4 protein, HSV (HSV-1 or HSV-2) ICP0 protein, or an
immunogenic fragment thereof.
[0045] In some embodiments, at least one antigenic polypeptide has
at least 95%, at least 96%, at least 97%, at least 98% or at least
99% to HSV (HSV-1 or HSV-2) glycoprotein B, HSV (HSV-1 or HSV-2)
glycoprotein C, HSV (HSV-1 or HSV-2) glycoprotein D, HSV (HSV-1 or
HSV-2) glycoprotein E, HSV (HSV-1 or HSV-2) glycoprotein I or HSV
(HSV-1 or HSV-2) ICP4 protein.
[0046] In some embodiments, at least one antigenic polypeptide is
HSV (HSV-1 or HSV-2) glycoprotein C, HSV (HSV-1 or HSV-2)
glycoprotein D, a combination of HSV (HSV-1 or HSV-2) glycoprotein
C and HSV (HSV-1 or HSV-2) glycoprotein D, or an immunogenic
fragment thereof.
[0047] In some embodiments, a HSV vaccine includes at least one RNA
polynucleotide having an open reading frame encoding HSV (HSV-1 or
HSV-2) glycoprotein D. In some embodiments, the HSV vaccine is
formulated for intramuscular injection.
[0048] In some embodiments, an open reading frame of a RNA (e.g.,
mRNA) vaccine is codon-optimized. In some embodiments, at least one
RNA polynucleotide encodes at least one antigenic polypeptide
comprising an amino acid sequence identified by any one of SEQ ID
NO: 31-59, 65-72, or 73-183 (Tables 2, 5 or 7; see also amino acid
sequences of Tables 3 and 6) and is codon optimized mRNA.
[0049] In some embodiments, a RNA (e.g., mRNA) vaccine further
comprising an adjuvant.
[0050] Tables 3 and 6 provide National Center for Biotechnology
Information (NCBI) accession numbers of interest. It should be
understood that the phrase "an amino acid sequence of Tables 3 and
6" refers to an amino acid sequence identified by one or more NCBI
accession numbers listed in Tables 3 and 6. Each of the amino acid
sequences, and variants having greater than 95% identity or greater
than 98% identity to each of the amino acid sequences encompassed
by the accession numbers of Tables 3 and 6 are included within the
constructs (polynucleotides/polypeptides) of the present
disclosure.
[0051] In some embodiments, at least one mRNA polynucleotide is
encoded by a nucleic acid comprising a sequence identified by any
one of SEQ ID NO: 1-28, 62-64 or 184-294 (Tables 1, 4 and 8) and
having less than 80% identity to wild-type mRNA sequence. In some
embodiments, at least one mRNA polynucleotide is encoded by a
nucleic acid comprising a sequence identified by any one of SEQ ID
NO: 1-28, 62-64 or 184-294 (Tables 1, 4 and 8) and having less than
75%, 85% or 95% identity to a wild-type mRNA sequence. In some
embodiments, at least one mRNA polynucleotide is encoded by nucleic
acid comprising a sequence identified by any one of SEQ ID NO:
1-28, 62-64 or 184-294 (Tables 1, 4 and 8) and having less than
50-80%, 60-80%, 40-80%, 30-80%, 70-80%, 75-80% or 78-80% identity
to wild-type mRNA sequence. In some embodiments, at least one mRNA
polynucleotide is encoded by a nucleic acid comprising a sequence
identified by any one of SEQ ID NO: 1-28, 62-64 or 184-294 (Tables
1, 4 and 8) and having less than 40-85%, 50-85%, 60-85%, 30-85%,
70-85%, 75-85% or 80-85% identity to wild-type mRNA sequence. In
some embodiments, at least one mRNA polynucleotide is encoded by a
nucleic acid comprising a sequence identified by any one of SEQ ID
NO: 1-28, 62-64 or 184-294 (Tables 1, 4 and 8) and having less than
40-90%, 50-90%, 60-90%, 30-90%, 70-90%, 75-90%, 80-90%, or 85-90%
identity to wild-type mRNA sequence.
[0052] In some embodiments, at least one RNA polynucleotide encodes
at least one antigenic polypeptide comprising an amino acid
sequence identified by any one of SEQ ID NO: 31-59, 65-72, or
73-183 (Tables 2, 5 or 7; see also amino acid sequences of Tables 3
and 6) and having at least 80% (e.g., 85%, 90%, 95%, 98%, 99%)
identity to wild-type mRNA sequence, but does not include wild-type
mRNA sequence.
[0053] In some embodiments, at least one RNA polynucleotide encodes
at least one antigenic polypeptide comprising an amino acid
sequence identified by any one of SEQ ID NO: 31-59, 65-72, or
73-183 (Tables 2, 5 or 7; see also amino acid sequences of Tables 3
and 6) and has less than 95%, 90%, 85%, 80% or 75% identity to
wild-type mRNA sequence. In some embodiments, at least one RNA
polynucleotide encodes at least one antigenic polypeptide
comprising an amino acid sequence identified by any one of SEQ ID
NO: 31-59, 65-72, or 73-183 (Tables 2, 5 or 7; see also amino acid
sequences of Tables 3 and 6) and has 30-80%, 40-80%, 50-80%,
60-80%, 70-80%, 75-80% or 78-80%, 30-85%, 40-85%, 50-805%, 60-85%,
70-85%, 75-85% or 78-85%, 30-90%, 40-90%, 50-90%, 60-90%, 70-90%,
75-90%, 80-90% or 85-90% identity to wild-type mRNA sequence.
[0054] In some embodiments, at least one RNA polynucleotide encodes
at least one antigenic polypeptide having at least 90%, at least
95%, at least 96%, at least 97%, at least 98%, or at least 99%
identity to an amino acid sequence identified by any one of SEQ ID
NO: 31-59, 65-72, or 73-183 (Tables 2, 5 or 7; see also amino acid
sequences of Tables 3 and 6). In some embodiments, at least one RNA
polynucleotide encodes at least one antigenic polypeptide having
95%-99% identity to an amino acid sequence identified by any one of
SEQ ID NO: 31-59, 65-72, or 73-183 (Tables 2, 5 or 7; see also
amino acid sequences of Tables 3 and 6).
[0055] In some embodiments, at least one RNA polynucleotide encodes
at least one antigenic polypeptide having at least 90%, at least
95%, at least 96%, at least 97%, at least 98%, or at least 99%
identity to amino acid sequence identified by any one of SEQ ID NO:
31-59, 65-72, or 73-183 (Tables 2, 5 or 7; see also amino acid
sequences of Tables 3 and 6) and having membrane fusion activity.
In some embodiments, at least one RNA polynucleotide encodes at
least one antigenic polypeptide having 95%-99% identity to amino
acid sequence identified by any one of SEQ ID NO: 31-59, 65-72, or
73-183 (Tables 2, 5 or 7; see also amino acid sequences of Tables 3
and 6) and having membrane fusion activity.
[0056] In some embodiments, at least one RNA polynucleotide encodes
at least one antigenic polypeptide (e.g., at least one HPV
antigenic polypeptide, at least one HSV antigenic polypeptide
and/or at least one Chlamydia (e.g., C. trachomatis) antigenic
polypeptide) that attaches to cell receptors.
[0057] In some embodiments, at least one RNA polynucleotide encodes
at least one antigenic polypeptide (e.g., at least one HPV
antigenic polypeptide, at least one HSV antigenic polypeptide
and/or at least one Chlamydia (e.g., C. trachomatis) antigenic
polypeptide) that causes fusion of viral and cellular
membranes.
[0058] In some embodiments, at least one RNA polynucleotide encodes
at least one antigenic polypeptide (e.g., at least one HPV
antigenic polypeptide, at least one HSV antigenic polypeptide
and/or at least one Chlamydia (e.g., C. trachomatis) antigenic
polypeptide) that is responsible for binding of the virus to a cell
being infected.
[0059] Some embodiments of the present disclosure provide a vaccine
that includes at least one ribonucleic acid (RNA) (e.g., mRNA)
polynucleotide having an open reading frame encoding at least one
antigenic polypeptide (e.g., at least one HPV antigenic
polypeptide, at least one HSV antigenic polypeptide and/or at least
one Chlamydia (e.g., C. trachomatis) antigenic polypeptide), at
least one 5' terminal cap and at least one chemical modification,
formulated within a lipid nanoparticle.
[0060] In some embodiments, a 5' terminal cap is
7mG(5')ppp(5')NlmpNp.
[0061] In some embodiments, at least one chemical modification is
selected from pseudouridine, N1-methylpseudouridine,
N1-ethylpseudouridine, 2-thiouridine, 4'-thiouridine,
5-methylcytosine, 5-methyluridine,
2-thio-1-methyl-1-deaza-pseudouridine,
2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine,
2-thio-dihydropseudouridine, 2-thio-dihydrouridine,
2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine,
4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine,
4-thio-pseudouridine, 5-aza-uridine, dihydropseudouridine,
5-methoxyuridine and 2'-O-methyl uridine. In some embodiments, the
chemical modification is in the 5-position of the uracil. In some
embodiments, the chemical modification is a N1-methylpseudouridine.
In some embodiments, the chemical modification is a
N1-ethylpseudouridine.
[0062] In some embodiments, a lipid nanoparticle comprises a
cationic lipid, a PEG-modified lipid, a sterol and a non-cationic
lipid. In some embodiments, a cationic lipid is an ionizable
cationic lipid and the non-cationic lipid is a neutral lipid, and
the sterol is a cholesterol. In some embodiments, a cationic lipid
is selected from the group consisting of
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA),
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319),
(12Z,15Z)--N,N-dimethyl-2-nonylhenicosa-12,15-dien-1-amine (L608),
and N,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]heptadecan-8-amine
(L530).
[0063] In some embodiments, the lipid is
##STR00001##
[0064] In some embodiments, the lipid is
##STR00002##
[0065] In some embodiments, a lipid nanoparticle comprises
compounds of Formula (I) and/or Formula (II), discussed below.
[0066] In some embodiments, a lipid nanoparticle comprises
Compounds 3, 18, 20, 25, 26, 29, 30, 60, 108-112, or 122, as
discussed below
[0067] Some embodiments of the present disclosure provide a vaccine
that includes at least one RNA (e.g., mRNA) polynucleotide having
an open reading frame encoding at least one antigenic polypeptide
(e.g., at least one HPV antigenic polypeptide, at least one HSV
antigenic polypeptide and/or at least one Chlamydia (e.g., C.
trachomatis) antigenic polypeptide), wherein at least 80% (e.g.,
85%, 90%, 95%, 98%, 99%) of the uracil in the open reading frame
have a chemical modification, optionally wherein the vaccine is
formulated in a lipid nanoparticle (e.g., a lipid nanoparticle
comprises a cationic lipid, a PEG-modified lipid, a sterol and a
non-cationic lipid).
[0068] In some embodiments, 100% of the uracil in the open reading
frame have a chemical modification. In some embodiments, a chemical
modification is in the 5-position of the uracil. In some
embodiments, a chemical modification is a N1-methyl pseudouridine.
In some embodiments, 100% of the uracil in the open reading frame
have a N1-methyl pseudouridine in the 5-position of the uracil.
[0069] In some embodiments, an open reading frame of a RNA (e.g.,
mRNA) polynucleotide encodes at least two antigenic polypeptides
(e.g., at least one HPV antigenic polypeptide, at least one HSV
antigenic polypeptide and/or at least one Chlamydia (e.g., C.
trachomatis) antigenic polypeptide). In some embodiments, the open
reading frame encodes at least five or at least ten antigenic
polypeptides. In some embodiments, the open reading frame encodes
at least 100 antigenic polypeptides. In some embodiments, the open
reading frame encodes 2-100 antigenic polypeptides.
[0070] In some embodiments, a vaccine comprises at least two RNA
(e.g., mRNA) polynucleotides, each having an open reading frame
encoding at least one antigenic polypeptide (e.g., at least one HPV
antigenic polypeptide, at least one HSV antigenic polypeptide
and/or at least one Chlamydia (e.g., C. trachomatis) antigenic
polypeptide). In some embodiments, the vaccine comprises at least
five or at least ten RNA (e.g., mRNA) polynucleotides, each having
an open reading frame encoding at least one antigenic polypeptide
or an immunogenic fragment thereof. In some embodiments, the
vaccine comprises at least 100 RNA (e.g., mRNA) polynucleotides,
each having an open reading frame encoding at least one antigenic
polypeptide. In some embodiments, the vaccine comprises 2-100 RNA
(e.g., mRNA) polynucleotides, each having an open reading frame
encoding at least one antigenic polypeptide.
[0071] In some embodiments, at least one antigenic polypeptide
(e.g., at least one HPV antigenic polypeptide, at least one HSV
antigenic polypeptide and/or at least one Chlamydia (e.g., C.
trachomatis) antigenic polypeptide) is fused to a signal peptide.
In some embodiments, the signal peptide is selected from: a HuIgGk
signal peptide (METPAQLLFLLLLWLPDTTG; SEQ ID NO: 304); IgE heavy
chain epsilon-1 signal peptide (MDWTWILFLVAAATRVHS; SEQ ID NO:
305); Japanese encephalitis PRM signal sequence
(MLGSNSGQRVVFTILLLLVAPAYS; SEQ ID NO: 306), VSVg protein signal
sequence (MKCLLYLAFLFIGVNCA; SEQ ID NO: 307) and Japanese
encephalitis JEV signal sequence (MWLVSLAIVTACAGA; SEQ ID NO:
308).
[0072] In some embodiments, the signal peptide is fused to the
N-terminus of at least one antigenic polypeptide. In some
embodiments, a signal peptide is fused to the C-terminus of at
least one antigenic polypeptide.
[0073] In some embodiments, at least one antigenic polypeptide
(e.g., at least one HPV antigenic polypeptide, at least one HSV
antigenic polypeptide and/or at least one Chlamydia (e.g., C.
trachomatis) antigenic polypeptide) comprises a mutated N-linked
glycosylation site.
[0074] Also provided herein is a RNA (e.g., mRNA) vaccine of any
one of the foregoing paragraphs (e.g., at least one HPV antigenic
polypeptide, at least one HSV antigenic polypeptide and/or at least
one Chlamydia (e.g., C. trachomatis) antigenic polypeptide),
formulated in a nanoparticle (e.g., a lipid nanoparticle).
[0075] In some embodiments, the nanoparticle has a mean diameter of
50-200 nm. In some embodiments, the nanoparticle is a lipid
nanoparticle. In some embodiments, the lipid nanoparticle comprises
a cationic lipid, a PEG-modified lipid, a sterol and a non-cationic
lipid. In some embodiments, the lipid nanoparticle comprises a
molar ratio of about 20-60% cationic lipid, 0.5-15% PEG-modified
lipid, 25-55% sterol, and 25% non-cationic lipid. In some
embodiments, the cationic lipid is an ionizable cationic lipid and
the non-cationic lipid is a neutral lipid, and the sterol is a
cholesterol. In some embodiments, the cationic lipid is selected
from 2,2-dilinoleyl-4-dimethylaminoethyl[1,3]-dioxolane
(DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate
(DLin-MC3-DMA), and di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319).
[0076] In some embodiments, a lipid nanoparticle comprises
compounds of Formula (I) and/or Formula (II), discussed below.
[0077] In some embodiments, a STD RNA (e.g., mRNA) vaccine is
formulated in a lipid nanoparticle that comprises a compound
selected from Compounds 3, 18, 20, 25, 26, 29, 30, 60, 108-112 and
122, described below.
[0078] In some embodiments, the nanoparticle has a polydispersity
value of less than 0.4 (e.g., less than 0.3, 0.2 or 0.1).
[0079] In some embodiments, the nanoparticle has a net neutral
charge at a neutral pH value.
[0080] In some embodiments, the RNA (e.g., mRNA) vaccine is
multivalent.
[0081] Some embodiments of the present disclosure provide methods
of inducing an antigen specific immune response in a subject,
comprising administering to the subject any of the RNA (e.g., mRNA)
vaccine as provided herein in an amount effective to produce an
antigen-specific immune response. In some embodiments, the RNA
(e.g., mRNA) vaccine is a HPV vaccine, a HSV vaccine or a Chlamydia
(e.g., C. trachomatis) vaccine. In some embodiments, the RNA (e.g.,
mRNA) vaccine is a combination vaccine comprising a combination of
HPV vaccine, a HSV vaccine and Chlamydia (e.g., C. trachomatis)
vaccine.
[0082] In some embodiments, an antigen-specific immune response
comprises a T cell response or a B cell response.
[0083] In some embodiments, a method of producing an
antigen-specific immune response comprises administering to a
subject a single dose (no booster dose) of a RNA (e.g., mRNA)
vaccine of the present disclosure. In some embodiments, the RNA
(e.g., mRNA) vaccine is a HPV vaccine, a HSV vaccine and/or
Chlamydia (e.g., C. trachomatis) vaccine. In some embodiments, the
RNA (e.g., mRNA) vaccine is a combination vaccine comprising a
combination of any two or more of the foregoing vaccines.
[0084] In some embodiments, a method further comprises
administering to the subject a second (booster) dose of a RNA
(e.g., mRNA) vaccine. Additional doses of a RNA (e.g., mRNA)
vaccine may be administered.
[0085] In some embodiments, the subjects exhibit a seroconversion
rate of at least 80% (e.g., at least 85%, at least 90%, or at least
95%) following the first dose or the second (booster) dose of the
vaccine. Seroconversion is the time period during which a specific
antibody develops and becomes detectable in the blood. After
seroconversion has occurred, a virus can be detected in blood tests
for the antibody. During an infection or immunization, antigens
enter the blood, and the immune system begins to produce antibodies
in response. Before seroconversion, the antigen itself may or may
not be detectable, but antibodies are considered absent. During
seroconversion, antibodies are present but not yet detectable. Any
time after seroconversion, the antibodies can be detected in the
blood, indicating a prior or current infection.
[0086] In some embodiments, a RNA (e.g., mRNA) vaccine is
administered to a subject by intradermal, intramuscular injection,
or by intranasal administration.
[0087] Some embodiments, of the present disclosure provide methods
of inducing an antigen specific immune response in a subject,
including administering to a subject a RNA (e.g., mRNA) vaccine in
an effective amount to produce an antigen specific immune response
in a subject. Antigen-specific immune responses in a subject may be
determined, in some embodiments, by assaying for antibody titer
(for titer of an antibody that binds to a HPV antigenic
polypeptide, a HSV antigenic polypeptide and/or a Chlamydia (e.g.,
C. trachomatis) antigenic polypeptide) following administration to
the subject of any of the RNA (e.g., mRNA) vaccines of the present
disclosure. In some embodiments, the anti-antigenic polypeptide
antibody titer produced in the subject is increased by at least 1
log relative to a control. In some embodiments, the anti-antigenic
polypeptide antibody titer produced in the subject is increased by
1-3 log relative to a control.
[0088] In some embodiments, the anti-antigenic polypeptide antibody
titer produced in a subject is increased at least 2 times relative
to a control. In some embodiments, the anti-antigenic polypeptide
antibody titer produced in the subject is increased at least 5
times relative to a control. In some embodiments, the
anti-antigenic polypeptide antibody titer produced in the subject
is increased at least 10 times relative to a control. In some
embodiments, the anti-antigenic polypeptide antibody titer produced
in the subject is increased 2-10 times relative to a control.
[0089] In some embodiments, the control is an anti-antigenic
polypeptide antibody titer produced in a subject who has not been
administered a RNA (e.g., mRNA) vaccine of the present disclosure.
In some embodiments, the control is an anti-antigenic polypeptide
antibody titer produced in a subject who has been administered a
live attenuated or inactivated HPV, HSV and/or Chlamydia vaccine
(see, e.g., Ren J. et al. J of Gen. Virol. 2015; 96: 1515-1520), or
wherein the control is an anti-antigenic polypeptide antibody titer
produced in a subject who has been administered a recombinant or
purified HPV, HSV and/or Chlamydia protein vaccine. In some
embodiments, the control is an anti-antigenic polypeptide antibody
titer produced in a subject who has been administered a HPV, HSV
and/or Chlamydia virus-like particle (VLP) vaccine (see, e.g., Cox
R G et al., J Virol. 2014 June; 88(11): 6368-6379).
[0090] A RNA (e.g., mRNA) vaccine of the present disclosure is
administered to a subject in an effective amount (an amount
effective to induce an immune response). In some embodiments, the
effective amount is a dose equivalent to an at least 2-fold, at
least 4-fold, at least 10-fold, at least 100-fold, at least
1000-fold reduction in the standard of care dose of a recombinant
HPV, HSV and/or Chlamydia protein vaccine, wherein the
anti-antigenic polypeptide antibody titer produced in the subject
is equivalent to an anti-antigenic polypeptide antibody titer
produced in a control subject administered the standard of care
dose of a recombinant HPV, HSV and/or Chlamydia protein vaccine, a
purified HPV, HSV and/or Chlamydia protein vaccine, a live
attenuated HPV, HSV and/or Chlamydia vaccine, an inactivated HPV,
HSV and/or Chlamydia vaccine, or a HPV, HSV and/or Chlamydia VLP
vaccine. In some embodiments, the effective amount is a dose
equivalent to 2-1000-fold reduction in the standard of care dose of
a recombinant HPV, HSV and/or Chlamydia protein vaccine, wherein
the anti-antigenic polypeptide antibody titer produced in the
subject is equivalent to an anti-antigenic polypeptide antibody
titer produced in a control subject administered the standard of
care dose of a recombinant HPV, HSV and/or Chlamydia protein
vaccine, a purified HPV, HSV and/or Chlamydia protein vaccine, a
live attenuated HPV, HSV and/or Chlamydia vaccine, an inactivated
HPV, HSV and/or Chlamydia vaccine, or a HPV, HSV and/or Chlamydia
VLP vaccine.
[0091] In some embodiments, the control is an anti-antigenic
polypeptide antibody titer produced in a subject who has been
administered a virus-like particle (VLP) vaccine comprising
structural proteins of HPV, HSV and/or Chlamydia.
[0092] In some embodiments, the RNA (e.g., mRNA) vaccine is
formulated in an effective amount to produce an antigen specific
immune response in a subject.
[0093] In some embodiments, the effective amount is a total dose of
25 .mu.g to 1000 .mu.g, or 50 .mu.g to 1000 .mu.g. In some
embodiments, the effective amount is a total dose of 100 .mu.g. In
some embodiments, the effective amount is a dose of 25 .mu.g
administered to the subject a total of two times. In some
embodiments, the effective amount is a dose of 100 .mu.g
administered to the subject a total of two times. In some
embodiments, the effective amount is a dose of 400 .mu.g
administered to the subject a total of two times. In some
embodiments, the effective amount is a dose of 500 .mu.g
administered to the subject a total of two times.
[0094] In some embodiments, the efficacy (or effectiveness) of a
RNA (e.g., mRNA) vaccine is greater than 60%. In some embodiments,
the RNA (e.g., mRNA) polynucleotide of the vaccine at least one HPV
antigenic polypeptide, at least one HSV antigenic polypeptide
and/or at least one Chlamydia (e.g., C. trachomatis) antigenic
polypeptide.
[0095] Vaccine efficacy may be assessed using standard analyses
(see, e.g., Weinberg et al., J Infect Dis. 2010 Jun. 1;
201(11):1607-10). For example, vaccine efficacy may be measured by
double-blind, randomized, clinical controlled trials. Vaccine
efficacy may be expressed as a proportionate reduction in disease
attack rate (AR) between the unvaccinated (ARU) and vaccinated
(ARV) study cohorts and can be calculated from the relative risk
(RR) of disease among the vaccinated group with use of the
following formulas:
Efficacy=(ARU-ARV)/ARU.times.100; and
Efficacy=(1-RR).times.100.
[0096] Likewise, vaccine effectiveness may be assessed using
standard analyses (see, e.g., Weinberg et al., J Infect Dis. 2010
Jun. 1; 201(11):1607-10). Vaccine effectiveness is an assessment of
how a vaccine (which may have already proven to have high vaccine
efficacy) reduces disease in a population. This measure can assess
the net balance of benefits and adverse effects of a vaccination
program, not just the vaccine itself, under natural field
conditions rather than in a controlled clinical trial. Vaccine
effectiveness is proportional to vaccine efficacy (potency) but is
also affected by how well target groups in the population are
immunized, as well as by other non-vaccine-related factors that
influence the `real-world` outcomes of hospitalizations, ambulatory
visits, or costs. For example, a retrospective case control
analysis may be used, in which the rates of vaccination among a set
of infected cases and appropriate controls are compared. Vaccine
effectiveness may be expressed as a rate difference, with use of
the odds ratio (OR) for developing infection despite
vaccination:
Effectiveness=(1-OR).times.100.
[0097] In some embodiments, the efficacy (or effectiveness) of a
RNA (e.g., mRNA) vaccine is at least 65%, at least 70%, at least
75%, at least 80%, at least 85%, or at least 90%.
[0098] In some embodiments, the vaccine immunizes the subject
against HPV, a HSV antigenic polypeptide and/or Chlamydia (e.g., C.
trachomatis) for up to 2 years. In some embodiments, the vaccine
immunizes the subject against HPV, HSV and/or Chlamydia (e.g., C.
trachomatis) for more than 2 years, more than 3 years, more than 4
years, or for 5-10 years.
[0099] In some embodiments, the subject is about 5 years old or
younger. For example, the subject may be between the ages of about
1 year and about 5 years (e.g., about 1, 2, 3, 5 or 5 years), or
between the ages of about 6 months and about 1 year (e.g., about 6,
7, 8, 9, 10, 11 or 12 months). In some embodiments, the subject is
about 12 months or younger (e.g., 12, 11, 10, 9, 8, 7, 6, 5, 4, 3,
2 months or 1 month). In some embodiments, the subject is about 6
months or younger.
[0100] In some embodiments, the subject was born full term (e.g.,
about 37-42 weeks). In some embodiments, the subject was born
prematurely, for example, at about 36 weeks of gestation or earlier
(e.g., about 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26 or 25
weeks). For example, the subject may have been born at about 32
weeks of gestation or earlier. In some embodiments, the subject was
born prematurely between about 32 weeks and about 36 weeks of
gestation. In such subjects, a RNA (e.g., mRNA) vaccine may be
administered later in life, for example, at the age of about 6
months to about 5 years, or older.
[0101] In some embodiments, the subject is a young adult between
the ages of about 20 years and about 50 years (e.g., about 20, 25,
30, 35, 40, 45 or 50 years old).
[0102] In some embodiments, the subject is an elderly subject about
60 years old, about 70 years old, or older (e.g., about 60, 65, 70,
75, 80, 85 or 90 years old).
[0103] In some embodiments, the subject has been exposed to HPV,
HSV and/or Chlamydia (e.g., C. trachomatis); the subject is
infected with HPV, HSV and/or Chlamydia (e.g., C. trachomatis); or
subject is at risk of infection by HPV, HSV and/or Chlamydia (e.g.,
C. trachomatis).
[0104] In some embodiments, the subject is immunocompromised (has
an impaired immune system, e.g., has an immune disorder or
autoimmune disorder).
[0105] In some embodiments the nucleic acid vaccines described
herein are chemically modified. In other embodiments the nucleic
acid vaccines are unmodified.
[0106] Yet other aspects provide compositions for and methods of
vaccinating a subject comprising administering to the subject a
nucleic acid vaccine comprising one or more RNA polynucleotides
having an open reading frame encoding a first respiratory virus
antigenic polypeptide, wherein the RNA polynucleotide does not
include a stabilization element, and wherein an adjuvant is not
coformulated or co-administered with the vaccine.
[0107] In other aspects the invention is a composition for or
method of vaccinating a subject comprising administering to the
subject a nucleic acid vaccine comprising one or more RNA
polynucleotides having an open reading frame encoding a first
antigenic polypeptide wherein a dosage of between 10 .mu.g/kg and
400 .mu.g/kg of the nucleic acid vaccine is administered to the
subject. In some embodiments the dosage of the RNA polynucleotide
is 1-5 .mu.g, 5-10 .mu.g, 10-15 .mu.g, 15-20 .mu.g, 10-25 .mu.g,
20-25 .mu.g, 20-50 .mu.g, 30-50 .mu.g, 40-50 .mu.g, 40-60 .mu.g,
60-80 .mu.g, 60-100 .mu.g, 50-100 .mu.g, 80-120 .mu.g, 40-120
.mu.g, 40-150 .mu.g, 50-150 .mu.g, 50-200 .mu.g, 80-200 .mu.g,
100-200 .mu.g, 120-250 .mu.g, 150-250 .mu.g, 180-280 .mu.g, 200-300
.mu.g, 50-300 .mu.g, 80-300 .mu.g, 100-300 .mu.g, 40-300 .mu.g,
50-350 .mu.g, 100-350 .mu.g, 200-350 .mu.g, 300-350 .mu.g, 320-400
.mu.g, 40-380 .mu.g, 40-100 .mu.g, 100-400 .mu.g, 200-400 .mu.g, or
300-400 .mu.g per dose. In some embodiments, the nucleic acid
vaccine is administered to the subject by intradermal or
intramuscular injection. In some embodiments, the nucleic acid
vaccine is administered to the subject on day zero. In some
embodiments, a second dose of the nucleic acid vaccine is
administered to the subject on day twenty one.
[0108] In some embodiments, a dosage of 25 micrograms of the RNA
polynucleotide is included in the nucleic acid vaccine administered
to the subject. In some embodiments, a dosage of 100 micrograms of
the RNA polynucleotide is included in the nucleic acid vaccine
administered to the subject. In some embodiments, a dosage of 50
micrograms of the RNA polynucleotide is included in the nucleic
acid vaccine administered to the subject. In some embodiments, a
dosage of 75 micrograms of the RNA polynucleotide is included in
the nucleic acid vaccine administered to the subject. In some
embodiments, a dosage of 150 micrograms of the RNA polynucleotide
is included in the nucleic acid vaccine administered to the
subject. In some embodiments, a dosage of 400 micrograms of the RNA
polynucleotide is included in the nucleic acid vaccine administered
to the subject. In some embodiments, a dosage of 200 micrograms of
the RNA polynucleotide is included in the nucleic acid vaccine
administered to the subject. In some embodiments, the RNA
polynucleotide accumulates at a 100 fold higher level in the local
lymph node in comparison with the distal lymph node. In other
embodiments the nucleic acid vaccine is chemically modified and in
other embodiments the nucleic acid vaccine is not chemically
modified.
[0109] Aspects of the invention provide a nucleic acid vaccine
comprising one or more RNA polynucleotides having an open reading
frame encoding a first antigenic polypeptide, wherein the RNA
polynucleotide does not include a stabilization element, and a
pharmaceutically acceptable carrier or excipient, wherein an
adjuvant is not included in the vaccine. In some embodiments, the
stabilization element is a histone stem-loop. In some embodiments,
the stabilization element is a nucleic acid sequence having
increased GC content relative to wild type sequence.
[0110] Aspects of the invention provide nucleic acid vaccines
comprising one or more RNA polynucleotides having an open reading
frame encoding a first antigenic polypeptide, wherein the RNA
polynucleotide is present in the formulation for in vivo
administration to a host, which confers an antibody titer superior
to the criterion for seroprotection for the first antigen for an
acceptable percentage of human subjects. In some embodiments, the
antibody titer produced by the mRNA vaccines of the invention is a
neutralizing antibody titer. In some embodiments the neutralizing
antibody titer is greater than a protein vaccine. In other
embodiments the neutralizing antibody titer produced by the mRNA
vaccines of the invention is greater than an adjuvanted protein
vaccine. In yet other embodiments the neutralizing antibody titer
produced by the mRNA vaccines of the invention is 1,000-10,000,
1,200-10,000, 1,400-10,000, 1,500-10,000, 1,000-5,000, 1,000-4,000,
1,800-10,000, 2000-10,000, 2,000-5,000, 2,000-3,000, 2,000-4,000,
3,000-5,000, 3,000-4,000, or 2,000-2,500. A neutralization titer is
typically expressed as the highest serum dilution required to
achieve a 50% reduction in the number of plaques.
[0111] Also provided are nucleic acid vaccines comprising one or
more RNA polynucleotides having an open reading frame encoding a
first antigenic polypeptide, wherein the RNA polynucleotide is
present in a formulation for in vivo administration to a host for
eliciting a longer lasting high antibody titer than an antibody
titer elicited by an mRNA vaccine having a stabilizing element or
formulated with an adjuvant and encoding the first antigenic
polypeptide. In some embodiments, the RNA polynucleotide is
formulated to produce a neutralizing antibodies within one week of
a single administration. In some embodiments, the adjuvant is
selected from a cationic peptide and an immunostimulatory nucleic
acid. In some embodiments, the cationic peptide is protamine.
[0112] Aspects provide nucleic acid vaccines comprising one or more
RNA polynucleotides having an open reading frame comprising at
least one chemical modification or optionally no chemical
modification, the open reading frame encoding a first antigenic
polypeptide, wherein the RNA polynucleotide is present in the
formulation for in vivo administration to a host such that the
level of antigen expression in the host significantly exceeds a
level of antigen expression produced by an mRNA vaccine having a
stabilizing element or formulated with an adjuvant and encoding the
first antigenic polypeptide.
[0113] Other aspects provide nucleic acid vaccines comprising one
or more RNA polynucleotides having an open reading frame comprising
at least one chemical modification or optionally no chemical
modification, the open reading frame encoding a first antigenic
polypeptide, wherein the vaccine has at least 10 fold less RNA
polynucleotide than is required for an unmodified mRNA vaccine to
produce an equivalent antibody titer. In some embodiments, the RNA
polynucleotide is present in a dosage of 25-100 micrograms.
[0114] Aspects of the invention also provide a unit of use vaccine,
comprising between 10 ug and 400 ug of one or more RNA
polynucleotides having an open reading frame comprising at least
one chemical modification or optionally no chemical modification,
the open reading frame encoding a first antigenic polypeptide, and
a pharmaceutically acceptable carrier or excipient, formulated for
delivery to a human subject. In some embodiments, the vaccine
further comprises a cationic lipid nanoparticle.
[0115] Aspects of the invention provide methods of creating,
maintaining or restoring antigenic memory to a respiratory virus
strain in an individual or population of individuals comprising
administering to said individual or population an antigenic memory
booster nucleic acid vaccine comprising (a) at least one RNA
polynucleotide, said polynucleotide comprising at least one
chemical modification or optionally no chemical modification and
two or more codon-optimized open reading frames, said open reading
frames encoding a set of reference antigenic polypeptides, and (b)
optionally a pharmaceutically acceptable carrier or excipient. In
some embodiments, the vaccine is administered to the individual via
a route selected from the group consisting of intramuscular
administration, intradermal administration and subcutaneous
administration. In some embodiments, the administering step
comprises contacting a muscle tissue of the subject with a device
suitable for injection of the composition. In some embodiments, the
administering step comprises contacting a muscle tissue of the
subject with a device suitable for injection of the composition in
combination with electroporation.
[0116] Aspects of the invention provide methods of vaccinating a
subject comprising administering to the subject a single dosage of
between 25 ug/kg and 400 ug/kg of a nucleic acid vaccine comprising
one or more RNA polynucleotides having an open reading frame
encoding a first antigenic polypeptide in an effective amount to
vaccinate the subject.
[0117] Other aspects provide nucleic acid vaccines comprising one
or more RNA polynucleotides having an open reading frame comprising
at least one chemical modification, the open reading frame encoding
a first antigenic polypeptide, wherein the vaccine has at least 10
fold less RNA polynucleotide than is required for an unmodified
mRNA vaccine to produce an equivalent antibody titer. In some
embodiments, the RNA polynucleotide is present in a dosage of
25-100 micrograms.
[0118] Other aspects provide nucleic acid vaccines comprising an
LNP formulated RNA polynucleotide having an open reading frame
comprising no modifications (unmodified), the open reading frame
encoding a first antigenic polypeptide, wherein the vaccine has at
least 10 fold less RNA polynucleotide than is required for an
unmodified mRNA vaccine not formulated in a LNP to produce an
equivalent antibody titer. In some embodiments, the RNA
polynucleotide is present in a dosage of 25-100 micrograms.
[0119] The data presented in the Examples demonstrate significant
enhanced immune responses using the formulations of the invention.
The data demonstrated the effectiveness of both chemically modified
and unmodified RNA vaccines of the invention. Surprisingly, in
contrast to prior art reports that it was preferable to use
chemically unmodified mRNA formulated in a carrier for the
production of vaccines, it was discovered herein that chemically
modified mRNA-LNP vaccines required a much lower effective mRNA
dose than unmodified mRNA, i.e., tenfold less than unmodified mRNA
when formulated in carriers other than LNP. Both the chemically
modified and unmodified RNA vaccines of the invention produce
better immune responses than mRNA vaccines formulated in a
different lipid carrier.
[0120] In other aspects the invention encompasses a method of
treating an elderly subject age 60 years or older comprising
administering to the subject a nucleic acid vaccine comprising one
or more RNA polynucleotides having an open reading frame encoding a
respiratory virus antigenic polypeptide in an effective amount to
vaccinate the subject.
[0121] In other aspects the invention encompasses a method of
treating a young subject age 17 years or younger comprising
administering to the subject a nucleic acid vaccine comprising one
or more RNA polynucleotides having an open reading frame encoding a
respiratory virus antigenic polypeptide in an effective amount to
vaccinate the subject.
[0122] In other aspects the invention encompasses a method of
treating an adult subject comprising administering to the subject a
nucleic acid vaccine comprising one or more RNA polynucleotides
having an open reading frame encoding a respiratory virus antigenic
polypeptide in an effective amount to vaccinate the subject.
[0123] In some aspects the invention is a method of vaccinating a
subject with a combination vaccine including at least two nucleic
acid sequences encoding respiratory antigens wherein the dosage for
the vaccine is a combined therapeutic dosage wherein the dosage of
each individual nucleic acid encoding an antigen is a sub
therapeutic dosage. In some embodiments, the combined dosage is 25
micrograms of the RNA polynucleotide in the nucleic acid vaccine
administered to the subject. In some embodiments, the combined
dosage is 100 micrograms of the RNA polynucleotide in the nucleic
acid vaccine administered to the subject. In some embodiments the
combined dosage is 50 micrograms of the RNA polynucleotide in the
nucleic acid vaccine administered to the subject. In some
embodiments, the combined dosage is 75 micrograms of the RNA
polynucleotide in the nucleic acid vaccine administered to the
subject. In some embodiments, the combined dosage is 150 micrograms
of the RNA polynucleotide in the nucleic acid vaccine administered
to the subject. In some embodiments, the combined dosage is 400
micrograms of the RNA polynucleotide in the nucleic acid vaccine
administered to the subject. In some embodiments, the sub
therapeutic dosage of each individual nucleic acid encoding an
antigen is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,
17, 18, 19, or 20 micrograms. In other embodiments the nucleic acid
vaccine is chemically modified and in other embodiments the nucleic
acid vaccine is not chemically modified.
[0124] The RNA polynucleotide is one of SEQ ID NO: 1-28, 62-64,
184-294 431-461 and includes at least one chemical modification. In
other embodiments the RNA polynucleotide is one of SEQ ID NO: 1-28,
62-64, 184-294 431-461 and does not include any nucleotide
modifications, or is unmodified. In yet other embodiments the at
least one RNA polynucleotide encodes an antigenic protein of any of
SEQ ID NO: 31-59, 65-72, or 73-183 and includes at least one
chemical modification. In other embodiments the RNA polynucleotide
encodes an antigenic protein of any of SEQ ID NO: 31-59, 65-72, or
73-183 and does not include any nucleotide modifications, or is
unmodified.
[0125] In preferred aspects, vaccines of the invention (e.g.,
LNP-encapsulated mRNA vaccines) produce prophylactically- and/or
therapeutically-efficacious levels, concentrations and/or titers of
antigen-specific antibodies in the blood or serum of a vaccinated
subject. As defined herein, the term antibody titer refers to the
amount of antigen-specific antibody produces in s subject, e.g., a
human subject. In exemplary embodiments, antibody titer is
expressed as the inverse of the greatest dilution (in a serial
dilution) that still gives a positive result. In exemplary
embodiments, antibody titer is determined or measured by
enzyme-linked immunosorbent assay (ELISA). In exemplary
embodiments, antibody titer is determined or measured by
neutralization assay, e.g., by microneutralization assay. In
certain aspects, antibody titer measurement is expressed as a
ratio, such as 1:40, 1:100, etc.
[0126] In exemplary embodiments of the invention, an efficacious
vaccine produces an antibody titer of greater than 1:40, greater
that 1:100, greater than 1:400, greater than 1:1000, greater than
1:2000, greater than 1:3000, greater than 1:4000, greater than
1:500, greater than 1:6000, greater than 1:7500, greater than
1:10000. In exemplary embodiments, the antibody titer is produced
or reached by 10 days following vaccination, by 20 days following
vaccination, by 30 days following vaccination, by 40 days following
vaccination, or by 50 or more days following vaccination. In
exemplary embodiments, the titer is produced or reached following a
single dose of vaccine administered to the subject. In other
embodiments, the titer is produced or reached following multiple
doses, e.g., following a first and a second dose (e.g., a booster
dose.)
[0127] In exemplary aspects of the invention, antigen-specific
antibodies are measured in units of .mu.g/ml or are measured in
units of IU/L (International Units per liter) or mIU/ml (milli
International Units per ml). In exemplary embodiments of the
invention, an efficacious vaccine produces >0.5 .mu.g/ml,
>0.1 .mu.g/ml, >0.2 .mu.g/ml, >0.35 .mu.g/ml, >0.5
.mu.g/ml, >1 .mu.g/ml, >2 .mu.g/ml, >5 .mu.g/ml or >10
.mu.g/ml. In exemplary embodiments of the invention, an efficacious
vaccine produces >10 mIU/ml, >20 mIU/ml, >50 mIU/ml,
>100 mIU/ml, >200 mIU/ml, >500 mIU/ml or >1000 mIU/ml.
In exemplary embodiments, the antibody level or concentration is
produced or reached by 10 days following vaccination, by 20 days
following vaccination, by 30 days following vaccination, by 40 days
following vaccination, or by 50 or more days following vaccination.
In exemplary embodiments, the level or concentration is produced or
reached following a single dose of vaccine administered to the
subject. In other embodiments, the level or concentration is
produced or reached following multiple doses, e.g., following a
first and a second dose (e.g., a booster dose.) In exemplary
embodiments, antibody level or concentration is determined or
measured by enzyme-linked immunosorbent assay (ELISA). In exemplary
embodiments, antibody level or concentration is determined or
measured by neutralization assay, e.g., by microneutralization
assay.
[0128] The details of various embodiments of the disclosure are set
forth in the description below. Other features, objects, and
advantages of the disclosure will be apparent from the description
and from the claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0129] FIGS. 1A-1B are western blot graphs showing the in vitro
expression of Chlamydia trachomatis antigens (Ct089, Ct858, and
Ct875) encoded by candidate mRNA vaccines. FIG. 2A shows the
expression of these antigens in concentrated or dilute supernatant
of HEK293K cells. Expression of Ct875 and Ct089 was detected in the
supernatants. FIG. 2B shows the expression of these antigens in
HEK293F cell lysates. Expression of Ct858 and Ct089 was detected in
the cell lysates.
[0130] FIGS. 2A-2B are western blot graphs showing the in vitro
expression of Chlamydia trachomatis antigens encoded by candidate
mRNA vaccines. All antigens tested expressed in HEK293F cells. FIG.
2A shows the expression of PmPG_pd, Ct460, and Ct622 in
concentrated supernatant of HEK293K cells. FIG. 2B shows the
expression of Cta1 in HEK293F cell lysates.
[0131] FIG. 3 is a western blot graph showing the in vitro
expression of Chlamydia trachomatis antigens (Ct 443 and Ct812pd_D)
encoded by candidate mRNA vaccines. The expression of Ct443 and
Ct812pd_D were detected in the cell lysates.
[0132] FIG. 4 shows data from an ELISA of sera collected from mice
bled on day 21 (post prime; left graph) and on day 35 (post-boost,
right graph), analyzed for IgG antibody titers against Ct089 using
rCt089 produced in E. coli as the antigen, following administration
of Ct089mRNA, Ct089NGM mRNA or rCt089.
DETAILED DESCRIPTION
[0133] The present disclosure provides, in some embodiments,
vaccines that comprise RNA (e.g., mRNA) polynucleotides encoding a
human papillomavirus (HPV) antigenic polypeptide, a herpes simplex
virus (HSV) antigenic polypeptide, and/or a Chlamydia (e.g., C.
trachomatis) antigenic polypeptide. The present disclosure also
provides, in some embodiments, combination vaccines that comprise
at least one RNA (e.g., mRNA) polynucleotide encoding at least two
antigenic polypeptides selected from HPV antigenic polypeptides,
HSV antigenic polypeptides, and Chlamydia (e.g., C. trachomatis)
antigenic polypeptides. Also provided herein are methods of
administering the RNA (e.g., mRNA) vaccines, methods of producing
the RNA (e.g., mRNA) vaccines, compositions (e.g., pharmaceutical
compositions) comprising the RNA (e.g., mRNA) vaccines, and nucleic
acids (e.g., DNA) encoding the RNA (e.g., mRNA) vaccines. In some
embodiments, a RNA (e.g., mRNA) vaccine comprises an adjuvant, such
as a flagellin adjuvant, as provided herein.
[0134] The RNA (e.g., mRNA) vaccines (e.g., HPV, HSV and/or
Chlamydia RNA vaccines), in some embodiments, may be used to induce
a balanced immune response, comprising both cellular and humoral
immunity, without many of the risks associated with DNA
vaccination.
[0135] The entire contents of International Application No.
PCT/US2015/02740 is incorporated herein by reference.
Human Papillomavirus (HPV)
[0136] Major capsid protein L1 forms an icosahedral capsid with a
T=7 symmetry and a 50 nm diameter. The capsid is composed of 72
pentamers linked to each other by disulfide bonds and associated
with L2 proteins. HPV capsid proteins bind to heparan sulfate
proteoglycans on the basement membrane of target cells to provide
initial virion attachment to the target cells. The basement
membrane is exposed only after epithelium trauma. Additionally, the
alpha6 integrin complexed with either beta1 or beta4 integrin acts
as a coreceptor recognized by L1. Once attached, the virion enters
the host cell via clathrin-mediated endocytosis, and the genomic
DNA is released to the host nucleus. The virion assembly takes
place within the cell nucleus. L1 protein encapsulates the genomic
DNA together with L2 protein.
[0137] A HPV vaccine may comprise, for example, at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
at least one HPV antigenic polypeptide identified by SEQ ID NO:
35-59 (Table 2).
[0138] A HPV vaccine may comprise, for example, at least one RNA
(e.g., mRNA) polynucleotide encoded by a nucleic acid (e.g., DNA)
identified by SEQ ID NO: 1-28 (Table 1).
[0139] The present disclosure is not limited by a particular strain
of HPV. The strain of HPV used in a vaccine may be any strain of
HPV. Non-limiting examples of strains of HPV are provided elsewhere
herein.
[0140] In some embodiments, HPV vaccines comprise RNA (e.g., mRNA)
encoding a HPV antigenic polypeptide having at least 95%, at least
96%, at least 97%, at least 98% or at least 99% identity with HPV
L1 or HPV L2 activity and having HPV L1 or HPV L2 activity,
respectively.
[0141] A protein is considered to have HPV L1 protein activity if,
for example, it binds to heparan sulfate proteoglycans on the
basement membrane to provide initial virion attachment to target
cells.
Chlamydia
[0142] Embodiments of the present disclosure provide RNA (e.g.,
mRNA) vaccines that include at least one polynucleotide encoding at
least one Chlamydia (e.g., C. trachomatis) antigen. Chlamydia
trachomatis, an obligate intracellular human pathogen, is one of
four bacterial species in the genus Chlamydia. Chlamydia
trachomatis is a Gram-negative bacterium, ovoid in shape. Chlamydia
trachomatis includes three human biovars (variant prokaryotic
strains): (1) serovars (or serotypes) Ab, B, Ba and C, which cause
trachoma infection of the eyes, which can lead to blindness; (2)
serovars D-K, which cause urethritis, pelvic inflammatory disease,
ectopic pregnancy, neonatal pneumonia, and neonatal conjunctivitis;
and (3) serovars L1, L2 and L3, which cause lymphogranuloma
venereum. Major outer membrane protein (MOMP) is the dominant
surface protein of the bacteria (contributing to 60% of the total
protein mass in the outer membrane) and consists of four variable
domains interspersed among five constant domains. The four variable
domains contain serovar-specific epitopes; the five constant
domains are highly conserved among the different serovars and
contain several conserved CD4 and CD8 T cell epitopes. MOMP, if its
native trimeric structure is preserved, induces protection against
Chlamydia infection in animals (Kari L et al. The Journal of
Immunology 2009; 182:8063-70).
[0143] Thus, in some embodiments, a Chlamydia (e.g., C.
trachomatis) RNA (e.g., mRNA) vaccine of the present disclosure
comprises a RNA polynucleotide encoding any one of, or any
combination of at least two of, MOMP serovar H, F, E, D, I, G, J
and K.
[0144] In some embodiments, a Chlamydia (e.g., C. trachomatis) RNA
(e.g., mRNA) vaccine of the present disclosure comprises at least
one RNA polynucleotide encoding major outer membrane protein
(MOMP), serovar H.
[0145] In some embodiments, a Chlamydia (e.g., C. trachomatis) RNA
(e.g., mRNA) vaccine of the present disclosure comprises at least
one RNA polynucleotide encoding MOMP serovar F.
[0146] In some embodiments, a Chlamydia (e.g., C. trachomatis) RNA
(e.g., mRNA) vaccine of the present disclosure comprises at least
one RNA polynucleotide encoding MOMP serovar E.
[0147] In some embodiments, a Chlamydia (e.g., C. trachomatis) RNA
(e.g., mRNA) vaccine of the present disclosure comprises at least
one RNA polynucleotide encoding MOMP serovar D.
[0148] In some embodiments, a Chlamydia (e.g., C. trachomatis) RNA
(e.g., mRNA) vaccine of the present disclosure comprises at least
one RNA polynucleotide encoding MOMP serovar I.
[0149] In some embodiments, a Chlamydia (e.g., C. trachomatis) RNA
(e.g., mRNA) vaccine of the present disclosure comprises at least
one RNA polynucleotide encoding MOMP serovar G.
[0150] In some embodiments, a Chlamydia (e.g., C. trachomatis) RNA
(e.g., mRNA) vaccine of the present disclosure comprises at least
one RNA polynucleotide encoding MOMP serovar J.
[0151] In some embodiments, a Chlamydia (e.g., C. trachomatis) RNA
(e.g., mRNA) vaccine of the present disclosure comprises at least
one RNA polynucleotide encoding MOMP serovar K.
[0152] In some embodiments, a Chlamydia (e.g., C. trachomatis)
vaccine may comprise, for example, at least one RNA (e.g., mRNA)
encoded by a nucleic acid sequence identified by SEQ ID NO: 62-64
or 184-294 (Table 4 or 8) or a variant thereof having at least 90
identity to a nucleic acid sequence identified by SEQ ID NO: 62-64
or 184-294 (Table 4 or 8).
[0153] In some embodiments, a Chlamydia trachomatis vaccine may
comprise, for example, at least one RNA (e.g., mRNA) encoding an
amino acid sequence identified by any one of SEQ ID NO: 65-183
(Tables 5 or 7) or a variant thereof having at least 90 identity to
an amino acid sequence identified by any one of SEQ ID NO: 65-183
(Tables 5 or 7).
[0154] It should be understood that the present disclosure is not
intended to be limited by a particular strain or serotype of
Chlamydia. The strain or serotype of Chlamydia used, as provided
herein, may be any strain or serotype of Chlamydia, including, for
example, Chlamydia trachomatis.
[0155] In some embodiments, a Chlamydia (e.g., C. trachomatis) RNA
(e.g., mRNA) vaccine of the present disclosure comprises a RNA
polynucleotide encoding a variable domain of Chlamydia (e.g., C.
trachomatis) MOMP. In some embodiments, a Chlamydia (e.g., C.
trachomatis) RNA (e.g., mRNA) vaccine of the present disclosure
comprises a RNA polynucleotide encoding a serovar-specific epitope
of a variable domain of Chlamydia (e.g., C. trachomatis) MOMP.
[0156] In some embodiments, Chlamydia vaccines comprise RNA (e.g.,
mRNA) encoding a Chlamydia (e.g., C. trachomatis) antigenic
polypeptide having at least 95%, at least 96%, at least 97%, at
least 98% or at least 99% identity with Chlamydia (e.g., C.
trachomatis) MOMP serovar H, F, E, D, I, G, J and K and having
Chlamydia trachomatis MOMP serovar H, F, E, D, I, G, J and K
activity, respectively.
[0157] A protein is considered to have major outer membrane protein
(MOMP) activity if, for example, it facilitates porin formation and
maintains the structural rigidity of the outer membrane. MOMP
permits the diffusion of specific solutes through the intracellular
reticulate body membrane. In elementary bodies (EBs, the infectious
stage, which is able to survive outside the host cell), MOMP
provides the structural integrity of the outer envelope through
disulfide cross-links with the small cysteine-rich protein and the
large cysteine-rich periplasmic protein. In Chlamydia trachomatis,
the protein contains four symmetrically-spaced variable domains (VD
I-IV). Disulfide bond interactions within and between MOMP
molecules and other components form high molecular weight oligomers
of the elementary shell. The protein determines the different
serotypes and serves as the functional equivalent of
peptidoglycan.
Herpes Simplex Virus
[0158] HSV is a double-stranded, linear DNA virus in the
Herpesviridae. Two members of the herpes simplex virus family
infect humans--known as HSV-1 and HSV-2. Symptoms of HSV infection
include the formation of blisters in the skin or mucous membranes
of the mouth, lips and/or genitals. HSV is a neuroinvasive virus
that can cause sporadic recurring episodes of viral reactivation in
infected individuals. HSV is transmitted by contact with an
infected area of the skin during a period of viral activation. HSV
most commonly infects via the oral or genital mucosa and replicates
in the stratified squamous epithelium, followed by uptake into
ramifying unmyelinated sensory nerve fibers within the stratified
squamous epithelium. The virus is then transported to the cell body
of the neuron in the dorsal root ganglion, where it persists in a
latent cellular infection (Cunningham A L et al. J Infect Dis.
(2006) 194 (Supplement 1): S11-S18).
[0159] The genome of Herpes Simplex Viruses (HSV-1 and HSV-2)
contains about 85 open reading frames, such that HSV can generate
at least 85 unique proteins. These genes encode 4 major classes of
proteins: (1) those associated with the outermost external lipid
bilayer of HSV (the envelope), (2) the internal protein coat (the
capsid), (3) an intermediate complex connecting the envelope with
the capsid coat (the tegument), and (4) proteins responsible for
replication and infection.
[0160] Examples of envelope proteins include UL1 (gL), UL10 (gM),
UL20, UL22, UL27 (gB), UL43, UL44 (gC), UL45, UL49A, UL53 (gK), US4
(gG), US5 (gJ), US6 (gD), US7 (gI), US8 (gE), and US10. Examples of
capsid proteins include UL6, UL18, UL19, UL35, and UL38. Tegument
proteins include UL11, UL13, UL21, UL36, UL37, UL41, UL45, UL46,
UL47, UL48, UL49, US9, and US10. Other HSV proteins include UL2,
UL3 UL4, UL5, UL7, UL8, UL9, UL12, UL14, UL15, UL16, UL17, UL23,
UL24, UL25, UL26, UL26.5, UL28, UL29, UL30, UL31, UL32, UL33, UL34,
UL39, UL40, UL42, UL50, UL51, UL52, UL54, UL55, UL56, US1, US2,
US3, US81, US11, US12, ICP0, and ICP4.
[0161] Since the envelope (most external portion of an HSV
particle) is the first to encounter target cells, the present
disclosure encompasses antigenic polypeptides associated with the
envelope as immunogenic agents. In brief, surface and membrane
proteins--glycoprotein D (gD), glycoprotein B (gB), glycoprotein H
(gH), glycoprotein L (gL)--as single antigens or in combination
with or without adjuvants may be used as HSV vaccine antigens.
[0162] In some embodiments, HSV vaccines comprise RNA (e.g., mRNA)
encoding HSV (HSV-1 or HSV-2) glycoprotein D.
[0163] In some embodiments, HSV vaccines comprise RNA (e.g., mRNA)
encoding HSV (HSV-1 or HSV-2) glycoprotein B.
[0164] In some embodiments, HSV vaccines comprise RNA (e.g., mRNA)
encoding HSV (HSV-1 or HSV-2) glycoprotein D and glycoprotein
C.
[0165] In some embodiments, HSV vaccines comprise RNA (e.g., mRNA)
encoding HSV (HSV-1 or HSV-2) glycoprotein D and glycoprotein E (or
glycoprotein I).
[0166] In some embodiments, HSV vaccines comprise RNA (e.g., mRNA)
encoding HSV (HSV-1 or HSV-2) glycoprotein B and glycoprotein
C.
[0167] In some embodiments, HSV vaccines comprise RNA (e.g., mRNA)
encoding HSV (HSV-1 or HSV-2) glycoprotein B and glycoprotein E (or
glycoprotein I).
[0168] In some embodiments, HSV vaccines comprise RNA (e.g., mRNA)
encoding a HSV (HSV-1 or HSV-2) antigenic polypeptide having at
least 95%, at least 96%, at least 97%, at least 98% or at least 99%
identity with HSV (HSV-1 or HSV-2) glycoprotein D and has HSV
(HSV-1 or HSV-2) glycoprotein D activity.
[0169] In some embodiments, HSV vaccines comprise RNA (e.g., mRNA)
encoding a HSV (HSV-1 or HSV-2) antigenic polypeptide having at
least 95%, at least 96%, at least 97%, at least 98% or at least 99%
identity with HSV (HSV-1 or HSV-2) glycoprotein C and has HSV
(HSV-1 or HSV-2) glycoprotein C activity.
[0170] In some embodiments, HSV vaccines comprise RNA (e.g., mRNA)
encoding a HSV (HSV-1 or HSV-2) antigenic polypeptide having at
least 95%, at least 96%, at least 97%, at least 98% or at least 99%
identity with HSV (HSV-1 or HSV-2) glycoprotein B and has HSV
(HSV-1 or HSV-2) glycoprotein B activity.
[0171] In some embodiments, HSV vaccines comprise RNA (e.g., mRNA)
encoding a HSV (HSV-1 or HSV-2) antigenic polypeptide having at
least 95%, at least 96%, at least 97%, at least 98% or at least 99%
identity with HSV (HSV-1 or HSV-2) glycoprotein E and has HSV
(HSV-1 or HSV-2) glycoprotein E activity.
[0172] In some embodiments, HSV vaccines comprise RNA (e.g., mRNA)
encoding a HSV (HSV-1 or HSV-2) antigenic polypeptide having at
least 95%, at least 96%, at least 97%, at least 98% or at least 99%
identity with HSV (HSV-1 or HSV-2) glycoprotein I and has HSV
(HSV-1 or HSV-2) glycoprotein I activity.
[0173] Glycoprotein "activity" of the present disclosure is
described below.
[0174] Glycoprotein C (gC) is a glycoprotein involved in viral
attachment to host cells; e.g., it acts as an attachment protein
that mediates binding of the HSV-2 virus to host adhesion
receptors, namely cell surface heparan sulfate and/or chondroitin
sulfate. gC plays a role in host immune evasion (aka viral
immunoevasion) by inhibiting the host complement cascade
activation. In particular, gC binds to and/or interacts with host
complement component C3b; this interaction then inhibits the host
immune response by disregulating the complement cascade (e.g.,
binds host complement C3b to block neutralization of virus).
[0175] Glycoprotein D (gD) is an envelope glycoprotein that binds
to cell surface receptors and/or is involved in cell attachment via
poliovirus receptor-related protein and/or herpesvirus entry
mediator, facilitating virus entry. gD binds to the potential host
cell entry receptors (tumor necrosis factor receptor superfamily,
member 14(TNFRSF14)/herpesvirus entry mediator (HVEM), poliovirus
receptor-related protein 1 (PVRL1) and or poliovirus
receptor-related protein 2 (PVRL2) and is proposed to trigger
fusion with host membrane, by recruiting the fusion machinery
composed of, for example, gB and gH/gL. gD interacts with host cell
receptors TNFRSF14 and/or PVRL1 and/or PVRL2 and (1) interacts (via
profusion domain) with gB; an interaction which can occur in the
absence of related HSV glycoproteins, e.g., gH and/or gL; and (2)
gD interacts (via profusion domain) with gH/gL heterodimer, an
interaction which can occur in the absence of gB. As such, gD
associates with the gB-gH/gL-gD complex. gD also interacts (via
C-terminus) with UL11 tegument protein.
[0176] Glycoprotein B (gB) is a viral glycoprotein involved in the
viral cell activity of herpes simplex virus (HSV) and is required
for the fusion of the HSV's envelope with the cellular membrane. It
is the most highly conserved of all surface glycoproteins and
primarily acts as a fusion protein, constituting the core fusion
machinery. gB, a class III membrane fusion glycoprotein, is a
type-1 transmembrane protein trimer of five structural domains.
Domain I includes two internal fusion loops and is through to
insert into the cellular membrane during virus-cell fusion. Domain
II appears to interact with gH/gL during the fusion process, domain
III contains an elongated alpha helix, and domain IV interacts with
cellular receptors. In epithelial cells, the heterodimer
glycoprotein E/glycoproteinl (gE/gI) is required for the
cell-to-cell spread of the virus, by sorting nascent virions to
cell junctions. Once the virus reaches the cell junctions, virus
particles can spread to adjacent cells extremely rapidly through
interactions with cellular receptors that accumulate at these
junctions. By similarity, it is implicated in basolateral spread in
polarized cells. In neuronal cells, gE/gI is essential for the
anterograde spread of the infection throughout the host nervous
system. Together with US9, the heterodimer gE/gI is involved in the
sorting and transport of viral structural components toward axon
tips. The heterodimer gE/gI serves as a receptor for the Fc part of
host IgG. Dissociation of gE/gI from IgG occurs at acidic pH, thus
may be involved in anti-HSV antibodies bipolar bridging, followed
by intracellular endocytosis and degradation, thereby interfering
with host IgG-mediated immune responses. gE/gI interacts (via
C-terminus) with VP22 tegument protein; this interaction is
necessary for the recruitment of VP22 to the Golgi and its
packaging into virions.
Combination Vaccines
[0177] Embodiments of the present disclosure also provide
combination RNA (e.g., mRNA) vaccines. A "combination RNA (e.g.,
mRNA) vaccine" of the present disclosure refers to a vaccine
comprising at least one (e.g., at least 2, 3, 4, or 5) RNA (e.g.,
mRNA) polynucleotide having an open reading frame encoding a
combination of at least one HPV antigenic polypeptide (e.g.,
selected from E1, E2, E4, E5, E6, E7, L1, and L2), at least one HSV
antigenic polypeptide (e.g., selected from glycoprotein D,
glycoprotein B, glycoprotein C, and glycoprotein E), at least one
Chlamydia antigenic polypeptide (e.g., selected from MOMP serovar
H, F, E, D, I, G, J and K), or any combination of two or more of
the foregoing antigenic polypeptides.
[0178] It has been discovered that the mRNA vaccines described
herein are superior to current vaccines in several ways. First, the
lipid nanoparticle (LNP) delivery is superior to other formulations
including a protamine base approach described in the literature and
no additional adjuvants are to be necessary. The use of LNPs
enables the effective delivery of chemically modified or unmodified
mRNA vaccines. Additionally it has been demonstrated herein that
both modified and unmodified LNP formulated mRNA vaccines were
superior to conventional vaccines by a significant degree. In some
embodiments the mRNA vaccines of the invention are superior to
conventional vaccines by a factor of at least 10 fold, 20 fold, 40
fold, 50 fold, 100 fold, 500 fold or 1,000 fold.
[0179] Although attempts have been made to produce functional RNA
vaccines, including mRNA vaccines and self-replicating RNA
vaccines, the therapeutic efficacy of these RNA vaccines have not
yet been fully established. Quite surprisingly, the inventors have
discovered, according to aspects of the invention a class of
formulations for delivering mRNA vaccines in vivo that results in
significantly enhanced, and in many respects synergistic, immune
responses including enhanced antigen generation and functional
antibody production with neutralization capability. These results
can be achieved even when significantly lower doses of the mRNA are
administered in comparison with mRNA doses used in other classes of
lipid based formulations. The formulations of the invention have
demonstrated significant unexpected in vivo immune responses
sufficient to establish the efficacy of functional mRNA vaccines as
prophylactic and therapeutic agents. Additionally, self-replicating
RNA vaccines rely on viral replication pathways to deliver enough
RNA to a cell to produce an immunogenic response. The formulations
of the invention do not require viral replication to produce enough
protein to result in a strong immune response. Thus, the mRNA of
the invention are not self-replicating RNA and do not include
components necessary for viral replication.
[0180] The invention involves, in some aspects, the surprising
finding that lipid nanoparticle (LNP) formulations significantly
enhance the effectiveness of mRNA vaccines, including chemically
modified and unmodified mRNA vaccines. The efficacy of mRNA
vaccines formulated in LNP was examined in vivo using several
distinct antigens. The results presented herein demonstrate the
unexpected superior efficacy of the mRNA vaccines formulated in LNP
over other commercially available vaccines.
[0181] In addition to providing an enhanced immune response, the
formulations of the invention generate a more rapid immune response
with fewer doses of antigen than other vaccines tested. The
mRNA-LNP formulations of the invention also produce quantitatively
and qualitatively better immune responses than vaccines formulated
in a different carriers.
[0182] The LNP used in the studies described herein has been used
previously to deliver siRNA in various animal models as well as in
humans. In view of the observations made in association with the
siRNA delivery of LNP formulations, the fact that LNP is useful in
vaccines is quite surprising. It has been observed that therapeutic
delivery of siRNA formulated in LNP causes an undesirable
inflammatory response associated with a transient IgM response,
typically leading to a reduction in antigen production and a
compromised immune response. In contrast to the findings observed
with siRNA, the LNP-mRNA formulations of the invention are
demonstrated herein to generate enhanced IgG levels, sufficient for
prophylactic and therapeutic methods rather than transient IgM
responses.
Nucleic Acids/Polynucleotides
[0183] STD vaccines, as provided herein, comprise at least one (one
or more) ribonucleic acid (RNA) (e.g., mRNA) polynucleotide having
an open reading frame encoding at least one HPV antigenic
polypeptide, at least one HSV antigenic polypeptide, and/or at
least one Chlamydia (e.g., C. trachomatis) antigenic polypeptide.
The term "nucleic acid" includes any compound and/or substance that
comprises a polymer of nucleotides (nucleotide monomer). These
polymers are referred to as polynucleotides. Thus, the terms
"nucleic acid" and "polynucleotide" are used interchangeably.
[0184] Nucleic acids may be or may include, for example,
ribonucleic acids (RNAs), deoxyribonucleic acids (DNAs), threose
nucleic acids (TNAs), glycol nucleic acids (GNAs), peptide nucleic
acids (PNAs), locked nucleic acids (LNAs, including LNA having a
.beta.-D-ribo configuration, .alpha.-LNA having an .alpha.-L-ribo
configuration (a diastereomer of LNA), 2'-amino-LNA having a
2'-amino functionalization, and 2'-amino-.alpha.-LNA having a
2'-amino functionalization), ethylene nucleic acids (ENA),
cyclohexenyl nucleic acids (CeNA) or chimeras or combinations
thereof.
[0185] In some embodiments, polynucleotides of the present
disclosure function as messenger RNA (mRNA). "Messenger RNA" (mRNA)
refers to any polynucleotide that encodes a (at least one)
polypeptide (a naturally-occurring, non-naturally-occurring, or
modified polymer of amino acids) and can be translated to produce
the encoded polypeptide in vitro, in vivo, in situ or ex vivo. The
skilled artisan will appreciate that, except where otherwise noted,
polynucleotide sequences set forth in the instant application will
recite "T"s in a representative DNA sequence but where the sequence
represents RNA (e.g., mRNA), the "T"s would be substituted for
"U"s. Thus, any of the RNA polynucleotides encoded by a DNA
identified by a particular sequence identification number may also
comprise the corresponding RNA (e.g., mRNA) sequence encoded by the
DNA, where each "T" of the DNA sequence is substituted with
"U."
[0186] The basic components of an mRNA molecule typically include
at least one coding region, a 5' untranslated region (UTR), a 3'
UTR, a 5' cap and a poly-A tail. Polynucleotides of the present
disclosure may function as mRNA but can be distinguished from
wild-type mRNA in their functional and/or structural design
features, which serve to overcome existing problems of effective
polypeptide expression using nucleic-acid based therapeutics.
[0187] In some embodiments, a RNA polynucleotide of an RNA (e.g.,
mRNA) vaccine encodes 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3,
3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5,
5-10, 5-9, 5-8, 5-7, 5-6, 6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8,
8-10, 8-9 or 9-10 antigenic polypeptides. In some embodiments, a
RNA (e.g., mRNA) polynucleotide of a STD vaccine encodes at least
10, 20, 30, 40, 50, 60, 70, 80, 90 or 100 antigenic
polypeptides.
[0188] In some embodiments, a RNA (e.g., mRNA) polynucleotide of a
STD vaccine encodes at least 100 or at least 200 antigenic
polypeptides. In some embodiments, a RNA polynucleotide of an STD
vaccine encodes 1-10, 5-15, 10-20, 15-25, 20-30, 25-35, 30-40,
35-45, 40-50, 1-50, 1-100, 2-50 or 2-100 antigenic
polypeptides.
[0189] Polynucleotides of the present disclosure, in some
embodiments, are codon optimized. Codon optimization methods are
known in the art and may be used as provided herein. Codon
optimization, in some embodiments, may be used to match codon
frequencies in target and host organisms to ensure proper folding;
bias GC content to increase mRNA stability or reduce secondary
structures; minimize tandem repeat codons or base runs that may
impair gene construction or expression; customize transcriptional
and translational control regions; insert or remove protein
trafficking sequences; remove/add post translation modification
sites in encoded protein (e.g. glycosylation sites); add, remove or
shuffle protein domains; insert or delete restriction sites; modify
ribosome binding sites and mRNA degradation sites; adjust
translational rates to allow the various domains of the protein to
fold properly; or to reduce or eliminate problem secondary
structures within the polynucleotide. Codon optimization tools,
algorithms and services are known in the art--non-limiting examples
include services from GeneArt (Life Technologies), DNA2.0 (Menlo
Park Calif.) and/or proprietary methods. In some embodiments, the
open reading frame (ORF) sequence is optimized using optimization
algorithms.
[0190] In some embodiments, a codon optimized sequence shares less
than 95% sequence identity, less than 90% sequence identity, less
than 85% sequence identity, less than 80% sequence identity, or
less than 75% sequence identity to a naturally-occurring or
wild-type sequence (e.g., a naturally-occurring or wild-type mRNA
sequence encoding a polypeptide or protein of interest (e.g., an
antigenic protein or antigenic polypeptide)).
[0191] In some embodiments, a codon-optimized sequence shares
between 65% and 85% (e.g., between about 67% and about 85%, or
between about 67% and about 80%) sequence identity to a
naturally-occurring sequence or a wild-type sequence (e.g., a
naturally-occurring or wild-type mRNA sequence encoding a
polypeptide or protein of interest (e.g., an antigenic protein or
polypeptide)). In some embodiments, a codon-optimized sequence
shares between 65% and 75%, or about 80% sequence identity to a
naturally-occurring sequence or wild-type sequence (e.g., a
naturally-occurring or wild-type mRNA sequence encoding a
polypeptide or protein of interest (e.g., an antigenic protein or
polypeptide)).
[0192] In some embodiments a codon-optimized RNA (e.g., mRNA) may,
for instance, be one in which the levels of G/C are enhanced. The
G/C-content of nucleic acid molecules may influence the stability
of the RNA. RNA having an increased amount of guanine (G) and/or
cytosine (C) residues may be functionally more stable than nucleic
acids containing a large amount of adenine (A) and thymine (T) or
uracil (U) nucleotides. WO02/098443 discloses a pharmaceutical
composition containing an mRNA stabilized by sequence modifications
in the translated region. Due to the degeneracy of the genetic
code, the modifications work by substituting existing codons for
those that promote greater RNA stability without changing the
resulting amino acid. The approach is limited to coding regions of
the RNA.
Antigens/Antigenic Polypeptides
[0193] In some embodiments, an antigenic polypeptide (e.g., HPV,
HSV and/or Chlamydia antigenic polypeptide) is longer than 25 amino
acids and shorter than 50 amino acids. Polypeptides include gene
products, naturally occurring polypeptides, synthetic polypeptides,
homologs, orthologs, paralogs, fragments and other equivalents,
variants, and analogs of the foregoing. A polypeptide may be a
single molecule or may be a multi-molecular complex such as a
dimer, trimer or tetramer. Polypeptides may also comprise single
chain polypeptides or multichain polypeptides, such as antibodies
or insulin, and may be associated or linked to each other. Most
commonly, disulfide linkages are found in multichain polypeptides.
The term "polypeptide" may also apply to amino acid polymers in
which at least one amino acid residue is an artificial chemical
analogue of a corresponding naturally-occurring amino acid.
[0194] A "polypeptide variant" is a molecule that differs in its
amino acid sequence relative to a native sequence or a reference
sequence. Amino acid sequence variants may possess substitutions,
deletions, insertions, or a combination of any two or three of the
foregoing, at certain positions within the amino acid sequence, as
compared to a native sequence or a reference sequence. Ordinarily,
variants possess at least 50% identity to a native sequence or a
reference sequence. In some embodiments, variants share at least
80% identity or at least 90% identity with a native sequence or a
reference sequence.
[0195] In some embodiments "variant mimics" are provided. A
"variant mimic" contains at least one amino acid that would mimic
an activated sequence. For example, glutamate may serve as a mimic
for phosphoro-threonine and/or phosphoro-serine. Alternatively,
variant mimics may result in deactivation or in an inactivated
product containing the mimic. For example, phenylalanine may act as
an inactivating substitution for tyrosine, or alanine may act as an
inactivating substitution for serine.
[0196] "Orthologs" refers to genes in different species that
evolved from a common ancestral gene by speciation. Normally,
orthologs retain the same function in the course of evolution.
Identification of orthologs is important for reliable prediction of
gene function in newly sequenced genomes.
[0197] "Analogs" is meant to include polypeptide variants that
differ by one or more amino acid alterations, for example,
substitutions, additions or deletions of amino acid residues that
still maintain one or more of the properties of the parent or
starting polypeptide.
[0198] The present disclosure provides several types of
compositions that are polynucleotide or polypeptide based,
including variants and derivatives. These include, for example,
substitutional, insertional, deletion and covalent variants and
derivatives. The term "derivative" is synonymous with the term
"variant" and generally refers to a molecule that has been modified
and/or changed in any way relative to a reference molecule or a
starting molecule.
[0199] As such, polynucleotides encoding peptides or polypeptides
containing substitutions, insertions and/or additions, deletions
and covalent modifications with respect to reference sequences, in
particular the polypeptide sequences disclosed herein, are included
within the scope of this disclosure. For example, sequence tags or
amino acids, such as one or more lysines, can be added to peptide
sequences (e.g., at the N-terminal or C-terminal ends). Sequence
tags can be used for peptide detection, purification or
localization. Lysines can be used to increase peptide solubility or
to allow for biotinylation. Alternatively, amino acid residues
located at the carboxy and amino terminal regions of the amino acid
sequence of a peptide or protein may optionally be deleted
providing for truncated sequences. Certain amino acids (e.g.,
C-terminal residues or N-terminal residues) alternatively may be
deleted depending on the use of the sequence, as for example,
expression of the sequence as part of a larger sequence that is
soluble, or linked to a solid support.
[0200] "Substitutional variants" when referring to polypeptides are
those that have at least one amino acid residue in a native or
starting sequence removed and a different amino acid inserted in
its place at the same position. Substitutions may be single, where
only one amino acid in the molecule has been substituted, or they
may be multiple, where two or more (e.g., 3, 4 or 5) amino acids
have been substituted in the same molecule.
[0201] As used herein the term "conservative amino acid
substitution" refers to the substitution of an amino acid that is
normally present in the sequence with a different amino acid of
similar size, charge, or polarity. Examples of conservative
substitutions include the substitution of a non-polar (hydrophobic)
residue such as isoleucine, valine and leucine for another
non-polar residue. Likewise, examples of conservative substitutions
include the substitution of one polar (hydrophilic) residue for
another such as between arginine and lysine, between glutamine and
asparagine, and between glycine and serine. Additionally, the
substitution of a basic residue such as lysine, arginine or
histidine for another, or the substitution of one acidic residue
such as aspartic acid or glutamic acid for another acidic residue
are additional examples of conservative substitutions. Examples of
non-conservative substitutions include the substitution of a
non-polar (hydrophobic) amino acid residue such as isoleucine,
valine, leucine, alanine, methionine for a polar (hydrophilic)
residue such as cysteine, glutamine, glutamic acid or lysine and/or
a polar residue for a non-polar residue.
[0202] "Features" when referring to polypeptide or polynucleotide
are defined as distinct amino acid sequence-based or
nucleotide-based components of a molecule respectively. Features of
the polypeptides encoded by the polynucleotides include surface
manifestations, local conformational shape, folds, loops,
half-loops, domains, half-domains, sites, termini and any
combination(s) thereof.
[0203] As used herein when referring to polypeptides the term
"domain" refers to a motif of a polypeptide having one or more
identifiable structural or functional characteristics or properties
(e.g., binding capacity, serving as a site for protein-protein
interactions).
[0204] As used herein when referring to polypeptides the terms
"site" as it pertains to amino acid based embodiments is used
synonymously with "amino acid residue" and "amino acid side chain."
As used herein when referring to polynucleotides the terms "site"
as it pertains to nucleotide based embodiments is used synonymously
with "nucleotide." A site represents a position within a peptide or
polypeptide or polynucleotide that may be modified, manipulated,
altered, derivatized or varied within the polypeptide-based or
polynucleotide-based molecules.
[0205] As used herein the terms "termini" or "terminus" when
referring to polypeptides or polynucleotides refers to an extremity
of a polypeptide or polynucleotide respectively. Such extremity is
not limited only to the first or final site of the polypeptide or
polynucleotide but may include additional amino acids or
nucleotides in the terminal regions. Polypeptide-based molecules
may be characterized as having both an N-terminus (terminated by an
amino acid with a free amino group (NH2)) and a C-terminus
(terminated by an amino acid with a free carboxyl group (COOH)).
Proteins are in some cases made up of multiple polypeptide chains
brought together by disulfide bonds or by non-covalent forces
(multimers, oligomers). These proteins have multiple N- and
C-termini. Alternatively, the termini of the polypeptides may be
modified such that they begin or end, as the case may be, with a
non-polypeptide based moiety such as an organic conjugate.
[0206] As recognized by those skilled in the art, protein
fragments, functional protein domains, and homologous proteins are
also considered to be within the scope of polypeptides of interest.
For example, provided herein is any protein fragment (meaning a
polypeptide sequence at least one amino acid residue shorter than a
reference polypeptide sequence but otherwise identical) of a
reference protein having a length of 10, 20, 30, 40, 50, 60, 70,
80, 90, 100 or longer than 100 amino acids. In another example, any
protein that includes a stretch of 20, 30, 40, 50, or 100
(contiguous) amino acids that are 40%, 50%, 60%, 70%, 80%, 90%,
95%, or 100% identical to any of the sequences described herein can
be utilized in accordance with the disclosure. In some embodiments,
a polypeptide includes 2, 3, 4, 5, 6, 7, 8, 9, 10, or more
mutations as shown in any of the sequences provided herein or
referenced herein. In another example, any protein that includes a
stretch of 20, 30, 40, 50, or 100 amino acids that are greater than
80%, 90%, 95%, or 100% identical to any of the sequences described
herein, wherein the protein has a stretch of 5, 10, 15, 20, 25, or
30 amino acids that are less than 80%, 75%, 70%, 65% to 60%
identical to any of the sequences described herein can be utilized
in accordance with the disclosure.
[0207] Polypeptide or polynucleotide molecules of the present
disclosure may share a certain degree of sequence similarity or
identity with the reference molecules (e.g., reference polypeptides
or reference polynucleotides), for example, with art-described
molecules (e.g., engineered or designed molecules or wild-type
molecules). The term "identity," as known in the art, refers to a
relationship between the sequences of two or more polypeptides or
polynucleotides, as determined by comparing the sequences. In the
art, identity also means the degree of sequence relatedness between
two sequences as determined by the number of matches between
strings of two or more amino acid residues or nucleic acid
residues.
[0208] Identity measures the percent of identical matches between
the smaller of two or more sequences with gap alignments (if any)
addressed by a particular mathematical model or computer program
(e.g., "algorithms"). Identity of related peptides can be readily
calculated by known methods. "% identity" as it applies to
polypeptide or polynucleotide sequences is defined as the
percentage of residues (amino acid residues or nucleic acid
residues) in the candidate amino acid or nucleic acid sequence that
are identical with the residues in the amino acid sequence or
nucleic acid sequence of a second sequence after aligning the
sequences and introducing gaps, if necessary, to achieve the
maximum percent identity. Methods and computer programs for the
alignment are well known in the art. Identity depends on a
calculation of percent identity but may differ in value due to gaps
and penalties introduced in the calculation. Generally, variants of
a particular polynucleotide or polypeptide have at least 40%, 45%,
50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%,
95%, 96%, 97%, 98%, 99% but less than 100% sequence identity to
that particular reference polynucleotide or polypeptide as
determined by sequence alignment programs and parameters described
herein and known to those skilled in the art. Such tools for
alignment include those of the BLAST suite (Stephen F. Altschul, et
al. (1997)." Gapped BLAST and PSI-BLAST: a new generation of
protein database search programs," Nucleic Acids Res.
25:3389-3402). Another popular local alignment technique is based
on the Smith-Waterman algorithm (Smith, T. F. & Waterman, M. S.
(1981) "Identification of common molecular subsequences." J. Mol.
Biol. 147:195-197). A general global alignment technique based on
dynamic programming is the Needleman-Wunsch algorithm (Needleman,
S. B. & Wunsch, C. D. (1970) "A general method applicable to
the search for similarities in the amino acid sequences of two
proteins." J. Mol. Biol. 48:443-453). More recently, a Fast Optimal
Global Sequence Alignment Algorithm (FOGSAA) was developed that
purportedly produces global alignment of nucleotide and protein
sequences faster than other optimal global alignment methods,
including the Needleman-Wunsch algorithm. Other tools are described
herein, specifically in the definition of "identity" below.
[0209] As used herein, the term "homology" refers to the overall
relatedness between polymeric molecules, e.g. between nucleic acid
molecules (e.g. DNA molecules and/or RNA molecules) and/or between
polypeptide molecules. Polymeric molecules (e.g. nucleic acid
molecules (e.g. DNA molecules and/or RNA molecules) and/or
polypeptide molecules) that share a threshold level of similarity
or identity determined by alignment of matching residues are termed
homologous. Homology is a qualitative term that describes a
relationship between molecules and can be based upon the
quantitative similarity or identity. Similarity or identity is a
quantitative term that defines the degree of sequence match between
two compared sequences. In some embodiments, polymeric molecules
are considered to be "homologous" to one another if their sequences
are at least 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%,
80%, 85%, 90%, 95%, or 99% identical or similar. The term
"homologous" necessarily refers to a comparison between at least
two sequences (polynucleotide or polypeptide sequences). Two
polynucleotide sequences are considered homologous if the
polypeptides they encode are at least 50%, 60%, 70%, 80%, 90%, 95%,
or even 99% for at least one stretch of at least 20 amino acids. In
some embodiments, homologous polynucleotide sequences are
characterized by the ability to encode a stretch of at least 4-5
uniquely specified amino acids. For polynucleotide sequences less
than 60 nucleotides in length, homology is determined by the
ability to encode a stretch of at least 4-5 uniquely specified
amino acids. Two protein sequences are considered homologous if the
proteins are at least 50%, 60%, 70%, 80%, or 90% identical for at
least one stretch of at least 20 amino acids.
[0210] Homology implies that the compared sequences diverged in
evolution from a common origin. The term "homolog" refers to a
first amino acid sequence or nucleic acid sequence (e.g., gene (DNA
or RNA) or protein sequence) that is related to a second amino acid
sequence or nucleic acid sequence by descent from a common
ancestral sequence. The term "homolog" may apply to the
relationship between genes and/or proteins separated by the event
of speciation or to the relationship between genes and/or proteins
separated by the event of genetic duplication. "Orthologs" are
genes (or proteins) in different species that evolved from a common
ancestral gene (or protein) by speciation. Typically, orthologs
retain the same function in the course of evolution. "Paralogs" are
genes (or proteins) related by duplication within a genome.
Orthologs retain the same function in the course of evolution,
whereas paralogs evolve new functions, even if these are related to
the original one.
[0211] The term "identity" refers to the overall relatedness
between polymeric molecules, for example, between polynucleotide
molecules (e.g. DNA molecules and/or RNA molecules) and/or between
polypeptide molecules. Calculation of the percent identity of two
polynucleic acid sequences, for example, can be performed by
aligning the two sequences for optimal comparison purposes (e.g.,
gaps can be introduced in one or both of a first and a second
nucleic acid sequences for optimal alignment and non-identical
sequences can be disregarded for comparison purposes). In certain
embodiments, the length of a sequence aligned for comparison
purposes is at least 30%, at least 40%, at least 50%, at least 60%,
at least 70%, at least 80%, at least 90%, at least 95%, or 100% of
the length of the reference sequence. The nucleotides at
corresponding nucleotide positions are then compared. When a
position in the first sequence is occupied by the same nucleotide
as the corresponding position in the second sequence, then the
molecules are identical at that position. The percent identity
between the two sequences is a function of the number of identical
positions shared by the sequences, taking into account the number
of gaps, and the length of each gap, which needs to be introduced
for optimal alignment of the two sequences. The comparison of
sequences and determination of percent identity between two
sequences can be accomplished using a mathematical algorithm. For
example, the percent identity between two nucleic acid sequences
can be determined using methods such as those described in
Computational Molecular Biology, Lesk, A. M., ed., Oxford
University Press, New York, 1988; Biocomputing: Informatics and
Genome Projects, Smith, D. W., ed., Academic Press, New York, 1993;
Sequence Analysis in Molecular Biology, von Heinje, G., Academic
Press, 1987; Computer Analysis of Sequence Data, Part I, Griffin,
A. M., and Griffin, H. G., eds., Humana Press, New Jersey, 1994;
and Sequence Analysis Primer, Gribskov, M. and Devereux, J., eds.,
M Stockton Press, New York, 1991; each of which is incorporated
herein by reference. For example, the percent identity between two
nucleic acid sequences can be determined using the algorithm of
Meyers and Miller (CABIOS, 1989, 4:11-17), which has been
incorporated into the ALIGN program (version 2.0) using a PAM120
weight residue table, a gap length penalty of 12 and a gap penalty
of 4. The percent identity between two nucleic acid sequences can,
alternatively, be determined using the GAP program in the GCG
software package using an NWSgapdna.CMP matrix. Methods commonly
employed to determine percent identity between sequences include,
but are not limited to those disclosed in Carillo, H., and Lipman,
D., SIAM J Applied Math., 48:1073 (1988); incorporated herein by
reference. Techniques for determining identity are codified in
publicly available computer programs. Exemplary computer software
to determine homology between two sequences include, but are not
limited to, GCG program package, Devereux, J., et al., Nucleic
Acids Research, 12, 387 (1984)), BLASTP, BLASTN, and FASTA
Altschul, S. F. et al., J. Molec. Biol., 215, 403 (1990)).
Multiprotein and Multicomponent Vaccines
[0212] The present disclosure encompasses STD vaccines comprising
multiple RNA (e.g., mRNA) polynucleotides, each encoding a single
antigenic polypeptide, as well as STD vaccines comprising a single
RNA polynucleotide encoding more than one antigenic polypeptide
(e.g., as a fusion polypeptide). Thus, a vaccine composition
comprising a RNA (e.g., mRNA) polynucleotide having an open reading
frame encoding a first antigenic polypeptide and a RNA (e.g., mRNA)
polynucleotide having an open reading frame encoding a second
antigenic polypeptide encompasses (a) vaccines that comprise a
first RNA polynucleotide encoding a first antigenic polypeptide and
a second RNA polynucleotide encoding a second antigenic
polypeptide, and (b) vaccines that comprise a single RNA
polynucleotide encoding a first and second antigenic polypeptide
(e.g., as a fusion polypeptide). RNA (e.g., mRNA) vaccines of the
present disclosure, in some embodiments, comprise 2-10 (e.g., 2, 3,
4, 5, 6, 7, 8, 9 or 10), or more, RNA polynucleotides having an
open reading frame, each of which encodes a different antigenic
polypeptide (or a single RNA polynucleotide encoding 2-10, or more,
different antigenic polypeptides). The antigenic polypeptides may
be selected from HPV antigenic polypeptides, HSV antigenic
polypeptides, and Chlamydia (e.g., C. trachomatis) antigenic
polypeptides.
[0213] In some embodiments, a STD vaccine comprises a RNA (e.g.,
mRNA) polynucleotide having an open reading frame encoding a viral
capsid protein, a RNA (e.g., mRNA) polynucleotide having an open
reading frame encoding a viral premembrane/membrane protein, and a
RNA (e.g., mRNA) polynucleotide having an open reading frame
encoding a viral envelope protein. In some embodiments, a STD
vaccine comprises a RNA (e.g., mRNA) polynucleotide having an open
reading frame encoding a viral fusion (F) protein and a RNA
polynucleotide having an open reading frame encoding a viral major
surface glycoprotein (G protein). In some embodiments, a vaccine
comprises a RNA (e.g., mRNA) polynucleotide having an open reading
frame encoding a viral F protein. In some embodiments, a vaccine
comprises a RNA (e.g., mRNA) polynucleotide having an open reading
frame encoding a viral G protein. In some embodiments, a vaccine
comprises a RNA (e.g., mRNA) polynucleotide having an open reading
frame encoding a HN protein.
[0214] In some embodiments, a multicomponent vaccine comprises at
least one RNA (e.g., mRNA) polynucleotide encoding at least one
antigenic polypeptide fused to a signal peptide (e.g., SEQ ID NO:
304-307). The signal peptide may be fused at the N-terminus or the
C-terminus of an antigenic polypeptide. An antigenic polypeptide
fused to a signal peptide may be selected from HPV antigenic
polypeptides, HSV antigenic polypeptides, and Chlamydia (e.g., C.
trachomatis) antigenic polypeptides.
Signal Peptides and Leader Sequences
[0215] In some embodiments, antigenic polypeptides encoded by STD
RNA (e.g., mRNA) polynucleotides comprise a signal peptide. Signal
peptides, comprising the N-terminal 15-60 amino acids of proteins,
are typically needed for the translocation across the membrane on
the secretory pathway and, thus, universally control the entry of
most proteins both in eukaryotes and prokaryotes to the secretory
pathway. Signal peptides generally include three regions: an
N-terminal region of differing length, which usually comprises
positively charged amino acids; a hydrophobic region; and a short
carboxy-terminal peptide region. In eukaryotes, the signal peptide
of a nascent precursor protein (pre-protein) directs the ribosome
to the rough endoplasmic reticulum (ER) membrane and initiates the
transport of the growing peptide chain across it for processing. ER
processing produces mature proteins, wherein the signal peptide is
cleaved from precursor proteins, typically by a ER-resident signal
peptidase of the host cell, or they remain uncleaved and function
as a membrane anchor. A signal peptide may also facilitate the
targeting of the protein to the cell membrane. The signal peptide,
however, is not responsible for the final destination of the mature
protein. Secretory proteins devoid of additional address tags in
their sequence are by default secreted to the external environment.
During recent years, a more advanced view of signal peptides has
evolved, showing that the functions and immunodominance of certain
signal peptides are much more versatile than previously
anticipated.
[0216] In some embodiments, a Chlamydia antigenic polypeptide may
be comprise a leader sequence to facilitate cell surface expression
of the antigenic polypeptide. In some embodiments, a Chlamydia
trachomatis MOMP antigenic polypeptide comprises a leader sequence
that facilitates cell surface expression of the MOMP. See, e.g.,
Jones H M, et al. Gene. 2000, 258: 173-181; and Findlay H E, et al.
BMC Microbiology. 2005, 5:5. In some embodiments, a Chlamydia
trachomatis antigenic polypeptide (e.g., a MOMP antigenic
polypeptide) comprises (is linked to) a leader sequence comprising
an amino acid identified by any one of SEQ ID NO: 301-316. It
should be understood that any antigenic polypeptide (e.g., HPV, HSV
and/or Chlamydia antigenic polypeptide) as provided herein may
comprise a leader sequence.
[0217] STD vaccines of the present disclosure may comprise, for
example, RNA (e.g., mRNA) polynucleotides encoding an artificial
signal peptide, wherein the signal peptide coding sequence is
operably linked to and is in frame with the coding sequence of the
antigenic polypeptide. Thus, STD vaccines of the present
disclosure, in some embodiments, produce an antigenic polypeptide
(e.g., a HPV antigenic polypeptide, HSV antigenic polypeptides
and/or a Chlamydia antigenic polypeptide) fused to a signal
peptide. In some embodiments, a signal peptide is fused to the
N-terminus of the antigenic polypeptide. In some embodiments, a
signal peptide is fused to the C-terminus of the antigenic
polypeptide.
[0218] In some embodiments, the signal peptide fused to the
antigenic polypeptide is an artificial signal peptide. In some
embodiments, an artificial signal peptide fused to the antigenic
polypeptide encoded by the RNA (e.g., mRNA) vaccine is obtained
from an immunoglobulin protein, e.g., an IgE signal peptide or an
IgG signal peptide. In some embodiments, a signal peptide fused to
the antigenic polypeptide encoded by a RNA (e.g., mRNA) vaccine is
an Ig heavy chain epsilon-1 signal peptide (IgE HC SP) having the
sequence of: MDWTWILFLVAAATRVHS; SEQ ID NO: 305. In some
embodiments, a signal peptide fused to the antigenic polypeptide
encoded by the (e.g., mRNA) RNA (e.g., mRNA) vaccine is an IgGk
chain V-III region HAH signal peptide (IgGk SP) having the sequence
of METPAQLLFLLLLWLPDTTG; SEQ ID NO: 304. In some embodiments, the
signal peptide is selected from: Japanese encephalitis PRM signal
sequence (MLGSNSGQRVVFTILLLLVAPAYS; SEQ ID NO: 306), VSVg protein
signal sequence (MKCLLYLAFLFIGVNCA; SEQ ID NO: 307) and Japanese
encephalitis JEV signal sequence (MWLVSLAIVTACAGA; SEQ ID NO:
308).
[0219] In some embodiments, the antigenic polypeptide encoded by a
RNA (e.g., mRNA) vaccine comprises an amino acid sequence
identified by any one of 8, 12-14, 24-34, 47-50 or 54-56 (Tables 3,
6, 11, 14 or 17; see also amino acid sequences of Tables 4, 7, 12
or 15) fused to a signal peptide identified by any one of -19
(Table 8). The examples disclosed herein are not meant to be
limiting and any signal peptide that is known in the art to
facilitate targeting of a protein to ER for processing and/or
targeting of a protein to the cell membrane may be used in
accordance with the present disclosure.
[0220] A signal peptide may have a length of 15-60 amino acids. For
example, a signal peptide may have a length of 15, 16, 17, 18, 19,
20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36,
37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,
54, 55, 56, 57, 58, 59, or 60 amino acids. In some embodiments, a
signal peptide has a length of 20-60, 25-60, 30-60, 35-60, 40-60,
45-60, 50-60, 55-60, 15-55, 20-55, 25-55, 30-55, 35-55, 40-55,
45-55, 50-55, 15-50, 20-50, 25-50, 30-50, 35-50, 40-50, 45-50,
15-45, 20-45, 25-45, 30-45, 35-45, 40-45, 15-40, 20-40, 25-40,
30-40, 35-40, 15-35, 20-35, 25-35, 30-35, 15-30, 20-30, 25-30,
15-25, 20-25, or 15-20 amino acids.
[0221] A signal peptide is typically cleaved from the nascent
polypeptide at the cleavage junction during ER processing. The
mature antigenic polypeptide produce by a STD RNA (e.g., mRNA)
vaccine of the present disclosure typically does not comprise a
signal peptide.
Chemical Modifications
[0222] STD vaccines of the present disclosure, in some embodiments,
comprise at least RNA (e.g. mRNA) polynucleotide having an open
reading frame encoding at least one antigenic polypeptide that
comprises at least one chemical modification.
[0223] The terms "chemical modification" and "chemically modified"
refer to modification with respect to adenosine (A), guanosine (G),
uridine (U), thymidine (T) or cytidine (C) ribonucleosides or
deoxyribnucleosides in at least one of their position, pattern,
percent or population. Generally, these terms do not refer to the
ribonucleotide modifications in naturally occurring 5'-terminal
mRNA cap moieties. With respect to a polypeptide, the term
"modification" refers to a modification relative to the canonical
set 20 amino acids. Polypeptides, as provided herein, are also
considered "modified" of they contain amino acid substitutions,
insertions or a combination of substitutions and insertions.
[0224] Polynucleotides (e.g., RNA polynucleotides, such as mRNA
polynucleotides), in some embodiments, comprise various (more than
one) different modifications. In some embodiments, a particular
region of a polynucleotide contains one, two or more (optionally
different) nucleoside or nucleotide modifications. In some
embodiments, a modified RNA polynucleotide (e.g., a modified mRNA
polynucleotide), introduced to a cell or organism, exhibits reduced
degradation in the cell or organism, respectively, relative to an
unmodified polynucleotide. In some embodiments, a modified RNA
polynucleotide (e.g., a modified mRNA polynucleotide), introduced
into a cell or organism, may exhibit reduced immunogenicity in the
cell or organism, respectively (e.g., a reduced innate
response).
[0225] Modifications of polynucleotides include, without
limitation, those described herein. Polynucleotides (e.g., RNA
polynucleotides, such as mRNA polynucleotides) may comprise
modifications that are naturally-occurring, non-naturally-occurring
or the polynucleotide may comprise a combination of
naturally-occurring and non-naturally-occurring modifications.
Polynucleotides may include any useful modification, for example,
of a sugar, a nucleobase, or an internucleoside linkage (e.g., to a
linking phosphate, to a phosphodiester linkage or to the
phosphodiester backbone).
[0226] Polynucleotides (e.g., RNA polynucleotides, such as mRNA
polynucleotides), in some embodiments, comprise non-natural
modified nucleotides that are introduced during synthesis or
post-synthesis of the polynucleotides to achieve desired functions
or properties. The modifications may be present on an
internucleotide linkages, purine or pyrimidine bases, or sugars.
The modification may be introduced with chemical synthesis or with
a polymerase enzyme at the terminal of a chain or anywhere else in
the chain. Any of the regions of a polynucleotide may be chemically
modified.
[0227] The present disclosure provides for modified nucleosides and
nucleotides of a polynucleotide (e.g., RNA polynucleotides, such as
mRNA polynucleotides). A "nucleoside" refers to a compound
containing a sugar molecule (e.g., a pentose or ribose) or a
derivative thereof in combination with an organic base (e.g., a
purine or pyrimidine) or a derivative thereof (also referred to
herein as "nucleobase"). A nucleotide" refers to a nucleoside,
including a phosphate group. Modified nucleotides may by
synthesized by any useful method, such as, for example, chemically,
enzymatically, or recombinantly, to include one or more modified or
non-natural nucleosides. Polynucleotides may comprise a region or
regions of linked nucleosides. Such regions may have variable
backbone linkages. The linkages may be standard phosphdioester
linkages, in which case the polynucleotides would comprise regions
of nucleotides.
[0228] Modified nucleotide base pairing encompasses not only the
standard adenosine-thymine, adenosine-uracil, or guanosine-cytosine
base pairs, but also base pairs formed between nucleotides and/or
modified nucleotides comprising non-standard or modified bases,
wherein the arrangement of hydrogen bond donors and hydrogen bond
acceptors permits hydrogen bonding between a non-standard base and
a standard base or between two complementary non-standard base
structures. One example of such non-standard base pairing is the
base pairing between the modified nucleotide inosine and adenine,
cytosine or uracil. Any combination of base/sugar or linker may be
incorporated into polynucleotides of the present disclosure.
[0229] Modifications of polynucleotides (e.g., RNA polynucleotides,
such as mRNA polynucleotides) that are useful in the vaccines of
the present disclosure include, but are not limited to the
following: 2-methylthio-N6-(cis-hydroxyisopentenyl)adenosine;
2-methylthio-N6-methyladenosine; 2-methylthio-N6-threonyl
carbamoyladenosine; N6-glycinylcarbamoyladenosine;
N6-isopentenyladenosine; N6-methyladenosine;
N6-threonylcarbamoyladenosine; 1,2'-O-dimethyladenosine;
1-methyladenosine; 2'-O-methyladenosine; 2'-O-ribosyladenosine
(phosphate); 2-methyladenosine; 2-methylthio-N6
isopentenyladenosine; 2-methylthio-N6-hydroxynorvalyl
carbamoyladenosine; 2'-O-methyladenosine; 2'-O-ribosyladenosine
(phosphate); Isopentenyladenosine;
N6-(cis-hydroxyisopentenyl)adenosine; N6,2'-O-dimethyladenosine;
N6,2'-O-dimethyladenosine; N6,N6,2'-O-trimethyladenosine;
N6,N6-dimethyladenosine; N6-acetyladenosine;
N6-hydroxynorvalylcarbamoyladenosine;
N6-methyl-N6-threonylcarbamoyladenosine; 2-methyladenosine;
2-methylthio-N6-isopentenyladenosine; 7-deaza-adenosine;
N1-methyl-adenosine; N6,N6 (dimethyl)adenine;
N6-cis-hydroxy-isopentenyl-adenosine; .alpha.-thio-adenosine; 2
(amino)adenine; 2 (aminopropyl)adenine; 2 (methylthio) N6
(isopentenyl)adenine; 2-(alkyl)adenine; 2-(aminoalkyl)adenine;
2-(aminopropyl)adenine; 2-(halo)adenine; 2-(halo)adenine;
2-(propyl)adenine; 2'-Amino-2'-deoxy-ATP; 2'-Azido-2'-deoxy-ATP;
2'-Deoxy-2'-.alpha.-aminoadenosine TP; 2'-Deoxy-2'-a-azidoadenosine
TP; 6 (alkyl)adenine; 6 (methyl)adenine; 6-(alkyl)adenine;
6-(methyl)adenine; 7 (deaza)adenine; 8 (alkenyl)adenine; 8
(alkynyl)adenine; 8 (amino)adenine; 8 (thioalkyl)adenine;
8-(alkenyl)adenine; 8-(alkyl)adenine; 8-(alkynyl)adenine;
8-(amino)adenine; 8-(halo)adenine; 8-(hydroxyl)adenine;
8-(thioalkyl)adenine; 8-(thiol)adenine; 8-azido-adenosine; aza
adenine; deaza adenine; N6 (methyl)adenine; N6-(isopentyl)adenine;
7-deaza-8-aza-adenosine; 7-methyladenine; 1-Deazaadenosine TP;
2'Fluoro-N6-Bz-deoxyadenosine TP; 2'-OMe-2-Amino-ATP;
2'O-methyl-N6-Bz-deoxyadenosine TP; 2'-a-Ethynyladenosine TP;
2-aminoadenine; 2-Aminoadenosine TP; 2-Amino-ATP;
2'-a-Trifluoromethyladenosine TP; 2-Azidoadenosine TP;
2'-b-Ethynyladenosine TP; 2-Bromoadenosine TP;
2'-b-Trifluoromethyladenosine TP; 2-Chloroadenosine TP;
2'-Deoxy-2',2'-difluoroadenosine TP;
2'-Deoxy-2'-a-mercaptoadenosine TP;
2'-Deoxy-2'-a-thiomethoxyadenosine TP; 2'-Deoxy-2'-b-aminoadenosine
TP; 2'-Deoxy-2'-b-azidoadenosine TP; 2'-Deoxy-2'-b-bromoadenosine
TP; 2'-Deoxy-2'-b-chloroadenosine TP; 2'-Deoxy-2'-b-fluoroadenosine
TP; 2'-Deoxy-2'-b-iodoadenosine TP; 2'-Deoxy-2'-b-mercaptoadenosine
TP; 2'-Deoxy-2'-b-thiomethoxyadenosine TP; 2-Fluoroadenosine TP;
2-Iodoadenosine TP; 2-Mercaptoadenosine TP; 2-methoxy-adenine;
2-methylthio-adenine; 2-Trifluoromethyladenosine TP;
3-Deaza-3-bromoadenosine TP; 3-Deaza-3-chloroadenosine TP;
3-Deaza-3-fluoroadenosine TP; 3-Deaza-3-iodoadenosine TP;
3-Deazaadenosine TP; 4'-Azidoadenosine TP; 4'-Carbocyclic adenosine
TP; 4'-Ethynyladenosine TP; 5'-Homo-adenosine TP; 8-Aza-ATP;
8-bromo-adenosine TP; 8-Trifluoromethyladenosine TP;
9-Deazaadenosine TP; 2-aminopurine; 7-deaza-2,6-diaminopurine;
7-deaza-8-aza-2,6-diaminopurine; 7-deaza-8-aza-2-aminopurine;
2,6-diaminopurine; 7-deaza-8-aza-adenine, 7-deaza-2-aminopurine;
2-thiocytidine; 3-methylcytidine; 5-formylcytidine;
5-hydroxymethylcytidine; 5-methylcytidine; N4-acetylcytidine;
2'-O-methylcytidine; 2'-O-methylcytidine; 5,2'-O-dimethylcytidine;
5-formyl-2'-O-methylcytidine; Lysidine; N4,2'-O-dimethylcytidine;
N4-acetyl-2'-O-methylcytidine; N4-methylcytidine;
N4,N4-Dimethyl-2'-OMe-Cytidine TP; 4-methylcytidine;
5-aza-cytidine; Pseudo-iso-cytidine; pyrrolo-cytidine;
.alpha.-thio-cytidine; 2-(thio)cytosine; 2'-Amino-2'-deoxy-CTP;
2'-Azido-2'-deoxy-CTP; 2'-Deoxy-2'-a-aminocytidine TP;
2'-Deoxy-2'-a-azidocytidine TP; 3 (deaza) 5 (aza)cytosine; 3
(methyl)cytosine; 3-(alkyl)cytosine; 3-(deaza) 5 (aza)cytosine;
3-(methyl)cytidine; 4,2'-O-dimethylcytidine; 5 (halo)cytosine; 5
(methyl)cytosine; 5 (propynyl)cytosine; 5
(trifluoromethyl)cytosine; 5-(alkyl)cytosine; 5-(alkynyl)cytosine;
5-(halo)cytosine; 5-(propynyl)cytosine;
5-(trifluoromethyl)cytosine; 5-bromo-cytidine; 5-iodo-cytidine;
5-propynyl cytosine; 6-(azo)cytosine; 6-aza-cytidine; aza cytosine;
deaza cytosine; N4 (acetyl)cytosine;
1-methyl-1-deaza-pseudoisocytidine; 1-methyl-pseudoisocytidine;
2-methoxy-5-methyl-cytidine; 2-methoxy-cytidine;
2-thio-5-methyl-cytidine; 4-methoxy-1-methyl-pseudoisocytidine;
4-methoxy-pseudoisocytidine;
4-thio-1-methyl-1-deaza-pseudoisocytidine;
4-thio-1-methyl-pseudoisocytidine; 4-thio-pseudoisocytidine;
5-aza-zebularine; 5-methyl-zebularine; pyrrolo-pseudoisocytidine;
Zebularine; (E)-5-(2-Bromo-vinyl)cytidine TP; 2,2'-anhydro-cytidine
TP hydrochloride; 2'Fluor-N4-Bz-cytidine TP;
2'Fluoro-N4-Acetyl-cytidine TP; 2'-O-Methyl-N4-Acetyl-cytidine TP;
2'O-methyl-N4-Bz-cytidine TP; 2'-a-Ethynylcytidine TP;
2'-a-Trifluoromethylcytidine TP; 2'-b-Ethynylcytidine TP;
2'-b-Trifluoromethylcytidine TP; 2'-Deoxy-2',2'-difluorocytidine
TP; 2'-Deoxy-2'-a-mercaptocytidine TP;
2'-Deoxy-2'-a-thiomethoxycytidine TP; 2'-Deoxy-2'-b-aminocytidine
TP; 2'-Deoxy-2'-b-azidocytidine TP; 2'-Deoxy-2'-b-bromocytidine TP;
2'-Deoxy-2'-b-chlorocytidine TP; 2'-Deoxy-2'-b-fluorocytidine TP;
2'-Deoxy-2'-b-iodocytidine TP; 2'-Deoxy-2'-b-mercaptocytidine TP;
2'-Deoxy-2'-b-thiomethoxycytidine TP;
2'-O-Methyl-5-(1-propynyl)cytidine TP; 3'-Ethynylcytidine TP;
4'-Azidocytidine TP; 4'-Carbocyclic cytidine TP; 4'-Ethynylcytidine
TP; 5-(1-Propynyl)ara-cytidine TP;
5-(2-Chloro-phenyl)-2-thiocytidine TP;
5-(4-Amino-phenyl)-2-thiocytidine TP; 5-Aminoallyl-CTP;
5-Cyanocytidine TP; 5-Ethynylara-cytidine TP; 5-Ethynylcytidine TP;
5'-Homo-cytidine TP; 5-Methoxycytidine TP;
5-Trifluoromethyl-Cytidine TP; N4-Amino-cytidine TP;
N4-Benzoyl-cytidine TP; Pseudoisocytidine; 7-methylguanosine;
N2,2'-O-dimethylguanosine; N2-methylguanosine; Wyosine;
1,2'-O-dimethylguanosine; 1-methylguanosine; 2'-O-methylguanosine;
2'-O-ribosylguanosine (phosphate); 2'-O-methylguanosine;
2'-O-ribosylguanosine (phosphate); 7-aminomethyl-7-deazaguanosine;
7-cyano-7-deazaguanosine; Archaeosine; Methylwyosine;
N2,7-dimethylguanosine; N2,N2,2'-O-trimethylguanosine;
N2,N2,7-trimethylguanosine; N2,N2-dimethylguanosine;
N2,7,2'-O-trimethylguanosine; 6-thio-guanosine; 7-deaza-guanosine;
8-oxo-guanosine; N1-methyl-guanosine; .alpha.-thio-guanosine; 2
(propyl)guanine; 2-(alkyl)guanine; 2'-Amino-2'-deoxy-GTP;
2'-Azido-2'-deoxy-GTP; 2'-Deoxy-2'-a-aminoguanosine TP;
2'-Deoxy-2'-a-azidoguanosine TP; 6 (methyl)guanine;
6-(alkyl)guanine; 6-(methyl)guanine; 6-methyl-guanosine; 7
(alkyl)guanine; 7 (deaza)guanine; 7 (methyl)guanine;
7-(alkyl)guanine; 7-(deaza)guanine; 7-(methyl)guanine; 8
(alkyl)guanine; 8 (alkynyl)guanine; 8 (halo)guanine; 8
(thioalkyl)guanine; 8-(alkenyl)guanine; 8-(alkyl)guanine;
8-(alkynyl)guanine; 8-(amino)guanine; 8-(halo)guanine;
8-(hydroxyl)guanine; 8-(thioalkyl)guanine; 8-(thiol)guanine; aza
guanine; deaza guanine; N (methyl)guanine; N-(methyl)guanine;
1-methyl-6-thio-guanosine; 6-methoxy-guanosine;
6-thio-7-deaza-8-aza-guanosine; 6-thio-7-deaza-guanosine;
6-thio-7-methyl-guanosine; 7-deaza-8-aza-guanosine;
7-methyl-8-oxo-guanosine; N2,N2-dimethyl-6-thio-guanosine;
N2-methyl-6-thio-guanosine; 1-Me-GTP;
2'Fluoro-N2-isobutyl-guanosine TP; 2'O-methyl-N2-isobutyl-guanosine
TP; 2'-a-Ethynylguanosine TP; 2'-a-Trifluoromethylguanosine TP;
2'-b-Ethynylguanosine TP; 2'-b-Trifluoromethylguanosine TP;
2'-Deoxy-2',2'-difluoroguanosine TP;
2'-Deoxy-2'-a-mercaptoguanosine TP;
2'-Deoxy-2'-a-thiomethoxyguanosine TP; 2'-Deoxy-2'-b-aminoguanosine
TP; 2'-Deoxy-2'-b-azidoguanosine TP; 2'-Deoxy-2'-b-bromoguanosine
TP; 2'-Deoxy-2'-b-chloroguanosine TP; 2'-Deoxy-2'-b-fluoroguanosine
TP; 2'-Deoxy-2'-b-iodoguanosine TP; 2'-Deoxy-2'-b-mercaptoguanosine
TP; 2'-Deoxy-2'-b-thiomethoxyguanosine TP; 4'-Azidoguanosine TP;
4'-Carbocyclic guanosine TP; 4'-Ethynylguanosine TP;
5'-Homo-guanosine TP; 8-bromo-guanosine TP; 9-Deazaguanosine TP;
N2-isobutyl-guanosine TP; 1-methylinosine; Inosine;
1,2'-O-dimethylinosine; 2'-O-methylinosine; 7-methylinosine;
2'-O-methylinosine; Epoxyqueuosine; galactosyl-queuosine;
Mannosylqueuosine; Queuosine; allyamino-thymidine; aza thymidine;
deaza thymidine; deoxy-thymidine; 2'-O-methyluridine;
2-thiouridine; 3-methyluridine; 5-carboxymethyluridine;
5-hydroxyuridine; 5-methyluridine; 5-taurinomethyl-2-thiouridine;
5-taurinomethyluridine; Dihydrouridine; Pseudouridine;
(3-(3-amino-3-carboxypropyl)uridine;
1-methyl-3-(3-amino-5-carboxypropyl)pseudouridine;
1-methylpseduouridine; 1-methyl-pseudouridine; 2'-O-methyluridine;
2'-O-methylpseudouridine; 2'-O-methyluridine;
2-thio-2'-O-methyluridine; 3-(3-amino-3-carboxypropyl)uridine;
3,2'-O-dimethyluridine; 3-Methyl-pseudo-Uridine TP; 4-thiouridine;
5-(carboxyhydroxymethyl)uridine; 5-(carboxyhydroxymethyl)uridine
methyl ester; 5,2'-O-dimethyluridine; 5,6-dihydro-uridine;
5-aminomethyl-2-thiouridine; 5-carbamoylmethyl-2'-O-methyluridine;
5-carbamoylmethyluridine; 5-carboxyhydroxymethyluridine;
5-carboxyhydroxymethyluridine methyl ester;
5-carboxymethylaminomethyl-2'-O-methyluridine;
5-carboxymethylaminomethyl-2-thiouridine;
5-carboxymethylaminomethyl-2-thiouridine;
5-carboxymethylaminomethyluridine;
5-carboxymethylaminomethyluridine; 5-Carbamoylmethyluridine TP;
5-methoxycarbonylmethyl-2'-O-methyluridine;
5-methoxycarbonylmethyl-2-thiouridine;
5-methoxycarbonylmethyluridine; 5-methoxyuridine;
5-methyl-2-thiouridine; 5-methylaminomethyl-2-selenouridine;
5-methylaminomethyl-2-thiouridine; 5-methylaminomethyluridine;
5-Methyldihydrouridine; 5-Oxyacetic acid-Uridine TP; 5-Oxyacetic
acid-methyl ester-Uridine TP; N1-methyl-pseudo-uridine; uridine
5-oxyacetic acid; uridine 5-oxyacetic acid methyl ester;
3-(3-Amino-3-carboxypropyl)-Uridine TP;
5-(iso-Pentenylaminomethyl)-2-thiouridine TP;
5-(iso-Pentenylaminomethyl)-2'-O-methyluridine TP;
5-(iso-Pentenylaminomethyl)uridine TP; 5-propynyl uracil;
.alpha.-thio-uridine; 1
(aminoalkylamino-carbonylethylenyl)-2(thio)-pseudouracil; 1
(aminoalkylaminocarbonylethylenyl)-2,4-(dithio)pseudouracil; 1
(aminoalkylaminocarbonylethylenyl)-4 (thio)pseudouracil; 1
(aminoalkylaminocarbonylethylenyl)-pseudouracil; 1
(aminocarbonylethylenyl)-2(thio)-pseudouracil; 1
(aminocarbonylethylenyl)-2,4-(dithio)pseudouracil; 1
(aminocarbonylethylenyl)-4 (thio)pseudouracil; 1
(aminocarbonylethylenyl)-pseudouracil; 1 substituted
2(thio)-pseudouracil; 1 substituted 2,4-(dithio)pseudouracil; 1
substituted 4 (thio)pseudouracil; 1 substituted pseudouracil;
1-(aminoalkylamino-carbonylethylenyl)-2-(thio)-pseudouracil;
1-Methyl-3-(3-amino-3-carboxypropyl) pseudouridine TP;
1-Methyl-3-(3-amino-3-carboxypropyl)pseudo-UTP;
1-Methyl-pseudo-UTP; 2 (thio)pseudouracil; 2' deoxy uridine; 2'
fluorouridine; 2-(thio)uracil; 2,4-(dithio)psuedouracil; 2' methyl,
2'amino, 2'azido, 2'fluro-guanosine; 2'-Amino-2'-deoxy-UTP;
2'-Azido-2'-deoxy-UTP; 2'-Azido-deoxyuridine TP;
2'-O-methylpseudouridine; 2' deoxy uridine; 2' fluorouridine;
2'-Deoxy-2'-a-aminouridine TP; 2'-Deoxy-2'-a-azidouridine TP;
2-methylpseudouridine; 3 (3 amino-3 carboxypropyl)uracil; 4
(thio)pseudouracil; 4-(thio)pseudouracil; 4-(thio)uracil;
4-thiouracil; 5 (1,3-diazole-1-alkyl)uracil; 5
(2-aminopropyl)uracil; 5 (aminoalkyl)uracil; 5
(dimethylaminoalkyl)uracil; 5 (guanidiniumalkyl)uracil; 5
(methoxycarbonylmethyl)-2-(thio)uracil; 5
(methoxycarbonyl-methyl)uracil; 5 (methyl) 2 (thio)uracil; 5
(methyl) 2,4 (dithio)uracil; 5 (methyl) 4 (thio)uracil; 5
(methylaminomethyl)-2 (thio)uracil; 5 (methylaminomethyl)-2,4
(dithio)uracil; 5 (methylaminomethyl)-4 (thio)uracil; 5
(propynyl)uracil; 5 (trifluoromethyl)uracil;
5-(2-aminopropyl)uracil; 5-(alkyl)-2-(thio)pseudouracil;
5-(alkyl)-2,4 (dithio)pseudouracil; 5-(alkyl)-4 (thio)pseudouracil;
5-(alkyl)pseudouracil; 5-(alkyl)uracil; 5-(alkynyl)uracil;
5-(allylamino)uracil; 5-(cyanoalkyl)uracil;
5-(dialkylaminoalkyl)uracil; 5-(dimethylaminoalkyl)uracil;
5-(guanidiniumalkyl)uracil; 5-(halo)uracil;
5-(1,3-diazole-1-alkyl)uracil; 5-(methoxy)uracil;
5-(methoxycarbonylmethyl)-2-(thio)uracil;
5-(methoxycarbonyl-methyl)uracil; 5-(methyl) 2(thio)uracil;
5-(methyl) 2,4 (dithio)uracil; 5-(methyl) 4 (thio)uracil;
5-(methyl)-2-(thio)pseudouracil; 5-(methyl)-2,4
(dithio)pseudouracil; 5-(methyl)-4 (thio)pseudouracil;
5-(methyl)pseudouracil; 5-(methylaminomethyl)-2 (thio)uracil;
5-(methylaminomethyl)-2,4(dithio)uracil;
5-(methylaminomethyl)-4-(thio)uracil; 5-(propynyl)uracil;
5-(trifluoromethyl)uracil; 5-aminoallyl-uridine; 5-bromo-uridine;
5-iodo-uridine; 5-uracil; 6 (azo)uracil; 6-(azo)uracil;
6-aza-uridine; allyamino-uracil; aza uracil; deaza uracil; N3
(methyl)uracil; Pseudo-UTP-1-2-ethanoic acid; Pseudouracil;
4-Thio-pseudo-UTP; 1-carboxymethyl-pseudouridine;
1-methyl-1-deaza-pseudouridine; 1-propynyl-uridine;
1-taurinomethyl-1-methyl-uridine; 1-taurinomethyl-4-thio-uridine;
1-taurinomethyl-pseudouridine; 2-methoxy-4-thio-pseudouridine;
2-thio-1-methyl-1-deaza-pseudouridine;
2-thio-1-methyl-pseudouridine; 2-thio-5-aza-uridine;
2-thio-dihydropseudouridine; 2-thio-dihydrouridine;
2-thio-pseudouridine; 4-methoxy-2-thio-pseudouridine;
4-methoxy-pseudouridine; 4-thio-1-methyl-pseudouridine;
4-thio-pseudouridine; 5-aza-uridine; Dihydropseudouridine;
(.+-.)1-(2-Hydroxypropyl)pseudouridine TP;
(2R)-1-(2-Hydroxypropyl)pseudouridine TP;
(2S)-1-(2-Hydroxypropyl)pseudouridine TP;
(E)-5-(2-Bromo-vinyl)ara-uridine TP; (E)-5-(2-Bromo-vinyl)uridine
TP; (Z)-5-(2-Bromo-vinyl)ara-uridine TP;
(Z)-5-(2-Bromo-vinyl)uridine TP;
1-(2,2,2-Trifluoroethyl)-pseudo-UTP;
1-(2,2,3,3,3-Pentafluoropropyl)pseudouridine TP;
1-(2,2-Diethoxyethyl)pseudouridine TP;
1-(2,4,6-Trimethylbenzyl)pseudouridine TP;
1-(2,4,6-Trimethyl-benzyl)pseudo-UTP;
1-(2,4,6-Trimethyl-phenyl)pseudo-UTP;
1-(2-Amino-2-carboxyethyl)pseudo-UTP; 1-(2-Amino-ethyl)pseudo-UTP;
1-(2-Hydroxyethyl)pseudouridine TP; 1-(2-Methoxyethyl)pseudouridine
TP; 1-(3,4-Bis-trifluoromethoxybenzyl)pseudouridine TP;
1-(3,4-Dimethoxybenzyl)pseudouridine TP;
1-(3-Amino-3-carboxypropyl)pseudo-UTP;
1-(3-Amino-propyl)pseudo-UTP;
1-(3-Cyclopropyl-prop-2-ynyl)pseudouridine TP;
1-(4-Amino-4-carboxybutyl)pseudo-UTP; 1-(4-Amino-benzyl)pseudo-UTP;
1-(4-Amino-butyl)pseudo-UTP; 1-(4-Amino-phenyl)pseudo-UTP;
1-(4-Azidobenzyl)pseudouridine TP; 1-(4-Bromobenzyl)pseudouridine
TP; 1-(4-Chlorobenzyl)pseudouridine TP;
1-(4-Fluorobenzyl)pseudouridine TP; 1-(4-Iodobenzyl)pseudouridine
TP; 1-(4-Methanesulfonylbenzyl)pseudouridine TP;
1-(4-Methoxybenzyl)pseudouridine TP;
1-(4-Methoxy-benzyl)pseudo-UTP; 1-(4-Methoxy-phenyl)pseudo-UTP;
1-(4-Methylbenzyl)pseudouridine TP; 1-(4-Methyl-benzyl)pseudo-UTP;
1-(4-Nitrobenzyl)pseudouridine TP; 1-(4-Nitro-benzyl)pseudo-UTP;
1(4-Nitro-phenyl)pseudo-UTP; 1-(4-Thiomethoxybenzyl)pseudouridine
TP; 1-(4-Trifluoromethoxybenzyl)pseudouridine TP;
1-(4-Trifluoromethylbenzyl)pseudouridine TP;
1-(5-Amino-pentyl)pseudo-UTP; 1-(6-Amino-hexyl)pseudo-UTP;
1,6-Dimethyl-pseudo-UTP;
1-[3-(2-{2-[2-(2-Aminoethoxy)-ethoxy]-ethoxy}-ethoxy)-propionyl]pseudouri-
dine TP; 1-{3-[2-(2-Aminoethoxy)-ethoxy]-propionyl}pseudouridine
TP; 1-Acetylpseudouridine TP; 1-Alkyl-6-(1-propynyl)-pseudo-UTP;
1-Alkyl-6-(2-propynyl)-pseudo-UTP; 1-Alkyl-6-allyl-pseudo-UTP;
1-Alkyl-6-ethynyl-pseudo-UTP; 1-Alkyl-6-homoallyl-pseudo-UTP;
1-Alkyl-6-vinyl-pseudo-UTP; 1-Allylpseudouridine TP;
1-Aminomethyl-pseudo-UTP; 1-Benzoylpseudouridine TP;
1-Benzyloxymethylpseudouridine TP; 1-Benzyl-pseudo-UTP;
1-Biotinyl-PEG2-pseudouridine TP; 1-Biotinylpseudouridine TP;
1-Butyl-pseudo-UTP; 1-Cyanomethylpseudouridine TP;
1-Cyclobutylmethyl-pseudo-UTP; 1-Cyclobutyl-pseudo-UTP;
1-Cycloheptylmethyl-pseudo-UTP; 1-Cycloheptyl-pseudo-UTP;
1-Cyclohexylmethyl-pseudo-UTP; 1-Cyclohexyl-pseudo-UTP;
1-Cyclooctylmethyl-pseudo-UTP; 1-Cyclooctyl-pseudo-UTP;
1-Cyclopentylmethyl-pseudo-UTP; 1-Cyclopentyl-pseudo-UTP;
1-Cyclopropylmethyl-pseudo-UTP; 1-Cyclopropyl-pseudo-UTP;
1-Ethyl-pseudo-UTP; 1-Hexyl-pseudo-UTP; 1-Homoallylpseudouridine
TP; 1-Hydroxymethylpseudouridine TP; 1-iso-propyl-pseudo-UTP;
1-Me-2-thio-pseudo-UTP; 1-Me-4-thio-pseudo-UTP;
1-Me-alpha-thio-pseudo-UTP; 1-Methanesulfonylmethylpseudouridine
TP; 1-Methoxymethylpseudouridine TP;
1-Methyl-6-(2,2,2-Trifluoroethyl)pseudo-UTP;
1-Methyl-6-(4-morpholino)-pseudo-UTP;
1-Methyl-6-(4-thiomorpholino)-pseudo-UTP; 1-Methyl-6-(substituted
phenyl)pseudo-UTP; 1-Methyl-6-amino-pseudo-UTP;
1-Methyl-6-azido-pseudo-UTP; 1-Methyl-6-bromo-pseudo-UTP;
1-Methyl-6-butyl-pseudo-UTP; 1-Methyl-6-chloro-pseudo-UTP;
1-Methyl-6-cyano-pseudo-UTP; 1-Methyl-6-dimethylamino-pseudo-UTP;
1-Methyl-6-ethoxy-pseudo-UTP;
1-Methyl-6-ethylcarboxylate-pseudo-UTP;
1-Methyl-6-ethyl-pseudo-UTP; 1-Methyl-6-fluoro-pseudo-UTP;
1-Methyl-6-formyl-pseudo-UTP; 1-Methyl-6-hydroxyamino-pseudo-UTP;
1-Methyl-6-hydroxy-pseudo-UTP; 1-Methyl-6-iodo-pseudo-UTP;
1-Methyl-6-iso-propyl-pseudo-UTP; 1-Methyl-6-methoxy-pseudo-UTP;
1-Methyl-6-methylamino-pseudo-UTP; 1-Methyl-6-phenyl-pseudo-UTP;
1-Methyl-6-propyl-pseudo-UTP; 1-Methyl-6-tert-butyl-pseudo-UTP;
1-Methyl-6-trifluoromethoxy-pseudo-UTP;
1-Methyl-6-trifluoromethyl-pseudo-UTP;
1-Morpholinomethylpseudouridine TP; 1-Pentyl-pseudo-UTP;
1-Phenyl-pseudo-UTP; 1-Pivaloylpseudouridine TP;
1-Propargylpseudouridine TP; 1-Propyl-pseudo-UTP;
1-propynyl-pseudouridine; 1-p-tolyl-pseudo-UTP;
1-tert-Butyl-pseudo-UTP; 1-Thiomethoxymethylpseudouridine TP;
1-Thiomorpholinomethylpseudouridine TP;
1-Trifluoroacetylpseudouridine TP; 1-Trifluoromethyl-pseudo-UTP;
1-Vinylpseudouridine TP; 2,2'-anhydro-uridine TP;
2'-bromo-deoxyuridine TP; 2'-F-5-Methyl-2'-deoxy-UTP;
2'-OMe-5-Me-UTP; 2'-OMe-pseudo-UTP; 2'-a-Ethynyluridine TP;
2'-a-Trifluoromethyluridine TP; 2'-b-Ethynyluridine TP;
2'-b-Trifluoromethyluridine TP; 2'-Deoxy-2',2'-difluorouridine TP;
2'-Deoxy-2'-a-mercaptouridine TP; 2'-Deoxy-2'-a-thiomethoxyuridine
TP; 2'-Deoxy-2'-b-aminouridine TP; 2'-Deoxy-2'-b-azidouridine TP;
2'-Deoxy-2'-b-bromouridine TP; 2'-Deoxy-2'-b-chlorouridine TP;
2'-Deoxy-2'-b-fluorouridine TP; 2'-Deoxy-2'-b-iodouridine TP;
2'-Deoxy-2'-b-mercaptouridine TP; 2'-Deoxy-2'-b-thiomethoxyuridine
TP; 2-methoxy-4-thio-uridine; 2-methoxyuridine;
2'-O-Methyl-5-(1-propynyl)uridine TP; 3-Alkyl-pseudo-UTP;
4'-Azidouridine TP; 4'-Carbocyclic uridine TP; 4'-Ethynyluridine
TP; 5-(1-Propynyl)ara-uridine TP; 5-(2-Furanyl)uridine TP;
5-Cyanouridine TP; 5-Dimethylaminouridine TP; 5'-Homo-uridine TP;
5-iodo-2'-fluoro-deoxyuridine TP; 5-Phenylethynyluridine TP;
5-Trideuteromethyl-6-deuterouridine TP; 5-Trifluoromethyl-Uridine
TP; 5-Vinylarauridine TP; 6-(2,2,2-Trifluoroethyl)-pseudo-UTP;
6-(4-Morpholino)-pseudo-UTP; 6-(4-Thiomorpholino)-pseudo-UTP;
6-(Substituted-Phenyl)-pseudo-UTP; 6-Amino-pseudo-UTP;
6-Azido-pseudo-UTP; 6-Bromo-pseudo-UTP; 6-Butyl-pseudo-UTP;
6-Chloro-pseudo-UTP; 6-Cyano-pseudo-UTP;
6-Dimethylamino-pseudo-UTP; 6-Ethoxy-pseudo-UTP;
6-Ethylcarboxylate-pseudo-UTP; 6-Ethyl-pseudo-UTP;
6-Fluoro-pseudo-UTP; 6-Formyl-pseudo-UTP;
6-Hydroxyamino-pseudo-UTP; 6-Hydroxy-pseudo-UTP; 6-Iodo-pseudo-UTP;
6-iso-Propyl-pseudo-UTP; 6-Methoxy-pseudo-UTP;
6-Methylamino-pseudo-UTP; 6-Methyl-pseudo-UTP; 6-Phenyl-pseudo-UTP;
6-Phenyl-pseudo-UTP; 6-Propyl-pseudo-UTP; 6-tert-Butyl-pseudo-UTP;
6-Trifluoromethoxy-pseudo-UTP; 6-Trifluoromethyl-pseudo-UTP;
Alpha-thio-pseudo-UTP; Pseudouridine 1-(4-methylbenzenesulfonic
acid) TP; Pseudouridine 1-(4-methylbenzoic acid) TP; Pseudouridine
TP 1-[3-(2-ethoxy)]propionic acid; Pseudouridine TP
1-[3-{2-(2-[2-(2-ethoxy)-ethoxy]-ethoxy)-ethoxy}]propionic acid;
Pseudouridine TP
1-[3-{2-(2-[2-{2(2-ethoxy)-ethoxy}-ethoxy]-ethoxy)-ethoxy}]propionic
acid; Pseudouridine TP
1-[3-{2-(2-[2-ethoxy]-ethoxy)-ethoxy}]propionic acid; Pseudouridine
TP 1-[3-{2-(2-ethoxy)-ethoxy}]propionic acid; Pseudouridine TP
1-methylphosphonic acid; Pseudouridine TP 1-methylphosphonic acid
diethyl ester; Pseudo-UTP-N1-3-propionic acid;
Pseudo-UTP-N1-4-butanoic acid; Pseudo-UTP-N1-5-pentanoic acid;
Pseudo-UTP-N1-6-hexanoic acid; Pseudo-UTP-N1-7-heptanoic acid;
Pseudo-UTP-N1-methyl-p-benzoic acid; Pseudo-UTP-N1-p-benzoic acid;
Wybutosine; Hydroxywybutosine; Isowyosine; Peroxywybutosine;
undermodified hydroxywybutosine; 4-demethylwyosine;
2,6-(diamino)purine; 1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl:
1,3-(diaza)-2-(oxo)-phenthiazin-1-yl;
1,3-(diaza)-2-(oxo)-phenoxazin-1-yl;
1,3,5-(triaza)-2,6-(dioxa)-naphthalene; 2 (amino)purine;
2,4,5-(trimethyl)phenyl; 2' methyl, 2'amino, 2'azido,
2'fluro-cytidine; 2' methyl, 2'amino, 2'azido, 2'fluro-adenine;
2'methyl, 2'amino, 2'azido, 2'fluro-uridine;
2'-amino-2'-deoxyribose; 2-amino-6-Chloro-purine; 2-aza-inosinyl;
2'-azido-2'-deoxyribose; 2'fluoro-2'-deoxyribose;
2'-fluoro-modified bases; 2'-O-methyl-ribose;
2-oxo-7-aminopyridopyrimidin-3-yl; 2-oxo-pyridopyrimidine-3-yl;
2-pyridinone; 3 nitropyrrole;
3-(methyl)-7-(propynyl)isocarbostyrilyl;
3-(methyl)isocarbostyrilyl; 4-(fluoro)-6-(methyl)benzimidazole;
4-(methyl)benzimidazole; 4-(methyl)indolyl; 4,6-(dimethyl)indolyl;
5 nitroindole; 5 substituted pyrimidines;
5-(methyl)isocarbostyrilyl; 5-nitroindole; 6-(aza)pyrimidine;
6-(azo)thymine; 6-(methyl)-7-(aza)indolyl; 6-chloro-purine;
6-phenyl-pyrrolo-pyrimidin-2-on-3-yl;
7-(aminoalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenthiazin-1-yl;
7-(aminoalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl;
7-(aminoalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenoxazin-1-yl;
7-(aminoalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenthiazin-1-yl;
7-(aminoalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenoxazin-1-yl;
7-(aza)indolyl;
7-(guanidiniumalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl;
7-(guanidiniumalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenthiazin-1-yl;
7-(guanidiniumalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl;
7-(guanidiniumalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenoxazin-1-yl;
7-(guanidiniumalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenthiazin-1-yl;
7-(guanidiniumalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenoxazin-1-yl;
7-(propynyl)isocarbostyrilyl; 7-(propynyl)isocarbostyrilyl,
propynyl-7-(aza)indolyl; 7-deaza-inosinyl; 7-substituted
1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl; 7-substituted
1,3-(diaza)-2-(oxo)-phenoxazin-1-yl; 9-(methyl)-imidizopyridinyl;
Aminoindolyl; Anthracenyl;
bis-ortho-(aminoalkylhydroxy)-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl;
bis-ortho-substituted-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl;
Difluorotolyl; Hypoxanthine; Imidizopyridinyl; Inosinyl;
Isocarbostyrilyl; Isoguanisine; N2-substituted purines;
N6-methyl-2-amino-purine; N6-substituted purines; N-alkylated
derivative; Napthalenyl; Nitrobenzimidazolyl; Nitroimidazolyl;
Nitroindazolyl; Nitropyrazolyl; Nubularine; O6-substituted purines;
O-alkylated derivative;
ortho-(aminoalkylhydroxy)-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl;
ortho-substituted-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; Oxoformycin
TP; para-(aminoalkylhydroxy)-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl;
para-substituted-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; Pentacenyl;
Phenanthracenyl; Phenyl; propynyl-7-(aza)indolyl; Pyrenyl;
pyridopyrimidin-3-yl; pyridopyrimidin-3-yl,
2-oxo-7-aminopyridopyrimidin-3-yl; pyrrolo-pyrimidin-2-on-3-yl;
Pyrrolopyrimidinyl; Pyrrolopyrizinyl; Stilbenzyl; substituted
1,2,4-triazoles; Tetracenyl; Tubercidine; Xanthine;
Xanthosine-5'-TP; 2-thio-zebularine; 5-aza-2-thio-zebularine;
7-deaza-2-amino-purine; pyridin-4-one ribonucleoside;
2-Amino-riboside-TP; Formycin A TP; Formycin B TP; Pyrrolosine TP;
2'-OH-ara-adenosine TP; 2'-OH-ara-cytidine TP; 2'-OH-ara-uridine
TP; 2'-OH-ara-guanosine TP; 5-(2-carbomethoxyvinyl)uridine TP; and
N6-(19-Amino-pentaoxanonadecyl)adenosine TP.
[0230] In some embodiments, polynucleotides (e.g., RNA
polynucleotides, such as mRNA polynucleotides) include a
combination of at least two (e.g., 2, 3, 4 or more) of the
aforementioned modified nucleobases.
[0231] In some embodiments, modified nucleobases in polynucleotides
(e.g., RNA polynucleotides, such as mRNA polynucleotides) are
selected from the group consisting of pseudouridine (.psi.),
N1-methylpseudouridine (m.sup.1.psi.), N1-ethylpseudouridine,
2-thiouridine, 4'-thiouridine, 5-methylcytosine,
2-thio-1-methyl-1-deaza-pseudouridine,
2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine,
2-thio-dihydropseudouridine, 2-thio-dihydrouridine,
2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine,
4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine,
4-thio-pseudouridine, 5-aza-uridine, dihydropseudouridine,
5-methoxyuridine and 2'-O-methyl uridine. In some embodiments,
polynucleotides (e.g., RNA polynucleotides, such as mRNA
polynucleotides) include a combination of at least two (e.g., 2, 3,
4 or more) of the aforementioned modified nucleobases.
[0232] In some embodiments, modified nucleobases in polynucleotides
(e.g., RNA polynucleotides, such as mRNA polynucleotides) are
selected from the group consisting of 1-methyl-pseudouridine
(m.sup.1.psi.), 5-methoxy-uridine (mo.sup.5U), 5-methyl-cytidine
(m.sup.5C), pseudouridine (.psi.), .alpha.-thio-guanosine and
.alpha.-thio-adenosine. In some embodiments, polynucleotides
includes a combination of at least two (e.g., 2, 3, 4 or more) of
the aforementioned modified nucleobases.
[0233] In some embodiments, polynucleotides (e.g., RNA
polynucleotides, such as mRNA polynucleotides) comprise
pseudouridine (.psi.) and 5-methyl-cytidine (m.sup.5C). In some
embodiments, polynucleotides (e.g., RNA polynucleotides, such as
mRNA polynucleotides) comprise 1-methyl-pseudouridine
(m.sup.1.psi.). In some embodiments, polynucleotides (e.g., RNA
polynucleotides, such as mRNA polynucleotides) comprise
1-methyl-pseudouridine (m.sup.1.psi.) and 5-methyl-cytidine
(m.sup.5C). In some embodiments, polynucleotides (e.g., RNA
polynucleotides, such as mRNA polynucleotides) comprise
2-thiouridine (s.sup.2U). In some embodiments, polynucleotides
(e.g., RNA polynucleotides, such as mRNA polynucleotides) comprise
2-thiouridine and 5-methyl-cytidine (m.sup.5C). In some
embodiments, polynucleotides (e.g., RNA polynucleotides, such as
mRNA polynucleotides) comprise methoxy-uridine (mo.sup.5U). In some
embodiments, polynucleotides (e.g., RNA polynucleotides, such as
mRNA polynucleotides) comprise 5-methoxy-uridine (mo.sup.5U) and
5-methyl-cytidine (m.sup.5C). In some embodiments, polynucleotides
(e.g., RNA polynucleotides, such as mRNA polynucleotides) comprise
2'-O-methyl uridine. In some embodiments polynucleotides (e.g., RNA
polynucleotides, such as mRNA polynucleotides) comprise 2'-O-methyl
uridine and 5-methyl-cytidine (m.sup.5C). In some embodiments,
polynucleotides (e.g., RNA polynucleotides, such as mRNA
polynucleotides) comprise N6-methyl-adenosine (m.sup.6A). In some
embodiments, polynucleotides (e.g., RNA polynucleotides, such as
mRNA polynucleotides) comprise N6-methyl-adenosine (m.sup.6A) and
5-methyl-cytidine (m.sup.5C).
[0234] In some embodiments, polynucleotides (e.g., RNA
polynucleotides, such as mRNA polynucleotides) are uniformly
modified (e.g., fully modified, modified throughout the entire
sequence) for a particular modification. For example, a
polynucleotide can be uniformly modified with 5-methyl-cytidine
(m.sup.5C), meaning that all cytosine residues in the mRNA sequence
are replaced with 5-methyl-cytidine (m.sup.5C). Similarly, a
polynucleotide can be uniformly modified for any type of nucleoside
residue present in the sequence by replacement with a modified
residue such as those set forth above.
[0235] Exemplary nucleobases and nucleosides having a modified
cytosine include N4-acetyl-cytidine (ac4C), 5-methyl-cytidine
(m5C), 5-halo-cytidine (e.g., 5-iodo-cytidine),
5-hydroxymethyl-cytidine (hm5C), 1-methyl-pseudoisocytidine,
2-thio-cytidine (s2C), and 2-thio-5-methyl-cytidine.
[0236] In some embodiments, a modified nucleobase is a modified
uridine. Exemplary nucleobases and In some embodiments, a modified
nucleobase is a modified cytosine. nucleosides having a modified
uridine include 5-cyano uridine, and 4'-thio uridine.
[0237] In some embodiments, a modified nucleobase is a modified
adenine. Exemplary nucleobases and nucleosides having a modified
adenine include 7-deaza-adenine, 1-methyl-adenosine (m1A),
2-methyl-adenine (m2A), and N6-methyl-adenosine (m6A).
[0238] In some embodiments, a modified nucleobase is a modified
guanine. Exemplary nucleobases and nucleosides having a modified
guanine include inosine (I), 1-methyl-inosine (m1I), wyosine (imG),
methylwyosine (mimG), 7-deaza-guanosine, 7-cyano-7-deaza-guanosine
(preQ0), 7-aminomethyl-7-deaza-guanosine (preQ1),
7-methyl-guanosine (m7G), 1-methyl-guanosine (m1G),
8-oxo-guanosine, 7-methyl-8-oxo-guanosine.
[0239] The polynucleotides of the present disclosure may be
partially or fully modified along the entire length of the
molecule. For example, one or more or all or a given type of
nucleotide (e.g., purine or pyrimidine, or any one or more or all
of A, G, U, C) may be uniformly modified in a polynucleotide of the
disclosure, or in a given predetermined sequence region thereof
(e.g., in the mRNA including or excluding the polyA tail). In some
embodiments, all nucleotides X in a polynucleotide of the present
disclosure (or in a given sequence region thereof) are modified
nucleotides, wherein X may any one of nucleotides A, G, U, C, or
any one of the combinations A+G, A+U, A+C, G+U, G+C, U+C, A+G+U,
A+G+C, G+U+C or A+G+C.
[0240] The polynucleotide may contain from about 1% to about 100%
modified nucleotides (either in relation to overall nucleotide
content, or in relation to one or more types of nucleotide, i.e.,
any one or more of A, G, U or C) or any intervening percentage
(e.g., from 1% to 20%, from 1% to 25%, from 1% to 50%, from 1% to
60%, from 1% to 70%, from 1% to 80%, from 1% to 90%, from 1% to
95%, from 10% to 20%, from 10% to 25%, from 10% to 50%, from 10% to
60%, from 10% to 70%, from 10% to 80%, from 10% to 90%, from 10% to
95%, from 10% to 100%, from 20% to 25%, from 20% to 50%, from 20%
to 60%, from 20% to 70%, from 20% to 80%, from 20% to 90%, from 20%
to 95%, from 20% to 100%, from 50% to 60%, from 50% to 70%, from
50% to 80%, from 50% to 90%, from 50% to 95%, from 50% to 100%,
from 70% to 80%, from 70% to 90%, from 70% to 95%, from 70% to
100%, from 80% to 90%, from 80% to 95%, from 80% to 100%, from 90%
to 95%, from 90% to 100%, and from 95% to 100%). Any remaining
percentage is accounted for by the presence of unmodified A, G, U,
or C.
[0241] The polynucleotides may contain at a minimum 1% and at
maximum 100% modified nucleotides, or any intervening percentage,
such as at least 5% modified nucleotides, at least 10% modified
nucleotides, at least 25% modified nucleotides, at least 50%
modified nucleotides, at least 80% modified nucleotides, or at
least 90% modified nucleotides. For example, the polynucleotides
may contain a modified pyrimidine such as a modified uracil or
cytosine. In some embodiments, at least 5%, at least 10%, at least
25%, at least 50%, at least 80%, at least 90% or 100% of the uracil
in the polynucleotide is replaced with a modified uracil (e.g., a
5-substituted uracil). The modified uracil can be replaced by a
compound having a single unique structure, or can be replaced by a
plurality of compounds having different structures (e.g., 2, 3, 4
or more unique structures). n some embodiments, at least 5%, at
least 10%, at least 25%, at least 50%, at least 80%, at least 90%
or 100% of the cytosine in the polynucleotide is replaced with a
modified cytosine (e.g., a 5-substituted cytosine). The modified
cytosine can be replaced by a compound having a single unique
structure, or can be replaced by a plurality of compounds having
different structures (e.g., 2, 3, 4 or more unique structures).
[0242] Thus, in some embodiments, the RNA (e.g., mRNA) vaccines
comprise a 5'UTR element, an optionally codon optimized open
reading frame, and a 3'UTR element, a poly(A) sequence and/or a
polyadenylation signal wherein the RNA is not chemically
modified.
[0243] In some embodiments, the modified nucleobase is a modified
uracil. Exemplary nucleobases and nucleosides having a modified
uracil include pseudouridine (w), pyridin-4-one ribonucleoside,
5-aza-uridine, 6-aza-uridine, 2-thio-5-aza-uridine, 2-thio-uridine
(s.sup.2U), 4-thio-uridine (s.sup.4U), 4-thio-pseudouridine,
2-thio-pseudouridine, 5-hydroxy-uridine (ho.sup.5U),
5-aminoallyl-uridine, 5-halo-uridine (e.g., 5-iodo-uridineor
5-bromo-uridine), 3-methyl-uridine (m.sup.3U), 5-methoxy-uridine
(mo.sup.5U), uridine 5-oxyacetic acid (cmo.sup.5U), uridine
5-oxyacetic acid methyl ester (mcmo.sup.5U),
5-carboxymethyl-uridine (cm.sup.5U), 1-carboxymethyl-pseudouridine,
5-carboxyhydroxymethyl-uridine (chm.sup.5U),
5-carboxyhydroxymethyl-uridine methyl ester (mchm.sup.5U),
5-methoxycarbonylmethyl-uridine (mcm.sup.5U),
5-methoxycarbonylmethyl-2-thio-uridine (mcm.sup.5s.sup.2U),
5-aminomethyl-2-thio-uridine (nm.sup.5s.sup.2U),
5-methylaminomethyl-uridine (mnm.sup.5U),
5-methylaminomethyl-2-thio-uridine (mnm.sup.5s.sup.2U),
5-methylaminomethyl-2-seleno-uridine (mnm.sup.5se.sup.2U),
5-carbamoylmethyl-uridine (ncm.sup.5U),
5-carboxymethylaminomethyl-uridine (cmnm.sup.5U),
5-carboxymethylaminomethyl-2-thio-uridine (cmnm.sup.5s.sup.2U),
5-propynyl-uridine, 1-propynyl-pseudouridine,
5-taurinomethyl-uridine (.tau.m.sup.5U),
1-taurinomethyl-pseudouridine,
5-taurinomethyl-2-thio-uridine(.tau.m.sup.5s.sup.2U),
1-taurinomethyl-4-thio-pseudouridine, 5-methyl-uridine (m.sup.5U,
i.e., having the nucleobase deoxythymine), 1-methyl-pseudouridine
(m.sup.1.psi.), 5-methyl-2-thio-uridine (m.sup.5s.sup.2U),
1-methyl-4-thio-pseudouridine(m.sup.1s.sup.4.psi.),
4-thio-1-methyl-pseudouridine, 3-methyl-pseudouridine
(m.sup.3.psi.), 2-thio-1-methyl-pseudouridine,
1-methyl-1-deaza-pseudouridine,
2-thio-1-methyl-1-deaza-pseudouridine, dihydrouridine (D),
dihydropseudouridine, 5,6-dihydrouridine, 5-methyldihydrouridine
(m.sup.5D), 2-thio-dihydrouridine, 2-thio-dihydropseudouridine,
2-methoxy-uridine, 2-methoxy-4-thio-uridine,
4-methoxy-pseudouridine, 4-methoxy-2-thio-pseudouridine,
N1-methyl-pseudouridine, 3-(3-amino-3-carboxypropyl)uridine
(acp.sup.3U), 1-methyl-3-(3-amino-3-carboxypropyl)pseudouridine
(acp.sup.3 .psi.), 5-(isopentenylaminomethyl)uridine (inm.sup.5U),
5-(isopentenylaminomethyl)-2-thio-uridine (inm.sup.5s.sup.2U),
.alpha.-thio-uridine, 2'-O-methyl-uridine (Um),
5,2'-O-dimethyl-uridine (m.sup.5Um), 2'-O-methyl-pseudouridine
(.psi.m), 2-thio-2'-O-methyl-uridine (s.sup.2Um),
5-methoxycarbonylmethyl-2'-O-methyl-uridine (mcm.sup.5Um),
5-carbamoylmethyl-2'-O-methyl-uridine (ncm.sup.5Um),
5-carboxymethylaminomethyl-2'-O-methyl-uridine (cmnm.sup.5Um),
3,2'-O-dimethyl-uridine (m.sup.3Um), and
5-(isopentenylaminomethyl)-2'-O-methyl-uridine (inm.sup.5Um),
1-thio-uridine, deoxythymidine, 2'-F-ara-uridine, 2'-F-uridine,
2'-OH-ara-uridine, 5-(2-carbomethoxyvinyl) uridine, and
5-[3-(1-E-propenylamino)]uridine.
[0244] In some embodiments, the modified nucleobase is a modified
cytosine. Exemplary nucleobases and nucleosides having a modified
cytosine include 5-aza-cytidine, 6-aza-cytidine, pseudoisocytidine,
3-methyl-cytidine (m.sup.3C), N4-acetyl-cytidine (ac.sup.4C),
5-formylcytidine (f.sup.5C), N4-methyl-cytidine (m.sup.4C),
5-methyl-cytidine (m.sup.5C), 5-halo-cytidine (e.g.,
5-iodo-cytidine), 5-hydroxymethyl-cytidine (hm.sup.5C),
1-methyl-pseudoisocytidine, pyrrolo-cytidine,
pyrrolo-pseudoisocytidine, 2-thio-cytidine (s.sup.2C),
2-thio-5-methyl-cytidine, 4-thio-pseudoisocytidine,
4-thio-1-methyl-pseudoisocytidine,
4-thio-1-methyl-1-deaza-pseudoisocytidine,
1-methyl-1-deaza-pseudoisocytidine, zebularine, 5-aza-zebularine,
5-methyl-zebularine, 5-aza-2-thio-zebularine, 2-thio-zebularine,
2-methoxy-cytidine, 2-methoxy-5-methyl-cytidine,
4-methoxy-pseudoisocytidine, 4-methoxy-1-methyl-pseudoisocytidine,
lysidine (k.sub.2C), .alpha.-thio-cytidine, 2'-O-methyl-cytidine
(Cm), 5,2'-O-dimethylcytidine (m.sup.5Cm),
N4-acetyl-2'-O-methyl-cytidine (ac.sup.4Cm),
N4,2'-O-dimethylcytidine (m.sup.4Cm), 5-formyl-2'-O-methyl-cytidine
(f.sup.5Cm), N4,N4,2'-O-trimethyl-cytidine (m.sup.4.sub.2Cm),
1-thio-cytidine, 2'-F-ara-cytidine, 2'-F-cytidine, and
2'-OH-ara-cytidine.
[0245] In some embodiments, the modified nucleobase is a modified
adenine. Exemplary nucleobases and nucleosides having a modified
adenine include 2-amino-purine, 2, 6-diaminopurine,
2-amino-6-halo-purine (e.g., 2-amino-6-chloro-purine),
6-halo-purine (e.g., 6-chloro-purine), 2-amino-6-methyl-purine,
8-azido-adenosine, 7-deaza-adenine, 7-deaza-8-aza-adenine,
7-deaza-2-amino-purine, 7-deaza-8-aza-2-amino-purine,
7-deaza-2,6-diaminopurine, 7-deaza-8-aza-2,6-diaminopurine,
1-methyl-adenosine (m.sup.1A), 2-methyl-adenine (m.sup.2A),
N6-methyl-adenosine (m.sup.6A), 2-methylthio-N6-methyl-adenosine
(ms.sup.2 m.sup.6A), N6-isopentenyl-adenosine (i.sup.6A),
2-methylthio-N6-isopentenyl-adenosine (ms.sup.2i.sup.6A),
N6-(cis-hydroxyisopentenyl)adenosine (io.sup.6A),
2-methylthio-N6-(cis-hydroxyisopentenyl)adenosine
(ms.sup.2io.sup.6A), N6-glycinylcarbamoyl-adenosine (g.sup.6A),
N6-threonylcarbamoyl-adenosine (t.sup.6A),
N6-methyl-N6-threonylcarbamoyl-adenosine (m.sup.6t.sup.6A),
2-methylthio-N6-threonylcarbamoyl-adenosine (ms.sup.2g.sup.6A),
N6,N6-dimethyl-adenosine (m.sup.6.sub.2A),
N6-hydroxynorvalylcarbamoyl-adenosine (hn.sup.6A),
2-methylthio-N6-hydroxynorvalylcarbamoyl-adenosine
(ms.sup.2hn.sup.6A), N6-acetyl-adenosine (ac.sup.6A),
7-methyl-adenine, 2-methylthio-adenine, 2-methoxy-adenine,
.alpha.-thio-adenosine, 2'-O-methyl-adenosine (Am),
N6,2'-O-dimethyl-adenosine (m.sup.6Am),
N6,N6,2'-O-trimethyl-adenosine (m.sup.6.sub.2Am),
1,2'-O-dimethyl-adenosine (m.sup.1Am), 2'-O-ribosyladenosine
(phosphate) (Ar(p)), 2-amino-N6-methyl-purine, 1-thio-adenosine,
8-azido-adenosine, 2'-F-ara-adenosine, 2'-F-adenosine,
2'-OH-ara-adenosine, and
N6-(19-amino-pentaoxanonadecyl)-adenosine.
[0246] In some embodiments, the modified nucleobase is a modified
guanine. Exemplary nucleobases and nucleosides having a modified
guanine include inosine (I), 1-methyl-inosine (m.sup.1I), wyosine
(imG), methylwyosine (mimG), 4-demethyl-wyosine (imG-14),
isowyosine (imG2), wybutosine (yW), peroxywybutosine (o.sub.2yW),
hydroxywybutosine (OhyW), undermodified hydroxywybutosine (OhyW*),
7-deaza-guanosine, queuosine (Q), epoxyqueuosine (oQ),
galactosyl-queuosine (galQ), mannosyl-queuosine (manQ),
7-cyano-7-deaza-guanosine (preQ.sub.0),
7-aminomethyl-7-deaza-guanosine (preQ.sub.1), archaeosine
(G.sup.+), 7-deaza-8-aza-guanosine, 6-thio-guanosine,
6-thio-7-deaza-guanosine, 6-thio-7-deaza-8-aza-guanosine,
7-methyl-guanosine (m.sup.7G), 6-thio-7-methyl-guanosine,
7-methyl-inosine, 6-methoxy-guanosine, 1-methyl-guanosine
(m.sup.1G), N2-methyl-guanosine (m.sup.2G),
N2,N2-dimethyl-guanosine (m.sup.2.sub.2G), N2,7-dimethyl-guanosine
(m.sup.2,7G), N2,N2,7-dimethyl-guanosine (m.sup.2,2,7G),
8-oxo-guanosine, 7-methyl-8-oxo-guanosine,
1-methyl-6-thio-guanosine, N2-methyl-6-thio-guanosine,
N2,N2-dimethyl-6-thio-guanosine, .alpha.-thio-guanosine,
2'-O-methyl-guanosine (Gm), N2-methyl-2'-O-methyl-guanosine
(m.sup.2Gm), N2,N2-dimethyl-2'-O-methyl-guanosine
(m.sup.2.sub.2Gm), 1-methyl-2'-O-methyl-guanosine (m.sup.1Gm),
N2,7-dimethyl-2'-O-methyl-guanosine (m.sup.2,7Gm),
2'-O-methyl-inosine (Im), 1,2'-O-dimethyl-inosine (m.sup.1Im),
2'-O-ribosylguanosine (phosphate) (Gr(p)), 1-thio-guanosine,
O6-methyl-guanosine, 2'-F-ara-guanosine, and 2'-F-guanosine.
N-Linked Glycosylation Site Mutants
[0247] N-linked glycans of viral proteins play important roles in
modulating the immune response. Glycans can be important for
maintaining the appropriate antigenic conformations, shielding
potential neutralization epitopes, and may alter the proteolytic
susceptibility of proteins. Some viruses have putative N-linked
glycosylation sites. Deletion or modification of an N-linked
glycosylation site may enhance the immune response. Thus, the
present disclosure provides, in some embodiments, RNA (e.g., mRNA)
vaccines comprising nucleic acids (e.g., mRNA) encoding antigenic
polypeptides that comprise a deletion or modification at one or
more N-linked glycosylation sites.
In Vitro Transcription of RNA (e.g., mRNA)
[0248] STD vaccines of the present disclosure comprise at least one
RNA polynucleotide, such as a mRNA (e.g., modified mRNA). mRNA, for
example, is transcribed in vitro from template DNA, referred to as
an "in vitro transcription template." In some embodiments, an in
vitro transcription template encodes a 5' untranslated (UTR)
region, contains an open reading frame, and encodes a 3' UTR and a
polyA tail. The particular nucleic acid sequence composition and
length of an in vitro transcription template will depend on the
mRNA encoded by the template.
[0249] A "5' untranslated region" (5'UTR) refers to a region of an
mRNA that is directly upstream (i.e., 5') from the start codon
(i.e., the first codon of an mRNA transcript translated by a
ribosome) that does not encode a polypeptide.
[0250] A "3' untranslated region" (3'UTR) refers to a region of an
mRNA that is directly downstream (i.e., 3') from the stop codon
(i.e., the codon of an mRNA transcript that signals a termination
of translation) that does not encode a polypeptide.
[0251] An "open reading frame" is a continuous stretch of DNA
beginning with a start codon (e.g., methionine (ATG)), and ending
with a stop codon (e.g., TAA, TAG or TGA) and encodes a
polypeptide.
[0252] A "polyA tail" is a region of mRNA that is downstream, e.g.,
directly downstream (i.e., 3'), from the 3' UTR that contains
multiple, consecutive adenosine monophosphates. A polyA tail may
contain 10 to 300 adenosine monophosphates. For example, a polyA
tail may contain 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120,
130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250,
260, 270, 280, 290 or 300 adenosine monophosphates. In some
embodiments, a polyA tail contains 50 to 250 adenosine
monophosphates. In a relevant biological setting (e.g., in cells,
in vivo) the poly(A) tail functions to protect mRNA from enzymatic
degradation, e.g., in the cytoplasm, and aids in transcription
termination, export of the mRNA from the nucleus and
translation.
[0253] In some embodiments, a polynucleotide includes 200 to 3,000
nucleotides. For example, a polynucleotide may include 200 to 500,
200 to 1000, 200 to 1500, 200 to 3000, 500 to 1000, 500 to 1500,
500 to 2000, 500 to 3000, 1000 to 1500, 1000 to 2000, 1000 to 3000,
1500 to 3000, or 2000 to 3000 nucleotides.
Flagellin Adjuvants
[0254] Flagellin is an approximately 500 amino acid monomeric
protein that polymerizes to form the flagella associated with
bacterial motion. Flagellin is expressed by a variety of
flagellated bacteria (Salmonella typhimurium for example) as well
as non-flagellated bacteria (such as Escherichia coli). Sensing of
flagellin by cells of the innate immune system (dendritic cells,
macrophages, etc.) is mediated by the Toll-like receptor 5 (TLR5)
as well as by Nod-like receptors (NLRs) Ipaf and Naip5. TLRs and
NLRs have been identified as playing a role in the activation of
innate immune response and adaptive immune response. As such,
flagellin provides an adjuvant effect in a vaccine.
[0255] The nucleotide and amino acid sequences encoding known
flagellin polypeptides are publicly available in the NCBI GenBank
database. The flagellin sequences from S. Typhimurium, H. Pylori,
V. Cholera, S. marcesens, S. flexneri, T. Pallidum, L. pneumophila,
B. burgdorferei, C. difficile, R. meliloti, A. tumefaciens, R.
lupini, B. clarridgeiae, P. Mirabilis, B. subtilus, L.
monocytogenes, P. aeruginosa, and E. coli, among others are
known.
[0256] A flagellin polypeptide, as used herein, refers to a full
length flagellin protein, immunogenic fragments thereof, and
peptides having at least 50% sequence identify to a flagellin
protein or immunogenic fragments thereof. Exemplary flagellin
proteins include flagellin from Salmonella typhi (UniPro Entry
number: Q56086), Salmonella typhimurium (A0A0C9DG09), Salmonella
enteritidis (A0A0C9BAB7), and Salmonella choleraesuis (Q6V2X8), and
-56 (Table 17). In some embodiments, the flagellin polypeptide has
at least 60%, 70%, 75%, 80%, 90%, 95%, 97%, 98%, or 99% sequence
identify to a flagellin protein or immunogenic fragments
thereof.
[0257] In some embodiments, the flagellin polypeptide is an
immunogenic fragment. An immunogenic fragment is a portion of a
flagellin protein that provokes an immune response. In some
embodiments, the immune response is a TLR5 immune response. An
example of an immunogenic fragment is a flagellin protein in which
all or a portion of a hinge region has been deleted or replaced
with other amino acids. For example, an antigenic polypeptide may
be inserted in the hinge region. Hinge regions are the
hypervariable regions of a flagellin. Hinge regions of a flagellin
are also referred to as "D3 domain or region, "propeller domain or
region," "hypervariable domain or region" and "variable domain or
region." "At least a portion of a hinge region," as used herein,
refers to any part of the hinge region of the flagellin, or the
entirety of the hinge region. In other embodiments an immunogenic
fragment of flagellin is a 20, 25, 30, 35, or 40 amino acid
C-terminal fragment of flagellin.
[0258] The flagellin monomer is formed by domains D0 through D3. D0
and D1, which form the stem, are composed of tandem long alpha
helices and are highly conserved among different bacteria. The D1
domain includes several stretches of amino acids that are useful
for TLR5 activation. The entire D1 domain or one or more of the
active regions within the domain are immunogenic fragments of
flagellin. Examples of immunogenic regions within the D1 domain
include residues 88-114 and residues 411-431 (in Salmonella
typhimurium FliC flagellin. Within the 13 amino acids in the 88-100
region, at least 6 substitutions are permitted between Salmonella
flagellin and other flagellins that still preserve TLR5 activation.
Thus, immunogenic fragments of flagellin include flagellin like
sequences that activate TLR5 and contain a 13 amino acid motif that
is 53% or more identical to the Salmonella sequence in 88-100 of
FliC (LQRVRELAVQSAN; SEQ ID NO: 462).
[0259] In some embodiments, the RNA (e.g., mRNA) vaccine includes
an RNA that encodes a fusion protein of flagellin and one or more
antigenic polypeptides. A "fusion protein" as used herein, refers
to a linking of two components of the construct. In some
embodiments, a carboxy-terminus of the antigenic polypeptide is
fused or linked to an amino terminus of the flagellin polypeptide.
In other embodiments, an amino-terminus of the antigenic
polypeptide is fused or linked to a carboxy-terminus of the
flagellin polypeptide. The fusion protein may include, for example,
one, two, three, four, five, six or more flagellin polypeptides
linked to one, two, three, four, five, six or more antigenic
polypeptides. When two or more flagellin polypeptides and/or two or
more antigenic polypeptides are linked such a construct may be
referred to as a "multimer."
[0260] Each of the components of a fusion protein may be directly
linked to one another or they may be connected through a linker.
For instance, the linker may be an amino acid linker. The amino
acid linker encoded for by the RNA (e.g., mRNA) vaccine to link the
components of the fusion protein may include, for instance, at
least one member selected from the group consisting of a lysine
residue, a glutamic acid residue, a serine residue and an arginine
residue. In some embodiments the linker is 1-30, 1-25, 1-25, 5-10,
5, 15, or 5-20 amino acids in length.
[0261] In other embodiments the RNA (e.g., mRNA) vaccine includes
at least two separate RNA polynucleotides, one encoding one or more
antigenic polypeptides and the other encoding the flagellin
polypeptide. The at least two RNA polynucleotides may be
co-formulated in a carrier such as a lipid nanoparticle.
Broad Spectrum RNA (e.g., mRNA) Vaccines
[0262] There may be situations where persons are at risk for
infection with more than one strain of HPV, HSV and/or Chlamydia.
RNA (e.g., mRNA) therapeutic vaccines are particularly amenable to
combination vaccination approaches due to a number of factors
including, but not limited to, speed of manufacture, ability to
rapidly tailor vaccines to accommodate perceived geographical
threat, and the like. Moreover, because the vaccines utilize the
human body to produce the antigenic protein, the vaccines are
amenable to the production of larger, more complex antigenic
proteins, allowing for proper folding, surface expression, antigen
presentation, etc. in the human subject. To protect against more
than one strain of HPV, HSV and/or Chlamydia, a combination vaccine
can be administered that includes RNA (e.g., mRNA) encoding at
least one antigenic polypeptide protein (or antigenic portion
thereof) of a first STD virus and further includes RNA encoding at
least one antigenic polypeptide protein (or antigenic portion
thereof) of a second STD virus. RNA (e.g., mRNA) can be
co-formulated, for example, in a single lipid nanoparticle (LNP) or
can be formulated in separate LNPs for co-administration.
Methods of Treatment
[0263] Provided herein are compositions (e.g., pharmaceutical
compositions), methods, kits and reagents for prevention and/or
treatment of STD s in humans and other mammals. STD RNA (e.g. mRNA)
vaccines can be used as therapeutic or prophylactic agents, alone
or in combination with other vaccine(s). They may be used in
medicine to prevent and/or treat STD. In exemplary aspects, the RNA
(e.g., mRNA) vaccines of the present disclosure are used to provide
prophylactic protection from HPV, HSV and/or Chlamydia.
Prophylactic protection from HPV, HSV and/or Chlamydia can be
achieved following administration of a RNA (e.g., mRNA) vaccine of
the present disclosure. STD RNA (e.g., mRNA) vaccines of the
present disclosure may be used to treat or prevent viral
"co-infections" containing two or more STD infections. Vaccines can
be administered once, twice, three times, four times or more, but
it is likely sufficient to administer the vaccine once (optionally
followed by a single booster). It is possible, although less
desirable, to administer the vaccine to an infected individual to
achieve a therapeutic response. Dosing may need to be adjusted
accordingly.
[0264] A method of eliciting an immune response in a subject
against HPV, HSV and/or Chlamydia is provided in aspects of the
present disclosure. The method involves administering to the
subject a STD RNA (e.g., mRNA) vaccine comprising at least one RNA
(e.g., mRNA) polynucleotide having an open reading frame encoding
at least one HPV antigenic polypeptide, HSV antigenic polypeptide
and/or at least one Chlamydia antigenic polypeptide, thereby
inducing in the subject an immune response specific to HPV, HSV
and/or Chlamydia antigenic polypeptide or an immunogenic fragment
thereof, wherein anti-antigenic polypeptide antibody titer in the
subject is increased following vaccination relative to
anti-antigenic polypeptide antibody titer in a subject vaccinated
with a prophylactically effective dose of a traditional vaccine
against HPV, HSV and/or Chlamydia. An "anti-antigenic polypeptide
antibody" is a serum antibody the binds specifically to the
antigenic polypeptide.
[0265] In some embodiments, a RNA (e.g., mRNA) vaccine (e.g., a HPV
RNA vaccine, a HSV RNA vaccine, or a Chlamydia RNA vaccine) capable
of eliciting an immune response is administered intramuscularly or
intranasally via a composition including a compound according to
Formula (I), (IA), (II), (IIa), (IIb), (IIc), (IId) or (IIe) (e.g.,
Compound 3, 18, 20, 25, 26, 29, 30, 60, 108-112, or 122).
[0266] A prophylactically effective dose is a therapeutically
effective dose that prevents infection with the virus at a
clinically acceptable level. In some embodiments the
therapeutically effective dose is a dose listed in a package insert
for the vaccine. A traditional vaccine, as used herein, refers to a
vaccine other than the RNA (e.g., mRNA) vaccines of the present
disclosure. For instance, a traditional vaccine includes but is not
limited to live/attenuated microorganism vaccines,
killed/inactivated microorganism vaccines, subunit vaccines,
protein antigen vaccines, DNA vaccines, VLP vaccines, etc. In
exemplary embodiments, a traditional vaccine is a vaccine that has
achieved regulatory approval and/or is registered by a national
drug regulatory body, for example the Food and Drug Administration
(FDA) in the United States or the European Medicines Agency
(EMA).
[0267] In some embodiments the anti-antigenic polypeptide antibody
titer in the subject is increased 1 log to 10 log following
vaccination relative to anti-antigenic polypeptide antibody titer
in a subject vaccinated with a prophylactically effective dose of a
traditional vaccine against HPV, HSV and/or Chlamydia.
[0268] In some embodiments the anti-antigenic polypeptide antibody
titer in the subject is increased 1 log, 2 log, 3 log, 5 log or 10
log following vaccination relative to anti-antigenic polypeptide
antibody titer in a subject vaccinated with a prophylactically
effective dose of a traditional vaccine against HPV, HSV and/or
Chlamydia.
[0269] A method of eliciting an immune response in a subject
against HPV, HSV and/or Chlamydia is provided in other aspects of
the disclosure. The method involves administering to the subject a
STD RNA (e.g., mRNA) vaccine comprising at least one RNA (e.g.,
mRNA) polynucleotide having an open reading frame encoding at least
one HPV antigenic polypeptide, HSV antigenic polypeptide, and/or
Chlamydia antigenic polypeptide or an immunogenic fragment thereof,
thereby inducing in the subject an immune response specific to HPV
antigenic polypeptide, HSV antigenic polypeptide, and/or Chlamydia
antigenic polypeptide or an immunogenic fragment thereof, wherein
the immune response in the subject is equivalent to an immune
response in a subject vaccinated with a traditional vaccine against
the HPV, HSV and/or Chlamydia at 2 times to 100 times the dosage
level relative to the RNA (e.g., mRNA) vaccine.
[0270] In some embodiments, the immune response in the subject is
equivalent to an immune response in a subject vaccinated with a
traditional vaccine at 2, 3, 4, 5, 10, 50, 100 times the dosage
level relative to the HPV, HSV and/or Chlamydia RNA (e.g., mRNA)
vaccine. In some embodiments the immune response in the subject is
equivalent to an immune response in a subject vaccinated with a
traditional vaccine at 10-100 times, or 100-1000 times, the dosage
level relative to the HPV, HSV and/or Chlamydia RNA (e.g., mRNA)
vaccine.
[0271] In some embodiments the immune response is assessed by
determining [protein] antibody titer in the subject.
[0272] Some aspects of the present disclosure provide a method of
eliciting an immune response in a subject against a In some
embodiments the immune response in the subject is equivalent to an
immune response in a subject vaccinated with a traditional vaccine
at 2, 3, 4, 5, 10, 50, 100 times the dosage level relative to the
HPV, HSV and/or Chlamydia RNA (e.g., mRNA) vaccine by administering
to the subject a STD RNA (e.g., mRNA) vaccine comprising at least
one RNA (e.g., mRNA) polynucleotide having an open reading frame
encoding at least one HPV, HSV and/or Chlamydia antigenic
polypeptide, thereby inducing in the subject an immune response
specific to the antigenic polypeptide or an immunogenic fragment
thereof, wherein the immune response in the subject is induced 2
days to 10 weeks earlier relative to an immune response induced in
a subject vaccinated with a prophylactically effective dose of a
traditional vaccine against HPV, HSV and/or Chlamydia. In some
embodiments, the immune response in the subject is induced in a
subject vaccinated with a prophylactically effective dose of a
traditional vaccine at 2 times to 100 times the dosage level
relative to the RNA (e.g., mRNA) vaccine.
[0273] In some embodiments, the immune response in the subject is
induced 2 days earlier, or 3 days earlier, relative to an immune
response induced in a subject vaccinated with a prophylactically
effective dose of a traditional vaccine.
[0274] In some embodiments the immune response in the subject is
induced 1 week, 2 weeks, 3 weeks, 5 weeks, or 10 weeks earlier
relative to an immune response induced in a subject vaccinated with
a prophylactically effective dose of a traditional vaccine.
[0275] Also provided herein is a method of eliciting an immune
response in a subject against HPV, HSV and/or Chlamydia by
administering to the subject a STD RNA (e.g., mRNA) vaccine having
an open reading frame encoding a first antigenic polypeptide,
wherein the RNA polynucleotide does not include a stabilization
element, and wherein an adjuvant is not co-formulated or
co-administered with the vaccine.
Therapeutic and Prophylactic Compositions
[0276] Provided herein are compositions (e.g., pharmaceutical
compositions), methods, kits and reagents for prevention, treatment
or diagnosis of HPV, HSV and/or Chlamydia in humans and other
mammals, for example. STD RNA (e.g. mRNA) vaccines can be used as
therapeutic or prophylactic agents. They may be used in medicine to
prevent and/or treat infectious disease. In some embodiments, the
respiratory RNA (e.g., mRNA) vaccines of the present disclosure are
used fin the priming of immune effector cells, for example, to
activate peripheral blood mononuclear cells (PBMCs) ex vivo, which
are then infused (re-infused) into a subject.
[0277] In some embodiments, STD vaccine containing RNA (e.g., mRNA)
polynucleotides as described herein can be administered to a
subject (e.g., a mammalian subject, such as a human subject), and
the RNA (e.g., mRNA) polynucleotides are translated in vivo to
produce an antigenic polypeptide.
[0278] The STD RNA (e.g., mRNA) vaccines may be induced for
translation of a polypeptide (e.g., antigen or immunogen) in a
cell, tissue or organism. In some embodiments, such translation
occurs in vivo, although such translation may occur ex vivo, in
culture or in vitro. In some embodiments, the cell, tissue or
organism is contacted with an effective amount of a composition
containing a STD RNA (e.g., mRNA) vaccine that contains a
polynucleotide that has at least one a translatable region encoding
an antigenic polypeptide.
[0279] An "effective amount" of an STD RNA (e.g. mRNA) vaccine is
provided based, at least in part, on the target tissue, target cell
type, means of administration, physical characteristics of the
polynucleotide (e.g., size, and extent of modified nucleosides) and
other components of the vaccine, and other determinants. In
general, an effective amount of the STD RNA (e.g., mRNA) vaccine
composition provides an induced or boosted immune response as a
function of antigen production in the cell, preferably more
efficient than a composition containing a corresponding unmodified
polynucleotide encoding the same antigen or a peptide antigen.
Increased antigen production may be demonstrated by increased cell
transfection (the percentage of cells transfected with the RNA,
e.g., mRNA, vaccine), increased protein translation from the
polynucleotide, decreased nucleic acid degradation (as
demonstrated, for example, by increased duration of protein
translation from a modified polynucleotide), or altered antigen
specific immune response of the host cell.
[0280] In some embodiments, RNA (e.g. mRNA) vaccines (including
polynucleotides their encoded polypeptides) in accordance with the
present disclosure may be used for treatment of HPV, HSV and/or
Chlamydia.
[0281] Respiratory RNA (e.g. mRNA) vaccines may be administered
prophylactically or therapeutically as part of an active
immunization scheme to healthy individuals or early in infection
during the incubation phase or during active infection after onset
of symptoms. In some embodiments, the amount of RNA (e.g., mRNA)
vaccine of the present disclosure provided to a cell, a tissue or a
subject may be an amount effective for immune prophylaxis.
[0282] STD RNA (e.g. mRNA) vaccines may be administrated with other
prophylactic or therapeutic compounds. As a non-limiting example, a
prophylactic or therapeutic compound may be an adjuvant or a
booster. As used herein, when referring to a prophylactic
composition, such as a vaccine, the term "booster" refers to an
extra administration of the prophylactic (vaccine) composition. A
booster (or booster vaccine) may be given after an earlier
administration of the prophylactic composition. The time of
administration between the initial administration of the
prophylactic composition and the booster may be, but is not limited
to, 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 6
minutes, 7 minutes, 8 minutes, 9 minutes, 10 minutes, 15 minutes,
20 minutes 35 minutes, 40 minutes, 45 minutes, 50 minutes, 55
minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7
hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14
hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours,
21 hours, 22 hours, 23 hours, 1 day, 36 hours, 2 days, 3 days, 4
days, 5 days, 6 days, 1 week, 10 days, 2 weeks, 3 weeks, 1 month, 2
months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months,
9 months, 10 months, 11 months, 1 year, 18 months, 2 years, 3
years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10
years, 11 years, 12 years, 13 years, 14 years, 15 years, 16 years,
17 years, 18 years, 19 years, 20 years, 25 years, 30 years, 35
years, 40 years, 45 years, 50 years, 55 years, 60 years, 65 years,
70 years, 75 years, 80 years, 85 years, 90 years, 95 years or more
than 99 years. In some embodiments, the time of administration
between the initial administration of the prophylactic composition
and the booster may be, but is not limited to, 1 week, 2 weeks, 3
weeks, 1 month, 2 months, 3 months, 6 months or 1 year.
[0283] In some embodiments, STD RNA (e.g. mRNA) vaccines may be
administered intramuscularly, intradermally, or intranasally,
similarly to the administration of inactivated vaccines known in
the art.
[0284] STD RNA (e.g. mRNA) vaccines may be utilized in various
settings depending on the prevalence of the infection or the degree
or level of unmet medical need. As a non-limiting example, the RNA
(e.g., mRNA) vaccines may be utilized to treat and/or prevent a
variety of STDs. RNA (e.g., mRNA) vaccines have superior properties
in that they produce much larger antibody titers and produce
responses early than commercially available anti-viral
agents/compositions.
[0285] Provided herein are pharmaceutical compositions including
STD RNA (e.g. mRNA) vaccines and RNA (e.g. mRNA) vaccine
compositions and/or complexes optionally in combination with one or
more pharmaceutically acceptable excipients.
[0286] HPV, HSV and/or Chlamydia RNA (e.g. mRNA) vaccines may be
formulated or administered alone or in conjunction with one or more
other components. For instance, HPV, HSV and/or Chlamydia RNA
(e.g., mRNA) vaccines (vaccine compositions) may comprise other
components including, but not limited to, adjuvants.
[0287] In some embodiments, STD (e.g. mRNA) vaccines do not include
an adjuvant (they are adjuvant free).
[0288] STD RNA (e.g. mRNA) vaccines may be formulated or
administered in combination with one or more
pharmaceutically-acceptable excipients. In some embodiments,
vaccine compositions comprise at least one additional active
substances, such as, for example, a therapeutically-active
substance, a prophylactically-active substance, or a combination of
both. Vaccine compositions may be sterile, pyrogen-free or both
sterile and pyrogen-free. General considerations in the formulation
and/or manufacture of pharmaceutical agents, such as vaccine
compositions, may be found, for example, in Remington: The Science
and Practice of Pharmacy 21st ed., Lippincott Williams &
Wilkins, 2005 (incorporated herein by reference in its
entirety).
[0289] In some embodiments, STD RNA (e.g. mRNA) vaccines are
administered to humans, human patients or subjects. For the
purposes of the present disclosure, the phrase "active ingredient"
generally refers to the RNA (e.g., mRNA) vaccines or the
polynucleotides contained therein, for example, RNA polynucleotides
(e.g., mRNA polynucleotides) encoding antigenic polypeptides.
[0290] Formulations of the STD vaccine compositions described
herein may be prepared by any method known or hereafter developed
in the art of pharmacology. In general, such preparatory methods
include the step of bringing the active ingredient (e.g., mRNA
polynucleotide) into association with an excipient and/or one or
more other accessory ingredients, and then, if necessary and/or
desirable, dividing, shaping and/or packaging the product into a
desired single- or multi-dose unit.
[0291] Relative amounts of the active ingredient, the
pharmaceutically acceptable excipient, and/or any additional
ingredients in a pharmaceutical composition in accordance with the
disclosure will vary, depending upon the identity, size, and/or
condition of the subject treated and further depending upon the
route by which the composition is to be administered. By way of
example, the composition may comprise between 0.1% and 100%, e.g.,
between 0.5 and 50%, between 1-30%, between 5-80%, at least 80%
(w/w) active ingredient.
[0292] STD RNA (e.g. mRNA) vaccines can be formulated using one or
more excipients to: increase stability; increase cell transfection;
permit the sustained or delayed release (e.g., from a depot
formulation); alter the biodistribution (e.g., target to specific
tissues or cell types); increase the translation of encoded protein
in vivo; and/or alter the release profile of encoded protein
(antigen) in vivo. In addition to traditional excipients such as
any and all solvents, dispersion media, diluents, or other liquid
vehicles, dispersion or suspension aids, surface active agents,
isotonic agents, thickening or emulsifying agents, preservatives,
excipients can include, without limitation, lipidoids, liposomes,
lipid nanoparticles, polymers, lipoplexes, core-shell
nanoparticles, peptides, proteins, cells transfected with STD RNA
(e.g. mRNA) vaccines (e.g., for transplantation into a subject),
hyaluronidase, nanoparticle mimics and combinations thereof.
Stabilizing Elements
[0293] Naturally-occurring eukaryotic mRNA molecules have been
found to contain stabilizing elements, including, but not limited
to untranslated regions (UTR) at their 5'-end (5'UTR) and/or at
their 3'-end (3'UTR), in addition to other structural features,
such as a 5'-cap structure or a 3'-poly(A) tail. Both the 5'UTR and
the 3'UTR are typically transcribed from the genomic DNA and are
elements of the premature mRNA. Characteristic structural features
of mature mRNA, such as the 5'-cap and the 3'-poly(A) tail are
usually added to the transcribed (premature) mRNA during mRNA
processing. The 3'-poly(A) tail is typically a stretch of adenine
nucleotides added to the 3'-end of the transcribed mRNA. It can
comprise up to about 400 adenine nucleotides. In some embodiments
the length of the 3'-poly(A) tail may be an essential element with
respect to the stability of the individual mRNA.
[0294] In some embodiments the RNA (e.g., mRNA) vaccine may include
one or more stabilizing elements. Stabilizing elements may include
for instance a histone stem-loop. A stem-loop binding protein
(SLBP), a 32 kDa protein has been identified. It is associated with
the histone stem-loop at the 3'-end of the histone messages in both
the nucleus and the cytoplasm. Its expression level is regulated by
the cell cycle; it is peaks during the S-phase, when histone mRNA
levels are also elevated. The protein has been shown to be
essential for efficient 3'-end processing of histone pre-mRNA by
the U7 snRNP. SLBP continues to be associated with the stem-loop
after processing, and then stimulates the translation of mature
histone mRNAs into histone proteins in the cytoplasm. The RNA
binding domain of SLBP is conserved through metazoa and protozoa;
its binding to the histone stem-loop depends on the structure of
the loop. The minimum binding site includes at least three
nucleotides 5' and two nucleotides 3' relative to the
stem-loop.
[0295] In some embodiments, the RNA (e.g., mRNA) vaccines include a
coding region, at least one histone stem-loop, and optionally, a
poly(A) sequence or polyadenylation signal. The poly(A) sequence or
polyadenylation signal generally should enhance the expression
level of the encoded protein. The encoded protein, in some
embodiments, is not a histone protein, a reporter protein (e.g.
Luciferase, GFP, EGFP, .beta.-Galactosidase, EGFP), or a marker or
selection protein (e.g. alpha-Globin, Galactokinase and
Xanthine:guanine phosphoribosyl transferase (GPT)).
[0296] In some embodiments, the combination of a poly(A) sequence
or polyadenylation signal and at least one histone stem-loop, even
though both represent alternative mechanisms in nature, acts
synergistically to increase the protein expression beyond the level
observed with either of the individual elements. It has been found
that the synergistic effect of the combination of poly(A) and at
least one histone stem-loop does not depend on the order of the
elements or the length of the poly(A) sequence.
[0297] In some embodiments, the RNA (e.g., mRNA) vaccine does not
comprise a histone downstream element (HDE). "Histone downstream
element" (HDE) includes a purine-rich polynucleotide stretch of
approximately 15 to 20 nucleotides 3' of naturally occurring
stem-loops, representing the binding site for the U7 snRNA, which
is involved in processing of histone pre-mRNA into mature histone
mRNA. Ideally, the inventive nucleic acid does not include an
intron.
[0298] In some embodiments, the RNA (e.g., mRNA) vaccine may or may
not contain a enhancer and/or promoter sequence, which may be
modified or unmodified or which may be activated or inactivated. In
some embodiments, the histone stem-loop is generally derived from
histone genes, and includes an intramolecular base pairing of two
neighbored partially or entirely reverse complementary sequences
separated by a spacer, including (e.g., consisting of) a short
sequence, which forms the loop of the structure. The unpaired loop
region is typically unable to base pair with either of the stem
loop elements. It occurs more often in RNA, as is a key component
of many RNA secondary structures, but may be present in
single-stranded DNA as well. Stability of the stem-loop structure
generally depends on the length, number of mismatches or bulges,
and base composition of the paired region. In some embodiments,
wobble base pairing (non-Watson-Crick base pairing) may result. In
some embodiments, the at least one histone stem-loop sequence
comprises a length of 15 to 45 nucleotides.
[0299] In other embodiments the RNA (e.g., mRNA) vaccine may have
one or more AU-rich sequences removed. These sequences, sometimes
referred to as AURES are destabilizing sequences found in the
3'UTR. The AURES may be removed from the RNA (e.g., mRNA) vaccines.
Alternatively the AURES may remain in the RNA (e.g., mRNA)
vaccine.
Nanoparticle Formulations
[0300] In some embodiments, STD RNA (e.g. mRNA) vaccines are
formulated in a nanoparticle. In some embodiments, STD RNA (e.g.
mRNA) vaccines are formulated in a lipid nanoparticle. In some
embodiments, STD RNA (e.g. mRNA) vaccines are formulated in a
lipid-polycation complex, referred to as a cationic lipid
nanoparticle. As a non-limiting example, the polycation may include
a cationic peptide or a polypeptide such as, but not limited to,
polylysine, polyornithine and/or polyarginine. In some embodiments,
STD RNA (e.g., mRNA) vaccines are formulated in a lipid
nanoparticle that includes a non-cationic lipid such as, but not
limited to, cholesterol or dioleoyl phosphatidylethanolamine
(DOPE).
[0301] A lipid nanoparticle formulation may be influenced by, but
not limited to, the selection of the cationic lipid component, the
degree of cationic lipid saturation, the nature of the PEGylation,
ratio of all components and biophysical parameters such as size. In
one example by Semple et al. (Nature Biotech. 2010 28:172-176), the
lipid nanoparticle formulation is composed of 57.1% cationic lipid,
7.1% dipalmitoylphosphatidylcholine, 34.3% cholesterol, and 1.4%
PEG-c-DMA. As another example, changing the composition of the
cationic lipid can more effectively deliver siRNA to various
antigen presenting cells (Basha et al. Mol Ther. 2011
19:2186-2200).
[0302] In some embodiments, lipid nanoparticle formulations may
comprise 35 to 45% cationic lipid, 40% to 50% cationic lipid, 50%
to 60% cationic lipid and/or 55% to 65% cationic lipid. In some
embodiments, the ratio of lipid to RNA (e.g., mRNA) in lipid
nanoparticles may be 5:1 to 20:1, 10:1 to 25:1, 15:1 to 30:1 and/or
at least 30:1.
[0303] In some embodiments, the ratio of PEG in the lipid
nanoparticle formulations may be increased or decreased and/or the
carbon chain length of the PEG lipid may be modified from C14 to
C18 to alter the pharmacokinetics and/or biodistribution of the
lipid nanoparticle formulations. As a non-limiting example, lipid
nanoparticle formulations may contain 0.5% to 3.0%, 1.0% to 3.5%,
1.5% to 4.0%, 2.0% to 4.5%, 2.5% to 5.0% and/or 3.0% to 6.0% of the
lipid molar ratio of PEG-c-DOMG
(R-3-[(.omega.-methoxy-poly(ethyleneglycol)2000)carbamoyl)]-1,2-dimyristy-
loxypropyl-3-amine) (also referred to herein as PEG-DOMG) as
compared to the cationic lipid, DSPC and cholesterol. In some
embodiments, the PEG-c-DOMG may be replaced with a PEG lipid such
as, but not limited to, PEG-DSG (1,2-Distearoyl-sn-glycerol,
methoxypolyethylene glycol), PEG-DMG (1,2-Dimyristoyl-sn-glycerol)
and/or PEG-DPG (1,2-Dipalmitoyl-sn-glycerol, methoxypolyethylene
glycol). The cationic lipid may be selected from any lipid known in
the art such as, but not limited to, DLin-MC3-DMA, DLin-DMA,
C12-200 and DLin-KC2-DMA.
[0304] In some embodiments, an STD RNA (e.g. mRNA) vaccine
formulation is a nanoparticle that comprises at least one lipid.
The lipid may be selected from, but is not limited to, DLin-DMA,
DLin-K-DMA, 98N12-5, C12-200, DLin-MC3-DMA, DLin-KC2-DMA, DODMA,
PLGA, PEG, PEG-DMG, PEGylated lipids and amino alcohol lipids. In
some embodiments, the lipid may be a cationic lipid such as, but
not limited to, DLin-DMA, DLin-D-DMA, DLin-MC3-DMA, DLin-KC2-DMA,
DODMA and amino alcohol lipids. The amino alcohol cationic lipid
may be the lipids described in and/or made by the methods described
in U.S. Patent Publication No. US20130150625, herein incorporated
by reference in its entirety. As a non-limiting example, the
cationic lipid may be
2-amino-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-2-{[(9Z,2Z)-octadeca-9,12-
-dien-1-yloxy]methyl}propan-1-ol (Compound 1 in US20130150625);
2-amino-3-[(9Z)-octadec-9-en-1-yloxy]-2-{[(9Z)-octadec-9-en-1-yloxy]methy-
l}propan-1-ol (Compound 2 in US20130150625);
2-amino-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-2-[(octyloxy)methyl]propa-
n-1-ol (Compound 3 in US20130150625); and
2-(dimethylamino)-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-2-{[(9Z,12Z)-oc-
tadeca-9,12-dien-1-yloxy]methyl}propan-1-ol (Compound 4 in
US20130150625); or any pharmaceutically acceptable salt or
stereoisomer thereof.
[0305] Lipid nanoparticle formulations typically comprise a lipid,
in particular, an ionizable cationic lipid, for example,
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), or
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), and
further comprise a neutral lipid, a sterol and a molecule capable
of reducing particle aggregation, for example a PEG or PEG-modified
lipid.
[0306] In some embodiments, a lipid nanoparticle formulation
consists essentially of (i) at least one lipid selected from the
group consisting of
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319); (ii) a
neutral lipid selected from DSPC, DPPC, POPC, DOPE and SM; (iii) a
sterol, e.g., cholesterol; and (iv) a PEG-lipid, e.g., PEG-DMG or
PEG-cDMA, in a molar ratio of 20-60% cationic lipid: 5-25% neutral
lipid: 25-55% sterol; 0.5-15% PEG-lipid.
[0307] In some embodiments, a lipid nanoparticle formulation
includes 25% to 75% on a molar basis of a cationic lipid selected
from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane
(DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate
(DLin-MC3-DMA), and di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), e.g.,
35 to 65%, 45 to 65%, 60%, 57.5%, 50% or 40% on a molar basis.
[0308] In some embodiments, a lipid nanoparticle formulation
includes 0.5% to 15% on a molar basis of the neutral lipid, e.g., 3
to 12%, 5 to 10% or 15%, 10%, or 7.5% on a molar basis. Examples of
neutral lipids include, without limitation, DSPC, POPC, DPPC, DOPE
and SM. In some embodiments, the formulation includes 5% to 50% on
a molar basis of the sterol (e.g., 15 to 45%, 20 to 40%, 40%,
38.5%, 35%, or 31% on a molar basis. A non-limiting example of a
sterol is cholesterol. In some embodiments, a lipid nanoparticle
formulation includes 0.5% to 20% on a molar basis of the PEG or
PEG-modified lipid (e.g., 0.5 to 10%, 0.5 to 5%, 1.5%, 0.5%, 1.5%,
3.5%, or 5% on a molar basis. In some embodiments, a PEG or PEG
modified lipid comprises a PEG molecule of an average molecular
weight of 2,000 Da. In some embodiments, a PEG or PEG modified
lipid comprises a PEG molecule of an average molecular weight of
less than 2,000, for example around 1,500 Da, around 1,000 Da, or
around 500 Da. Non-limiting examples of PEG-modified lipids include
PEG-distearoyl glycerol (PEG-DMG) (also referred herein as PEG-C14
or C14-PEG), PEG-cDMA (further discussed in Reyes et al. J.
Controlled Release, 107, 276-287 (2005) the contents of which are
herein incorporated by reference in their entirety).
[0309] In some embodiments, lipid nanoparticle formulations include
25-75% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), 0.5-15%
of the neutral lipid, 5-50% of the sterol, and 0.5-20% of the PEG
or PEG-modified lipid on a molar basis.
[0310] In some embodiments, lipid nanoparticle formulations include
35-65% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), 3-12%
of the neutral lipid, 15-45% of the sterol, and 0.5-10% of the PEG
or PEG-modified lipid on a molar basis.
[0311] In some embodiments, lipid nanoparticle formulations include
45-65% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), 5-10%
of the neutral lipid, 25-40% of the sterol, and 0.5-10% of the PEG
or PEG-modified lipid on a molar basis.
[0312] In some embodiments, lipid nanoparticle formulations include
60% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), 7.5% of
the neutral lipid, 31% of the sterol, and 1.5% of the PEG or
PEG-modified lipid on a molar basis.
[0313] In some embodiments, lipid nanoparticle formulations include
50% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), 10% of
the neutral lipid, 38.5% of the sterol, and 1.5% of the PEG or
PEG-modified lipid on a molar basis.
[0314] In some embodiments, lipid nanoparticle formulations include
50% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), 10% of
the neutral lipid, 35% of the sterol, 4.5% or 5% of the PEG or
PEG-modified lipid, and 0.5% of the targeting lipid on a molar
basis.
[0315] In some embodiments, lipid nanoparticle formulations include
40% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), 15% of
the neutral lipid, 40% of the sterol, and 5% of the PEG or
PEG-modified lipid on a molar basis.
[0316] In some embodiments, lipid nanoparticle formulations include
57.2% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), 7.1% of
the neutral lipid, 34.3% of the sterol, and 1.4% of the PEG or
PEG-modified lipid on a molar basis.
[0317] In some embodiments, lipid nanoparticle formulations include
57.5% of a cationic lipid selected from the PEG lipid is PEG-cDMA
(PEG-cDMA is further discussed in Reyes et al. (J. Controlled
Release, 107, 276-287 (2005), the contents of which are herein
incorporated by reference in their entirety), 7.5% of the neutral
lipid, 31.5% of the sterol, and 3.5% of the PEG or PEG-modified
lipid on a molar basis.
[0318] In some embodiments, lipid nanoparticle formulations
consists essentially of a lipid mixture in molar ratios of 20-70%
cationic lipid: 5-45% neutral lipid: 20-55% cholesterol: 0.5-15%
PEG-modified lipid. In some embodiments, lipid nanoparticle
formulations consists essentially of a lipid mixture in a molar
ratio of 20-60% cationic lipid: 5-25% neutral lipid: 25-55%
cholesterol: 0.5-15% PEG-modified lipid.
[0319] In some embodiments, the molar lipid ratio is 50/10/38.5/1.5
(mol % cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified
lipid, e.g., PEG-DMG, PEG-DSG or PEG-DPG), 57.2/7.1134.3/1.4 (mol %
cationic lipid/neutral lipid, e.g., DPPC/Chol/PEG-modified lipid,
e.g., PEG-cDMA), 40/15/40/5 (mol % cationic lipid/neutral lipid,
e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG),
50/10/35/4.5/0.5 (mol % cationic lipid/neutral lipid, e.g.,
DSPC/Chol/PEG-modified lipid, e.g., PEG-DSG), 50/10/35/5 (cationic
lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g.,
PEG-DMG), 40/10/40/10 (mol % cationic lipid/neutral lipid, e.g.,
DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG or PEG-cDMA),
35/15/40/10 (mol % cationic lipid/neutral lipid, e.g.,
DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG or PEG-cDMA) or
52/13/30/5 (mol % cationic lipid/neutral lipid, e.g.,
DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG or PEG-cDMA).
[0320] Non-limiting examples of lipid nanoparticle compositions and
methods of making them are described, for example, in Semple et al.
(2010) Nat. Biotechnol. 28:172-176; Jayarama et al. (2012), Angew.
Chem. Int. Ed., 51: 8529-8533; and Maier et al. (2013) Molecular
Therapy 21, 1570-1578 (the contents of each of which are
incorporated herein by reference in their entirety).
[0321] In some embodiments, lipid nanoparticle formulations may
comprise a cationic lipid, a PEG lipid and a structural lipid and
optionally comprise a non-cationic lipid. As a non-limiting
example, a lipid nanoparticle may comprise 40-60% of cationic
lipid, 5-15% of a non-cationic lipid, 1-2% of a PEG lipid and
30-50% of a structural lipid. As another non-limiting example, the
lipid nanoparticle may comprise 50% cationic lipid, 10%
non-cationic lipid, 1.5% PEG lipid and 38.5% structural lipid. As
yet another non-limiting example, a lipid nanoparticle may comprise
55% cationic lipid, 10% non-cationic lipid, 2.5% PEG lipid and
32.5% structural lipid. In some embodiments, the cationic lipid may
be any cationic lipid described herein such as, but not limited to,
DLin-KC2-DMA, DLin-MC3-DMA and L319.
[0322] In some embodiments, the lipid nanoparticle formulations
described herein may be 4 component lipid nanoparticles. The lipid
nanoparticle may comprise a cationic lipid, a non-cationic lipid, a
PEG lipid and a structural lipid. As a non-limiting example, the
lipid nanoparticle may comprise 40-60% of cationic lipid, 5-15% of
a non-cationic lipid, 1-2% of a PEG lipid and 30-50% of a
structural lipid. As another non-limiting example, the lipid
nanoparticle may comprise 50% cationic lipid, 10% non-cationic
lipid, 1.5% PEG lipid and 38.5% structural lipid. As yet another
non-limiting example, the lipid nanoparticle may comprise 55%
cationic lipid, 10% non-cationic lipid, 2.5% PEG lipid and 32.5%
structural lipid. In some embodiments, the cationic lipid may be
any cationic lipid described herein such as, but not limited to,
DLin-KC2-DMA, DLin-MC3-DMA and L319.
[0323] In some embodiments, the lipid nanoparticle formulations
described herein may comprise a cationic lipid, a non-cationic
lipid, a PEG lipid and a structural lipid. As a non-limiting
example, the lipid nanoparticle comprise 50% of the cationic lipid
DLin-KC2-DMA, 10% of the non-cationic lipid DSPC, 1.5% of the PEG
lipid PEG-DOMG and 38.5% of the structural lipid cholesterol. As a
non-limiting example, the lipid nanoparticle comprise 50% of the
cationic lipid DLin-MC3-DMA, 10% of the non-cationic lipid DSPC,
1.5% of the PEG lipid PEG-DOMG and 38.5% of the structural lipid
cholesterol. As a non-limiting example, the lipid nanoparticle
comprise 50% of the cationic lipid DLin-MC3-DMA, 10% of the
non-cationic lipid DSPC, 1.5% of the PEG lipid PEG-DMG and 38.5% of
the structural lipid cholesterol. As yet another non-limiting
example, the lipid nanoparticle comprise 55% of the cationic lipid
L319, 10% of the non-cationic lipid DSPC, 2.5% of the PEG lipid
PEG-DMG and 32.5% of the structural lipid cholesterol.
[0324] Relative amounts of the active ingredient, the
pharmaceutically acceptable excipient, and/or any additional
ingredients in a vaccine composition may vary, depending upon the
identity, size, and/or condition of the subject being treated and
further depending upon the route by which the composition is to be
administered. For example, the composition may comprise between
0.1% and 99% (w/w) of the active ingredient. By way of example, the
composition may comprise between 0.1% and 100%, e.g., between 0.5
and 50%, between 1-30%, between 5-80%, at least 80% (w/w) active
ingredient.
[0325] In some embodiments, the STD RNA (e.g. mRNA) vaccine
composition may comprise the polynucleotide described herein,
formulated in a lipid nanoparticle comprising MC3, Cholesterol,
DSPC and PEG2000-DMG, the buffer trisodium citrate, sucrose and
water for injection. As a non-limiting example, the composition
comprises: 2.0 mg/mL of drug substance, 21.8 mg/mL of MC3, 10.1
mg/mL of cholesterol, 5.4 mg/mL of DSPC, 2.7 mg/mL of PEG2000-DMG,
5.16 mg/mL of trisodium citrate, 71 mg/mL of sucrose and 1.0 mL of
water for injection.
[0326] In some embodiments, a nanoparticle (e.g., a lipid
nanoparticle) has a mean diameter of 10-500 nm, 20-400 nm, 30-300
nm, 40-200 nm. In some embodiments, a nanoparticle (e.g., a lipid
nanoparticle) has a mean diameter of 50-150 nm, 50-200 nm, 80-100
nm or 80-200 nm.
[0327] Liposomes, Lipoplexes, and Lipid Nanoparticles
[0328] The RNA (e.g., mRNA) vaccines of the disclosure can be
formulated using one or more liposomes, lipoplexes, or lipid
nanoparticles. In some embodiments, pharmaceutical compositions of
RNA (e.g., mRNA) vaccines include liposomes. Liposomes are
artificially-prepared vesicles which may primarily be composed of a
lipid bilayer and may be used as a delivery vehicle for the
administration of nutrients and pharmaceutical formulations.
Liposomes can be of different sizes such as, but not limited to, a
multilamellar vesicle (MLV) which may be hundreds of nanometers in
diameter and may contain a series of concentric bilayers separated
by narrow aqueous compartments, a small unicellular vesicle (SUV)
which may be smaller than 50 nm in diameter, and a large
unilamellar vesicle (LUV) which may be between 50 and 500 nm in
diameter. Liposome design may include, but is not limited to,
opsonins or ligands in order to improve the attachment of liposomes
to unhealthy tissue or to activate events such as, but not limited
to, endocytosis. Liposomes may contain a low or a high pH in order
to improve the delivery of the pharmaceutical formulations.
[0329] The formation of liposomes may depend on the physicochemical
characteristics such as, but not limited to, the pharmaceutical
formulation entrapped and the liposomal ingredients, the nature of
the medium in which the lipid vesicles are dispersed, the effective
concentration of the entrapped substance and its potential
toxicity, any additional processes involved during the application
and/or delivery of the vesicles, the optimization size,
polydispersity and the shelf-life of the vesicles for the intended
application, and the batch-to-batch reproducibility and possibility
of large-scale production of safe and efficient liposomal
products.
[0330] In some embodiments, pharmaceutical compositions described
herein may include, without limitation, liposomes such as those
formed from 1,2-dioleyloxy-N,N-dimethylaminopropane (DODMA)
liposomes, DiLa2 liposomes from Marina Biotech (Bothell, Wash.),
1,2-dilinoleyloxy-3-dimethylaminopropane (DLin-DMA),
2,2-dilinoleyl-4-(2-dimethylaminoethyl)[1,3]-dioxolane
(DLin-KC2-DMA), and MC3 (US20100324120; herein incorporated by
reference in its entirety) and liposomes which may deliver small
molecule drugs such as, but not limited to, DOXIL.RTM. from Janssen
Biotech, Inc. (Horsham, Pa.).
[0331] In some embodiments, pharmaceutical compositions described
herein may include, without limitation, liposomes such as those
formed from the synthesis of stabilized plasmid-lipid particles
(SPLP) or stabilized nucleic acid lipid particle (SNALP) that have
been previously described and shown to be suitable for
oligonucleotide delivery in vitro and in vivo (see Wheeler et al.
Gene Therapy. 1999 6:271-281; Zhang et al. Gene Therapy. 1999
6:1438-1447; Jeffs et al. Pharm Res. 2005 22:362-372; Morrissey et
al., Nat Biotechnol. 2005 2:1002-1007; Zimmermann et al., Nature.
2006 441:111-114; Heyes et al. J Contr Rel. 2005 107:276-287;
Semple et al. Nature Biotech. 2010 28:172-176; Judge et al. J Clin
Invest. 2009 119:661-673; deFougerolles Hum Gene Ther. 2008
19:125-132; U.S. Patent Publication No US20130122104; all of which
are incorporated herein in their entireties). The original
manufacture method by Wheeler et al. was a detergent dialysis
method, which was later improved by Jeffs et al. and is referred to
as the spontaneous vesicle formation method. The liposome
formulations are composed of 3 to 4 lipid components in addition to
the polynucleotide. As an example a liposome can contain, but is
not limited to, 55% cholesterol, 20% disteroylphosphatidyl choline
(DSPC), 10% PEG-S-DSG, and 15%
1,2-dioleyloxy-N,N-dimethylaminopropane (DODMA), as described by
Jeffs et al. As another example, certain liposome formulations may
contain, but are not limited to, 48% cholesterol, 20% DSPC, 2%
PEG-c-DMA, and 30% cationic lipid, where the cationic lipid can be
1,2-distearloxy-N,N-dimethylaminopropane (DSDMA), DODMA, DLin-DMA,
or 1,2-dilinolenyloxy-3-dimethylaminopropane (DLenDMA), as
described by Heyes et al.
[0332] In some embodiments, liposome formulations may comprise from
about 25.0% cholesterol to about 40.0% cholesterol, from about
30.0% cholesterol to about 45.0% cholesterol, from about 35.0%
cholesterol to about 50.0% cholesterol and/or from about 48.5%
cholesterol to about 60% cholesterol. In some embodiments,
formulations may comprise a percentage of cholesterol selected from
the group consisting of 28.5%, 31.5%, 33.5%, 36.5%, 37.0%, 38.5%,
39.0% and 43.5%. In some embodiments, formulations may comprise
from about 5.0% to about 10.0% DSPC and/or from about 7.0% to about
15.0% DSPC.
[0333] In some embodiments, the RNA (e.g., mRNA) vaccine
pharmaceutical compositions may be formulated in liposomes such as,
but not limited to, DiLa2 liposomes (Marina Biotech, Bothell,
Wash.), SMARTICLES.RTM. (Marina Biotech, Bothell, Wash.), neutral
DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) based liposomes
(e.g., siRNA delivery for ovarian cancer (Landen et al. Cancer
Biology & Therapy 2006 5(12)1708-1713); herein incorporated by
reference in its entirety) and hyaluronan-coated liposomes (Quiet
Therapeutics, Israel).
[0334] In some embodiments, the cationic lipid may be a low
molecular weight cationic lipid such as those described in U.S.
Patent Application No. 20130090372, the contents of which are
herein incorporated by reference in their entirety.
[0335] In some embodiments, the RNA (e.g., mRNA) vaccines may be
formulated in a lipid vesicle, which may have crosslinks between
functionalized lipid bilayers.
[0336] In some embodiments, the RNA (e.g., mRNA) vaccines may be
formulated in a lipid-polycation complex. The formation of the
lipid-polycation complex may be accomplished by methods known in
the art and/or as described in U.S. Pub. No. 20120178702, herein
incorporated by reference in its entirety. As a non-limiting
example, the polycation may include a cationic peptide or a
polypeptide such as, but not limited to, polylysine, polyornithine
and/or polyarginine. In some embodiments, the RNA (e.g., mRNA)
vaccines may be formulated in a lipid-polycation complex, which may
further include a non-cationic lipid such as, but not limited to,
cholesterol or dioleoyl phosphatidylethanolamine (DOPE).
[0337] In some embodiments, the ratio of PEG in the lipid
nanoparticle (LNP) formulations may be increased or decreased
and/or the carbon chain length of the PEG lipid may be modified
from C14 to C18 to alter the pharmacokinetics and/or
biodistribution of the LNP formulations. As a non-limiting example,
LNP formulations may contain from about 0.5% to about 3.0%, from
about 1.0% to about 3.5%, from about 1.5% to about 4.0%, from about
2.0% to about 4.5%, from about 2.5% to about 5.0% and/or from about
3.0% to about 6.0% of the lipid molar ratio of PEG-c-DOMG
(R-3-[(.omega.-methoxy-poly(ethyleneglycol)2000)carbamoyl)]-1,2-dimyristy-
loxypropyl-3-amine) (also referred to herein as PEG-DOMG) as
compared to the cationic lipid, DSPC and cholesterol. In some
embodiments, the PEG-c-DOMG may be replaced with a PEG lipid such
as, but not limited to, PEG-DSG (1,2-Distearoyl-sn-glycerol,
methoxypolyethylene glycol), PEG-DMG (1,2-Dimyristoyl-sn-glycerol)
and/or PEG-DPG (1,2-Dipalmitoyl-sn-glycerol, methoxypolyethylene
glycol). The cationic lipid may be selected from any lipid known in
the art such as, but not limited to, DLin-MC3-DMA, DLin-DMA,
C12-200 and DLin-KC2-DMA.
[0338] In some embodiments, the RNA (e.g., mRNA) vaccines may be
formulated in a lipid nanoparticle.
[0339] In some embodiments, the RNA (e.g., mRNA) vaccine
formulation comprising the polynucleotide is a nanoparticle which
may comprise at least one lipid. The lipid may be selected from,
but is not limited to, DLin-DMA, DLin-K-DMA, 98N12-5, C12-200,
DLin-MC3-DMA, DLin-KC2-DMA, DODMA, PLGA, PEG, PEG-DMG, PEGylated
lipids and amino alcohol lipids. In another aspect, the lipid may
be a cationic lipid such as, but not limited to, DLin-DMA,
DLin-D-DMA, DLin-MC3-DMA, DLin-KC2-DMA, DODMA and amino alcohol
lipids. The amino alcohol cationic lipid may be the lipids
described in and/or made by the methods described in U.S. Patent
Publication No. US20130150625, herein incorporated by reference in
its entirety. As a non-limiting example, the cationic lipid may be
2-amino-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-2-{[(9Z,2Z)-octadeca-9,12-
-dien-1-yloxy]methyl}propan-1-ol (Compound 1 in US20130150625);
2-amino-3-[(9Z)-octadec-9-en-1-yloxy]-2-{[(9Z)-octadec-9-en-1-yloxy]methy-
l}propan-1-ol (Compound 2 in US20130150625);
2-amino-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-2-[(octyloxy)methyl]propa-
n-1-ol (Compound 3 in US20130150625); and
2-(dimethylamino)-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-2-{[(9Z,12Z)-oc-
tadeca-9,12-dien-1-yloxy]methyl}propan-1-ol (Compound 4 in
US20130150625); or any pharmaceutically acceptable salt or
stereoisomer thereof.
[0340] Lipid nanoparticle formulations typically comprise a lipid,
in particular, an ionizable cationic lipid, for example,
2,2-dilinoleyl-4-dimethylaminoethyl[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), or
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), and
further comprise a neutral lipid, a sterol and a molecule capable
of reducing particle aggregation, for example a PEG or PEG-modified
lipid.
[0341] In some embodiments, the lipid nanoparticle formulation
consists essentially of (i) at least one lipid selected from the
group consisting of
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319); (ii) a
neutral lipid selected from DSPC, DPPC, POPC, DOPE and SM; (iii) a
sterol, e.g., cholesterol; and (iv) a PEG-lipid, e.g., PEG-DMG or
PEG-cDMA, in a molar ratio of about 20-60% cationic lipid: 5-25%
neutral lipid: 25-55% sterol; 0.5-15% PEG-lipid.
[0342] In some embodiments, the formulation includes from about 25%
to about 75% on a molar basis of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), e.g.,
from about 35 to about 65%, from about 45 to about 65%, about 60%,
about 57.5%, about 50% or about 40% on a molar basis.
[0343] In some embodiments, the formulation includes from about
0.5% to about 15% on a molar basis of the neutral lipid e.g., from
about 3 to about 12%, from about 5 to about 10% or about 15%, about
10%, or about 7.5% on a molar basis. Examples of neutral lipids
include, but are not limited to, DSPC, POPC, DPPC, DOPE and SM. In
some embodiments, the formulation includes from about 5% to about
50% on a molar basis of the sterol (e.g., about 15 to about 45%,
about 20 to about 40%, about 40%, about 38.5%, about 35%, or about
31% on a molar basis. An exemplary sterol is cholesterol. In some
embodiments, the formulation includes from about 0.5% to about 20%
on a molar basis of the PEG or PEG-modified lipid (e.g., about 0.5
to about 10%, about 0.5 to about 5%, about 1.5%, about 0.5%, about
1.5%, about 3.5%, or about 5% on a molar basis. In some
embodiments, the PEG or PEG modified lipid comprises a PEG molecule
of an average molecular weight of 2,000 Da. In other embodiments,
the PEG or PEG modified lipid comprises a PEG molecule of an
average molecular weight of less than 2,000, for example around
1,500 Da, around 1,000 Da, or around 500 Da. Examples of
PEG-modified lipids include, but are not limited to, PEG-distearoyl
glycerol (PEG-DMG) (also referred herein as PEG-C14 or C14-PEG),
PEG-cDMA (further discussed in Reyes et al. J. Controlled Release,
107, 276-287 (2005) the contents of which are herein incorporated
by reference in their entirety)
[0344] In some embodiments, the formulations of the present
disclosure include 25-75% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), 0.5-15%
of the neutral lipid, 5-50% of the sterol, and 0.5-20% of the PEG
or PEG-modified lipid on a molar basis.
[0345] In some embodiments, the formulations of the present
disclosure include 35-65% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), 3-12%
of the neutral lipid, 15-45% of the sterol, and 0.5-10% of the PEG
or PEG-modified lipid on a molar basis.
[0346] In some embodiments, the formulations of the present
disclosure include 45-65% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), 5-10%
of the neutral lipid, 25-40% of the sterol, and 0.5-10% of the PEG
or PEG-modified lipid on a molar basis.
[0347] In some embodiments, the formulations of the present
disclosure include about 60% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), about
7.5% of the neutral lipid, about 31% of the sterol, and about 1.5%
of the PEG or PEG-modified lipid on a molar basis.
[0348] In some embodiments, the formulations of the present
disclosure include about 50% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), about
10% of the neutral lipid, about 38.5% of the sterol, and about 1.5%
of the PEG or PEG-modified lipid on a molar basis.
[0349] In some embodiments, the formulations of the present
disclosure include about 50% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), about
10% of the neutral lipid, about 35% of the sterol, about 4.5% or
about 5% of the PEG or PEG-modified lipid, and about 0.5% of the
targeting lipid on a molar basis.
[0350] In some embodiments, the formulations of the present
disclosure include about 40% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), about
15% of the neutral lipid, about 40% of the sterol, and about 5% of
the PEG or PEG-modified lipid on a molar basis.
[0351] In some embodiments, the formulations of the present
disclosure include about 57.2% of a cationic lipid selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), about
7.1% of the neutral lipid, about 34.3% of the sterol, and about
1.4% of the PEG or PEG-modified lipid on a molar basis.
[0352] In some embodiments, the formulations of the present
disclosure include about 57.5% of a cationic lipid selected from
the PEG lipid is PEG-cDMA (PEG-cDMA is further discussed in Reyes
et al. (J. Controlled Release, 107, 276-287 (2005), the contents of
which are herein incorporated by reference in their entirety),
about 7.5% of the neutral lipid, about 31.5% of the sterol, and
about 3.5% of the PEG or PEG-modified lipid on a molar basis.
[0353] In some embodiments, lipid nanoparticle formulation consists
essentially of a lipid mixture in molar ratios of about 20-70%
cationic lipid: 5-45% neutral lipid: 20-55% cholesterol: 0.5-15%
PEG-modified lipid; more preferably in a molar ratio of about
20-60% cationic lipid: 5-25% neutral lipid: 25-55% cholesterol:
0.5-15% PEG-modified lipid.
[0354] In some embodiments, the molar lipid ratio is approximately
50/10/38.5/1.5 (mol % cationic lipid/neutral lipid, e.g.,
DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG, PEG-DSG or PEG-DPG),
57.2/7.1134.3/1.4 (mol % cationic lipid/neutral lipid, e.g.,
DPPC/Chol/PEG-modified lipid, e.g., PEG-cDMA), 40/15/40/5 (mol %
cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid,
e.g., PEG-DMG), 50/10/35/4.5/0.5 (mol % cationic lipid/neutral
lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DSG),
50/10/35/5 (cationic lipid/neutral lipid, e.g.,
DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG), 40/10/40/10 (mol %
cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid,
e.g., PEG-DMG or PEG-cDMA), 35/15/40/10 (mol % cationic
lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g.,
PEG-DMG or PEG-cDMA) or 52/13/30/5 (mol % cationic lipid/neutral
lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG or
PEG-cDMA).
[0355] Examples of lipid nanoparticle compositions and methods of
making same are described, for example, in Semple et al. (2010)
Nat. Biotechnol. 28:172-176; Jayarama et al. (2012), Angew. Chem.
Int. Ed., 51: 8529-8533; and Maier et al. (2013) Molecular Therapy
21, 1570-1578 (the contents of each of which are incorporated
herein by reference in their entirety).
[0356] In some embodiments, the lipid nanoparticle formulations
described herein may comprise a cationic lipid, a PEG lipid and a
structural lipid and optionally comprise a non-cationic lipid. As a
non-limiting example, the lipid nanoparticle may comprise about
40-60% of cationic lipid, about 5-15% of a non-cationic lipid,
about 1-2% of a PEG lipid and about 30-50% of a structural lipid.
As another non-limiting example, the lipid nanoparticle may
comprise about 50% cationic lipid, about 10% non-cationic lipid,
about 1.5% PEG lipid and about 38.5% structural lipid. As yet
another non-limiting example, the lipid nanoparticle may comprise
about 55% cationic lipid, about 10% non-cationic lipid, about 2.5%
PEG lipid and about 32.5% structural lipid. In some embodiments,
the cationic lipid may be any cationic lipid described herein such
as, but not limited to, DLin-KC2-DMA, DLin-MC3-DMA and L319.
[0357] In some embodiments, the lipid nanoparticle formulations
described herein may be 4 component lipid nanoparticles. The lipid
nanoparticle may comprise a cationic lipid, a non-cationic lipid, a
PEG lipid and a structural lipid. As a non-limiting example, the
lipid nanoparticle may comprise about 40-60% of cationic lipid,
about 5-15% of a non-cationic lipid, about 1-2% of a PEG lipid and
about 30-50% of a structural lipid. As another non-limiting
example, the lipid nanoparticle may comprise about 50% cationic
lipid, about 10% non-cationic lipid, about 1.5% PEG lipid and about
38.5% structural lipid. As yet another non-limiting example, the
lipid nanoparticle may comprise about 55% cationic lipid, about 10%
non-cationic lipid, about 2.5% PEG lipid and about 32.5% structural
lipid. In some embodiments, the cationic lipid may be any cationic
lipid described herein such as, but not limited to, DLin-KC2-DMA,
DLin-MC3-DMA and L319.
[0358] In some embodiments, the lipid nanoparticle formulations
described herein may comprise a cationic lipid, a non-cationic
lipid, a PEG lipid and a structural lipid. As a non-limiting
example, the lipid nanoparticle comprise about 50% of the cationic
lipid DLin-KC2-DMA, about 10% of the non-cationic lipid DSPC, about
1.5% of the PEG lipid PEG-DOMG and about 38.5% of the structural
lipid cholesterol. As a non-limiting example, the lipid
nanoparticle comprise about 50% of the cationic lipid DLin-MC3-DMA,
about 10% of the non-cationic lipid DSPC, about 1.5% of the PEG
lipid PEG-DOMG and about 38.5% of the structural lipid cholesterol.
As a non-limiting example, the lipid nanoparticle comprise about
50% of the cationic lipid DLin-MC3-DMA, about 10% of the
non-cationic lipid DSPC, about 1.5% of the PEG lipid PEG-DMG and
about 38.5% of the structural lipid cholesterol. As yet another
non-limiting example, the lipid nanoparticle comprise about 55% of
the cationic lipid L319, about 10% of the non-cationic lipid DSPC,
about 2.5% of the PEG lipid PEG-DMG and about 32.5% of the
structural lipid cholesterol.
[0359] As a non-limiting example, the cationic lipid may be
selected from (20Z,23Z)--N,N-dimethylnonacosa-20,23-dien-10-amine,
(17Z,20Z)--N,N-dimemylhexacosa-17,20-dien-9-amine,
(1Z,19Z)--N5N-dimethylpentacosa-16, 19-dien-8-amine,
(13Z,16Z)--N,N-dimethyldocosa-13,16-dien-5-amine,
(12Z,15Z)--N,N-dimethylhenicosa-12,15-dien-4-amine,
(14Z,17Z)--N,N-dimethyltricosa-14,17-dien-6-amine,
(15Z,18Z)--N,N-dimethyltetracosa-15,18-dien-7-amine,
(18Z,21Z)--N,N-dimethylheptacosa-18,21-dien-10-amine,
(15Z,18Z)--N,N-dimethyltetracosa-15,18-dien-5-amine,
(14Z,17Z)--N,N-dimethyltricosa-14,17-dien-4-amine,
(19Z,22Z)--N,N-dimeihyloctacosa-19,22-dien-9-amine, (18Z,21
Z)--N,N-dimethylheptacosa-18,21-dien-8-amine,
(17Z,20Z)--N,N-dimethylhexacosa-17,20-dien-7-amine,
(16Z,19Z)--N,N-dimethylpentacosa-16,19-dien-6-amine,
(22Z,25Z)--N,N-dimethylhentriaconta-22,25-dien-10-amine, (21
Z,24Z)--N,N-dimethyltriaconta-21,24-dien-9-amine,
(18Z)--N,N-dimetylheptacos-18-en-10-amine,
(17Z)--N,N-dimethylhexacos-17-en-9-amine,
(19Z,22Z)--N,N-dimethyloctacosa-19,22-dien-7-amine,
N,N-dimethylheptacosan-10-amine,
(20Z,23Z)--N-ethyl-N-methylnonacosa-20,23-dien-10-amine,
1-[(11Z,14Z)-1-nonylicosa-11,14-dien-1-yl]pyrrolidine,
(20Z)--N,N-dimethylheptacos-20-en-10-amine, (15Z)--N,N-dimethyl
eptacos-15-en-10-amine, (14Z)--N,N-dimethylnonacos-14-en-10-amine,
(17Z)--N,N-dimethylnonacos-17-en-10-amine,
(24Z)--N,N-dimethyltritriacont-24-en-10-amine,
(20Z)--N,N-dimethylnonacos-20-en-10-amine,
(22Z)--N,N-dimethylhentriacont-22-en-10-amine,
(16Z)--N,N-dimethylpentacos-16-en-8-amine,
(12Z,15Z)--N,N-dimethyl-2-nonylhenicosa-12,15-dien-1-amine,
(13Z,16Z)--N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine,
N,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]eptadecan-8-amine,
1-[(1S,2R)-2-hexylcyclopropyl]-N,N-dimethylnonadecan-10-amine,
N,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]nonadecan-10-amine,
N,N-dimethyl-21-[(1S,2R)-2-octylcyclopropyl]henicosan-10-amine,N,N-dimeth-
yl-1-[(1S,2S)-2-{[(1R,2R)-2-pentylcycIopropyl]methyl}cyclopropyl]nonadecan-
-10-amine,N,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]hexadecan-8-amine,
N,N-dimethyl-[(1R,2S)-2-undecyIcyclopropyl]tetradecan-5-amine,
N,N-dimethyl-3-{7-[(1S,2R)-2-octylcyclopropyl]heptyl}dodecan-1-amine,
1-[(1R,2S)-2-heptylcyclopropyl]-N,N-dimethyloctadecan-9-amine,
1-[(1S,2R)-2-decylcyclopropyl]-N,N-dimethylpentadecan-6-amine,
N,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]pentadecan-8-amine,
R--N,N-dimethyl-1-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-3-(octyloxy)propa-
n-2-amine,
S--N,N-dimethyl-1-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-3-(octy-
loxy)propan-2-amine,
1-{2-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-1-[(octyloxy)methyl]ethyl}pyrr-
olidine,
(2S)--N,N-dimethyl-1-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-3-[(S2-
)-oct-5-en-1-yloxy]propan-2-amine,
1-{2-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-1-[(octyloxy)methyl]ethyl}azet-
idine,
(2S)-1-(hexyloxy)-N,N-dimethyl-3-[(9Z,12Z)-octadeca-9,12-dien-1-ylo-
xy]propan-2-amine,
(2S)-1-(heptyloxy)-N,N-dimethyl-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]pr-
opan-2-amine,
N,N-dimethyl-1-(nonyloxy)-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]propan-2-
-amine,
N,N-dimethyl-1-[(9Z)-octadec-9-en-1-yloxy]-3-(octyloxy)propan-2-am-
ine;
(2S)--N,N-dimethyl-1-[(6Z,9Z,12Z)-octadeca-6,9,12-trien-1-yloxy]-3-(o-
ctyloxy)propan-2-amine,
(2S)-1-[(11Z,14Z)-icosa-11,14-dien-1-yloxy]-N,N-dimethyl-3-(pentyloxy)pro-
pan-2-amine,
(2S)-1-(hexyloxy)-3-[(11Z,14Z)-icosa-11,14-dien-1-yloxy]-N,N-dimethylprop-
an-2-amine,
1-[(11Z,14Z)-icosa-11,14-dien-1-yloxy]-N,N-dimethyl-3-(octyloxy)propan-2--
amine,
1-[(13Z,16Z)-docosa-13,16-dien-1-yloxy]-N,N-dimethyl-3-(octyloxy)pr-
opan-2-amine,
(2S)-1-[(13Z,16Z)-docosa-13,16-dien-1-yloxy]-3-(hexyloxy)-N,N-dimethylpro-
pan-2-amine,
(2S)-1-[(13Z)-docos-13-en-1-yloxy]-3-(hexyloxy)-N,N-dimethylpropan-2-amin-
e,
1-[(13Z)-docos-13-en-1-yloxy]-N,N-dimethyl-3-(octyloxy)propan-2-amine,
1-[(9Z)-hexadec-9-en-1-yloxy]-N,N-dimethyl-3-(octyloxy)propan-2-amine,
(2R)--N,N-dimethyl-H(1-metoyloctyl)oxy]-3-[(9Z,12Z)-octadeca-9,12-dien-1--
yloxy]propan-2-amine,
(2R)-1-[(3,7-dimethyloctyl)oxy]-N,N-dimethyl-3-[(9Z,12Z)-octadeca-9,12-di-
en-1-yloxy]propan-2-amine,
N,N-dimethyl-1-(octyloxy)-3-({8-[(1S,2S)-2-{[(1R,2R)-2-pentylcyclopropyl]-
methyl}cyclopropyl]octyl}oxy)propan-2-amine,
N,N-dimethyl-1-{[8-(2-oclylcyclopropyl)octyl]oxy}-3-(octyloxy)propan-2-am-
ine and (11E,20Z,23Z)--N,N-dimethylnonacosa-11,20,2-trien-10-amine
or a pharmaceutically acceptable salt or stereoisomer thereof.
[0360] In some embodiments, the LNP formulations of the RNA (e.g.,
mRNA) vaccines may contain PEG-c-DOMG at 3% lipid molar ratio. In
some embodiments, the LNP formulations of the RNA (e.g., mRNA)
vaccines may contain PEG-c-DOMG at 1.5% lipid molar ratio.
[0361] In some embodiments, the pharmaceutical compositions of the
RNA (e.g., mRNA) vaccines may include at least one of the PEGylated
lipids described in International Publication No. WO2012099755, the
contents of which are herein incorporated by reference in their
entirety.
[0362] In some embodiments, the LNP formulation may contain PEG-DMG
2000
(1,2-dimyristoyl-sn-glycero-3-phophoethanolamine-N-[methoxy(polyethylene
glycol)-2000). In some embodiments, the LNP formulation may contain
PEG-DMG 2000, a cationic lipid known in the art and at least one
other component. In some embodiments, the LNP formulation may
contain PEG-DMG 2000, a cationic lipid known in the art, DSPC and
cholesterol. As a non-limiting example, the LNP formulation may
contain PEG-DMG 2000, DLin-DMA, DSPC and cholesterol. As another
non-limiting example the LNP formulation may contain PEG-DMG 2000,
DLin-DMA, DSPC and cholesterol in a molar ratio of 2:40:10:48 (see
e.g., Geall et al., Nonviral delivery of self-amplifying RNA (e.g.,
mRNA) vaccines, PNAS 2012; PMID: 22908294, the contents of each of
which are herein incorporated by reference in their entirety).
[0363] The lipid nanoparticles described herein may be made in a
sterile environment.
[0364] In some embodiments, the LNP formulation may be formulated
in a nanoparticle such as a nucleic acid-lipid particle. As a
non-limiting example, the lipid particle may comprise one or more
active agents or therapeutic agents; one or more cationic lipids
comprising from about 50 mol % to about 85 mol % of the total lipid
present in the particle; one or more non-cationic lipids comprising
from about 13 mol % to about 49.5 mol % of the total lipid present
in the particle; and one or more conjugated lipids that inhibit
aggregation of particles comprising from about 0.5 mol % to about 2
mol % of the total lipid present in the particle.
[0365] The nanoparticle formulations may comprise a phosphate
conjugate. The phosphate conjugate may increase in vivo circulation
times and/or increase the targeted delivery of the nanoparticle. As
a non-limiting example, the phosphate conjugates may include a
compound of any one of the formulas described in International
Application No. WO2013033438, the contents of which are herein
incorporated by reference in its entirety.
[0366] The nanoparticle formulation may comprise a polymer
conjugate. The polymer conjugate may be a water soluble conjugate.
The polymer conjugate may have a structure as described in U.S.
Patent Application No. 20130059360, the contents of which are
herein incorporated by reference in its entirety. In some
embodiments, polymer conjugates with the polynucleotides of the
present disclosure may be made using the methods and/or segmented
polymeric reagents described in U.S. Patent Application No.
20130072709, the contents of which are herein incorporated by
reference in its entirety. In some embodiments, the polymer
conjugate may have pendant side groups comprising ring moieties
such as, but not limited to, the polymer conjugates described in
U.S. Patent Publication No. US20130196948, the contents which are
herein incorporated by reference in its entirety.
[0367] The nanoparticle formulations may comprise a conjugate to
enhance the delivery of nanoparticles of the present disclosure in
a subject. Further, the conjugate may inhibit phagocytic clearance
of the nanoparticles in a subject. In one aspect, the conjugate may
be a "self" peptide designed from the human membrane protein CD47
(e.g., the "self" particles described by Rodriguez et al. (Science
2013 339, 971-975), herein incorporated by reference in its
entirety). As shown by Rodriguez et al., the self peptides delayed
macrophage-mediated clearance of nanoparticles which enhanced
delivery of the nanoparticles. In another aspect, the conjugate may
be the membrane protein CD47 (e.g., see Rodriguez et al. Science
2013 339, 971-975, herein incorporated by reference in its
entirety). Rodriguez et al. showed that, similarly to "self"
peptides, CD47 can increase the circulating particle ratio in a
subject as compared to scrambled peptides and PEG coated
nanoparticles.
[0368] In some embodiments, the RNA (e.g., mRNA) vaccines of the
present disclosure are formulated in nanoparticles which comprise a
conjugate to enhance the delivery of the nanoparticles of the
present disclosure in a subject. The conjugate may be the CD47
membrane or the conjugate may be derived from the CD47 membrane
protein, such as the "self" peptide described previously. In some
embodiments, the nanoparticle may comprise PEG and a conjugate of
CD47 or a derivative thereof. In some embodiments, the nanoparticle
may comprise both the "self" peptide described above and the
membrane protein CD47.
[0369] In some embodiments, a "self" peptide and/or CD47 protein
may be conjugated to a virus-like particle or pseudovirion, as
described herein for delivery of the RNA (e.g., mRNA) vaccines of
the present disclosure.
[0370] In some embodiments, RNA (e.g., mRNA) vaccine pharmaceutical
compositions comprising the polynucleotides of the present
disclosure and a conjugate that may have a degradable linkage.
Non-limiting examples of conjugates include an aromatic moiety
comprising an ionizable hydrogen atom, a spacer moiety, and a
water-soluble polymer. As a non-limiting example, pharmaceutical
compositions comprising a conjugate with a degradable linkage and
methods for delivering such pharmaceutical compositions are
described in U.S. Patent Publication No. US20130184443, the
contents of which are herein incorporated by reference in their
entirety.
[0371] The nanoparticle formulations may be a carbohydrate
nanoparticle comprising a carbohydrate carrier and a RNA (e.g.,
mRNA) vaccine. As a non-limiting example, the carbohydrate carrier
may include, but is not limited to, an anhydride-modified
phytoglycogen or glycogen-type material, phtoglycogen octenyl
succinate, phytoglycogen beta-dextrin, anhydride-modified
phytoglycogen beta-dextrin. (See e.g., International Publication
No. WO2012109121; the contents of which are herein incorporated by
reference in their entirety).
[0372] Nanoparticle formulations of the present disclosure may be
coated with a surfactant or polymer in order to improve the
delivery of the particle. In some embodiments, the nanoparticle may
be coated with a hydrophilic coating such as, but not limited to,
PEG coatings and/or coatings that have a neutral surface charge.
The hydrophilic coatings may help to deliver nanoparticles with
larger payloads such as, but not limited to, RNA (e.g., mRNA)
vaccines within the central nervous system. As a non-limiting
example nanoparticles comprising a hydrophilic coating and methods
of making such nanoparticles are described in U.S. Patent
Publication No. US20130183244, the contents of which are herein
incorporated by reference in their entirety.
[0373] In some embodiments, the lipid nanoparticles of the present
disclosure may be hydrophilic polymer particles. Non-limiting
examples of hydrophilic polymer particles and methods of making
hydrophilic polymer particles are described in U.S. Patent
Publication No. US20130210991, the contents of which are herein
incorporated by reference in their entirety.
[0374] In some embodiments, the lipid nanoparticles of the present
disclosure may be hydrophobic polymer particles.
[0375] Lipid nanoparticle formulations may be improved by replacing
the cationic lipid with a biodegradable cationic lipid which is
known as a rapidly eliminated lipid nanoparticle (reLNP). Ionizable
cationic lipids, such as, but not limited to, DLinDMA,
DLin-KC2-DMA, and DLin-MC3-DMA, have been shown to accumulate in
plasma and tissues over time and may be a potential source of
toxicity. The rapid metabolism of the rapidly eliminated lipids can
improve the tolerability and therapeutic index of the lipid
nanoparticles by an order of magnitude from a 1 mg/kg dose to a 10
mg/kg dose in rat. Inclusion of an enzymatically degraded ester
linkage can improve the degradation and metabolism profile of the
cationic component, while still maintaining the activity of the
reLNP formulation. The ester linkage can be internally located
within the lipid chain or it may be terminally located at the
terminal end of the lipid chain. The internal ester linkage may
replace any carbon in the lipid chain.
[0376] In some embodiments, the internal ester linkage may be
located on either side of the saturated carbon.
[0377] In some embodiments, an immune response may be elicited by
delivering a lipid nanoparticle which may include a nanospecies, a
polymer and an immunogen. (U.S. Publication No. 20120189700 and
International Publication No. WO2012099805; each of which is herein
incorporated by reference in their entirety). The polymer may
encapsulate the nanospecies or partially encapsulate the
nanospecies. The immunogen may be a recombinant protein, a modified
RNA and/or a polynucleotide described herein. In some embodiments,
the lipid nanoparticle may be formulated for use in a vaccine such
as, but not limited to, against a pathogen.
[0378] Lipid nanoparticles may be engineered to alter the surface
properties of particles so the lipid nanoparticles may penetrate
the mucosal barrier. Mucus is located on mucosal tissue such as,
but not limited to, oral (e.g., the buccal and esophageal membranes
and tonsil tissue), ophthalmic, gastrointestinal (e.g., stomach,
small intestine, large intestine, colon, rectum), nasal,
respiratory (e.g., nasal, pharyngeal, tracheal and bronchial
membranes), genital (e.g., vaginal, cervical and urethral
membranes). Nanoparticles larger than 10-200 nm which are preferred
for higher drug encapsulation efficiency and the ability to provide
the sustained delivery of a wide array of drugs have been thought
to be too large to rapidly diffuse through mucosal barriers. Mucus
is continuously secreted, shed, discarded or digested and recycled
so most of the trapped particles may be removed from the mucosa
tissue within seconds or within a few hours. Large polymeric
nanoparticles (200 nm-500 nm in diameter) which have been coated
densely with a low molecular weight polyethylene glycol (PEG)
diffused through mucus only 4 to 6-fold lower than the same
particles diffusing in water (Lai et al. PNAS 2007 104:1482-487;
Lai et al. Adv Drug Deliv Rev. 2009 61: 158-171; each of which is
herein incorporated by reference in their entirety). The transport
of nanoparticles may be determined using rates of permeation and/or
fluorescent microscopy techniques including, but not limited to,
fluorescence recovery after photobleaching (FRAP) and high
resolution multiple particle tracking (MPT). As a non-limiting
example, compositions which can penetrate a mucosal barrier may be
made as described in U.S. Pat. No. 8,241,670 or International
Patent Publication No. WO2013110028, the contents of each of which
are herein incorporated by reference in its entirety.
[0379] The lipid nanoparticle engineered to penetrate mucus may
comprise a polymeric material (i.e. a polymeric core) and/or a
polymer-vitamin conjugate and/or a tri-block co-polymer. The
polymeric material may include, but is not limited to, polyamines,
polyethers, polyamides, polyesters, polycarbamates, polyureas,
polycarbonates, poly(styrenes), polyimides, polysulfones,
polyurethanes, polyacetylenes, polyethylenes, polyethyeneimines,
polyisocyanates, polyacrylates, polymethacrylates,
polyacrylonitriles, and polyarylates. The polymeric material may be
biodegradable and/or biocompatible. Non-limiting examples of
biocompatible polymers are described in International Patent
Publication No. WO2013116804, the contents of which are herein
incorporated by reference in their entirety. The polymeric material
may additionally be irradiated. As a non-limiting example, the
polymeric material may be gamma irradiated (see e.g., International
App. No. WO201282165, herein incorporated by reference in its
entirety). Non-limiting examples of specific polymers include
poly(caprolactone) (PCL), ethylene vinyl acetate polymer (EVA),
poly(lactic acid) (PLA), poly(L-lactic acid) (PLLA), poly(glycolic
acid) (PGA), poly(lactic acid-co-glycolic acid) (PLGA),
poly(L-lactic acid-co-glycolic acid) (PLLGA), poly(D,L-lactide)
(PDLA), poly(L-lactide) (PLLA), poly(D,L-lactide-co-caprolactone),
poly(D,L-lactide-co-caprolactone-co-glycolide),
poly(D,L-lactide-co-PEO-co-D,L-lactide),
poly(D,L-lactide-co-PPO-co-D,L-lactide), polyalkyl cyanoacralate,
polyurethane, poly-L-lysine (PLL), hydroxypropyl methacrylate
(HPMA), polyethyleneglycol, poly-L-glutamic acid, poly(hydroxy
acids), polyanhydrides, polyorthoesters, poly(ester amides),
polyamides, poly(ester ethers), polycarbonates, polyalkylenes such
as polyethylene and polypropylene, polyalkylene glycols such as
poly(ethylene glycol) (PEG), polyalkylene oxides (PEO),
polyalkylene terephthalates such as poly(ethylene terephthalate),
polyvinyl alcohols (PVA), polyvinyl ethers, polyvinyl esters such
as poly(vinyl acetate), polyvinyl halides such as poly(vinyl
chloride) (PVC), polyvinylpyrrolidone, polysiloxanes, polystyrene
(PS), polyurethanes, derivatized celluloses such as alkyl
celluloses, hydroxyalkyl celluloses, cellulose ethers, cellulose
esters, nitro celluloses, hydroxypropylcellulose,
carboxymethylcellulose, polymers of acrylic acids, such as
poly(methyl(meth)acrylate) (PMMA), poly(ethyl(meth)acrylate),
poly(butyl(meth)acrylate), poly(isobutyl(meth)acrylate),
poly(hexyl(meth)acrylate), poly(isodecyl(meth)acrylate),
poly(lauryl(meth)acrylate), poly(phenyl(meth)acrylate), poly(methyl
acrylate), poly(isopropyl acrylate), poly(isobutyl acrylate),
poly(octadecyl acrylate) and copolymers and mixtures thereof,
polydioxanone and its copolymers, polyhydroxyalkanoates,
polypropylene fumarate, polyoxymethylene, poloxamers,
poly(ortho)esters, poly(butyric acid), poly(valeric acid),
poly(lactide-co-caprolactone), PEG-PLGA-PEG and trimethylene
carbonate, polyvinylpyrrolidone. The lipid nanoparticle may be
coated or associated with a co-polymer such as, but not limited to,
a block co-polymer (such as a branched polyether-polyamide block
copolymer described in International Publication No. WO2013012476,
herein incorporated by reference in its entirety), and
(poly(ethylene glycol))-(poly(propylene oxide))-(poly(ethylene
glycol)) triblock copolymer (see e.g., U.S. Publication 20120121718
and U.S. Publication 20100003337 and U.S. Pat. No. 8,263,665, the
contents of each of which is herein incorporated by reference in
their entirety). The co-polymer may be a polymer that is generally
regarded as safe (GRAS) and the formation of the lipid nanoparticle
may be in such a way that no new chemical entities are created. For
example, the lipid nanoparticle may comprise poloxamers coating
PLGA nanoparticles without forming new chemical entities which are
still able to rapidly penetrate human mucus (Yang et al. Angew.
Chem. Int. Ed. 2011 50:2597-2600; the contents of which are herein
incorporated by reference in their entirety). A non-limiting
scalable method to produce nanoparticles which can penetrate human
mucus is described by Xu et al. (see, e.g., J Control Release 2013,
170:279-86; the contents of which are herein incorporated by
reference in their entirety).
[0380] The vitamin of the polymer-vitamin conjugate may be vitamin
E. The vitamin portion of the conjugate may be substituted with
other suitable components such as, but not limited to, vitamin A,
vitamin E, other vitamins, cholesterol, a hydrophobic moiety, or a
hydrophobic component of other surfactants (e.g., sterol chains,
fatty acids, hydrocarbon chains and alkylene oxide chains).
[0381] The lipid nanoparticle engineered to penetrate mucus may
include surface altering agents such as, but not limited to,
polynucleotides, anionic proteins (e.g., bovine serum albumin),
surfactants (e.g., cationic surfactants such as for example
dimethyldioctadecylammonium bromide), sugars or sugar derivatives
(e.g., cyclodextrin), nucleic acids, polymers (e.g., heparin,
polyethylene glycol and poloxamer), mucolytic agents (e.g.,
N-acetylcysteine, mugwort, bromelain, papain, clerodendrum,
acetylcysteine, bromhexine, carbocisteine, eprazinone, mesna,
ambroxol, sobrerol, domiodol, letosteine, stepronin, tiopronin,
gelsolin, thymosin .beta.4 dornase alfa, neltenexine, erdosteine)
and various DNases including rhDNase. The surface altering agent
may be embedded or enmeshed in the particle's surface or disposed
(e.g., by coating, adsorption, covalent linkage, or other process)
on the surface of the lipid nanoparticle. (see e.g., U.S.
Publication 20100215580 and U.S. Publication 20080166414 and
US20130164343; the contents of each of which are herein
incorporated by reference in their entirety).
[0382] In some embodiments, the mucus penetrating lipid
nanoparticles may comprise at least one polynucleotide described
herein. The polynucleotide may be encapsulated in the lipid
nanoparticle and/or disposed on the surface of the particle. The
polynucleotide may be covalently coupled to the lipid nanoparticle.
Formulations of mucus penetrating lipid nanoparticles may comprise
a plurality of nanoparticles. Further, the formulations may contain
particles which may interact with the mucus and alter the
structural and/or adhesive properties of the surrounding mucus to
decrease mucoadhesion, which may increase the delivery of the mucus
penetrating lipid nanoparticles to the mucosal tissue.
[0383] In some embodiments, the mucus penetrating lipid
nanoparticles may be a hypotonic formulation comprising a mucosal
penetration enhancing coating. The formulation may be hypotonic for
the epithelium to which it is being delivered. Non-limiting
examples of hypotonic formulations may be found in International
Patent Publication No. WO2013110028, the contents of which are
herein incorporated by reference in their entirety.
[0384] In some embodiments, in order to enhance the delivery
through the mucosal barrier the RNA (e.g., mRNA) vaccine
formulation may comprise or be a hypotonic solution. Hypotonic
solutions were found to increase the rate at which mucoinert
particles such as, but not limited to, mucus-penetrating particles,
were able to reach the vaginal epithelial surface (see e.g., Ensign
et al. Biomaterials 2013 34(28):6922-9, the contents of which are
herein incorporated by reference in their entirety).
[0385] In some embodiments, the RNA (e.g., mRNA) vaccine is
formulated as a lipoplex, such as, without limitation, the
ATUPLEX.TM. system, the DACC system, the DBTC system and other
siRNA-lipoplex technology from Silence Therapeutics (London, United
Kingdom), STEMFECT.TM. from STEMGENT.RTM. (Cambridge, Mass.), and
polyethylenimine (PEI) or protamine-based targeted and non-targeted
delivery of nucleic acids (Aleku et al. Cancer Res. 2008
68:9788-9798; Strumberg et al. Int J Clin Pharmacol Ther 2012
50:76-78; Santel et al., Gene Ther 2006 13:1222-1234; Santel et
al., Gene Ther 2006 13:1360-1370; Gutbier et al., Pulm Pharmacol.
Ther. 2010 23:334-344; Kaufmann et al. Microvasc Res 2010
80:286-293Weide et al. J Immunother. 2009 32:498-507; Weide et al.
J Immunother. 2008 31:180-188; Pascolo Expert Opin. Biol. Ther.
4:1285-1294; Fotin-Mleczek et al., 2011 J. Immunother. 34:1-15;
Song et al., Nature Biotechnol. 2005, 23:709-717; Peer et al., Proc
Natl Acad Sci USA. 2007 6; 104:4095-4100; deFougerolles Hum Gene
Ther. 2008 19:125-132, the contents of each of which are
incorporated herein by reference in their entirety).
[0386] In some embodiments, such formulations may also be
constructed or compositions altered such that they passively or
actively are directed to different cell types in vivo, including
but not limited to hepatocytes, immune cells, tumor cells,
endothelial cells, antigen presenting cells, and leukocytes (Akinc
et al. Mol Ther. 2010 18:1357-1364; Song et al., Nat Biotechnol.
2005 23:709-717; Judge et al., J Clin Invest. 2009 119:661-673;
Kaufmann et al., Microvasc Res 2010 80:286-293; Santel et al., Gene
Ther 2006 13:1222-1234; Santel et al., Gene Ther 2006 13:1360-1370;
Gutbier et al., Pulm Pharmacol. Ther. 2010 23:334-344; Basha et
al., Mol. Ther. 2011 19:2186-2200; Fenske and Cullis, Expert Opin
Drug Deliv. 2008 5:25-44; Peer et al., Science. 2008 319:627-630;
Peer and Lieberman, Gene Ther. 2011 18:1127-1133, the contents of
each of which are incorporated herein by reference in their
entirety). One example of passive targeting of formulations to
liver cells includes the DLin-DMA, DLin-KC2-DMA and
DLin-MC3-DMA-based lipid nanoparticle formulations, which have been
shown to bind to apolipoprotein E and promote binding and uptake of
these formulations into hepatocytes in vivo (Akinc et al. Mol Ther.
2010 18:1357-1364, the contents of which are incorporated herein by
reference in their entirety). Formulations can also be selectively
targeted through expression of different ligands on their surface
as exemplified by, but not limited by, folate, transferrin,
N-acetylgalactosamine (GalNAc), and antibody targeted approaches
(Kolhatkar et al., Curr Drug Discov Technol. 2011 8:197-206;
Musacchio and Torchilin, Front Biosci. 2011 16:1388-1412; Yu et
al., Mol Membr Biol. 2010 27:286-298; Patil et al., Crit Rev Ther
Drug Carrier Syst. 2008 25:1-61; Benoit et al., Biomacromolecules.
2011 12:2708-2714; Zhao et al., Expert Opin Drug Deliv. 2008
5:309-319; Akinc et al., Mol Ther. 2010 18:1357-1364; Srinivasan et
al., Methods Mol Biol. 2012 820:105-116; Ben-Arie et al., Methods
Mol Biol. 2012 757:497-507; Peer 2010 J Control Release. 20:63-68;
Peer et al., Proc Natl Acad Sci USA. 2007 104:4095-4100; Kim et
al., Methods Mol Biol. 2011 721:339-353; Subramanya et al., Mol
Ther. 2010 18:2028-2037; Song et al., Nat Biotechnol. 2005
23:709-717; Peer et al., Science. 2008 319:627-630; Peer and
Lieberman, Gene Ther. 2011 18:1127-1133, the contents of each of
which are incorporated herein by reference in their entirety).
[0387] In some embodiments, the RNA (e.g., mRNA) vaccine is
formulated as a solid lipid nanoparticle. A solid lipid
nanoparticle (SLN) may be spherical with an average diameter
between 10 to 1000 nm. SLN possess a solid lipid core matrix that
can solubilize lipophilic molecules and may be stabilized with
surfactants and/or emulsifiers. In some embodiments, the lipid
nanoparticle may be a self-assembly lipid-polymer nanoparticle (see
Zhang et al., ACS Nano, 2008, 2, pp 1696-1702; the contents of
which are herein incorporated by reference in their entirety). As a
non-limiting example, the SLN may be the SLN described in
International Patent Publication No. WO2013105101, the contents of
which are herein incorporated by reference in their entirety. As
another non-limiting example, the SLN may be made by the methods or
processes described in International Patent Publication No.
WO2013105101, the contents of which are herein incorporated by
reference in their entirety.
[0388] Liposomes, lipoplexes, or lipid nanoparticles may be used to
improve the efficacy of polynucleotides directed protein production
as these formulations may be able to increase cell transfection by
the RNA (e.g., mRNA) vaccine; and/or increase the translation of
encoded protein. One such example involves the use of lipid
encapsulation to enable the effective systemic delivery of polyplex
plasmid DNA (Heyes et al., Mol Ther. 2007 15:713-720; the contents
of which are incorporated herein by reference in their entirety).
The liposomes, lipoplexes, or lipid nanoparticles may also be used
to increase the stability of the polynucleotide.
[0389] In some embodiments, the RNA (e.g., mRNA) vaccines of the
present disclosure can be formulated for controlled release and/or
targeted delivery. As used herein, "controlled release" refers to a
pharmaceutical composition or compound release profile that
conforms to a particular pattern of release to effect a therapeutic
outcome. In some embodiments, the RNA (e.g., mRNA) vaccines may be
encapsulated into a delivery agent described herein and/or known in
the art for controlled release and/or targeted delivery. As used
herein, the term "encapsulate" means to enclose, surround or
encase. As it relates to the formulation of the compounds of the
disclosure, encapsulation may be substantial, complete or partial.
The term "substantially encapsulated" means that at least greater
than 50, 60, 70, 80, 85, 90, 95, 96, 97, 98, 99, 99.9, 99.9 or
greater than 99.999% of the pharmaceutical composition or compound
of the disclosure may be enclosed, surrounded or encased within the
delivery agent. "Partially encapsulation" means that less than 10,
10, 20, 30, 40 50 or less of the pharmaceutical composition or
compound of the disclosure may be enclosed, surrounded or encased
within the delivery agent. Advantageously, encapsulation may be
determined by measuring the escape or the activity of the
pharmaceutical composition or compound of the disclosure using
fluorescence and/or electron micrograph. For example, at least 1,
5, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 95, 96, 97, 98, 99,
99.9, 99.99 or greater than 99.99% of the pharmaceutical
composition or compound of the disclosure are encapsulated in the
delivery agent.
[0390] In some embodiments, the controlled release formulation may
include, but is not limited to, tri-block co-polymers. As a
non-limiting example, the formulation may include two different
types of tri-block co-polymers (International Pub. No. WO2012131104
and WO2012131106, the contents of each of which are incorporated
herein by reference in their entirety).
[0391] In some embodiments, the RNA (e.g., mRNA) vaccines may be
encapsulated into a lipid nanoparticle or a rapidly eliminated
lipid nanoparticle and the lipid nanoparticles or a rapidly
eliminated lipid nanoparticle may then be encapsulated into a
polymer, hydrogel and/or surgical sealant described herein and/or
known in the art. As a non-limiting example, the polymer, hydrogel
or surgical sealant may be PLGA, ethylene vinyl acetate (EVAc),
poloxamer, GELSITE.RTM. (Nanotherapeutics, Inc. Alachua, Fla.),
HYLENEX.RTM. (Halozyme Therapeutics, San Diego Calif.), surgical
sealants such as fibrinogen polymers (Ethicon Inc. Cornelia, Ga.),
TISSELL.RTM. (Baxter International, Inc Deerfield, Ill.), PEG-based
sealants, and COSEAL.RTM. (Baxter International, Inc Deerfield,
Ill.).
[0392] In some embodiments, the lipid nanoparticle may be
encapsulated into any polymer known in the art which may form a gel
when injected into a subject. As another non-limiting example, the
lipid nanoparticle may be encapsulated into a polymer matrix which
may be biodegradable.
[0393] In some embodiments, the RNA (e.g., mRNA) vaccine
formulation for controlled release and/or targeted delivery may
also include at least one controlled release coating. Controlled
release coatings include, but are not limited to, OPADRY.RTM.,
polyvinylpyrrolidone/vinyl acetate copolymer, polyvinylpyrrolidone,
hydroxypropyl methylcellulose, hydroxypropyl cellulose,
hydroxyethyl cellulose, EUDRAGIT RL.RTM., EUDRAGIT RS.RTM. and
cellulose derivatives such as ethylcellulose aqueous dispersions
(AQUACOAT.RTM. and SURELEASE.RTM.).
[0394] In some embodiments, the RNA (e.g., mRNA) vaccine controlled
release and/or targeted delivery formulation may comprise at least
one degradable polyester which may contain polycationic side
chains. Degradeable polyesters include, but are not limited to,
poly(serine ester), poly(L-lactide-co-L-lysine),
poly(4-hydroxy-L-proline ester), and combinations thereof. In some
embodiments, the degradable polyesters may include a PEG
conjugation to form a PEGylated polymer.
[0395] In some embodiments, the RNA (e.g., mRNA) vaccine controlled
release and/or targeted delivery formulation comprising at least
one polynucleotide may comprise at least one PEG and/or PEG related
polymer derivatives as described in U.S. Pat. No. 8,404,222, the
contents of which are incorporated herein by reference in their
entirety.
[0396] In some embodiments, the RNA (e.g., mRNA) vaccine controlled
release delivery formulation comprising at least one polynucleotide
may be the controlled release polymer system described in
US20130130348, the contents of which are incorporated herein by
reference in their entirety.
[0397] In some embodiments, the RNA (e.g., mRNA) vaccines of the
present disclosure may be encapsulated in a therapeutic
nanoparticle, referred to herein as "therapeutic nanoparticle RNA
(e.g., mRNA) vaccines." Therapeutic nanoparticles may be formulated
by methods described herein and known in the art such as, but not
limited to, International Pub Nos. WO2010005740, WO2010030763,
WO2010005721, WO2010005723, WO2012054923, U.S. Publication Nos.
US20110262491, US20100104645, US20100087337, US20100068285,
US20110274759, US20100068286, US20120288541, US20130123351 and
US20130230567 and U.S. Pat. Nos. 8,206,747, 8,293,276, 8,318,208
and 8,318,211; the contents of each of which are herein
incorporated by reference in their entirety. In some embodiments,
therapeutic polymer nanoparticles may be identified by the methods
described in US Pub No. US20120140790, the contents of which are
herein incorporated by reference in their entirety.
[0398] In some embodiments, the therapeutic nanoparticle RNA (e.g.,
mRNA) vaccine may be formulated for sustained release. As used
herein, "sustained release" refers to a pharmaceutical composition
or compound that conforms to a release rate over a specific period
of time. The period of time may include, but is not limited to,
hours, days, weeks, months and years. As a non-limiting example,
the sustained release nanoparticle may comprise a polymer and a
therapeutic agent such as, but not limited to, the polynucleotides
of the present disclosure (see International Pub No. 2010075072 and
US Pub No. US20100216804, US20110217377 and US20120201859, the
contents of each of which are incorporated herein by reference in
their entirety). In another non-limiting example, the sustained
release formulation may comprise agents which permit persistent
bioavailability such as, but not limited to, crystals,
macromolecular gels and/or particulate suspensions (see U.S. Patent
Publication No US20130150295, the contents of each of which are
incorporated herein by reference in their entirety).
[0399] In some embodiments, the therapeutic nanoparticle RNA (e.g.,
mRNA) vaccines may be formulated to be target specific. As a
non-limiting example, the therapeutic nanoparticles may include a
corticosteroid (see International Pub. No. WO2011084518, the
contents of which are incorporated herein by reference in their
entirety). As a non-limiting example, the therapeutic nanoparticles
may be formulated in nanoparticles described in International Pub
No. WO2008121949, WO2010005726, WO2010005725, WO2011084521 and US
Pub No. US20100069426, US20120004293 and US20100104655, the
contents of each of which are incorporated herein by reference in
their entirety.
[0400] In some embodiments, the nanoparticles of the present
disclosure may comprise a polymeric matrix. As a non-limiting
example, the nanoparticle may comprise two or more polymers such
as, but not limited to, polyethylenes, polycarbonates,
polyanhydrides, polyhydroxyacids, polypropylfumerates,
polycaprolactones, polyamides, polyacetals, polyethers, polyesters,
poly(orthoesters), polycyanoacrylates, polyvinyl alcohols,
polyurethanes, polyphosphazenes, polyacrylates, polymethacrylates,
polycyanoacrylates, polyureas, polystyrenes, polyamines,
polylysine, poly(ethylene imine), poly(serine ester),
poly(L-lactide-co-L-lysine), poly(4-hydroxy-L-proline ester) or
combinations thereof.
[0401] In some embodiments, the therapeutic nanoparticle comprises
a diblock copolymer. In some embodiments, the diblock copolymer may
include PEG in combination with a polymer such as, but not limited
to, polyethylenes, polycarbonates, polyanhydrides,
polyhydroxyacids, polypropylfumerates, polycaprolactones,
polyamides, polyacetals, polyethers, polyesters, poly(orthoesters),
polycyanoacrylates, polyvinyl alcohols, polyurethanes,
polyphosphazenes, polyacrylates, polymethacrylates,
polycyanoacrylates, polyureas, polystyrenes, polyamines,
polylysine, poly(ethylene imine), poly(serine ester),
poly(L-lactide-co-L-lysine), poly(4-hydroxy-L-proline ester) or
combinations thereof. In yet another embodiment, the diblock
copolymer may be a high-X diblock copolymer such as those described
in International Patent Publication No. WO2013120052, the contents
of which are incorporated herein by reference in their
entirety.
[0402] As a non-limiting example the therapeutic nanoparticle
comprises a PLGA-PEG block copolymer (see U.S. Publication No.
US20120004293 and U.S. Pat. No. 8,236,330, each of which is herein
incorporated by reference in their entirety). In another
non-limiting example, the therapeutic nanoparticle is a stealth
nanoparticle comprising a diblock copolymer of PEG and PLA or PEG
and PLGA (see U.S. Pat. No. 8,246,968 and International Publication
No. WO2012166923, the contents of each of which are herein
incorporated by reference in their entirety). In yet another
non-limiting example, the therapeutic nanoparticle is a stealth
nanoparticle or a target-specific stealth nanoparticle as described
in U.S. Patent Publication No. US20130172406, the contents of which
are herein incorporated by reference in their entirety.
[0403] In some embodiments, the therapeutic nanoparticle may
comprise a multiblock copolymer (see e.g., U.S. Pat. Nos. 8,263,665
and 8,287,910 and U.S. Patent Pub. No. US20130195987, the contents
of each of which are herein incorporated by reference in their
entirety).
[0404] In yet another non-limiting example, the lipid nanoparticle
comprises the block copolymer PEG-PLGA-PEG (see e.g., the
thermosensitive hydrogel (PEG-PLGA-PEG) was used as a TGF-beta1
gene delivery vehicle in Lee et al. Thermosensitive Hydrogel as a
TGF-.beta.1 Gene Delivery Vehicle Enhances Diabetic Wound Healing.
Pharmaceutical Research, 2003 20(12): 1995-2000; as a controlled
gene delivery system in Li et al. Controlled Gene Delivery System
Based on Thermosensitive Biodegradable Hydrogel. Pharmaceutical
Research 2003 20:884-888; and Chang et al., Non-ionic amphiphilic
biodegradable PEG-PLGA-PEG copolymer enhances gene delivery
efficiency in rat skeletal muscle. J Controlled Release. 2007
118:245-253, the contents of each of which are herein incorporated
by reference in their entirety). The RNA (e.g., mRNA) vaccines of
the present disclosure may be formulated in lipid nanoparticles
comprising the PEG-PLGA-PEG block copolymer.
[0405] In some embodiments, the therapeutic nanoparticle may
comprise a multiblock copolymer (see e.g., U.S. Pat. Nos. 8,263,665
and 8,287,910 and U.S. Patent Pub. No. US20130195987, the contents
of each of which are herein incorporated by reference in their
entirety).
[0406] In some embodiments, the block copolymers described herein
may be included in a polyion complex comprising a non-polymeric
micelle and the block copolymer. (see e.g., U.S. Publication No.
20120076836, the contents of which are herein incorporated by
reference in their entirety).
[0407] In some embodiments, the therapeutic nanoparticle may
comprise at least one acrylic polymer. Acrylic polymers include but
are not limited to, acrylic acid, methacrylic acid, acrylic acid
and methacrylic acid copolymers, methyl methacrylate copolymers,
ethoxyethyl methacrylates, cyanoethyl methacrylate, amino alkyl
methacrylate copolymer, poly(acrylic acid), poly(methacrylic acid),
polycyanoacrylates and combinations thereof.
[0408] In some embodiments, the therapeutic nanoparticles may
comprise at least one poly(vinyl ester) polymer. The poly(vinyl
ester) polymer may be a copolymer such as a random copolymer. As a
non-limiting example, the random copolymer may have a structure
such as those described in International Application No.
WO2013032829 or U.S. Patent Publication No US20130121954, the
contents of each of which are herein incorporated by reference in
their entirety. In some embodiments, the poly(vinyl ester) polymers
may be conjugated to the polynucleotides described herein.
[0409] In some embodiments, the therapeutic nanoparticle may
comprise at least one diblock copolymer. The diblock copolymer may
be, but it not limited to, a poly(lactic) acid-poly(ethylene)glycol
copolymer (see, e.g., International Patent Publication No.
WO2013044219, the contents of which are herein incorporated by
reference in their entirety). As a non-limiting example, the
therapeutic nanoparticle may be used to treat cancer (see
International publication No. WO2013044219, the contents of which
are herein incorporated by reference in their entirety).
[0410] In some embodiments, the therapeutic nanoparticles may
comprise at least one cationic polymer described herein and/or
known in the art.
[0411] In some embodiments, the therapeutic nanoparticles may
comprise at least one amine-containing polymer such as, but not
limited to polylysine, polyethylene imine, poly(amidoamine)
dendrimers, poly(beta-amino esters) (see, e.g., U.S. Pat. No.
8,287,849, the contents of which are herein incorporated by
reference in their entirety) and combinations thereof.
[0412] In some embodiments, the nanoparticles described herein may
comprise an amine cationic lipid such as those described in
International Patent Application No. WO2013059496, the contents of
which are herein incorporated by reference in their entirety. In
some embodiments, the cationic lipids may have an amino-amine or an
amino-amide moiety.
[0413] In some embodiments, the therapeutic nanoparticles may
comprise at least one degradable polyester which may contain
polycationic side chains. Degradeable polyesters include, but are
not limited to, poly(serine ester), poly(L-lactide-co-L-lysine),
poly(4-hydroxy-L-proline ester), and combinations thereof. In some
embodiments, the degradable polyesters may include a PEG
conjugation to form a PEGylated polymer.
[0414] In some embodiments, the synthetic nanocarriers may contain
an immunostimulatory agent to enhance the immune response from
delivery of the synthetic nanocarrier. As a non-limiting example,
the synthetic nanocarrier may comprise a Th1 immunostimulatory
agent, which may enhance a Th1-based response of the immune system
(see International Pub No. WO2010123569 and U.S. Publication No.
US20110223201, the contents of each of which are herein
incorporated by reference in their entirety).
[0415] In some embodiments, the synthetic nanocarriers may be
formulated for targeted release. In some embodiments, the synthetic
nanocarrier is formulated to release the polynucleotides at a
specified pH and/or after a desired time interval. As a
non-limiting example, the synthetic nanoparticle may be formulated
to release the RNA (e.g., mRNA) vaccines after 24 hours and/or at a
pH of 4.5 (see International Publication Nos. WO2010138193 and
WO2010138194 and US Pub Nos. US20110020388 and US20110027217, each
of which is herein incorporated by reference in their
entireties).
[0416] In some embodiments, the synthetic nanocarriers may be
formulated for controlled and/or sustained release of the
polynucleotides described herein. As a non-limiting example, the
synthetic nanocarriers for sustained release may be formulated by
methods known in the art, described herein and/or as described in
International Pub No. WO2010138192 and US Pub No. 20100303850, each
of which is herein incorporated by reference in their entirety.
[0417] In some embodiments, the RNA (e.g., mRNA) vaccine may be
formulated for controlled and/or sustained release wherein the
formulation comprises at least one polymer that is a crystalline
side chain (CYSC) polymer. CYSC polymers are described in U.S. Pat.
No. 8,399,007, herein incorporated by reference in its
entirety.
[0418] In some embodiments, the synthetic nanocarrier may be
formulated for use as a vaccine. In some embodiments, the synthetic
nanocarrier may encapsulate at least one polynucleotide which
encode at least one antigen. As a non-limiting example, the
synthetic nanocarrier may include at least one antigen and an
excipient for a vaccine dosage form (see International Publication
No. WO2011150264 and U.S. Publication No. US20110293723, the
contents of each of which are herein incorporated by reference in
their entirety). As another non-limiting example, a vaccine dosage
form may include at least two synthetic nanocarriers with the same
or different antigens and an excipient (see International
Publication No. WO2011150249 and U.S. Publication No.
US20110293701, the contents of each of which are herein
incorporated by reference in their entirety). The vaccine dosage
form may be selected by methods described herein, known in the art
and/or described in International Publication No. WO2011150258 and
U.S. Publication No. US20120027806, the contents of each of which
are herein incorporated by reference in their entirety).
[0419] In some embodiments, the synthetic nanocarrier may comprise
at least one polynucleotide which encodes at least one adjuvant. As
non-limiting example, the adjuvant may comprise
dimethyldioctadecylammonium-bromide,
dimethyldioctadecylammonium-chloride,
dimethyldioctadecylammonium-phosphate or
dimethyldioctadecylammonium-acetate (DDA) and an apolar fraction or
part of said apolar fraction of a total lipid extract of a
mycobacterium (see, e.g., U.S. Pat. No. 8,241,610, the content of
which is herein incorporated by reference in its entirety). In some
embodiments, the synthetic nanocarrier may comprise at least one
polynucleotide and an adjuvant. As a non-limiting example, the
synthetic nanocarrier comprising and adjuvant may be formulated by
the methods described in International Publication No. WO2011150240
and U.S. Publication No. US20110293700, the contents of each of
which are herein incorporated by reference in their entirety.
[0420] In some embodiments, the synthetic nanocarrier may
encapsulate at least one polynucleotide that encodes a peptide,
fragment or region from a virus. As a non-limiting example, the
synthetic nanocarrier may include, but is not limited to, any of
the nanocarriers described in International Publication No.
WO2012024621, WO201202629, WO2012024632 and U.S. Publication No.
US20120064110, US20120058153 and US20120058154, the contents of
each of which are herein incorporated by reference in their
entirety.
[0421] In some embodiments, the synthetic nanocarrier may be
coupled to a polynucleotide which may be able to trigger a humoral
and/or cytotoxic T lymphocyte (CTL) response (see, e.g.,
International Publication No. WO2013019669, the contents of which
are herein incorporated by reference in their entirety).
[0422] In some embodiments, the RNA (e.g., mRNA) vaccine may be
encapsulated in, linked to and/or associated with zwitterionic
lipids. Non-limiting examples of zwitterionic lipids and methods of
using zwitterionic lipids are described in U.S. Patent Publication
No. US20130216607, the contents of which are herein incorporated by
reference in their entirety. In some aspects, the zwitterionic
lipids may be used in the liposomes and lipid nanoparticles
described herein.
[0423] In some embodiments, the RNA (e.g., mRNA) vaccine may be
formulated in colloid nanocarriers as described in U.S. Patent
Publication No. US20130197100, the contents of which are herein
incorporated by reference in their entirety.
[0424] In some embodiments, the nanoparticle may be optimized for
oral administration. The nanoparticle may comprise at least one
cationic biopolymer such as, but not limited to, chitosan or a
derivative thereof. As a non-limiting example, the nanoparticle may
be formulated by the methods described in U.S. Publication No.
20120282343, the contents of which are herein incorporated by
reference in their entirety.
[0425] In some embodiments, LNPs comprise the lipid KL52 (an
amino-lipid disclosed in U.S. Application Publication No.
2012/0295832, the contents of which are herein incorporated by
reference in their entirety. Activity and/or safety (as measured by
examining one or more of ALT/AST, white blood cell count and
cytokine induction, for example) of LNP administration may be
improved by incorporation of such lipids. LNPs comprising
[0426] KL52 may be administered intravenously and/or in one or more
doses. In some embodiments, administration of LNPs comprising KL52
results in equal or improved mRNA and/or protein expression as
compared to LNPs comprising MC3.
[0427] In some embodiments, RNA (e.g., mRNA) vaccine may be
delivered using smaller LNPs. Such particles may comprise a
diameter from below 0.1 um up to 100 nm such as, but not limited
to, less than 0.1 um, less than 1.0 um, less than 5 um, less than
10 um, less than 15 um, less than 20 um, less than 25 um, less than
30 um, less than 35 um, less than 40 um, less than 50 um, less than
55 um, less than 60 um, less than 65 um, less than 70 um, less than
75 um, less than 80 um, less than 85 um, less than 90 um, less than
95 um, less than 100 um, less than 125 um, less than 150 um, less
than 175 um, less than 200 um, less than 225 um, less than 250 um,
less than 275 um, less than 300 um, less than 325 um, less than 350
um, less than 375 um, less than 400 um, less than 425 um, less than
450 um, less than 475 um, less than 500 um, less than 525 um, less
than 550 um, less than 575 um, less than 600 um, less than 625 um,
less than 650 um, less than 675 um, less than 700 um, less than 725
um, less than 750 um, less than 775 um, less than 800 um, less than
825 um, less than 850 um, less than 875 um, less than 900 um, less
than 925 um, less than 950 um, less than 975 um, or less than 1000
um.
[0428] In some embodiments, RNA (e.g., mRNA) vaccines may be
delivered using smaller LNPs, which may comprise a diameter from
about 1 nm to about 100 nm, from about 1 nm to about 10 nm, about 1
nm to about 20 nm, from about 1 nm to about 30 nm, from about 1 nm
to about 40 nm, from about 1 nm to about 50 nm, from about 1 nm to
about 60 nm, from about 1 nm to about 70 nm, from about 1 nm to
about 80 nm, from about 1 nm to about 90 nm, from about 5 nm to
about from 100 nm, from about 5 nm to about 10 nm, about 5 nm to
about 20 nm, from about 5 nm to about 30 nm, from about 5 nm to
about 40 nm, from about 5 nm to about 50 nm, from about 5 nm to
about 60 nm, from about 5 nm to about 70 nm, from about 5 nm to
about 80 nm, from about 5 nm to about 90 nm, about 10 to about 50
nm, from about 20 to about 50 nm, from about 30 to about 50 nm,
from about 40 to about 50 nm, from about 20 to about 60 nm, from
about 30 to about 60 nm, from about 40 to about 60 nm, from about
20 to about 70 nm, from about 30 to about 70 nm, from about 40 to
about 70 nm, from about 50 to about 70 nm, from about 60 to about
70 nm, from about 20 to about 80 nm, from about 30 to about 80 nm,
from about 40 to about 80 nm, from about 50 to about 80 nm, from
about 60 to about 80 nm, from about 20 to about 90 nm, from about
30 to about 90 nm, from about 40 to about 90 nm, from about 50 to
about 90 nm, from about 60 to about 90 nm and/or from about 70 to
about 90 nm.
[0429] In some embodiments, such LNPs are synthesized using methods
comprising microfluidic mixers. Examples of microfluidic mixers may
include, but are not limited to, a slit interdigital micromixer
including, but not limited to those manufactured by Microinnova
(Allerheiligen bei Wildon, Austria) and/or a staggered herringbone
micromixer (SHM) (Zhigaltsev, I. V. et al., Bottom-up design and
synthesis of limit size lipid nanoparticle systems with aqueous and
triglyceride cores using millisecond microfluidic mixing have been
published (Langmuir. 2012. 28:3633-40; Belliveau, N. M. et al.,
Microfluidic synthesis of highly potent limit-size lipid
nanoparticles for in vivo delivery of siRNA. Molecular
Therapy-Nucleic Acids. 2012. 1:e37; Chen, D. et al., Rapid
discovery of potent siRNA-containing lipid nanoparticles enabled by
controlled microfluidic formulation. J Am Chem Soc. 2012.
134(16):6948-51, the contents of each of which are herein
incorporated by reference in their entirety). In some embodiments,
methods of LNP generation comprising SHM, further comprise the
mixing of at least two input streams wherein mixing occurs by
microstructure-induced chaotic advection (MICA). According to this
method, fluid streams flow through channels present in a
herringbone pattern causing rotational flow and folding the fluids
around each other. This method may also comprise a surface for
fluid mixing wherein the surface changes orientations during fluid
cycling. Methods of generating LNPs using SHM include those
disclosed in U.S. Application Publication Nos. 2004/0262223 and
2012/0276209, the contents of each of which are herein incorporated
by reference in their entirety.
[0430] In some embodiments, the RNA (e.g., mRNA) vaccine of the
present disclosure may be formulated in lipid nanoparticles created
using a micromixer such as, but not limited to, a Slit Interdigital
Microstructured Mixer (SIMM-V2) or a Standard Slit Interdigital
Micro Mixer (SSIMM) or Caterpillar (CPMM) or Impinging-jet (IJMM)
from the Institut fur Mikrotechnik Mainz GmbH, Mainz Germany).
[0431] In some embodiments, the RNA (e.g., mRNA) vaccines of the
present disclosure may be formulated in lipid nanoparticles created
using microfluidic technology (see, e.g., Whitesides, George M. The
Origins and the Future of Microfluidics. Nature, 2006 442: 368-373;
and Abraham et al. Chaotic Mixer for Microchannels. Science, 2002
295: 647-651; each of which is herein incorporated by reference in
its entirety). As a non-limiting example, controlled microfluidic
formulation includes a passive method for mixing streams of steady
pressure-driven flows in micro channels at a low Reynolds number
(see, e.g., Abraham et al. Chaotic Mixer for Microchannels.
Science, 2002 295: 647-651, the contents of which are herein
incorporated by reference in their entirety).
[0432] In some embodiments, the RNA (e.g., mRNA) vaccines of the
present disclosure may be formulated in lipid nanoparticles created
using a micromixer chip such as, but not limited to, those from
Harvard Apparatus (Holliston, Mass.) or Dolomite Microfluidics
(Royston, UK). A micromixer chip can be used for rapid mixing of
two or more fluid streams with a split and recombine mechanism.
[0433] In some embodiments, the RNA (e.g., mRNA) vaccines of the
disclosure may be formulated for delivery using the drug
encapsulating microspheres described in International Patent
Publication No. WO2013063468 or U.S. Pat. No. 8,440,614, the
contents of each of which are herein incorporated by reference in
their entirety. The microspheres may comprise a compound of the
formula (I), (II), (III), (IV), (V) or (VI) as described in
International Patent Publication No. WO2013063468, the contents of
which are herein incorporated by reference in their entirety. In
some embodiments, the amino acid, peptide, polypeptide, lipids
(APPL) are useful in delivering the RNA (e.g., mRNA) vaccines of
the disclosure to cells (see International Patent Publication No.
WO2013063468, the contents of which are herein incorporated by
reference in their entirety).
[0434] In some embodiments, the RNA (e.g., mRNA) vaccines of the
disclosure may be formulated in lipid nanoparticles having a
diameter from about 10 to about 100 nm such as, but not limited to,
about 10 to about 20 nm, about 10 to about 30 nm, about 10 to about
40 nm, about 10 to about 50 nm, about 10 to about 60 nm, about 10
to about 70 nm, about 10 to about 80 nm, about 10 to about 90 nm,
about 20 to about 30 nm, about 20 to about 40 nm, about 20 to about
50 nm, about 20 to about 60 nm, about 20 to about 70 nm, about 20
to about 80 nm, about 20 to about 90 nm, about 20 to about 100 nm,
about 30 to about 40 nm, about 30 to about 50 nm, about 30 to about
60 nm, about 30 to about 70 nm, about 30 to about 80 nm, about 30
to about 90 nm, about 30 to about 100 nm, about 40 to about 50 nm,
about 40 to about 60 nm, about 40 to about 70 nm, about 40 to about
80 nm, about 40 to about 90 nm, about 40 to about 100 nm, about 50
to about 60 nm, about 50 to about 70 nm about 50 to about 80 nm,
about 50 to about 90 nm, about 50 to about 100 nm, about 60 to
about 70 nm, about 60 to about 80 nm, about 60 to about 90 nm,
about 60 to about 100 nm, about 70 to about 80 nm, about 70 to
about 90 nm, about 70 to about 100 nm, about 80 to about 90 nm,
about 80 to about 100 nm and/or about 90 to about 100 nm.
[0435] In some embodiments, the lipid nanoparticles may have a
diameter from about 10 to 500 nm.
[0436] In some embodiments, the lipid nanoparticle may have a
diameter greater than 100 nm, greater than 150 nm, greater than 200
nm, greater than 250 nm, greater than 300 nm, greater than 350 nm,
greater than 400 nm, greater than 450 nm, greater than 500 nm,
greater than 550 nm, greater than 600 nm, greater than 650 nm,
greater than 700 nm, greater than 750 nm, greater than 800 nm,
greater than 850 nm, greater than 900 nm, greater than 950 nm or
greater than 1000 nm.
[0437] In some embodiments, the lipid nanoparticle may be a limit
size lipid nanoparticle described in International Patent
Publication No. WO2013059922, the contents of which are herein
incorporated by reference in their entirety. The limit size lipid
nanoparticle may comprise a lipid bilayer surrounding an aqueous
core or a hydrophobic core; where the lipid bilayer may comprise a
phospholipid such as, but not limited to,
diacylphosphatidylcholine, a diacylphosphatidylethanolamine, a
ceramide, a sphingomyelin, a dihydrosphingomyelin, a cephalin, a
cerebroside, a C8-C20 fatty acid diacylphophatidylcholine, and
1-palmitoyl-2-oleoyl phosphatidylcholine (POPC). In some
embodiments, the limit size lipid nanoparticle may comprise a
polyethylene glycol-lipid such as, but not limited to, DLPE-PEG,
DMPE-PEG, DPPC-PEG and DSPE-PEG.
[0438] In some embodiments, the RNA (e.g., mRNA) vaccines may be
delivered, localized and/or concentrated in a specific location
using the delivery methods described in International Patent
Publication No. WO2013063530, the contents of which are herein
incorporated by reference in their entirety. As a non-limiting
example, a subject may be administered an empty polymeric particle
prior to, simultaneously with or after delivering the RNA (e.g.,
mRNA) vaccines to the subject. The empty polymeric particle
undergoes a change in volume once in contact with the subject and
becomes lodged, embedded, immobilized or entrapped at a specific
location in the subject.
[0439] In some embodiments, the RNA (e.g., mRNA) vaccines may be
formulated in an active substance release system (see, e.g., U.S.
Patent Publication No. US20130102545, the contents of which are
herein incorporated by reference in their entirety). The active
substance release system may comprise 1) at least one nanoparticle
bonded to an oligonucleotide inhibitor strand which is hybridized
with a catalytically active nucleic acid and 2) a compound bonded
to at least one substrate molecule bonded to a therapeutically
active substance (e.g., polynucleotides described herein), where
the therapeutically active substance is released by the cleavage of
the substrate molecule by the catalytically active nucleic
acid.
[0440] In some embodiments, the RNA (e.g., mRNA) vaccines may be
formulated in a nanoparticle comprising an inner core comprising a
non-cellular material and an outer surface comprising a cellular
membrane. The cellular membrane may be derived from a cell or a
membrane derived from a virus. As a non-limiting example, the
nanoparticle may be made by the methods described in International
Patent Publication No. WO2013052167, the contents of which are
herein incorporated by reference in their entirety. As another
non-limiting example, the nanoparticle described in International
Patent Publication No. WO2013052167, the contents of which are
herein incorporated by reference in their entirety, may be used to
deliver the RNA (e.g., mRNA) vaccines described herein.
[0441] In some embodiments, the RNA (e.g., mRNA) vaccines may be
formulated in porous nanoparticle-supported lipid bilayers
(protocells). Protocells are described in International Patent
Publication No. WO2013056132, the contents of which are herein
incorporated by reference in their entirety.
[0442] In some embodiments, the RNA (e.g., mRNA) vaccines described
herein may be formulated in polymeric nanoparticles as described in
or made by the methods described in U.S. Pat. Nos. 8,420,123 and
8,518,963 and European Patent No. EP2073848B1, the contents of each
of which are herein incorporated by reference in their entirety. As
a non-limiting example, the polymeric nanoparticle may have a high
glass transition temperature such as the nanoparticles described in
or nanoparticles made by the methods described in U.S. Pat. No.
8,518,963, the contents of which are herein incorporated by
reference in their entirety. As another non-limiting example, the
polymer nanoparticle for oral and parenteral formulations may be
made by the methods described in European Patent No. EP2073848B1,
the contents of which are herein incorporated by reference in their
entirety.
[0443] In some embodiments, the RNA (e.g., mRNA) vaccines described
herein may be formulated in nanoparticles used in imaging. The
nanoparticles may be liposome nanoparticles such as those described
in U.S. Patent Publication No US20130129636, herein incorporated by
reference in its entirety. As a non-limiting example, the liposome
may comprise
gadolinium(III)2-{4,7-bis-carboxymethyl-10-[(N,N-distearylamidomethyl-N'--
amido-methyl]-1,4,7,10-tetra-azacyclododec-1-yl}-acetic acid and a
neutral, fully saturated phospholipid component (see, e.g., U.S.
Patent Publication No US20130129636, the contents of which are
herein incorporated by reference in their entirety).
[0444] In some embodiments, the nanoparticles which may be used in
the present disclosure are formed by the methods described in U.S.
Patent Application No. US20130130348, the contents of which are
herein incorporated by reference in their entirety.
[0445] The nanoparticles of the present disclosure may further
include nutrients such as, but not limited to, those which
deficiencies can lead to health hazards from anemia to neural tube
defects (see, e.g., the nanoparticles described in International
Patent Publication No WO2013072929, the contents of which are
herein incorporated by reference in their entirety). As a
non-limiting example, the nutrient may be iron in the form of
ferrous, ferric salts or elemental iron, iodine, folic acid,
vitamins or micronutrients.
[0446] In some embodiments, the RNA (e.g., mRNA) vaccines of the
present disclosure may be formulated in a swellable nanoparticle.
The swellable nanoparticle may be, but is not limited to, those
described in U.S. Pat. No. 8,440,231, the contents of which are
herein incorporated by reference in their entirety. As a
non-limiting embodiment, the swellable nanoparticle may be used for
delivery of the RNA (e.g., mRNA) vaccines of the present disclosure
to the pulmonary system (see, e.g., U.S. Pat. No. 8,440,231, the
contents of which are herein incorporated by reference in their
entirety).
[0447] The RNA (e.g., mRNA) vaccines of the present disclosure may
be formulated in polyanhydride nanoparticles such as, but not
limited to, those described in U.S. Pat. No. 8,449,916, the
contents of which are herein incorporated by reference in their
entirety.
[0448] The nanoparticles and microparticles of the present
disclosure may be geometrically engineered to modulate macrophage
and/or the immune response. In some embodiments, the geometrically
engineered particles may have varied shapes, sizes and/or surface
charges in order to incorporated the polynucleotides of the present
disclosure for targeted delivery such as, but not limited to,
pulmonary delivery (see, e.g., International Publication No
WO2013082111, the contents of which are herein incorporated by
reference in their entirety). Other physical features the
geometrically engineering particles may have include, but are not
limited to, fenestrations, angled arms, asymmetry and surface
roughness, charge which can alter the interactions with cells and
tissues. As a non-limiting example, nanoparticles of the present
disclosure may be made by the methods described in International
Publication No WO2013082111, the contents of which are herein
incorporated by reference in their entirety.
[0449] In some embodiments, the nanoparticles of the present
disclosure may be water soluble nanoparticles such as, but not
limited to, those described in International Publication No.
WO2013090601, the contents of which are herein incorporated by
reference in their entirety. The nanoparticles may be inorganic
nanoparticles which have a compact and zwitterionic ligand in order
to exhibit good water solubility. The nanoparticles may also have
small hydrodynamic diameters (HD), stability with respect to time,
pH, and salinity and a low level of non-specific protein
binding.
[0450] In some embodiments the nanoparticles of the present
disclosure may be developed by the methods described in U.S. Patent
Publication No. US20130172406, the contents of which are herein
incorporated by reference in their entirety.
[0451] In some embodiments, the nanoparticles of the present
disclosure are stealth nanoparticles or target-specific stealth
nanoparticles such as, but not limited to, those described in U.S.
Patent Publication No. US20130172406, the contents of which are
herein incorporated by reference in their entirety. The
nanoparticles of the present disclosure may be made by the methods
described in U.S. Patent Publication No. US20130172406, the
contents of which are herein incorporated by reference in their
entirety.
[0452] In some embodiments, the stealth or target-specific stealth
nanoparticles may comprise a polymeric matrix. The polymeric matrix
may comprise two or more polymers such as, but not limited to,
polyethylenes, polycarbonates, polyanhydrides, polyhydroxyacids,
polypropylfumerates, polycaprolactones, polyamides, polyacetals,
polyethers, polyesters, poly(orthoesters), polycyanoacrylates,
polyvinyl alcohols, polyurethanes, polyphosphazenes, polyacrylates,
polymethacrylates, polycyanoacrylates, polyureas, polystyrenes,
polyamines, polyesters, polyanhydrides, polyethers, polyurethanes,
polymethacrylates, polyacrylates, polycyanoacrylates or
combinations thereof.
[0453] In some embodiments, the nanoparticle may be a
nanoparticle-nucleic acid hybrid structure having a high density
nucleic acid layer. As a non-limiting example, the
nanoparticle-nucleic acid hybrid structure may made by the methods
described in U.S. Patent Publication No. US20130171646, the
contents of which are herein incorporated by reference in their
entirety. The nanoparticle may comprise a nucleic acid such as, but
not limited to, polynucleotides described herein and/or known in
the art.
[0454] At least one of the nanoparticles of the present disclosure
may be embedded in in the core a nanostructure or coated with a low
density porous 3-D structure or coating which is capable of
carrying or associating with at least one payload within or on the
surface of the nanostructure. Non-limiting examples of the
nanostructures comprising at least one nanoparticle are described
in International Patent Publication No. WO2013123523, the contents
of which are herein incorporated by reference in their
entirety.
[0455] In some embodiments the RNA (e.g., mRNA) vaccine may be
associated with a cationic or polycationic compounds, including
protamine, nucleoline, spermine or spermidine, or other cationic
peptides or proteins, such as poly-L-lysine (PLL), polyarginine,
basic polypeptides, cell penetrating peptides (CPPs), including
HIV-binding peptides, HIV-1 Tat (HIV), Tat-derived peptides,
Penetratin, VP.sup.22 derived or analog peptides, Pestivirus Ems,
HSV, VP.sup.22 (Herpes simplex), MAP, KALA or protein transduction
domains (PTDs), PpT620, prolin-rich peptides, arginine-rich
peptides, lysine-rich peptides, MPG-peptide(s), Pep-1, L-oligomers,
Calcitonin peptide(s), Antennapedia-derived peptides (particularly
from Drosophila antennapedia), pAntp, plsl, FGF, Lactoferrin,
Transportan, Buforin-2, Bac715-24, SynB, SynB, pVEC, hCT-derived
peptides, SAP, histones, cationic polysaccharides, for example
chitosan, polybrene, cationic polymers, e.g. polyethyleneimine
(PEI), cationic lipids, e.g. DOTMA:
[1-(2,3-sioleyloxy)propyl)]-N,N,N-trimethylammonium chloride,
DMRIE, di-C14-amidine, DOTIM, SAINT, DC-Chol, BGTC, CTAP, DOPC,
DODAP, DOPE: Dioleyl phosphatidylethanol-amine, DOSPA, DODAB, DOIC,
DMEPC, DOGS: Dioctadecylamidoglicylspermin, DIMRI:
Dimyristooxypropyl dimethyl hydroxyethyl ammonium bromide, DOTAP:
dioleoyloxy-3-(trimethylammonio)propane, DC-6-14:
O,O-ditetradecanoyl-N-.alpha.-trimethylammonioacetyl)diethanolamine
chloride, CLIP 1:
rac-[(2,3-dioctadecyloxypropyl)(2-hydroxyethyl)]-dimethylammonium
chloride, CLIP6:
rac-[2(2,3-dihexadecyloxypropyloxymethyloxy)ethyl]-trimethylammonium,
CLIP9:
rac-[2(2,3-dihexadecyloxypropyloxysuccinyloxy)ethyl]-trimethylammo-
-nium, oligofectamine, or cationic or polycationic polymers, e.g.
modified polyaminoacids, such as beta-aminoacid-polymers or
reversed polyamides, etc., modified polyethylenes, such as PVP
(poly(N-ethyl-4-vinylpyridinium bromide)), etc., modified
acrylates, such as pDMAEMA (poly(dimethylaminoethyl
methylacrylate)), etc., modified amidoamines such as pAMAM
(poly(amidoamine)), etc., modified polybetaminoester (PBAE), such
as diamine end modified 1,4 butanediol
diacrylate-co-5-amino-1-pentanol polymers, etc., dendrimers, such
as polypropylamine dendrimers or pAMAM based dendrimers, etc.,
polyimine(s), such as PEI: poly(ethyleneimine),
poly(propyleneimine), etc., polyallylamine, sugar backbone based
polymers, such as cyclodextrin based polymers, dextran based
polymers, chitosan, etc., silan backbone based polymers, such as
PMOXA-PDMS copolymers, etc., blockpolymers consisting of a
combination of one or more cationic blocks (e.g. selected from a
cationic polymer as mentioned above) and of one or more hydrophilic
or hydrophobic blocks (e.g. polyethyleneglycole), etc.
[0456] In other embodiments the RNA (e.g., mRNA) vaccine is not
associated with a cationic or polycationic compounds.
[0457] In some embodiments, a nanoparticle comprises compounds of
Formula (I):
##STR00003##
[0458] or a salt or isomer thereof, wherein:
[0459] R.sub.1 is selected from the group consisting of C.sub.5-30
alkyl, C.sub.5-20 alkenyl, --R*YR'', --YR'', and --R''M'R';
[0460] R.sub.2 and R.sub.3 are independently selected from the
group consisting of H, C.sub.1-14 alkyl, C.sub.2-14 alkenyl,
--R*YR'', --YR'', and --R*OR'', or R.sub.2 and R.sub.3, together
with the atom to which they are attached, form a heterocycle or
carbocycle;
[0461] R.sub.4 is selected from the group consisting of a C.sub.3-6
carbocycle, --(CH.sub.2).sub.nQ, --(CH.sub.2).sub.nCHQR, --CHQR,
--CQ(R).sub.2, and unsubstituted C.sub.1-6 alkyl, where Q is
selected from a carbocycle, heterocycle, --OR,
--O(CH.sub.2).sub.nN(R).sub.2, --C(O)OR, --OC(O)R, --CX.sub.3,
--CX.sub.2H, --CXH.sub.2, --CN, --N(R).sub.2, --C(O)N(R).sub.2,
--N(R)C(O)R, --N(R)S(O).sub.2R, --N(R)C(O)N(R).sub.2,
--N(R)C(S)N(R).sub.2, --N(R)R.sub.8, --O(CH.sub.2).sub.nOR,
--N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)N(R).sub.2,
--C(.dbd.NR.sub.9)R, --C(O)N(R)OR, and --C(R)N(R).sub.2C(O)OR, and
each n is independently selected from 1, 2, 3, 4, and 5;
[0462] each R.sub.5 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0463] each R.sub.6 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0464] M and M' are independently selected from --C(O)O--,
--OC(O)--, --C(O)N(R')--,
[0465] --N(R')C(O)--, --C(O)--, --C(S)--, --C(S)S--, --SC(S)--,
--CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--, --S--S--, an aryl
group, and a heteroaryl group;
[0466] R.sub.7 is selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H;
[0467] R.sub.8 is selected from the group consisting of C.sub.3-6
carbocycle and heterocycle;
[0468] R.sub.9 is selected from the group consisting of H, CN,
NO.sub.2, C.sub.1-6 alkyl, --OR, --S(O).sub.2R,
--S(O).sub.2N(R).sub.2, C.sub.2-6 alkenyl, C.sub.3-6 carbocycle and
heterocycle;
[0469] each R is independently selected from the group consisting
of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0470] each R' is independently selected from the group consisting
of C.sub.1-18 alkyl, C.sub.2-18 alkenyl, --R*YR'', --YR'', and H;
[0471] each R'' is independently selected from the group consisting
of C.sub.3-14 alkyl and C.sub.3-14 alkenyl; [0472] each R* is
independently selected from the group consisting of C.sub.1-12
alkyl and C.sub.2-12 alkenyl;
[0473] each Y is independently a C.sub.3-6 carbocycle;
[0474] each X is independently selected from the group consisting
of F, Cl, Br, and I; and
[0475] m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.
[0476] In some embodiments, a subset of compounds of Formula (I)
includes those in which when R.sub.4 is --(CH.sub.2).sub.nQ,
--(CH.sub.2).sub.nCHQR, --CHQR, or --CQ(R).sub.2, then (i) Q is not
--N(R).sub.2 when n is 1, 2, 3, 4 or 5, or (ii) Q is not 5, 6, or
7-membered heterocycloalkyl when n is 1 or 2.
[0477] In some embodiments, another subset of compounds of Formula
(I) includes those in which
[0478] R.sub.1 is selected from the group consisting of C.sub.5-30
alkyl, C.sub.5-20 alkenyl, --R*YR'', --YR'', and --R''M'R';
[0479] R.sub.2 and R.sub.3 are independently selected from the
group consisting of H, C.sub.1-14 alkyl, C.sub.2-14 alkenyl,
--R*YR'', --YR'', and --R*OR'', or R.sub.2 and R.sub.3, together
with the atom to which they are attached, form a heterocycle or
carbocycle;
[0480] R.sub.4 is selected from the group consisting of a
C.sub.3-6
carbocycle, --(CH.sub.2).sub.nQ, --(CH.sub.2).sub.nCHQR, --CHQR,
--CQ(R).sub.2, and unsubstituted C.sub.1-6 alkyl, where Q is
selected from a C.sub.3-6 carbocycle, a 5- to 14-membered
heteroaryl having one or more heteroatoms selected from N, O, and
S, --OR, --O(CH.sub.2).sub.nN(R).sub.2, --C(O)OR, --OC(O)R,
--CX.sub.3, --CX.sub.2H, --CXH.sub.2, --CN, --C(O)N(R).sub.2,
--N(R)C(O)R, --N(R)S(O).sub.2R, --N(R)C(O)N(R).sub.2,
--N(R)C(S)N(R).sub.2, --CRN(R).sub.2C(O)OR, --N(R)R.sub.8,
--O(CH.sub.2).sub.nOR, --N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)N(R).sub.2,
--C(.dbd.NR.sub.9)R, --C(O)N(R)O R, and a 5- to 14-membered
heterocycloalkyl having one or more heteroatoms selected from N, O,
and S which is substituted with one or more substituents selected
from oxo (.dbd.O), OH, amino, mono- or di-alkylamino, and C.sub.1-3
alkyl, and each n is independently selected from 1, 2, 3, 4, and
5;
[0481] each R.sub.5 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0482] each R.sub.6 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0483] M and M' are independently selected from --C(O)O--,
--OC(O)--, --C(O)N(R')--, --N(R')C(O)--, --C(O)--, --C(S)--,
--C(S)S--, --SC(S)--, --CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--,
--S--S--, an aryl group, and a heteroaryl group;
[0484] R.sub.7 is selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H;
[0485] R.sub.8 is selected from the group consisting of C.sub.3-6
carbocycle and heterocycle;
[0486] R.sub.9 is selected from the group consisting of H, CN,
NO.sub.2, C.sub.1-6 alkyl, --OR, --S(O).sub.2R,
--S(O).sub.2N(R).sub.2, C.sub.2-6 alkenyl, C.sub.3-6 carbocycle and
heterocycle;
[0487] each R is independently selected from the group consisting
of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0488] each R' is independently selected from the group consisting
of C.sub.1-18 alkyl, C.sub.2-18 alkenyl, --R*YR'', --YR'', and
H;
[0489] each R'' is independently selected from the group consisting
of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
[0490] each R* is independently selected from the group consisting
of C.sub.1-12 alkyl and C.sub.2-12 alkenyl;
[0491] each Y is independently a C.sub.3-6 carbocycle;
[0492] each X is independently selected from the group consisting
of F, Cl, Br, and I; and
[0493] m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,
[0494] or salts or isomers thereof.
[0495] In some embodiments, another subset of compounds of Formula
(I) includes those in which
[0496] R.sub.1 is selected from the group consisting of C.sub.5-30
alkyl, C.sub.5-20 alkenyl, --R*YR'', --YR'', and --R''M'R';
[0497] R.sub.2 and R.sub.3 are independently selected from the
group consisting of H, C.sub.1-14 alkyl, C.sub.2-14 alkenyl,
--R*YR'', --YR'', and --R*OR'', or R.sub.2 and R.sub.3, together
with the atom to which they are attached, form a heterocycle or
carbocycle;
[0498] R.sub.4 is selected from the group consisting of a
C.sub.3-6
carbocycle, --(CH.sub.2).sub.nQ, --(CH.sub.2).sub.nCHQR, --CHQR,
--CQ(R).sub.2, and unsubstituted C.sub.1-6 alkyl, where Q is
selected from a C.sub.3-6 carbocycle, a 5- to 14-membered
heterocycle having one or more heteroatoms selected from N, O, and
S, --OR, --O(CH.sub.2).sub.nN(R).sub.2, --C(O)OR, --OC(O)R,
--CX.sub.3, --CX.sub.2H, --CXH.sub.2, --CN, --C(O)N(R).sub.2,
--N(R)C(O)R, --N(R)S(O).sub.2R, --N(R)C(O)N(R).sub.2,
--N(R)C(S)N(R).sub.2, --CRN(R).sub.2C(O)OR, --N(R)R.sub.8,
--O(CH.sub.2).sub.nOR, --N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)R,
--C(O)N(R)OR, and --C(.dbd.NR.sub.9)N(R).sub.2, and each n is
independently selected from 1, 2, 3, 4, and 5; and when Q is a 5-
to 14-membered heterocycle and (i) R.sub.4 is --(CH.sub.2).Q in
which n is 1 or 2, or (ii) R.sub.4 is --(CH.sub.2).sub.nCHQR in
which n is 1, or (iii) R.sub.4 is --CHQR, and --CQ(R).sub.2, then Q
is either a 5- to 14-membered heteroaryl or 8- to 14-membered
heterocycloalkyl;
[0499] each R.sub.5 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0500] each R.sub.6 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0501] M and M' are independently selected from --C(O)O--,
--OC(O)--, --C(O)N(R')--, --N(R')C(O)--, --C(O)--, --C(S)--,
--C(S)S--, --SC(S)--, --CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--,
--S--S--, an aryl group, and a heteroaryl group;
[0502] R.sub.7 is selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H;
[0503] R.sub.8 is selected from the group consisting of C.sub.3-6
carbocycle and heterocycle;
[0504] R.sub.9 is selected from the group consisting of H, CN,
NO.sub.2, C.sub.1-6 alkyl, --OR, --S(O).sub.2R,
--S(O).sub.2N(R).sub.2, C.sub.2-6 alkenyl, C.sub.3-6 carbocycle and
heterocycle;
[0505] each R is independently selected from the group consisting
of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0506] each R' is independently selected from the group consisting
of C.sub.1-18 alkyl, C.sub.2-18 alkenyl, --R*YR'', --YR'', and
H;
[0507] each R'' is independently selected from the group consisting
of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
[0508] each R* is independently selected from the group consisting
of C.sub.1-12 alkyl and C.sub.2-12 alkenyl;
[0509] each Y is independently a C.sub.3-6 carbocycle;
[0510] each X is independently selected from the group consisting
of F, Cl, Br, and I; and
[0511] m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,
[0512] or salts or isomers thereof.
[0513] In some embodiments, another subset of compounds of Formula
(I) includes those in which
[0514] R.sub.1 is selected from the group consisting of C.sub.5-30
alkyl, C.sub.5-20 alkenyl, --R*YR'', --YR'', and --R''M'R';
[0515] R.sub.2 and R.sub.3 are independently selected from the
group consisting of H, C.sub.1-14 alkyl, C.sub.2-14 alkenyl,
--R*YR'', --YR'', and --R*OR'', or R.sub.2 and R.sub.3, together
with the atom to which they are attached, form a heterocycle or
carbocycle;
[0516] R.sub.4 is selected from the group consisting of a
C.sub.3-6
carbocycle, --(CH.sub.2).sub.nQ, --(CH.sub.2).sub.nCHQR, --CHQR,
--CQ(R).sub.2, and unsubstituted C.sub.1-6 alkyl, where Q is
selected from a C.sub.3-6 carbocycle, a 5- to 14-membered
heteroaryl having one or more heteroatoms selected from N, O, and
S, --OR, --O(CH.sub.2), N(R).sub.2, --C(O)OR, --OC(O)R, --CX.sub.3,
--CX.sub.2H, --CXH.sub.2, --CN, --C(O)N(R).sub.2, --N(R)C(O)R,
--N(R)S(O).sub.2R, --N(R)C(O)N(R).sub.2, --N(R)C(S)N(R).sub.2,
--CRN(R).sub.2C(O)OR, --N(R)R.sub.8, --O(CH.sub.2).sub.nOR,
--N(R)C(.dbd.NR.sub.9)N(R).sub.2,
--N(R)C(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
--N(OR)C(O)R, --N(OR)S(O).sub.2R, --N(OR)C(O)OR,
--N(OR)C(O)N(R).sub.2, --N(OR)C(S)N(R).sub.2,
--N(OR)C(.dbd.NR.sub.9)N(R).sub.2,
--N(OR)C(.dbd.CHR.sub.9)N(R).sub.2, --C(.dbd.NR.sub.9)R,
--C(O)N(R)OR, and --C(.dbd.NR.sub.9)N(R).sub.2, and each n is
independently selected from 1, 2, 3, 4, and 5;
[0517] each R.sub.5 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0518] each R.sub.6 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0519] M and M' are independently selected from --C(O)O--,
--OC(O)--, --C(O)N(R')--, --N(R')C(O)--, --C(O)--, --C(S)--,
--C(S)S--, --SC(S)--, --CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--,
--S--S--, an aryl group, and a heteroaryl group;
[0520] R.sub.7 is selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H;
[0521] R.sub.8 is selected from the group consisting of C.sub.3-6
carbocycle and heterocycle;
[0522] R.sub.9 is selected from the group consisting of H, CN,
NO.sub.2, C.sub.1-6 alkyl, --OR, --S(O).sub.2R,
--S(O).sub.2N(R).sub.2, C.sub.2-6 alkenyl, C.sub.3-6 carbocycle and
heterocycle;
[0523] each R is independently selected from the group consisting
of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0524] each R' is independently selected from the group consisting
of C.sub.1-18 alkyl, C.sub.2-18 alkenyl, --R*YR'', --YR'', and
H;
[0525] each R'' is independently selected from the group consisting
of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
[0526] each R* is independently selected from the group consisting
of C.sub.1-12 alkyl and C.sub.2-12 alkenyl;
[0527] each Y is independently a C.sub.3-6 carbocycle;
[0528] each X is independently selected from the group consisting
of F, Cl, Br, and I; and
[0529] m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,
[0530] or salts or isomers thereof.
[0531] In some embodiments, another subset of compounds of Formula
(I) includes those in which
[0532] R.sub.1 is selected from the group consisting of C.sub.5-30
alkyl, C.sub.5-20 alkenyl, --R*YR'', --YR'', and --R''M'R';
[0533] R.sub.2 and R.sub.3 are independently selected from the
group consisting of H, C.sub.2-14 alkyl, C.sub.2-14 alkenyl,
--R*YR'', --YR'', and --R*OR'', or R.sub.2 and R.sub.3, together
with the atom to which they are attached, form a heterocycle or
carbocycle;
[0534] R.sub.4 is --(CH.sub.2).sub.nQ or --(CH.sub.2).sub.nCHQR,
where Q is --N(R).sub.2, and n is selected from 3, 4, and 5;
[0535] each R.sub.5 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0536] each R.sub.6 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0537] M and M' are independently selected from --C(O)O--,
--OC(O)--, --C(O)N(R')--, --N(R')C(O)--, --C(O)--, --C(S)--,
--C(S)S--, --SC(S)--, --CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--,
--S--S--, an aryl group, and a heteroaryl group;
[0538] R.sub.7 is selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H;
[0539] each R is independently selected from the group consisting
of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0540] each R' is independently selected from the group consisting
of C.sub.1-18 alkyl, C.sub.2-18 alkenyl, --R*YR'', --YR'', and
H;
[0541] each R'' is independently selected from the group consisting
of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
[0542] each R* is independently selected from the group consisting
of C.sub.1-12 alkyl and C.sub.1-12 alkenyl;
[0543] each Y is independently a C.sub.3-6 carbocycle;
[0544] each X is independently selected from the group consisting
of F, Cl, Br, and I; and
[0545] m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,
[0546] or salts or isomers thereof.
[0547] In some embodiments, another subset of compounds of Formula
(I) includes those in which
[0548] R.sub.1 is selected from the group consisting of C.sub.5-30
alkyl, C.sub.5-20 alkenyl, --R*YR'', --YR'', and --R''M'R';
[0549] R.sub.2 and R.sub.3 are independently selected from the
group consisting of C.sub.1-14 alkyl, C.sub.2-14 alkenyl, --R*YR'',
--YR'', and --R*OR'', or R.sub.2 and R.sub.3, together with the
atom to which they are attached, form a heterocycle or
carbocycle;
[0550] R.sub.4 is selected from the group consisting of
--(CH.sub.2).sub.nQ, --(CH.sub.2).sub.nCHQR, --CHQR, and
--CQ(R).sub.2, where Q is --N(R).sub.2, and n is selected from 1,
2, 3, 4, and 5;
[0551] each R.sub.5 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0552] each R.sub.6 is independently selected from the group
consisting of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0553] M and M' are independently selected from --C(O)O--,
--OC(O)--, --C(O)N(R')--, --N(R')C(O)--, --C(O)--, --C(S)--,
--C(S)S--, --SC(S)--, --CH(OH)--, --P(O)(OR')O--, --S(O).sub.2--,
--S--S--, an aryl group, and a heteroaryl group;
[0554] R.sub.7 is selected from the group consisting of C.sub.1-3
alkyl, C.sub.2-3 alkenyl, and H;
[0555] each R is independently selected from the group consisting
of C.sub.1-3 alkyl, C.sub.2-3 alkenyl, and H;
[0556] each R' is independently selected from the group consisting
of C.sub.1-18 alkyl, C.sub.2-18 alkenyl, --R*YR'', --YR'', and
H;
[0557] each R'' is independently selected from the group consisting
of C.sub.3-14 alkyl and C.sub.3-14 alkenyl;
[0558] each R* is independently selected from the group consisting
of C.sub.1-12 alkyl and C.sub.1-12 alkenyl;
[0559] each Y is independently a C.sub.3-6 carbocycle;
[0560] each X is independently selected from the group consisting
of F, Cl, Br, and I; and
[0561] m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13,
[0562] or salts or isomers thereof.
[0563] In some embodiments, a subset of compounds of Formula (I)
includes those of Formula (IA):
##STR00004##
[0564] or a salt or isomer thereof, wherein 1 is selected from 1,
2, 3, 4, and 5; m is selected from 5, 6, 7, 8, and 9; M.sub.1 is a
bond or M'; R.sub.4 is unsubstituted C.sub.1-3 alkyl, or
--(CH.sub.2).sub.nQ, in which Q is OH, --NHC(S)N(R).sub.2,
--NHC(O)N(R).sub.2, --N(R)C(O)R, --N(R)S(O).sub.2R, --N(R)R.sub.8,
--NHC(.dbd.NR.sub.9)N(R).sub.2, --NHC(.dbd.CHR.sub.9)N(R).sub.2,
--OC(O)N(R).sub.2, --N(R)C(O)OR, heteroaryl or heterocycloalkyl; M
and M' are independently selected
from --C(O)O--, --OC(O)--, --C(O)N(R')--, --P(O)(OR')O--, --S--S--,
an aryl group, and a heteroaryl group; and R.sub.2 and R.sub.3 are
independently selected from the group consisting of H, C.sub.1-14
alkyl, and C.sub.2-14 alkenyl.
[0565] In some embodiments, a subset of compounds of Formula (I)
includes those of Formula (II):
##STR00005##
or a salt or isomer thereof, wherein 1 is selected from 1, 2, 3, 4,
and 5; M.sub.1 is a bond or M'; R.sub.4 is unsubstituted C.sub.1-3
alkyl, or --(CH.sub.2).sub.nQ, in which n is 2, 3, or 4, and Q is
OH, --NHC(S)N(R).sub.2, --NHC(O)N(R).sub.2, --N(R)C(O)R,
--N(R)S(O).sub.2R, --N(R)R.sub.8, --NHC(.dbd.NR.sub.9)N(R).sub.2,
--NHC(.dbd.CHR.sub.9)N(R).sub.2, --OC(O)N(R).sub.2, --N(R)C(O)OR,
heteroaryl or heterocycloalkyl; M and M' are independently selected
from --C(O)O--, --OC(O)--, --C(O)N(R')--, --P(O)(OR')O--, --S--S--,
an aryl group, and a heteroaryl group; and R.sub.2 and R.sub.3 are
independently selected from the group consisting of H, C.sub.1-14
alkyl, and C.sub.2-14 alkenyl.
[0566] In some embodiments, a subset of compounds of Formula (I)
includes those of Formula (IIa), (IIb), (IIc), or (IIe):
##STR00006##
[0567] or a salt or isomer thereof, wherein R.sub.4 is as described
herein.
[0568] In some embodiments, a subset of compounds of Formula (I)
includes those of Formula (IId):
##STR00007##
[0569] or a salt or isomer thereof, wherein n is 2, 3, or 4; and m,
R', R'', and R.sub.2 through R.sub.6 are as described herein. For
example, each of R.sub.2 and R.sub.3 may be independently selected
from the group consisting of C.sub.5-14 alkyl and C.sub.5-14
alkenyl.
[0570] In some embodiments, the compound of Formula (I) is selected
from the group consisting of:
##STR00008## ##STR00009## ##STR00010## ##STR00011## ##STR00012##
##STR00013## ##STR00014## ##STR00015## ##STR00016## ##STR00017##
##STR00018##
[0571] In further embodiments, the compound of Formula (I) is
selected from the group consisting of:
##STR00019##
[0572] In some embodiments, the compound of Formula (I) is selected
from the group consisting of:
##STR00020## ##STR00021## ##STR00022## ##STR00023## ##STR00024##
##STR00025## ##STR00026## ##STR00027## ##STR00028## ##STR00029##
##STR00030## ##STR00031## ##STR00032## ##STR00033## ##STR00034##
##STR00035## ##STR00036## ##STR00037## ##STR00038## ##STR00039##
##STR00040## ##STR00041## ##STR00042## ##STR00043## ##STR00044##
##STR00045## ##STR00046## ##STR00047## ##STR00048## ##STR00049##
##STR00050## ##STR00051## ##STR00052## ##STR00053##
and salts and isomers thereof.
[0573] In some embodiments, a nanoparticle comprises the following
compound:
##STR00054##
or salts and isomers thereof.
[0574] In some embodiments, the disclosure features a nanoparticle
composition including a lipid component comprising a compound as
described herein (e.g., a compound according to Formula (I), (IA),
(II), (IIa), (IIb), (IIc), (IId) or (IIe)).
[0575] In some embodiments, the disclosure features a
pharmaceutical composition comprising a nanoparticle composition
according to the preceding embodiments and a pharmaceutically
acceptable carrier. For example, the pharmaceutical composition is
refrigerated or frozen for storage and/or shipment (e.g., being
stored at a temperature of 4.degree. C. or lower, such as a
temperature between about -150.degree. C. and about 0.degree. C. or
between about -80.degree. C. and about -20.degree. C. (e.g., about
-5.degree. C., -10.degree. C., -15.degree. C., -20.degree. C.,
-25.degree. C., -30.degree. C., -40.degree. C., -50.degree. C.,
-60.degree. C., -70.degree. C., -80.degree. C., -90.degree. C.,
-130.degree. C. or -150.degree. C.). For example, the
pharmaceutical composition is a solution that is refrigerated for
storage and/or shipment at, for example, about -20.degree. C.,
-30.degree. C., -40.degree. C., -50.degree. C., -60.degree. C.,
-70.degree. C., or -80.degree. C.
[0576] In some embodiments, the disclosure provides a method of
delivering a therapeutic and/or prophylactic (e.g., RNA, such as
mRNA) to a cell (e.g., a mammalian cell). This method includes the
step of administering to a subject (e.g., a mammal, such as a
human) a nanoparticle composition including (i) a lipid component
including a phospholipid (such as a polyunsaturated lipid), a PEG
lipid, a structural lipid, and a compound of Formula (I), (IA),
(II), (IIa), (IIb), (IIc), (IId) or (IIe) and (ii) a therapeutic
and/or prophylactic, in which administering involves contacting the
cell with the nanoparticle composition, whereby the therapeutic
and/or prophylactic is delivered to the cell.
[0577] In some embodiments, the disclosure provides a method of
producing a polypeptide of interest in a cell (e.g., a mammalian
cell). The method includes the step of contacting the cell with a
nanoparticle composition including (i) a lipid component including
a phospholipid (such as a polyunsaturated lipid), a PEG lipid, a
structural lipid, and a compound of Formula (I), (IA), (II), (IIa),
(IIb), (IIc), (IId) or (IIe) and (ii) an mRNA encoding the
polypeptide of interest, whereby the mRNA is capable of being
translated in the cell to produce the polypeptide.
[0578] In some embodiments, the disclosure provides a method of
treating a disease or disorder in a mammal (e.g., a human) in need
thereof. The method includes the step of administering to the
mammal a therapeutically effective amount of a nanoparticle
composition including (i) a lipid component including a
phospholipid (such as a polyunsaturated lipid), a PEG lipid, a
structural lipid, and a compound of Formula (I), (IA), (II), (IIa),
(IIb), (IIc), (IId) or (IIe) and (ii) a therapeutic and/or
prophylactic (e.g., an mRNA). In some embodiments, the disease or
disorder is characterized by dysfunctional or aberrant protein or
polypeptide activity. For example, the disease or disorder is
selected from the group consisting of rare diseases, infectious
diseases, cancer and proliferative diseases, genetic diseases
(e.g., cystic fibrosis), autoimmune diseases, diabetes,
neurodegenerative diseases, cardio- and reno-vascular diseases, and
metabolic diseases.
[0579] In some embodiments, the disclosure provides a method of
delivering (e.g., specifically delivering) a therapeutic and/or
prophylactic to a mammalian organ (e.g., a liver, spleen, lung, or
femur). This method includes the step of administering to a subject
(e.g., a mammal) a nanoparticle composition including (i) a lipid
component including a phospholipid, a PEG lipid, a structural
lipid, and a compound of Formula (I), (IA), (II), (IIa), (IIb),
(IIc), (IId) or (IIe) and (ii) a therapeutic and/or prophylactic
(e.g., an mRNA), in which administering involves contacting the
cell with the nanoparticle composition, whereby the therapeutic
and/or prophylactic is delivered to the target organ (e.g., a
liver, spleen, lung, or femur).
[0580] In some embodiments, the disclosure features a method for
the enhanced delivery of a therapeutic and/or prophylactic (e.g.,
an mRNA) to a target tissue (e.g., a liver, spleen, lung, or
femur). This method includes administering to a subject (e.g., a
mammal) a nanoparticle composition, the composition including (i) a
lipid component including a compound of Formula (I), (IA), (II),
(IIa), (IIb), (IIc), (IId) or (IIe), a phospholipid, a structural
lipid, and a PEG lipid; and (ii) a therapeutic and/or prophylactic,
the administering including contacting the target tissue with the
nanoparticle composition, whereby the therapeutic and/or
prophylactic is delivered to the target tissue.
[0581] In some embodiments, the disclosure features a method of
lowering immunogenicity comprising introducing the nanoparticle
composition of the disclosure into cells, wherein the nanoparticle
composition reduces the induction of the cellular immune response
of the cells to the nanoparticle composition, as compared to the
induction of the cellular immune response in cells induced by a
reference composition which comprises a reference lipid instead of
a compound of Formula (I), (IA), (II), (IIa), (IIb), (IIc), (IId)
or (IIe). For example, the cellular immune response is an innate
immune response, an adaptive immune response, or both.
[0582] The disclosure also includes methods of synthesizing a
compound of Formula (I), (IA), (II), (IIa), (IIb), (IIc), (IId) or
(IIe) and methods of making a nanoparticle composition including a
lipid component comprising the compound of Formula (I), (IA), (II),
(IIa), (IIb), (IIc), (IId) or (IIe).
Modes of Vaccine Administration
[0583] STD RNA (e.g. mRNA) vaccines may be administered by any
route which results in a therapeutically effective outcome. These
include, but are not limited, to intradermal, intramuscular,
intranasal and/or subcutaneous administration. The present
disclosure provides methods comprising administering RNA (e.g.,
mRNA) vaccines to a subject in need thereof. The exact amount
required will vary from subject to subject, depending on the
species, age, and general condition of the subject, the severity of
the disease, the particular composition, its mode of
administration, its mode of activity, and the like. STD RNA (e.g.,
mRNA) vaccines compositions are typically formulated in dosage unit
form for ease of administration and uniformity of dosage. It will
be understood, however, that the total daily usage of RNA (e.g.,
mRNA) vaccine compositions may be decided by the attending
physician within the scope of sound medical judgment. The specific
therapeutically effective, prophylactically effective, or
appropriate imaging dose level for any particular patient will
depend upon a variety of factors including the disorder being
treated and the severity of the disorder; the activity of the
specific compound employed; the specific composition employed; the
age, body weight, general health, sex and diet of the patient; the
time of administration, route of administration, and rate of
excretion of the specific compound employed; the duration of the
treatment; drugs used in combination or coincidental with the
specific compound employed; and like factors well known in the
medical arts.
[0584] In some embodiments, STD RNA (e.g. mRNA) vaccines
compositions may be administered at dosage levels sufficient to
deliver 0.0001 mg/kg to 100 mg/kg, 0.001 mg/kg to 0.05 mg/kg, 0.005
mg/kg to 0.05 mg/kg, 0.001 mg/kg to 0.005 mg/kg, 0.05 mg/kg to 0.5
mg/kg, 0.01 mg/kg to 50 mg/kg, 0.1 mg/kg to 40 mg/kg, 0.5 mg/kg to
30 mg/kg, 0.01 mg/kg to 10 mg/kg, 0.1 mg/kg to 10 mg/kg, or 1 mg/kg
to 25 mg/kg, of subject body weight per day, one or more times a
day, per week, per month, etc. to obtain the desired therapeutic,
diagnostic, prophylactic, or imaging effect (see, e.g., the range
of unit doses described in International Publication No
WO2013078199, the contents of which are herein incorporated by
reference in their entirety). The desired dosage may be delivered
three times a day, two times a day, once a day, every other day,
every third day, every week, every two weeks, every three weeks,
every four weeks, every 2 months, every three months, every 6
months, etc. In some embodiments, the desired dosage may be
delivered using multiple administrations (e.g., two, three, four,
five, six, seven, eight, nine, ten, eleven, twelve, thirteen,
fourteen, or more administrations). When multiple administrations
are employed, split dosing regimens such as those described herein
may be used. In exemplary embodiments, STD RNA (e.g., mRNA)
vaccines compositions may be administered at dosage levels
sufficient to deliver 0.0005 mg/kg to 0.01 mg/kg, e.g., about
0.0005 mg/kg to about 0.0075 mg/kg, e.g., about 0.0005 mg/kg, about
0.001 mg/kg, about 0.002 mg/kg, about 0.003 mg/kg, about 0.004
mg/kg or about 0.005 mg/kg.
[0585] In some embodiments, STD RNA (e.g., mRNA) vaccine
compositions may be administered once or twice (or more) at dosage
levels sufficient to deliver 0.025 mg/kg to 0.250 mg/kg, 0.025
mg/kg to 0.500 mg/kg, 0.025 mg/kg to 0.750 mg/kg, or 0.025 mg/kg to
1.0 mg/kg.
[0586] In some embodiments, STD RNA (e.g., mRNA) vaccine
compositions may be administered twice (e.g., Day 0 and Day 7, Day
0 and Day 14, Day 0 and Day 21, Day 0 and Day 28, Day 0 and Day 60,
Day 0 and Day 90, Day 0 and Day 120, Day 0 and Day 150, Day 0 and
Day 180, Day 0 and 3 months later, Day 0 and 6 months later, Day 0
and 9 months later, Day 0 and 12 months later, Day 0 and 18 months
later, Day 0 and 2 years later, Day 0 and 5 years later, or Day 0
and 10 years later) at a total dose of or at dosage levels
sufficient to deliver a total dose of 0.0100 mg, 0.025 mg, 0.050
mg, 0.075 mg, 0.100 mg, 0.125 mg, 0.150 mg, 0.175 mg, 0.200 mg,
0.225 mg, 0.250 mg, 0.275 mg, 0.300 mg, 0.325 mg, 0.350 mg, 0.375
mg, 0.400 mg, 0.425 mg, 0.450 mg, 0.475 mg, 0.500 mg, 0.525 mg,
0.550 mg, 0.575 mg, 0.600 mg, 0.625 mg, 0.650 mg, 0.675 mg, 0.700
mg, 0.725 mg, 0.750 mg, 0.775 mg, 0.800 mg, 0.825 mg, 0.850 mg,
0.875 mg, 0.900 mg, 0.925 mg, 0.950 mg, 0.975 mg, or 1.0 mg. Higher
and lower dosages and frequency of administration are encompassed
by the present disclosure. For example, a STD RNA (e.g., mRNA)
vaccine composition may be administered three or four times.
[0587] In some embodiments, STD RNA (e.g., mRNA) vaccine
compositions may be administered twice (e.g., Day 0 and Day 7, Day
0 and Day 14, Day 0 and Day 21, Day 0 and Day 28, Day 0 and Day 60,
Day 0 and Day 90, Day 0 and Day 120, Day 0 and Day 150, Day 0 and
Day 180, Day 0 and 3 months later, Day 0 and 6 months later, Day 0
and 9 months later, Day 0 and 12 months later, Day 0 and 18 months
later, Day 0 and 2 years later, Day 0 and 5 years later, or Day 0
and 10 years later) at a total dose of or at dosage levels
sufficient to deliver a total dose of 0.010 mg, 0.025 mg, 0.100 mg
or 0.400 mg.
[0588] In some embodiments, the STD RNA (e.g., mRNA) vaccine for
use in a method of vaccinating a subject is administered to the
subject as a single dosage of between 10 .mu.g/kg and 400 .mu.g/kg
of the nucleic acid vaccine (in an effective amount to vaccinate
the subject). In some embodiments the RNA (e.g., mRNA) vaccine for
use in a method of vaccinating a subject is administered to the
subject as a single dosage of between 10 .mu.g and 400 .mu.g of the
nucleic acid vaccine (in an effective amount to vaccinate the
subject). In some embodiments, a STD RNA (e.g., mRNA) vaccine for
use in a method of vaccinating a subject is administered to the
subject as a single dosage of 25-1000 .mu.g (e.g., a single dosage
of mRNA encoding HPV, HSV and/or Chlamydia antigen). In some
embodiments, a STD RNA (e.g., mRNA) vaccine is administered to the
subject as a single dosage of 25, 50, 100, 150, 200, 250, 300, 350,
400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950 or 1000
.mu.g. For example, a STD RNA (e.g., mRNA) vaccine may be
administered to a subject as a single dose of 25-100, 25-500,
50-100, 50-500, 50-1000, 100-500, 100-1000, 250-500, 250-1000, or
500-1000 .mu.g. In some embodiments, a STD RNA (e.g., mRNA) vaccine
for use in a method of vaccinating a subject is administered to the
subject as two dosages, the combination of which equals 25-1000
.mu.g of the STD RNA (e.g., mRNA) vaccine.
[0589] A STD RNA (e.g. mRNA) vaccine pharmaceutical composition
described herein can be formulated into a dosage form described
herein, such as an intranasal, intratracheal, or injectable (e.g.,
intravenous, intraocular, intravitreal, intramuscular, intradermal,
intracardiac, intraperitoneal, intranasal and subcutaneous).
STD RNA (e.g., mRNA) Vaccine Formulations and Methods of Use
[0590] Some aspects of the present disclosure provide formulations
of the STD RNA (e.g., mRNA) vaccine, wherein the RNA (e.g., mRNA)
vaccine is formulated in an effective amount to produce an antigen
specific immune response in a subject (e.g., production of
antibodies specific to an HPV, HSV and/or Chlamydia antigenic
polypeptide). "An effective amount" is a dose of an RNA (e.g.,
mRNA) vaccine effective to produce an antigen-specific immune
response. Also provided herein are methods of inducing an
antigen-specific immune response in a subject.
[0591] In some embodiments, the antigen-specific immune response is
characterized by measuring an anti-HPV, anti-HSV and/or
anti-Chlamydia antigenic polypeptide antibody titer produced in a
subject administered a STD RNA (e.g., mRNA) vaccine as provided
herein. An antibody titer is a measurement of the amount of
antibodies within a subject, for example, antibodies that are
specific to a particular antigen (e.g., an anti-HPV, anti-HSV
and/or anti-Chlamydia antigenic polypeptide) or epitope of an
antigen. Antibody titer is typically expressed as the inverse of
the greatest dilution that provides a positive result.
Enzyme-linked immunosorbent assay (ELISA) is a common assay for
determining antibody titers, for example.
[0592] In some embodiments, an antibody titer is used to assess
whether a subject has had an infection or to determine whether
immunizations are required. In some embodiments, an antibody titer
is used to determine the strength of an autoimmune response, to
determine whether a booster immunization is needed, to determine
whether a previous vaccine was effective, and to identify any
recent or prior infections. In accordance with the present
disclosure, an antibody titer may be used to determine the strength
of an immune response induced in a subject by the STD RNA (e.g.,
mRNA) vaccine.
[0593] In some embodiments, an anti-antigenic polypeptide (e.g., an
anti-HPV, HSV and/or Chlamydia antigenic polypeptide) antibody
titer produced in a subject is increased by at least 1 log relative
to a control. For example, anti-antigenic polypeptide antibody
titer produced in a subject may be increased by at least 1.5, at
least 2, at least 2.5, or at least 3 log relative to a control. In
some embodiments, the anti-antigenic polypeptide antibody titer
produced in the subject is increased by 1, 1.5, 2, 2.5 or 3 log
relative to a control. In some embodiments, the anti-antigenic
polypeptide antibody titer produced in the subject is increased by
1-3 log relative to a control. For example, the anti-antigenic
polypeptide antibody titer produced in a subject may be increased
by 1-1.5, 1-2, 1-2.5, 1-3, 1.5-2, 1.5-2.5, 1.5-3, 2-2.5, 2-3, or
2.5-3 log relative to a control.
[0594] In some embodiments, the anti-antigenic polypeptide (e.g.,
an anti-HPV, HSV and/or Chlamydia antigenic polypeptide) antibody
titer produced in a subject is increased at least 2 times relative
to a control. For example, the anti-antigenic polypeptide antibody
titer produced in a subject may be increased at least 3 times, at
least 4 times, at least 5 times, at least 6 times, at least 7
times, at least 8 times, at least 9 times, or at least 10 times
relative to a control. In some embodiments, the anti-antigenic
polypeptide antibody titer produced in the subject is increased 2,
3, 4, 5, 6, 7, 8, 9, or 10 times relative to a control. In some
embodiments, the anti-antigenic polypeptide antibody titer produced
in a subject is increased 2-10 times relative to a control. For
example, the anti-antigenic polypeptide antibody titer produced in
a subject may be increased 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3,
3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5,
5-10, 5-9, 5-8, 5-7, 5-6, 6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8,
8-10, 8-9, or 9-10 times relative to a control.
[0595] A control, in some embodiments, is the anti-antigenic
polypeptide (e.g., an anti-HPV, HSV and/or Chlamydia antigenic
polypeptide) antibody titer produced in a subject who has not been
administered a STD RNA (e.g., mRNA) vaccine of the present
disclosure. In some embodiments, a control is an anti-antigenic
polypeptide (e.g., an anti-HPV, HSV and/or Chlamydia antigenic
polypeptide) antibody titer produced in a subject who has been
administered a live attenuated HPV, HSV and/or Chlamydia vaccine.
An attenuated vaccine is a vaccine produced by reducing the
virulence of a viable (live). An attenuated virus is altered in a
manner that renders it harmless or less virulent relative to live,
unmodified virus. In some embodiments, a control is an
anti-antigenic polypeptide (e.g., an anti-HPV, HSV and/or Chlamydia
antigenic polypeptide) antibody titer produced in a subject
administered inactivated HPV, HSV and/or Chlamydia vaccine. In some
embodiments, a control is an anti-antigenic polypeptide (e.g., an
anti-HPV, HSV and/or Chlamydia antigenic polypeptide) antibody
titer produced in a subject administered a recombinant or purified
HPV, HSV and/or Chlamydia protein vaccine. Recombinant protein
vaccines typically include protein antigens that either have been
produced in a heterologous expression system (e.g., bacteria or
yeast) or purified from large amounts of the pathogenic organism.
In some embodiments, a control is an anti-antigenic polypeptide
(e.g., an anti-HPV, HSV and/or Chlamydia antigenic polypeptide)
antibody titer produced in a subject who has been administered an
HPV, HSV and/or Chlamydia virus-like particle (VLP) vaccine.
[0596] In some embodiments, an effective amount of a STD RNA (e.g.,
mRNA) vaccine is a dose that is reduced compared to the standard of
care dose of a recombinant HPV, HSV and/or Chlamydia protein
vaccine. A "standard of care," as provided herein, refers to a
medical or psychological treatment guideline and can be general or
specific. "Standard of care" specifies appropriate treatment based
on scientific evidence and collaboration between medical
professionals involved in the treatment of a given condition. It is
the diagnostic and treatment process that a physician/clinician
should follow for a certain type of patient, illness or clinical
circumstance. A "standard of care dose," as provided herein, refers
to the dose of a recombinant or purified HPV, HSV and/or Chlamydia
protein vaccine, or a live attenuated or inactivated HPV, HSV
and/or Chlamydia vaccine, that a physician/clinician or other
medical professional would administer to a subject to treat or
prevent HPV, HSV and/or Chlamydia, or a related condition, while
following the standard of care guideline for treating or preventing
HPV, HSV and/or Chlamydia, or a related condition.
[0597] In some embodiments, the anti-antigenic polypeptide (e.g.,
an anti-HPV, anti-HSV and/or anti Chlamydia antigenic polypeptide)
antibody titer produced in a subject administered an effective
amount of a STD RNA (e.g., mRNA) vaccine is equivalent to an
anti-antigenic polypeptide (e.g., an anti-HPV, anti-HSV and/or anti
Chlamydia antigenic polypeptide) antibody titer produced in a
control subject administered a standard of care dose of a
recombinant or purified HPV, HSV and/or Chlamydia protein vaccine
or a live attenuated or inactivated HPV, HSV and/or Chlamydia
vaccine.
[0598] In some embodiments, an effective amount of a STD RNA (e.g.,
mRNA) vaccine is a dose equivalent to an at least 2-fold reduction
in a standard of care dose of a recombinant or purified HPV, HSV
and/or Chlamydia protein vaccine. For example, an effective amount
of a STD RNA (e.g., mRNA) vaccine may be a dose equivalent to an at
least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold, at
least 7-fold, at least 8-fold, at least 9-fold, or at least 10-fold
reduction in a standard of care dose of a recombinant or purified
HPV, HSV and/or Chlamydia protein vaccine. In some embodiments, an
effective amount of a STD RNA (e.g., mRNA) vaccine is a dose
equivalent to an at least at least 100-fold, at least 500-fold, or
at least 1000-fold reduction in a standard of care dose of a
recombinant or purified HPV, HSV and/or Chlamydia protein vaccine.
In some embodiments, an effective amount of a STD RNA (e.g., mRNA)
vaccine is a dose equivalent to a 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-,
10-, 20-, 50-, 100-, 250-, 500-, or 1000-fold reduction in a
standard of care dose of a recombinant or purified HPV, HSV and/or
Chlamydia protein vaccine. In some embodiments, the anti-antigenic
polypeptide antibody titer produced in a subject administered an
effective amount of a STD RNA (e.g., mRNA) vaccine is equivalent to
an anti-antigenic polypeptide antibody titer produced in a control
subject administered the standard of care dose of a recombinant or
protein HPV, HSV and/or Chlamydia protein vaccine or a live
attenuated or inactivated HPV, HSV and/or Chlamydia vaccine. In
some embodiments, an effective amount of a STD RNA (e.g., mRNA)
vaccine is a dose equivalent to a 2-fold to 1000-fold (e.g., 2-fold
to 100-fold, 10-fold to 1000-fold) reduction in the standard of
care dose of a recombinant or purified HPV, HSV and/or Chlamydia
protein vaccine, wherein the anti-antigenic polypeptide antibody
titer produced in the subject is equivalent to an anti-antigenic
polypeptide antibody titer produced in a control subject
administered the standard of care dose of a recombinant or purified
HPV, HSV and/or Chlamydia protein vaccine or a live attenuated or
inactivated HPV, HSV and/or Chlamydia vaccine.
[0599] In some embodiments, the effective amount of a STD RNA
(e.g., mRNA) vaccine is a dose equivalent to a 2 to 1000-, 2 to
900-, 2 to 800-, 2 to 700-, 2 to 600-, 2 to 500-, 2 to 400-, 2 to
300-, 2 to 200-, 2 to 100-, 2 to 90-, 2 to 80-, 2 to 70-, 2 to 60-,
2 to 50-, 2 to 40-, 2 to 30-, 2 to 20-, 2 to 10-, 2 to 9-, 2 to 8-,
2 to 7-, 2 to 6-, 2 to 5-, 2 to 4-, 2 to 3-, 3 to 1000-, 3 to 900-,
3 to 800-, 3 to 700-, 3 to 600-, 3 to 500-, 3 to 400-, 3 to 3 to
00-, 3 to 200-, 3 to 100-, 3 to 90-, 3 to 80-, 3 to 70-, 3 to 60-,
3 to 50-, 3 to 40-, 3 to 30-, 3 to 20-, 3 to 10-, 3 to 9-, 3 to 8-,
3 to 7-, 3 to 6-, 3 to 5-, 3 to 4-, 4 to 1000-, 4 to 900-, 4 to
800-, 4 to 700-, 4 to 600-, 4 to 500-, 4 to 400-, 4 to 4 to 00-, 4
to 200-, 4 to 100-, 4 to 90-, 4 to 80-, 4 to 70-, 4 to 60-, 4 to
50-, 4 to 40-, 4 to 30-, 4 to 20-, 4 to 10-, 4 to 9-, 4 to 8-, 4 to
7-, 4 to 6-, 4 to 5-, 4 to 4-, 5 to 1000-, 5 to 900-, 5 to 800-, 5
to 700-, 5 to 600-, 5 to 500-, 5 to 400-, 5 to 300-, 5 to 200-, 5
to 100-, 5 to 90-, 5 to 80-, 5 to 70-, 5 to 60-, 5 to 50-, 5 to
40-, 5 to 30-, 5 to 20-, 5 to 10-, 5 to 9-, 5 to 8-, 5 to 7-, 5 to
6-, 6 to 1000-, 6 to 900-, 6 to 800-, 6 to 700-, 6 to 600-, 6 to
500-, 6 to 400-, 6 to 300-, 6 to 200-, 6 to 100-, 6 to 90-, 6 to
80-, 6 to 70-, 6 to 60-, 6 to 50-, 6 to 40-, 6 to 30-, 6 to 20-, 6
to 10-, 6 to 9-, 6 to 8-, 6 to 7-, 7 to 1000-, 7 to 900-, 7 to
800-, 7 to 700-, 7 to 600-, 7 to 500-, 7 to 400-, 7 to 300-, 7 to
200-, 7 to 100-, 7 to 90-, 7 to 80-, 7 to 70-, 7 to 60-, 7 to 50-,
7 to 40-, 7 to 30-, 7 to 20-, 7 to 10-, 7 to 9-, 7 to 8-, 8 to
1000-, 8 to 900-, 8 to 800-, 8 to 700-, 8 to 600-, 8 to 500-, 8 to
400-, 8 to 300-, 8 to 200-, 8 to 100-, 8 to 90-, 8 to 80-, 8 to
70-, 8 to 60-, 8 to 50-, 8 to 40-, 8 to 30-, 8 to 20-, 8 to 10-, 8
to 9-, 9 to 1000-, 9 to 900-, 9 to 800-, 9 to 700-, 9 to 600-, 9 to
500-, 9 to 400-, 9 to 300-, 9 to 200-, 9 to 100-, 9 to 90-, 9 to
80-, 9 to 70-, 9 to 60-, 9 to 50-, 9 to 40-, 9 to 30-, 9 to 20-, 9
to 10-, 10 to 1000-, 10 to 900-, 10 to 800-, 10 to 700-, 10 to
600-, 10 to 500-, 10 to 400-, 10 to 300-, 10 to 200-, 10 to 100-,
10 to 90-, 10 to 80-, 10 to 70-, 10 to 60-, 10 to 50-, 10 to 40-,
10 to 30-, 10 to 20-, 20 to 1000-, 20 to 900-, 20 to 800-, 20 to
700-, 20 to 600-, 20 to 500-, 20 to 400-, 20 to 300-, 20 to 200-,
20 to 100-, 20 to 90-, 20 to 80-, 20 to 70-, 20 to 60-, 20 to 50-,
20 to 40-, 20 to 30-, 30 to 1000-, 30 to 900-, 30 to 800-, 30 to
700-, 30 to 600-, 30 to 500-, 30 to 400-, 30 to 300-, 30 to 200-,
30 to 100-, 30 to 90-, 30 to 80-, 30 to 70-, 30 to 60-, 30 to 50-,
30 to 40-, 40 to 1000-, 40 to 900-, 40 to 800-, 40 to 700-, 40 to
600-, 40 to 500-, 40 to 400-, 40 to 300-, 40 to 200-, 40 to 100-,
40 to 90-, 40 to 80-, 40 to 70-, 40 to 60-, 40 to 50-, 50 to 1000-,
50 to 900-, 50 to 800-, 50 to 700-, 50 to 600-, 50 to 500-, 50 to
400-, 50 to 300-, 50 to 200-, 50 to 100-, 50 to 90-, 50 to 80-, 50
to 70-, 50 to 60-, 60 to 1000-, 60 to 900-, 60 to 800-, 60 to 700-,
60 to 600-, 60 to 500-, 60 to 400-, 60 to 300-, 60 to 200-, 60 to
100-, 60 to 90-, 60 to 80-, 60 to 70-, 70 to 1000-, 70 to 900-, 70
to 800-, 70 to 700-, 70 to 600-, 70 to 500-, 70 to 400-, 70 to
300-, 70 to 200-, 70 to 100-, 70 to 90-, 70 to 80-, 80 to 1000-, 80
to 900-, 80 to 800-, 80 to 700-, 80 to 600-, 80 to 500-, 80 to
400-, 80 to 300-, 80 to 200-, 80 to 100-, 80 to 90-, 90 to 1000-,
90 to 900-, 90 to 800-, 90 to 700-, 90 to 600-, 90 to 500-, 90 to
400-, 90 to 300-, 90 to 200-, 90 to 100-, 100 to 1000-, 100 to
900-, 100 to 800-, 100 to 700-, 100 to 600-, 100 to 500-, 100 to
400-, 100 to 300-, 100 to 200-, 200 to 1000-, 200 to 900-, 200 to
800-, 200 to 700-, 200 to 600-, 200 to 500-, 200 to 400-, 200 to
300-, 300 to 1000-, 300 to 900-, 300 to 800-, 300 to 700-, 300 to
600-, 300 to 500-, 300 to 400-, 400 to 1000-, 400 to 900-, 400 to
800-, 400 to 700-, 400 to 600-, 400 to 500-, 500 to 1000-, 500 to
900-, 500 to 800-, 500 to 700-, 500 to 600-, 600 to 1000-, 600 to
900-, 600 to 800-, 600 to 700-, 700 to 1000-, 700 to 900-, 700 to
800-, 800 to 1000-, 800 to 900-, or 900 to 1000-fold reduction in
the standard of care dose of a recombinant HPV, HSV and/or
Chlamydia protein vaccine. In some embodiments, the anti-antigenic
polypeptide antibody titer produced in the subject is equivalent to
an anti-antigenic polypeptide antibody titer produced in a control
subject administered the standard of care dose of a recombinant or
purified HPV, HSV and/or Chlamydia protein vaccine or a live
attenuated or inactivated HPV, HSV and/or Chlamydia vaccine. In
some embodiments, the effective amount is a dose equivalent to (or
equivalent to an at least) 2-, 3-,4-,5-,6-, 7-, 8-, 9-, 10-, 20-,
30-, 40-, 50-, 60-, 70-, 80-, 90-, 100-, 110-, 120-, 130-, 140-,
150-, 160-, 170-, 1280-, 190-, 200-, 210-, 220-, 230-, 240-, 250-,
260-, 270-, 280-, 290-, 300-, 310-, 320-, 330-, 340-, 350-, 360-,
370-, 380-, 390-, 400-, 410-, 420-, 430-, 440-, 450-, 4360-, 470-,
480-, 490-, 500-, 510-, 520-, 530-, 540-, 550-, 560-, 5760-, 580-,
590-, 600-, 610-, 620-, 630-, 640-, 650-, 660-, 670-, 680-, 690-,
700-, 710-, 720-, 730-, 740-, 750-, 760-, 770-, 780-, 790-, 800-,
810-, 820--, 830-, 840-, 850-, 860-, 870-, 880-, 890-, 900-, 910-,
920-, 930-, 940-, 950-, 960-, 970-, 980-, 990-, or 1000-fold
reduction in the standard of care dose of a recombinant HPV, HSV
and/or Chlamydia protein vaccine. In some embodiments, an
anti-antigenic polypeptide antibody titer produced in the subject
is equivalent to an anti-antigenic polypeptide antibody titer
produced in a control subject administered the standard of care
dose of a recombinant or purified HPV, HSV and/or Chlamydia protein
vaccine or a live attenuated or inactivated HPV, HSV and/or
Chlamydia vaccine.
[0600] In some embodiments, the effective amount of a STD RNA
(e.g., mRNA) vaccine is a total dose of 50-1000 .mu.g. In some
embodiments, the effective amount of a STD RNA (e.g., mRNA) vaccine
is a total dose of 50-1000, 50-900, 50-800, 50-700, 50-600, 50-500,
50-400, 50-300, 50-200, 50-100, 50-90, 50-80, 50-70, 50-60,
60-1000, 60-900, 60-800, 60-700, 60-600, 60-500, 60-400, 60-300,
60-200, 60-100, 60-90, 60-80, 60-70, 70-1000, 70-900, 70-800,
70-700, 70-600, 70-500, 70-400, 70-300, 70-200, 70-100, 70-90,
70-80, 80-1000, 80-900, 80-800, 80-700, 80-600, 80-500, 80-400,
80-300, 80-200, 80-100, 80-90, 90-1000, 90-900, 90-800, 90-700,
90-600, 90-500, 90-400, 90-300, 90-200, 90-100, 100-1000, 100-900,
100-800, 100-700, 100-600, 100-500, 100-400, 100-300, 100-200,
200-1000, 200-900, 200-800, 200-700, 200-600, 200-500, 200-400,
200-300, 300-1000, 300-900, 300-800, 300-700, 300-600, 300-500,
300-400, 400-1000, 400-900, 400-800, 400-700, 400-600, 400-500,
500-1000, 500-900, 500-800, 500-700, 500-600, 600-1000, 600-900,
600-900, 600-700, 700-1000, 700-900, 700-800, 800-1000, 800-900, or
900-1000 .mu.g. In some embodiments, the effective amount of a STD
RNA (e.g., mRNA) vaccine is a total dose of 50, 100, 150, 200, 250,
300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900,
950 or 1000 .mu.g. In some embodiments, the effective amount is a
dose of 25-500 .mu.g administered to the subject a total of two
times. In some embodiments, the effective amount of a STD RNA
(e.g., mRNA) vaccine is a dose of 25-500, 25-400, 25-300, 25-200,
25-100, 25-50, 50-500, 50-400, 50-300, 50-200, 50-100, 100-500,
100-400, 100-300, 100-200, 150-500, 150-400, 150-300, 150-200,
200-500, 200-400, 200-300, 250-500, 250-400, 250-300, 300-500,
300-400, 350-500, 350-400, 400-500 or 450-500 .mu.g administered to
the subject a total of two times. In some embodiments, the
effective amount of a STD RNA (e.g., mRNA) vaccine is a total dose
of 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, or 500 .mu.g
administered to the subject a total of two times.
Additional Embodiments
[0601] 1. A sexually transmitted disease (STD) vaccine,
comprising:
[0602] at least one RNA polynucleotide having an open reading frame
encoding at least one human papillomavirus (HPV) antigenic
polypeptide and at least one herpes simplex virus (HSV) antigenic
polypeptide, optionally formulated in a cationic lipid nanoparticle
having a molar ratio of about 20-60% cationic lipid, about 5-25%
non-cationic lipid, about 25-55% sterol, and about 0.5-15%
PEG-modified lipid, optionally wherein the at least one RNA
polynucleotide comprises at least one chemical modification.
2. A sexually transmitted disease (STD) vaccine, comprising:
[0603] at least one RNA polynucleotide having an open reading frame
encoding at least one human papillomavirus (HPV) antigenic
polypeptide and at least one Chlamydia trachomatis antigenic
polypeptide, optionally formulated in a cationic lipid nanoparticle
having a molar ratio of about 20-60% cationic lipid, about 5-25%
non-cationic lipid, about 25-55% sterol, and about 0.5-15%
PEG-modified lipid, optionally wherein the at least one RNA
polynucleotide comprises at least one chemical modification.
3. A sexually transmitted disease (STD) vaccine, comprising:
[0604] at least one RNA polynucleotide having an open reading frame
encoding at least one herpes simplex virus (HSV) antigenic
polypeptide and at least one Chlamydia trachomatis antigenic
polypeptide, optionally formulated in a cationic lipid nanoparticle
having a molar ratio of about 20-60% cationic lipid, about 5-25%
non-cationic lipid, about 25-55% sterol, and about 0.5-15%
PEG-modified lipid, optionally wherein the at least one RNA
polynucleotide comprises at least one chemical modification.
4. The vaccine of paragraph 1 or 2, wherein the at least one
antigenic polypeptide is selected from HPV E1 protein, HPV E2
protein, HPV E4 protein, HPV E5 protein, HPV E6 protein, HPV E7
protein, HPV L1 protein, and HPV L2 protein, optionally wherein the
HPV serotype is selected from HPV serotypes 6, 11, 16, 18, 31, 33,
35, 39, 45, 51, 52, 56, 58, 59, 68, 73 and 82. 5. The vaccine of
paragraph 1, 2 or 4, wherein the vaccine comprises at least one RNA
polynucleotide having an open reading frame encoding at least two
antigenic polypeptides or immunogenic fragments thereof selected
from HPV E1 protein, HPV E2 protein, HPV E4 protein, HPV E5
protein, HPV E6 protein, HPV E7 protein, HPV L1 protein, and HPV L2
protein. 6. The vaccine of paragraph 1, 2, 4 or 5, wherein the
vaccine comprises at least two RNA polynucleotides, each having an
open reading frame encoding at least one antigenic polypeptide or
an immunogenic fragment thereof selected from HPV E1 protein, HPV
E2 protein, HPV E4 protein, HPV E5 protein, HPV E6 protein, HPV E7
protein, HPV L1 protein, and HPV L2 protein, wherein the HPV
antigenic polypeptide encoded by one of the open reading frames
differs from the HPV antigenic polypeptide encoded by another of
the open reading frames. 7. The vaccine of any one of paragraphs 1,
2 or 4-6, wherein the at least one antigenic polypeptide comprises
an amino acid sequence identified by any one of SEQ ID NO: 31-61.
8. The vaccine of any one of paragraphs 1, 2 or 4-7, wherein the at
least one RNA polypeptide is encoded by a nucleic acid sequence
identified by any one of SEQ ID NO: 1-30, and/or wherein the at
least one RNA polypeptide comprises a nucleic acid sequence
identified by any one of SEQ ID NO: 431-461. 9. The vaccine of any
one of paragraphs 1, 2 or 4-8, wherein the at least one antigenic
polypeptide has an amino acid sequence that has at least 95%
identity to an amino acid sequence identified by any one of SEQ ID
NO: 31-61. 10. The vaccine of any one of paragraphs 1, 2 or 4-9,
wherein the at least one antigenic polypeptide has an amino acid
sequence that has 95%-99% identity to an amino acid sequence
identified by any one of SEQ ID NO: 31-61. 11. The vaccine of any
one of paragraphs 1, 2 or 4-10, wherein the at least one antigenic
polypeptide has an amino acid sequence that has at least 90%
identity to an amino acid sequence of SEQ ID NO: 31-61 and wherein
the antigenic polypeptide or immunogenic fragment thereof has
membrane fusion activity, attaches to cell receptors, causes fusion
of viral and cellular membranes, and/or is responsible for binding
of the virus to a cell being infected. 12. The vaccine of any one
of paragraphs 1, 2 or 4-11, wherein the at least one antigenic
polypeptide has an amino acid sequence that has 90%-99% identity to
an amino acid sequence of SEQ ID NO: 31-61 and wherein the
antigenic polypeptide or immunogenic fragment thereof has membrane
fusion activity, attaches to cell receptors, causes fusion of viral
and cellular membranes, and/or is responsible for binding of the
virus to a cell being infected. 13. The vaccine of any one of
paragraphs 2-12, wherein the at least one antigenic polypeptide is
a major outer membrane protein (MOMP) or an immunogenic fragment
thereof, optionally having a Chlamydia trachomatis serovar selected
serovar H, F, E, D, I, G, J and K. 14. The vaccine of any one of
paragraphs 2-13, wherein the vaccine comprises at least one RNA
polynucleotide having an open reading frame encoding at least two
antigenic polypeptides or immunogenic fragments thereof selected
from a MOMP of serovar H, a MOMP of serovar F, a MOMP of serovar E,
a MOMP of serovar D, a MOMP of serovar I, a MOMP of serovar G, a
MOMP of serovar J, and a MOMP of serovar K. 15. The vaccine of any
one of paragraphs 2-14, wherein the vaccine comprises at least two
RNA polynucleotides, each having an open reading frame encoding at
least one antigenic polypeptide or an immunogenic fragment thereof
selected from a MOMP of serovar H, a MOMP of serovar F, a MOMP of
serovar E, a MOMP of serovar D, a MOMP of serovar I, a MOMP of
serovar G, a MOMP of serovar J, and a MOMP of serovar K, wherein
the antigenic polypeptide encoded by one of the open reading frames
differs from the antigenic polypeptide encoded by another of the
open reading frames. 16. The vaccine of any one of paragraphs 2-15,
wherein the at least one antigenic polypeptide comprises an amino
acid sequence identified by any one of SEQ ID NO: 65-183. 17. The
vaccine of any one of paragraphs 2-16, wherein the at least one RNA
polypeptide is encoded by a nucleic acid sequence identified by any
one of SEQ ID NO: 62-64 or 184-294, and/or wherein the at least one
RNA polypeptide comprises a nucleic acid sequence identified by any
one of SEQ ID NO: 317-430. 18. The vaccine of any one of paragraphs
2-17, wherein the at least one antigenic polypeptide has an amino
acid sequence that has at least 95% identity to an amino acid
sequence identified by any one of SEQ ID NO: 65-183. 19. The
vaccine of any one of paragraphs 2-18, wherein the at least one
antigenic polypeptide has an amino acid sequence that has 95%-99%
identity to an amino acid sequence identified by any one of SEQ ID
NO: 65-183. 20. The vaccine of any one of paragraphs 2-19, wherein
the at least one antigenic polypeptide has an amino acid sequence
that has at least 90% identity to an amino acid sequence of SEQ ID
NO: 65-183 and wherein the antigenic polypeptide or immunogenic
fragment thereof has membrane fusion activity, attaches to cell
receptors, causes fusion of viral and cellular membranes, and/or is
responsible for binding of the virus to a cell being infected. 21.
The vaccine of any one of paragraphs 2-20, wherein the at least one
antigenic polypeptide has an amino acid sequence that has 90%-99%
identity to an amino acid sequence of SEQ ID NO: 65-183 and wherein
the antigenic polypeptide or immunogenic fragment thereof has
membrane fusion activity, attaches to cell receptors, causes fusion
of viral and cellular membranes, and/or is responsible for binding
of the virus to a cell being infected. 22. The vaccine of any one
of paragraphs 1-21, wherein the at least one RNA polynucleotide has
less than 80% identity to wild-type mRNA sequence. 23. The vaccine
of any one of paragraphs 1-21, wherein at least one RNA
polynucleotide has at least 80% identity to wild-type mRNA
sequence, but does not include wild-type mRNA sequence. 24. The
vaccine of any one of paragraphs 1-23, wherein the at least one
antigenic polypeptide has membrane fusion activity, attaches to
cell receptors, causes fusion of viral and cellular membranes,
and/or is responsible for binding of the virus to a cell being
infected. 25. The vaccine of any one of paragraphs 1-24, wherein
the at least one RNA polynucleotide comprises at least one chemical
modification. 26. The vaccine of paragraph 1-25, wherein the
chemical modification is selected from pseudouridine,
N1-methylpseudouridine, N1-ethylpseudouridine, 2-thiouridine,
4'-thiouridine, 5-methylcytosine, 5-methyluridine,
2-thio-1-methyl-1-deaza-pseudouridine,
2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine,
2-thio-dihydropseudouridine, 2-thio-dihydrouridine,
2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine,
4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine,
4-thio-pseudouridine, 5-aza-uridine, dihydropseudouridine,
5-methoxyuridine and 2'-O-methyl uridine. 27. The vaccine of
paragraph 1-26, wherein the chemical modification is in the
5-position of the uracil. 28. The vaccine of any one of paragraphs
1-27, wherein the chemical modification is a N1-methylpseudouridine
or N1-ethylpseudouridine. 29. The vaccine of any one of paragraphs
1-28, wherein at least 80% of the uracil in the open reading frame
have a chemical modification. 30. The vaccine of any one of
paragraphs 1-29, wherein at least 90% of the uracil in the open
reading frame have a chemical modification. 31. The vaccine of any
one of paragraphs 1-30, wherein 100% of the uracil in the open
reading frame have a chemical modification. 32. The vaccine of any
one of paragraphs 1-31, wherein at least one RNA polynucleotide
further encodes at least one 5' terminal cap. 33. The vaccine of
paragraph 32, wherein the 5' terminal cap is 7mG(5')ppp(5')NlmpNp.
34. The vaccine of any one of paragraphs 1-33, wherein at least one
antigenic polypeptide or immunogenic fragment thereof is fused to a
signal peptide selected from: a HuIgGk signal peptide
(METPAQLLFLLLLWLPDTTG; SEQ ID NO: 304); IgE heavy chain epsilon-1
signal peptide (MDWTWILFLVAAATRVHS; SEQ ID NO: 305); Japanese
encephalitis PRM signal sequence (MLGSNSGQRVVFTILLLLVAPAYS; SEQ ID
NO: 306), VSVg protein signal sequence (MKCLLYLAFLFIGVNCA; SEQ ID
NO: 307) and Japanese encephalitis JEV signal sequence
(MWLVSLAIVTACAGA; SEQ ID NO: 308). 35. The vaccine of paragraph 34,
wherein the signal peptide is fused to the N-terminus of at least
one antigenic polypeptide. 36. The vaccine of paragraph 34, wherein
the signal peptide is fused to the C-terminus of at least one
antigenic polypeptide. 37. The vaccine of any one of paragraphs
1-36, wherein the antigenic polypeptide or immunogenic fragment
thereof comprises a mutated N-linked glycosylation site. 38. The
vaccine of any one of paragraphs 1-37, formulated in a
nanoparticle. 39. The vaccine of paragraph 38, wherein the
nanoparticle is a lipid nanoparticle. 40. The vaccine of any one of
paragraphs 1-39, wherein the nanoparticle has a mean diameter of
50-200 nm. 41. The vaccine of any one of paragraphs 1-40, wherein
the lipid nanoparticle comprises a cationic lipid, a PEG-modified
lipid, a sterol and a non-cationic lipid. 42. The vaccine of
paragraph 41, wherein the lipid nanoparticle carrier comprises a
molar ratio of about 20-60% cationic lipid, 0.5-15% PEG-modified
lipid, 25-55% sterol, and 25% non-cationic lipid. 43. The vaccine
of paragraph 41 or 42, wherein the cationic lipid is an ionizable
cationic lipid and the non-cationic lipid is a neutral lipid, and
the sterol is a cholesterol. 44. The vaccine of any one of
paragraphs 41-43, wherein the cationic lipid is selected from
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA),
dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and
di((Z)-non-2-en-1-yl)
9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319). 45. The
vaccine of any one of paragraphs 1-44, wherein the lipid
nanoparticle comprises a compound of Formula (I), optionally
Compound 3, 18, 20, 25, 26, 29, 30, 60, 108-112, or 122. 46. The
vaccine of any one of paragraphs 1-45, wherein the lipid
nanoparticle comprises a compound of Formula (II). 47. The vaccine
of any one of paragraphs 1-46, wherein the nanoparticle has a
polydispersity value of less than 0.4. 48. The vaccine of any one
of paragraphs 1-47, wherein the nanoparticle has a net neutral
charge at a neutral pH value. 49. The vaccine of any one of
paragraphs 1-48 further comprising an adjuvant. 50. The vaccine of
paragraph 49, wherein the adjuvant is a flagellin protein or
peptide. 51. The vaccine of paragraph 50, wherein the flagellin
protein or peptide comprises an amino acid sequence identified by
any one of SEQ ID NO: 301-303. 52. The vaccine of any one of
paragraphs 1-51, wherein the open reading frame is codon-optimized.
53. The vaccine of any one of paragraphs 1-52, wherein the vaccine
is multivalent. 54. The vaccine of any one of paragraphs 1-53
formulated in an effective amount to produce an antigen-specific
immune response. 55. A method of inducing an immune response in a
subject, the method comprising administering to the subject the
vaccine of any one of paragraphs 1-54 in an amount effective to
produce an antigen-specific immune response in the subject. 56. The
method of paragraph 55, wherein the antigen specific immune
response comprises a T cell response or a B cell response. 57. The
method of paragraph 55 or 56, wherein the subject is administered a
single dose of the vaccine. 58. The method of paragraph 55 or 56
wherein the subject is administered a booster dose of the vaccine.
59. The method of any one of paragraphs 55-58, wherein the vaccine
is administered to the subject by intradermal injection or
intramuscular injection. 60. The method of any one of paragraphs
55-59, wherein an anti-antigenic polypeptide antibody titer
produced in the subject is increased by at least 1 log relative to
a control. 61. The method of any one of paragraphs 55-60, wherein
an anti-antigenic polypeptide antibody titer produced in the
subject is increased by 1-3 log relative to a control. 62 The
method of any one of paragraphs 55-61, wherein the anti-antigenic
polypeptide antibody titer produced in the subject is increased at
least 2 times relative to a control. 63. The method of any one of
paragraphs 55-62, wherein the anti-antigenic polypeptide antibody
titer produced in the subject is increased 2-10 times relative to a
control. 64. The method of any one of paragraphs 60-63, wherein the
control is an anti-antigenic polypeptide antibody titer produced in
a subject who has not been administered a vaccine against the
virus. 65. The method of any one of paragraphs 60-63, wherein the
control is an anti-antigenic polypeptide antibody titer produced in
a subject who has been administered a live attenuated vaccine or an
inactivated vaccine against the virus. 66. The method of any one of
paragraphs 60-63, wherein the control is an anti-antigenic
polypeptide antibody titer produced in a subject who has been
administered a recombinant protein vaccine or purified protein
vaccine against the virus. 67. The method of any one of paragraphs
60-63, wherein the control is an anti-antigenic polypeptide
antibody titer produced in a subject who has been administered a
VLP vaccine against the virus. 68. The method of any one of
paragraphs 55-67, wherein the effective amount is a dose equivalent
to an at least 2-fold reduction in the standard of care dose of a
recombinant protein vaccine or a purified protein vaccine against
the virus, and wherein an anti-antigenic polypeptide antibody titer
produced in the subject is equivalent to an anti-antigenic
polypeptide antibody titer produced in a control subject
administered the standard of care dose of a recombinant protein
vaccine or a purified protein vaccine against the virus,
respectively. 69. The method of any one of paragraphs 55-67,
wherein the effective amount is a dose equivalent to an at least
2-fold reduction in the standard of care dose of a live attenuated
vaccine or an inactivated vaccine against the virus, and wherein an
anti-antigenic polypeptide antibody titer produced in the subject
is equivalent to an anti-antigenic polypeptide antibody titer
produced in a control subject administered the standard of care
dose of a live attenuated vaccine or an inactivated vaccine against
the virus, respectively. 70. The method of any one of paragraphs
55-67, wherein the effective amount is a dose equivalent to an at
least 2-fold reduction in the standard of care dose of a VLP
vaccine against the virus, and wherein an anti-antigenic
polypeptide antibody titer produced in the subject is equivalent to
an anti-antigenic polypeptide antibody titer produced in a control
subject administered the standard of care dose of a VLP vaccine
against the virus. 71. The method of any one of paragraphs 55-70,
wherein the effective amount is a total dose of 50 .mu.g-1000
.mu.g. 72. The method of paragraph 55-71, wherein the effective
amount is a dose of 25 .mu.g, 100 .mu.g, 400 .mu.g, or 500 .mu.g
administered to the subject a total of two times. 73. The method of
any one of paragraphs 55-72, wherein the efficacy of the vaccine
against the virus is greater than 65%. 74. The method of any one of
paragraphs 55-73, wherein the efficacy of the vaccine against the
virus is greater than 80%. 75. The method of any one of paragraphs
55-74, wherein the vaccine immunizes the subject against the virus
for up to 2 years. 76. The method of any one of paragraphs 55-74,
wherein the vaccine immunizes the subject against the virus for
more than 2 years. 77. The method of any one of paragraphs 55-76,
wherein the subject has an age of about 12 to about 50 years old.
78. The method of any one of paragraphs 55-77, wherein the subject
has been exposed to the virus, wherein the subject is infected with
the virus, or wherein the subject is at risk of infection by the
virus. 79. The method of any one of paragraphs 55-78, wherein the
subject is immunocompromised. 80. The vaccine of any one of
paragraphs 1-54 for use in a method of inducing an antigen specific
immune response in a subject, the method comprising administering
to the subject the vaccine in an amount effective to produce an
antigen specific immune response in the subject. 81. Use of the
vaccine of any one of paragraphs 1-54 in the manufacture of a
medicament for use in a method of inducing an antigen specific
immune response in a subject, the method comprising administering
to the subject the vaccine in an amount effective to produce an
antigen specific immune response in the subject. 82. An engineered
nucleic acid encoding at least one RNA polynucleotide of a vaccine
of any one of paragraphs 1-54. 83. A tropical disease vaccine,
comprising:
[0605] at least one messenger ribonucleic acid (mRNA)
polynucleotide having a 5' terminal cap, an open reading frame
encoding at least one tropical disease antigenic polypeptide, and a
3' polyA tail.
84. The vaccine of paragraph 1, wherein the at least one mRNA
polynucleotide is encoded by a sequence identified by any one of
SEQ ID NO: 1-28. 85. The vaccine of paragraph 1, wherein the at
least one mRNA polynucleotide comprises a sequence identified by
any one of SEQ ID NO: 431-461. 86. The vaccine of paragraph 1,
wherein the at least one antigenic polypeptide comprises a sequence
identified by any one of SEQ ID NO: 31-61. 87. The vaccine of
paragraph 1, wherein the at least one mRNA polynucleotide is
encoded by a sequence identified by any one of SEQ ID NO: 62-64.
88. The vaccine of paragraph 1, wherein the at least one mRNA
polynucleotide comprises a sequence identified by any one of SEQ ID
NO: 317-319. 89. The vaccine of paragraph 1, wherein the at least
one antigenic polypeptide comprises a sequence identified by any
one of SEQ ID NO: 65-72. 90. The vaccine of paragraph 1, wherein
the at least one mRNA polynucleotide is encoded by a sequence
identified by any one of SEQ ID NO: 184-294. 91. The vaccine of
paragraph 1, wherein the at least one mRNA polynucleotide comprises
a sequence identified by any one of SEQ ID NO: 320-430. 92. The
vaccine of paragraph 1, wherein the at least one antigenic
polypeptide comprises a sequence identified by any one of SEQ ID
NO: 73-183. 93. The vaccine of any one of paragraphs 83-92, wherein
the 5' terminal cap is or comprises 7mG(5')ppp(5')NlmpNp. 94. The
vaccine of any one of paragraphs 83-93, wherein 100% of the uracil
in the open reading frame is modified to include N1-methyl
pseudouridine at the 5-position of the uracil. 95. The vaccine of
any one of paragraphs 83-94, wherein the vaccine is formulated in a
lipid nanoparticle comprising: DLin-MC3-DMA; cholesterol;
1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC); and polyethylene
glycol (PEG)2000-DMG. 96. The vaccine of paragraph 95, wherein the
lipid nanoparticle further comprises trisodium citrate buffer,
sucrose and water. 97. A sexually transmitted disease (STD)
vaccine, comprising:
[0606] at least one messenger ribonucleic acid (mRNA)
polynucleotide having a 5' terminal cap 7mG(5')ppp(5')NlmpNp, a
sequence identified by SEQ ID NO: 431-461 and a 3' polyA tail,
wherein the uracil nucleotides of the sequence identified by SEQ ID
NO: 431-461 are modified to include N1-methyl pseudouridine at the
5-position of the uracil nucleotide.
98. A sexually transmitted disease (STD) vaccine, comprising:
[0607] at least one messenger ribonucleic acid (mRNA)
polynucleotide having a 5' terminal cap 7mG(5')ppp(5')NlmpNp, a
sequence identified by SEQ ID NO: 317-319 and a 3' polyA tail,
wherein the uracil nucleotides of the sequence identified by SEQ ID
NO: 317-319 are modified to include N1-methyl pseudouridine at the
5-position of the uracil nucleotide.
99. A sexually transmitted disease (STD) vaccine, comprising:
[0608] at least one messenger ribonucleic acid (mRNA)
polynucleotide having a 5' terminal cap 7mG(5')ppp(5')NlmpNp, a
sequence identified by SEQ ID NO: 320-430 and a 3' polyA tail,
wherein the uracil nucleotides of the sequence identified by SEQ ID
NO: 320-430 are modified to include N1-methyl pseudouridine at the
5-position of the uracil nucleotide.
100. The vaccine of paragraph X formulated in a lipid nanoparticle
comprising DLin-MC3-DMA, cholesterol,
1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC), and polyethylene
glycol (PEG)2000-DMG.
[0609] This disclosure is not limited in its application to the
details of construction and the arrangement of components set forth
in the following description or illustrated in the drawings. The
disclosure is capable of other embodiments and of being practiced
or of being carried out in various ways. Also, the phraseology and
terminology used herein is for the purpose of description and
should not be regarded as limiting. The use of "including,"
"comprising," or "having," "containing," "involving," and
variations thereof herein, is meant to encompass the items listed
thereafter and equivalents thereof as well as additional items.
EXAMPLES
Example 1: Manufacture of Polynucleotides
[0610] According to the present disclosure, the manufacture of
polynucleotides and/or parts or regions thereof may be accomplished
utilizing the methods taught in International Publication
WO2014/152027, entitled "Manufacturing Methods for Production of
RNA Transcripts," the contents of which is incorporated herein by
reference in its entirety.
[0611] Purification methods may include those taught in
International Publication WO2014/152030 and International
Publication WO2014/152031, each of which is incorporated herein by
reference in its entirety.
[0612] Detection and characterization methods of the
polynucleotides may be performed as taught in International
Publication WO2014/144039, which is incorporated herein by
reference in its entirety.
[0613] Characterization of the polynucleotides of the disclosure
may be accomplished using polynucleotide mapping, reverse
transcriptase sequencing, charge distribution analysis, detection
of RNA impurities, or any combination of two or more of the
foregoing. "Characterizing" comprises determining the RNA
transcript sequence, determining the purity of the RNA transcript,
or determining the charge heterogeneity of the RNA transcript, for
example. Such methods are taught in, for example, International
Publication WO2014/144711 and International Publication
WO2014/144767, the content of each of which is incorporated herein
by reference in its entirety.
Example 2: Chimeric Polynucleotide Synthesis
[0614] According to the present disclosure, two regions or parts of
a chimeric polynucleotide may be joined or ligated using
triphosphate chemistry. A first region or part of 100 nucleotides
or less is chemically synthesized with a 5' monophosphate and
terminal 3'desOH or blocked OH, for example. If the region is
longer than 80 nucleotides, it may be synthesized as two strands
for ligation.
[0615] If the first region or part is synthesized as a
non-positionally modified region or part using in vitro
transcription (IVT), conversion the 5'monophosphate with subsequent
capping of the 3' terminus may follow.
[0616] Monophosphate protecting groups may be selected from any of
those known in the art.
[0617] The second region or part of the chimeric polynucleotide may
be synthesized using either chemical synthesis or IVT methods. IVT
methods may include an RNA polymerase that can utilize a primer
with a modified cap. Alternatively, a cap of up to 130 nucleotides
may be chemically synthesized and coupled to the IVT region or
part.
[0618] For ligation methods, ligation with DNA T4 ligase, followed
by treatment with DNase should readily avoid concatenation.
[0619] The entire chimeric polynucleotide need not be manufactured
with a phosphate-sugar backbone. If one of the regions or parts
encodes a polypeptide, then such region or part may comprise a
phosphate-sugar backbone.
[0620] Ligation is then performed using any known click chemistry,
orthoclick chemistry, solulink, or other bioconjugate chemistries
known to those in the art.
[0621] Synthetic Route
[0622] The chimeric polynucleotide may be made using a series of
starting segments. Such segments include:
[0623] (a) a capped and protected 5' segment comprising a normal
3'OH (SEG. 1)
[0624] (b) a 5' triphosphate segment, which may include the coding
region of a polypeptide and a normal 3'OH (SEG. 2)
[0625] (c) a 5' monophosphate segment for the 3' end of the
chimeric polynucleotide (e.g., the tail) comprising cordycepin or
no 3'OH (SEG. 3)
[0626] After synthesis (chemical or IVT), segment 3 (SEG. 3) may be
treated with cordycepin and then with pyrophosphatase to create the
5' monophosphate.
[0627] Segment 2 (SEG. 2) may then be ligated to SEG. 3 using RNA
ligase. The ligated polynucleotide is then purified and treated
with pyrophosphatase to cleave the diphosphate. The treated
SEG.2-SEG. 3 construct may then be purified and SEG. 1 is ligated
to the 5' terminus. A further purification step of the chimeric
polynucleotide may be performed.
[0628] Where the chimeric polynucleotide encodes a polypeptide, the
ligated or joined segments may be represented as: 5'UTR (SEG. 1),
open reading frame or ORF (SEG. 2) and 3'UTR+PolyA (SEG. 3).
[0629] The yields of each step may be as much as 90-95%.
Example 3: PCR for cDNA Production
[0630] PCR procedures for the preparation of cDNA may be performed
using 2.times.KAPA HIFI.TM. HotStart ReadyMix by Kapa Biosystems
(Woburn, Mass.). This system includes 2.times.KAPA ReadyMix 12.5
.mu.l; Forward Primer (10 .mu.M) 0.75 .mu.l; Reverse Primer (10
.mu.M) 0.75 .mu.l; Template cDNA 100 ng; and dH.sub.2O diluted to
25.0 .mu.l. The reaction conditions may be at 95.degree. C. for 5
min. The reaction may be performed for 25 cycles of 98.degree. C.
for 20 sec, then 58.degree. C. for 15 sec, then 72.degree. C. for
45 sec, then 72.degree. C. for 5 min, then 4.degree. C. to
termination.
[0631] The reaction may be cleaned up using Invitrogen's
PURELINK.TM. PCR Micro Kit (Carlsbad, Calif.) per manufacturer's
instructions (up to 5 .mu.g). Larger reactions may require a
cleanup using a product with a larger capacity. Following the
cleanup, the cDNA may be quantified using the NANODROP.TM. and
analyzed by agarose gel electrophoresis to confirm that the cDNA is
the expected size. The cDNA may then be submitted for sequencing
analysis before proceeding to the in vitro transcription
reaction.
Example 4: In Vitro Transcription (IVT)
[0632] The in vitro transcription reaction generates RNA
polynucleotides. Such polynucleotides may comprise a region or part
of the polynucleotides of the disclosure, including chemically
modified RNA (e.g., mRNA) polynucleotides. The chemically modified
RNA polynucleotides can be uniformly modified polynucleotides. The
in vitro transcription reaction utilizes a custom mix of nucleotide
triphosphates (NTPs). The NTPs may comprise chemically modified
NTPs, or a mix of natural and chemically modified NTPs, or natural
NTPs.
[0633] A typical in vitro transcription reaction includes the
following:
TABLE-US-00001 1) Template cDNA 1.0 .mu.g 2) 10x transcription
buffer 2.0 .mu.l (400 mM Tris-HCl pH 8.0, 190 mM MgCl.sub.2, 50 mM
DTT, 10 mM Spermidine) 3) Custom NTPs (25 mM each) 0.2 .mu.l 4)
RNase Inhibitor 20 U 5) T7 RNA polymerase 3000 U 6) dH.sub.20 up to
20.0 .mu.l. and 7) Incubation at 37.degree. C. for 3 hr-5 hrs.
[0634] The crude IVT mix may be stored at 4.degree. C. overnight
for cleanup the next day. 1 U of RNase-free DNase may then be used
to digest the original template. After 15 minutes of incubation at
37.degree. C., the mRNA may be purified using Ambion's
MEGACLEAR.TM. Kit (Austin, Tex.) following the manufacturer's
instructions. This kit can purify up to 500 .mu.g of RNA. Following
the cleanup, the RNA polynucleotide may be quantified using the
NanoDrop and analyzed by agarose gel electrophoresis to confirm the
RNA polynucleotide is the proper size and that no degradation of
the RNA has occurred.
Example 5: Enzymatic Capping
[0635] Capping of a RNA polynucleotide is performed as follows
where the mixture includes: IVT RNA 60 .mu.g-180 .mu.g and
dH.sub.2O up to 72 .mu.l. The mixture is incubated at 65.degree. C.
for 5 minutes to denature RNA, and then is transferred immediately
to ice.
[0636] The protocol then involves the mixing of 10.times. Capping
Buffer (0.5 M Tris-HCl (pH 8.0), 60 mM KCl, 12.5 mM MgCl.sub.2)
(10.0 .mu.l); 20 mM GTP (5.0 .mu.l); 20 mM S-Adenosyl Methionine
(2.5 .mu.l); RNase Inhibitor (100 U); 2'-O-Methyltransferase
(400U); Vaccinia capping enzyme (Guanylyl transferase) (40 U);
dH.sub.2O (Up to 28 .mu.l); and incubation at 37.degree. C. for 30
minutes for 60 .mu.g RNA or up to 2 hours for 180 .mu.g of RNA.
[0637] The RNA polynucleotide may then be purified using Ambion's
MEGACLEAR.TM. Kit (Austin, Tex.) following the manufacturer's
instructions. Following the cleanup, the RNA may be quantified
using the NANODROP.TM. (ThermoFisher, Waltham, Mass.) and analyzed
by agarose gel electrophoresis to confirm the RNA polynucleotide is
the proper size and that no degradation of the RNA has occurred.
The RNA polynucleotide product may also be sequenced by running a
reverse-transcription-PCR to generate the cDNA for sequencing.
Example 6: PolyA Tailing Reaction
[0638] Without a poly-T in the cDNA, a poly-A tailing reaction must
be performed before cleaning the final product. This is done by
mixing capped IVT RNA (100 .mu.l); RNase Inhibitor (20 U);
10.times. Tailing Buffer (0.5 M Tris-HCl (pH 8.0), 2.5 M NaCl, 100
mM MgCl.sub.2) (12.0 .mu.l); 20 mM ATP (6.0 .mu.l); Poly-A
Polymerase (20 U); dH.sub.2O up to 123.5 .mu.l and incubation at
37.degree. C. for 30 min. If the poly-A tail is already in the
transcript, then the tailing reaction may be skipped and proceed
directly to cleanup with Ambion's MEGACLEAR.TM. kit (Austin, Tex.)
(up to 500 .mu.g). Poly-A Polymerase may be a recombinant enzyme
expressed in yeast.
[0639] It should be understood that the processivity or integrity
of the polyA tailing reaction may not always result in an exact
size polyA tail. Hence, polyA tails of approximately between 40-200
nucleotides, e.g., about 40, 50, 60, 70, 80, 90, 91, 92, 93, 94,
95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108,
109, 110, 150-165, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164
or 165 are within the scope of the present disclosure.
Example 7: Natural 5' Caps and 5' Cap Analogues
[0640] 5'-capping of polynucleotides may be completed concomitantly
during the in vitro-transcription reaction using the following
chemical RNA cap analogs to generate the 5'-guanosine cap structure
according to manufacturer protocols: 3'-O-Me-m7G(5')ppp(5') G [the
ARCA cap]; G(5')ppp(5')A; G(5')ppp(5')G; m7G(5')ppp(5')A;
m7G(5')ppp(5')G (New England BioLabs, Ipswich, Mass.). 5'-capping
of modified RNA may be completed post-transcriptionally using a
Vaccinia Virus Capping Enzyme to generate the "Cap 0" structure:
m7G(5')ppp(5')G (New England BioLabs, Ipswich, Mass.). Cap 1
structure may be generated using both Vaccinia Virus Capping Enzyme
and a 2'-O methyl-transferase to generate:
m7G(5')ppp(5')G-2'-O-methyl. Cap 2 structure may be generated from
the Cap 1 structure followed by the 2'-O-methylation of the
5'-antepenultimate nucleotide using a 2'-O methyl-transferase. Cap
3 structure may be generated from the Cap 2 structure followed by
the 2'-O-methylation of the 5'-preantepenultimate nucleotide using
a 2'-O methyl-transferase. Enzymes are preferably derived from a
recombinant source.
[0641] When transfected into mammalian cells, the modified mRNAs
have a stability of between 12-18 hours or more than 18 hours,
e.g., 24, 36, 48, 60, 72 or greater than 72 hours.
Example 8: Capping Assays
Protein Expression Assay
[0642] Polynucleotides (e.g., mRNA) encoding a polypeptide,
containing any of the caps taught herein, can be transfected into
cells at equal concentrations. The amount of protein secreted into
the culture medium can be assayed by ELISA at 6, 12, 24 and/or 36
hours post-transfection. Synthetic polynucleotides that secrete
higher levels of protein into the medium correspond to a synthetic
polynucleotide with a higher translationally-competent cap
structure.
Purity Analysis Synthesis
[0643] RNA (e.g., mRNA) polynucleotides encoding a polypeptide,
containing any of the caps taught herein can be compared for purity
using denaturing Agarose-Urea gel electrophoresis or HPLC analysis.
RNA polynucleotides with a single, consolidated band by
electrophoresis correspond to the higher purity product compared to
polynucleotides with multiple bands or streaking bands. Chemically
modified RNA polynucleotides with a single HPLC peak also
correspond to a higher purity product. The capping reaction with a
higher efficiency provides a more pure polynucleotide
population.
Cytokine Analysis
[0644] RNA (e.g., mRNA) polynucleotides encoding a polypeptide,
containing any of the caps taught herein can be transfected into
cells at multiple concentrations. The amount of pro-inflammatory
cytokines, such as TNF-alpha and IFN-beta, secreted into the
culture medium can be assayed by ELISA at 6, 12, 24 and/or 36 hours
post-transfection. RNA polynucleotides resulting in the secretion
of higher levels of pro-inflammatory cytokines into the medium
correspond to a polynucleotides containing an immune-activating cap
structure.
Capping Reaction Efficiency
[0645] RNA (e.g., mRNA) polynucleotides encoding a polypeptide,
containing any of the caps taught herein can be analyzed for
capping reaction efficiency by LC-MS after nuclease treatment.
Nuclease treatment of capped polynucleotides yield a mixture of
free nucleotides and the capped 5'-5-triphosphate cap structure
detectable by LC-MS. The amount of capped product on the LC-MS
spectra can be expressed as a percent of total polynucleotide from
the reaction and correspond to capping reaction efficiency. The cap
structure with a higher capping reaction efficiency has a higher
amount of capped product by LC-MS.
Example 9: Agarose Gel Electrophoresis of Modified RNA or RT PCR
Products
[0646] Individual RNA polynucleotides (200-400 ng in a 20 .mu.l
volume) or reverse transcribed PCR products (200-400 ng) may be
loaded into a well on a non-denaturing 1.2% Agarose E-Gel
(Invitrogen, Carlsbad, Calif.) and run for 12-15 minutes, according
to the manufacturer protocol.
Example 10: Nanodrop Modified RNA Quantification and UV Spectral
Data
[0647] Chemically modified RNA polynucleotides in TE buffer (1
.mu.l) are used for Nanodrop UV absorbance readings to quantitate
the yield of each polynucleotide from an chemical synthesis or in
vitro transcription reaction.
Example 11: Formulation of Modified mRNA Using Lipidoids
[0648] RNA (e.g., mRNA) polynucleotides may be formulated for in
vitro experiments by mixing the polynucleotides with the lipidoid
at a set ratio prior to addition to cells. In vivo formulation may
require the addition of extra ingredients to facilitate circulation
throughout the body. To test the ability of these lipidoids to form
particles suitable for in vivo work, a standard formulation process
used for siRNA-lipidoid formulations may be used as a starting
point. After formation of the particle, polynucleotide is added and
allowed to integrate with the complex. The encapsulation efficiency
is determined using a standard dye exclusion assays.
Example 12: HPV Immunogenicity Study
[0649] The instant study is designed to test the immunogenicity in
mice of candidate HPV vaccines comprising a chemically modified or
unmodified mRNA polynucleotide encoding HPV L1 protein obtained
from HPV serotypes 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56,
58, 59, 68, 73 or 82.
[0650] Mice are immunized intravenously (IV), intramuscularly (IM),
or intradermally (ID) with candidate vaccines. Up to three
immunizations are given at 3-week intervals (i.e., at weeks 0, 3,
6, and 9), and sera are collected after each immunization until
weeks 33-51. Serum antibody titers against HPV L1 protein are
determined by ELISA.
Example 13: HPV Challenge
[0651] The instant study is designed to test the efficacy in guinea
pig of candidate HPV vaccines against a lethal challenge using a
HPV vaccine comprising a chemically modified or unmodified mRNA
encoding HPV L1 protein obtained from HPV serotypes 6, 11, 16, 18,
31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73 or 82. Animals are
challenged with a lethal dose of the HPV.
[0652] Animals are immunized intravenously (IV), intramuscularly
(IM), or intradermally (ID) at week 0 and week 3 with candidate HPV
vaccines with and without adjuvant. The animals are then challenged
with a lethal dose of HPV on week 7 via IV, IM or ID. Endpoint is
day 13 post infection, death or euthanasia. Animals displaying
severe illness as determined by >30% weight loss, extreme
lethargy or paralysis are euthanized. Body temperature and weight
are assessed and recorded daily.
[0653] In experiments where a lipid nanoparticle (LNP) formulation
is used, the formulation may include a cationic lipid, non-cationic
lipid, PEG lipid and structural lipid in the ratios 50:10:1.5:38.5.
The cationic lipid is DLin-KC2-DMA (50 mol %) or DLin-MC3-DMA (50
mol %), the non-cationic lipid is DSPC (10 mol %), the PEG lipid is
PEG-DOMG (1.5 mol %) and the structural lipid is cholesterol (38.5
mol %), for example.
[0654] Efficacy of HPV vaccine candidates against HPV challenge are
compared to efficacy of vaccination of animals with Gardasil.RTM.
(Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18)
Vaccine, Recombinant, Merck).
Example 14: Chlamydia Immunogenicity Study
[0655] The instant study was designed to test the immunogenicity in
C57BL/6 mice with different Chlamydia Ct089mRNA vaccines. Mice
(n=10) were immunized intramuscularly (IM) with candidate vaccines
designated Ct089mRNA, Ct089NGM mRNA (N-glycosylated) or rCt089
protein (in Addvax). 2 .mu.g or 10 .mu.g doses in a 50 .mu.l volume
were administered to mice on day 0 and on day 21 (boost). The
MC3/mRNA concentration used was 0.2 mg/ml for 10 .mu.g dose, or
0.04 mg/ml for 2 .mu.g dose. Mice were bled for serum preparation
on day -3, 21 and 35. Anti-Ct089 antibody titers in serum were
measured using rCt089 produced in E. coli as the antigen. FIG. 4
shows antibody titers measured on day 21 and on day 35.
[0656] Excellent IgG titers were detected with native Ct089mRNA
(present after single dose and boosted after second dose). Dose
titration was observed with lower dose immunization, but positive
titers were observed with both 2 .mu.g and 10 .mu.g doses. 10 .mu.g
Ct089mRNA responses surpass the 10 .mu.g rCt089 protein
control.
[0657] N-glycosylation mutant Ct089 (Ct089NGM) mRNA was also
immunogenic but to a slightly weaker extent.
[0658] Ct089 is a promising Ct vaccine antigen candidate. Ct089
displayed both N- and O-glycosylation when expressed in mammalian
cells. Given the extensive glycosylation observed with Ct089,
mammalian glycosylation of mRNA encoded bacterial proteins in
mammalian cells does not appear to mask immune epitopes or impede
immunogenicity.
Example 15: Chlamydia trachomatis Rodent Challenge
[0659] The instant study is designed to test the efficacy in Guinea
pigs of candidate Chlamydia vaccines against a lethal challenge
using a Chlamydia vaccine comprising chemically modified or
unmodified mRNA encoding MOMP obtained from Chlamydia trachomatis
serovar H, F, E, D, I, G, J or K. Mice are challenged with a lethal
dose of the Chlamydia trachomatis.
[0660] Animals are immunized intravaginally (IG), intramuscularly
(IM), or intradermally (ID) at week 0 and week 3 with candidate
Chlamydia vaccines with and without adjuvant. The animals are then
challenged with a lethal dose of Chlamydia trachomatis on week 7
via an IG, IM or ID route. Endpoint is day 13 post infection, death
or euthanasia. Animals displaying severe illness as determined by
>30% weight loss, extreme lethargy or paralysis are euthanized.
Body temperature and weight are assessed and recorded daily.
[0661] In experiments where a lipid nanoparticle (LNP) formulation
is used, the formulation may include a cationic lipid, non-cationic
lipid, PEG lipid and structural lipid in the ratios 50:10:1.5:38.5.
The cationic lipid is DLin-KC2-DMA (50 mol %), the non-cationic
lipid is DSPC (10 mol %), the PEG lipid is PEG-DOMG (1.5 mol %) and
the structural lipid is cholesterol (38.5 mol %), for example.
Example 16: In Vitro Expression of Chlamydia trachomatis Antigens
from Candidate mRNA Vaccines
[0662] This study was designed to test the in vitro expression of
Chlamydia trachomatis antigens from candidate mRNA vaccines.
Candidate mRNA vaccines encoding MOMP, Ct875, Ct858, Ct089,
PmPG_pd, Ct460, Ct622, Cta1, Ct443, or Ct812pd_D were tested. The
candidate mRNA vaccines encoding MOMP were transfected into Hela
cells. The expression of MOMP in Hela cells was visualized by
immunofluorescence by staining the transfected Hela cells using
mouse anti-MOMP antibodies. Fluorescent microscopy images showed
co-localization of the anti-MOMP antibodies and Hela cells (data
not shown). The mRNA vaccine constructs encoding Ct875, Ct858,
Ct089, PmPG_pd, Ct460, Ct622, Cta1, Ct443, or Ct812pd_D were
transfected into HEK293F cells. Twenty hours post transfection, the
cell culture supernatant (concentrated or dilute) or HEK293F cell
lysates were collected and the expression of the antigens were
analyzed by Western blot. The Chlamydia trachomatis antigens were
tagged with a HisX6 tag. Mouse anti-6.times.His antibodies were
used as the primary antibody, and anti-mouse A1647 antibodies were
used as the secondary antibody. The cellular GAPDH was also
detected as control. Rabbit anti-GAPDH antibodies were used as the
primary antibody, and anti-rabbit Cy3 antibodies were used as the
secondary antibody. The results of the Western blot are shown in
FIGS. 1A-1B, FIGS. 2A-2B, FIG. 3 and Table 14.
[0663] Each of the sequences described herein encompasses a
chemically modified sequence or an unmodified sequence which
includes no modifications.
TABLE-US-00002 TABLE 1 HPV Nucleic Acid Sequences SEQ ID
Description Sequence NO: HPV6_L1
ATGTGGCGGCCTAGCGACAGCACAGTATATGTGCCTCCT 1
CCTAACCCTGTATCCAAAGTTGTTGCCACGGATGCTTAT
GTTACTCGCACCAACATATTTTATCATGCCAGCAGTTCC
AGACTTCTTGCAGTGGGACATCCTTATTTTTCCATAAAA
CGGGCTAACAAAACTGTTGTGCCAAAGGTGTCAGGATA
TCAATACAGGGTATTTAAGGTGGTGTTACCAGATCCTAA
CAAATTTGCATTGCCTGACTCGTCTCTTTTCGATCCCACA
ACACAACGTTTAGTATGGGCATGCACAGGCCTAGAGGT
GGGCAGGGGACAGCCATTAGGTGTGGGTGTAAGTGGAC
ATCCTTTCCTAAATAAATATGATGATGTTGAAAATTCAG
GGAGTGGTGGTAACCCTGGACAGGATAACAGGGTTAAT
GTAGGTATGGATTATAAACAAACACAATTATGCATGGTT
GGATGTGCCCCCCCTTTGGGCGAGCATTGGGGTAAAGGT
AAACAGTGTACTAATACACCTGTACAGGCTGGTGACTGC
CCGCCCTTAGAACTTATTACCAGTGTTATACAGGATGGC
GATATGGTTGACACAGGCTTTGGTGCTATGAATTTTGCT
GATTTGCAGACCAATAAATCAGATGTTCCTATTGACATA
TGTGGCACTACATGTAAATATCCAGATTATTTACAAATG
GCTGCAGACCCATATGGTGATAGATTATTTTTTTTTCTAC
GGAAGGAACAAATGTTTGCCAGACATTTTTTTAACAGGG
CTGGCGAGGTGGGGGAACCTGTGCCTGATACACTTATAA
TTAAGGGTAGTGGAAATCGCACGTCTGTAGGGAGTAGT
ATATATGTTAACACCCCGAGCGGCTCTTTGGTGTCCTCT
GAGGCACAATTGTTTAATAAGCCATATTGGCTACAAAAA
GCCCAGGGACATAACAATGGTATTTGTTGGGGTAATCAA
CTGTTTGTTACTGTGGTAGATACCACACGCAGTACCAAC
ATGACATTATGTGCATCCGTAACTACATCTTCCACATAC
ACCAATTCTGATTATAAAGAGTACATGCGTCATGTGGAA
GAGTATGATTTACAATTTATTTTTCAATTATGTAGCATTA
CATTGTCTGCTGAAGTAATGGCCTATATTCACACAATGA
ATCCCTCTGTTTTGGAAGACTGGAACTTTGGGTTATCGC
CTCCCCCAAATGGTACATTAGAAGATACCTATAGGTATG
TGCAGTCACAGGCCATTACCTGTCAAAAGCCCACTCCTG
AAAAGGAAAAGCCAGATCCCTATAAGAACCTTAGTTTTT
GGGAGGTTAATTTAAAAGAAAAGTTTTCTAGTGAATTGG
ATCAGTATCCTTTGGGACGCAAGTTTTTGTTACAAAGTG
GATATAGGGGACGGTCCTCTATTCGTACAGGTGTTAAGC
GCCCTGCTGTTTCCAAAGCCTCTGCTGCCCCTAAACGTA AGCGCGCCAAAACTAAAAGG
HPV11_L1 ATGTGGCGGCCTAGCGACAGCACAGTATATGTGCCTCCT 2
CCCAACCCTGTATCCAAGGTTGTTGCCACGGATGCGTAT
GTTAAACGCACCAACATATTTTATCATGCCAGCAGTTCC
AGACTCCTTGCTGTGGGACATCCATATTACTCTATCAAA
AAAGTTAACAAAACAGTTGTACCAAAGGTGTCTGGATA
TCAATATAGAGTGTTTAAGGTAGTGTTGCCAGATCCTAA
CAAGTTTGCATTACCTGATTCATCCCTGTTTGACCCCACT
ACACAGCGTTTAGTATGGGCGTGCACAGGGTTGGAGGT
AGGCAGGGGTCAACCTTTAGGCGTTGGTGTTAGTGGGCA
TCCATTGCTAAACAAATATGATGATGTAGAAAATAGTGG
TGGGTATGGTGGTAATCCTGGTCAGGATAATAGGGTTAA
TGTAGGTATGGATTATAAACAAACCCAGCTATGTATGGT
GGGCTGTGCTCCACCGTTAGGTGAACATTGGGGTAAGG
GTACACAATGTTCAAATACCTCTGTACAAAATGGTGACT
GCCCCCCGTTGGAACTTATTACCAGTGTTATACAGGATG
GGGACATGGTTGATACAGGCTTTGGTGCTATGAATTTTG
CAGACTTACAAACCAATAAATCGGATGTTCCCCTTGATA
TTTGTGGAACTGTCTGCAAATATCCTGATTATTTGCAAA
TGGCTGCAGACCCTTATGGTGATAGGTTGTTTTTTTATTT
GCGAAAGGAACAAATGTTTGCTAGACACTTTTTTAATAG
GGCCGGTACTGTGGGGGAACCTGTGCCTGATGACCTGTT
GGTAAAAGGGGGTAATAACAGATCATCTGTAGCTAGTA
GTATTTATGTACATACACCTAGTGGCTCATTGGTGTCTTC
AGAGGCTCAATTATTTAATAAACCATATTGGCTTCAAAA
GGCTCAGGGACATAACAATGGTATTTGCTGGGGAAACC
ACTTGTTTGTTACTGTGGTAGATACCACACGCAGTACAA
ATATGACACTATGTGCATCTGTGTCTAAATCTGCTACAT
ACACTAATTCAGATTATAAGGAATACATGCGCCATGTGG
AGGAGTTTGATTTACAGTTTATTTTTCAATTGTGTAGCAT
TACATTATCTGCAGAAGTCATGGCCTATATACACACAAT
GAATCCTTCTGTTTTGGAGGACTGGAACTTTGGTTTATC
GCCTCCACCAAATGGTACACTGGAGGATACTTATAGATA
TGTACAGTCACAGGCCATTACCTGTCAGAAACCCACACC
TGAAAAAGAAAAACAGGATCCCTATAAGGATATGAGTT
TTTGGGAGGTTAACTTAAAAGAAAAGTTTTCAAGTGAAT
TAGATCAGTTTCCCCTTGGACGTAAGTTTTTATTGCAAA
GTGGATATCGAGGACGGACGTCTGCTCGTACAGGTATA
AAGCGCCCAGCTGTGTCTAAGCCCTCTACAGCCCCCAAA CGAAAACGTACCAAAACCAAAAAG
HPV16_L1 ATGTCTCTTTGGCTGCCTAGTGAGGCCACTGTCTACTTGC 3
CTCCTGTCCCAGTATCTAAGGTTGTAAGCACGGATGAAT
ATGTTGCACGCACAAACATATATTATCATGCAGGAACAT
CCAGACTACTTGCAGTTGGACATCCCTATTTTCCTATTAA
AAAACCTAACAATAACAAAATATTAGTTCCTAAAGTATC
AGGATTACAATACAGGGTATTTAGAATACATTTACCTGA
CCCCAATAAGTTTGGTTTTCCTGACACCTCATTTTATAAT
CCAGATACACAGCGGCTGGTTTGGGCCTGTGTAGGTGTT
GAGGTAGGTCGTGGTCAGCCATTAGGTGTGGGCATTAGT
GGCCATCCTTTATTAAATAAATTGGATGACACAGAAAAT
GCTAGTGCTTATGCAGCAAATGCAGGTGTGGATAATAG
AGAATGTATATCTATGGATTACAAACAAACACAATTGTG
TTTAATTGGTTGCAAACCACCTATAGGGGAACACTGGGG
CAAAGGATCCCCATGTACCAATGTTGCAGTAAATCCAGG
TGATTGTCCACCATTAGAGTTAATAAACACAGTTATTCA
GGATGGTGATATGGTTGATACTGGCTTTGGTGCTATGGA
CTTTACTACATTACAGGCTAACAAAAGTGAAGTTCCACT
GGATATTTGTACATCTATTTGCAAATATCCAGATTATATT
AAAATGGTGTCAGAACCATATGGCGACAGCTTATTTTTT
TATTTACGAAGGGAACAAATGTTTGTTAGACATTTATTT
AATAGGGCTGGTACTGTTGGTGAAAATGTACCAGACGA
TTTATACATTAAAGGCTCTGGGTCTACTGCAAATTTAGC
CAGTTCAAATTATTTTCCTACACCTAGTGGTTCTATGGTT
ACCTCTGATGCCCAAATATTCAATAAACCTTATTGGTTA
CAACGAGCACAGGGCCACAATAATGGCATTTGTTGGGG
TAACCAACTATTTGTTACTGTTGTTGATACTACACGCAG
TACAAATATGTCATTATGTGCTGCCATATCTACTTCAGA
AACTACATATAAAAATACTAACTTTAAGGAGTACCTACG
ACATGGGGAGGAATATGATTTACAGTTTATTTTTCAACT
GTGCAAAATAACCTTAACTGCAGACGTTATGACATACAT
ACATTCTATGAATTCCACTATTTTGGAGGACTGGAATTT
TGGTCTACAACCTCCCCCAGGAGGCACACTAGAAGATA
CTTATAGGTTTGTAACATCCCAGGCAATTGCTTGTCAAA
AACATACACCTCCAGCACCTAAAGAAGATCCCCTTAAA
AAATACACTTTTTGGGAAGTAAATTTAAAGGAAAAGTTT
TCTGCAGACCTAGATCAGTTTCCTTTAGGACGCAAATTT
TTACTACAAGCAGGATTGAAGGCCAAACCAAAATTTAC
ATTAGGAAAACGAAAAGCTACACCCACCACCTCATCTA
CCTCTACAACTGCTAAACGCAAAAAACGTAAGCTG HPV18_L1
ATGGCTTTGTGGCGGCCTAGTGACAATACCGTATATCTT 4
CCACCTCCTTCTGTGGCAAGAGTTGTAAATACCGATGAT
TATGTGACTCGCACAAGCATATTTTATCATGCTGGCAGC
TCCAGATTATTAACTGTTGGTAATCCATATTTTAGGGTTC
CTGCAGGTGGTGGCAATAAGCAGGATATTCCTAAGGTTT
CTGCATACCAATATAGAGTATTTAGGGTGCAGTTACCTG
ACCCAAATAAATTTGGTTTACCTGATACTAGTATTTATA
ATCCTGAAACACAACGTTTAGTGTGGGCCTGTGCTGGAG
TGGAAATTGGCCGTGGTCAGCCTTTAGGTGTTGGCCTTA
GTGGGCATCCATTTTATAATAAATTAGATGACACTGAAA
GTTCCCATGCCGCCACGTCTAATGTTTCTGAGGACGTTA
GGGACAATGTGTCTGTAGATTATAAGCAGACACAGTTAT
GTATTTTGGGCTGTGCCCCTGCTATTGGGGAACACTGGG
CTAAAGGCACTGCTTGTAAATCGCGTCCTTTATCACAGG
GCGATTGCCCCCCTTTAGAACTTAAAAACACAGTTTTGG
AAGATGGTGATATGGTAGATACTGGATATGGTGCCATG
GACTTTAGTACATTGCAAGATACTAAATGTGAGGTACCA
TTGGATATTTGTCAGTCTATTTGTAAATATCCTGATTATT
TACAAATGTCTGCAGATCCTTATGGGGATTCCATGTTTTT
TTGCTTACGGCGTGAGCAGCTTTTTGCTAGGCATTTTTGG
AATAGAGCAGGTACTATGGGTGACACTGTGCCTCAATCC
TTATATATTAAAGGCACAGGTATGCGTGCTTCACCTGGC
AGCTGTGTGTATTCTCCCTCTCCAAGTGGCTCTATTGTTA
CCTCTGACTCCCAGTTGTTTAATAAACCATATTGGTTAC
ATAAGGCACAGGGTCATAACAATGGTGTTTGCTGGCATA
ATCAATTATTTGTTACTGTGGTAGATACCACTCGCAGTA
CCAATTTAACAATATGTGCTTCTACACAGTCTCCTGTAC
CTGGGCAATATGATGCTACCAAATTTAAGCAGTATAGCA
GACATGTTGAGGAATATGATTTGCAGTTTATTTTTCAGTT
GTGTACTATTACTTTAACTGCAGATGTTATGTCCTATATT
CATAGTATGAATAGCAGTATTTTAGAGGATTGGAACTTT
GGTGTTCCCCCCCCGCCAACTACTAGTTTGGTGGATACA
TATCGTTTTGTACAATCTGTTGCTATTACCTGTCAAAAGG
ATGCTGCACCGGCTGAAAATAAGGATCCCTATGATAAGT
TAAAGTTTTGGAATGTGGATTTAAAGGAAAAGTTTTCTT
TAGACTTAGATCAATATCCCCTTGGACGTAAATTTTTGG
TTCAGGCTGGATTGCGTCGCAAGCCCACCATAGGCCCTC
GCAAACGTTCTGCTCCATCTGCCACTACGTCTTCTAAAC
CTGCCAAGCGTGTGCGTGTACGTGCCAGGAAG HPV31_L1
ATGTCTCTGTGGCGGCCTAGCGAGGCTACTGTCTACTTA 5
CCACCTGTCCCAGTGTCTAAAGTTGTAAGCACGGATGAA
TATGTAACACGAACCAACATATATTATCACGCAGGCAGT
GCTAGGCTGCTTACAGTAGGCCATCCATATTATTCCATA
CCTAAATCTGACAATCCTAAAAAAATAGTTGTACCAAAG
GTGTCAGGATTACAATATAGGGTATTTAGGGTTCGTTTA
CCAGATCCAAACAAATTTGGATTTCCTGATACATCTTTTT
ATAATCCTGAAACTCAACGCTTAGTTTGGGCCTGTGTTG
GTTTAGAGGTAGGTCGCGGGCAGCCATTAGGTGTAGGT
ATTAGTGGTCATCCATTATTAAATAAATTTGATGACACT
GAAAACTCTAATAGATATGCCGGTGGTCCTGGCACTGAT
AATAGGGAATGTATATCAATGGATTATAAACAAACACA
ACTGTGTTTACTTGGTTGCAAACCACCTATTGGAGAGCA
TTGGGGTAAAGGTAGTCCTTGTAGTAACAATGCTATTAC
CCCTGGTGATTGTCCTCCATTAGAATTAAAAAATTCAGT
TATACAAGATGGGGATATGGTTGATACAGGCTTTGGAGC
TATGGATTTTACTGCTTTACAAGACACTAAAAGTAATGT
TCCTTTGGACATTTGTAATTCTATTTGTAAATATCCAGAT
TATCTTAAAATGGTTGCTGAGCCATATGGCGATACATTA
TTTTTTTATTTACGTAGGGAACAAATGTTTGTAAGGCATT
TTTTTAATAGATCAGGCACGGTTGGTGAATCGGTCCCTA
CTGACTTATATATTAAAGGCTCCGGTTCAACAGCTACTT
TAGCTAACAGTACATACTTTCCTACACCTAGCGGCTCCA
TGGTTACTTCAGATGCACAAATTTTTAATAAACCATATT
GGATGCAACGTGCTCAGGGACACAATAATGGTATTTGTT
GGGGCAATCAGTTATTTGTTACTGTGGTAGATACCACAC
GTAGTACCAATATGTCTGTTTGTGCTGCAATTGCAAACA
GTGATACTACATTTAAAAGTAGTAATTTTAAAGAGTATT
TAAGACATGGTGAGGAATTTGATTTACAATTTATATTTC
AGTTATGCAAAATAACATTATCTGCAGACATAATGACAT
ATATTCACAGTATGAATCCTGCTATTTTGGAAGATTGGA
ATTTTGGATTGACCACACCTCCCTCAGGTTCTTTGGAGG
ATACCTATAGGTTTGTCACCTCACAGGCCATTACATGTC
AAAAAACTGCCCCCCAAAAGCCCAAGGAAGATCCATTT
AAAGATTATGTATTTTGGGAGGTTAATTTAAAAGAAAAG
TTTTCTGCAGATTTAGATCAGTTTCCACTGGGTCGCAAA
TTTTTATTACAGGCAGGATATAGGGCACGTCCTAAATTT
AAAGCAGGTAAACGTAGTGCACCCTCAGCATCTACCACT
ACACCAGCAAAACGTAAAAAAACTAAAAAG HPV33_L1
ATGTCCGTGTGGCGGCCTAGTGAGGCCACAGTGTACCTG 6
CCTCCTGTACCTGTATCTAAAGTTGTCAGCACTGATGAA
TATGTGTCTCGCACAAGCATTTATTATTATGCTGGTAGTT
CCAGACTTCTTGCTGTTGGCCATCCATATTTTTCTATTAA
AAATCCTACTAACGCTAAAAAATTATTGGTACCCAAAGT
ATCAGGCTTGCAATATAGGGTTTTTAGGGTCCGTTTACC
AGATCCTAATAAATTTGGATTTCCTGACACCTCCTTTTAT
AACCCTGATACACAACGATTAGTATGGGCATGTGTAGGC
CTTGAAATAGGTAGAGGGCAGCCATTAGGCGTTGGCAT
AAGTGGTCATCCTTTATTAAACAAATTTGATGACACTGA
AACCGGTAACAAGTATCCTGGACAACCGGGTGCTGATA
ATAGGGAATGTTTATCCATGGATTATAAACAAACACAGT
TATGTTTACTTGGATGTAAGCCTCCAACAGGGGAACATT
GGGGTAAAGGTGTTGCTTGTACTAATGCAGCACCTGCCA
ATGATTGTCCACCTTTAGAACTTATAAATACTATTATTG
AGGATGGTGATATGGTGGACACAGGATTTGGTTGCATG
GATTTTAAAACATTGCAGGCTAATAAAAGTGATGTTCCT
ATTGATATTTGTGGCAGTACATGCAAATATCCAGATTAT
TTAAAAATGACTAGTGAGCCTTATGGTGATAGTTTATTT
TTCTTTCTTCGACGTGAACAAATGTTTGTAAGACACTTTT
TTAATAGGGCTGGTACATTAGGAGAGGCTGTTCCCGATG
ACCTGTACATTAAAGGTTCAGGAACTACTGCCTCTATTC
AAAGCAGTGCTTTTTTTCCCACTCCTAGTGGATCAATGG
TTACTTCCGAATCTCAGTTATTTAATAAGCCATATTGGCT
ACAACGTGCACAAGGTCATAATAATGGTATTTGTTGGGG
CAATCAGGTATTTGTTACTGTGGTAGATACCACTCGCAG
TACTAATATGACTTTATGCACACAAGTAACTAGTGACAG
TACATATAAAAATGAAAATTTTAAAGAATATATAAGAC
ATGTTGAAGAATATGATCTACAGTTTGTTTTTCAACTAT
GCAAAGTTACCTTAACTGCAGAAGTTATGACATATATTC
ATGCTATGAATCCAGATATTTTAGAAGATTGGCAATTTG
GTTTAACACCTCCTCCATCTGCTAGTTTACAGGATACCT
ATAGGTTTGTTACCTCTCAGGCTATTACGTGTCAAAAAA
CAGTACCTCCAAAGGAAAAGGAAGACCCCTTAGGTAAA
TATACATTTTGGGAAGTGGATTTAAAGGAAAAATTTTCA
GCAGATTTAGATCAGTTTCCTTTGGGACGCAAGTTTTTA
TTACAGGCAGGTCTTAAAGCAAAACCTAAACTTAAACGT
GCAGCCCCCACATCCACCCGCACATCGTCTGCAAAACGC AAAAAGGTTAAAAAA HPV35_L1_DX
ATGTCTCTGTGGCGGTCTAACGAAGCCACTGTCTACCTG 7
CCTCCAGTGTCAGTGTCTAAGGTTGTTAGCACTGATGAA
TATGTAACACGCACAAACATCTACTATCATGCAGGCAGT
TCTAGGCTATTAGCTGTGGGTCACCCATACTATGCTATT
AAAAAACAAGATTCTAATAAAATAGCAGTACCCAAGGT
ATCTGGTTTGCAATACAGAGTATTTAGAGTAAAATTACC
AGATCCTAATAAGTTTGGATTTCCAGACACATCATTTTA
TGATCCTGCCTCCCAGCGTTTGGTTTGGGCCTGTACAGG
AGTTGAAGTAGGTCGTGGTCAGCCATTGGGTGTAGGTAT
TAGTGGTCATCCTTTACTCAATAAATTGGATGATACTGA
AAATTCTAATAAATATGTTGGTAACTCTGGTACAGATAA
CAGGGAATGCATTTCTATGGATTATAAACAAACACAATT
GTGTTTAATAGGTTGTAGGCCTCCTATAGGTGAACATTG
GGGAAAAGGCACACCTTGTAATGCTAACCAGGTAAAAG
CAGGAGAATGTCCTCCTTTGGAGTTACTAAACACTGTAC
TACAAGACGGGGACATGGTAGACACAGGATTTGGTGCA
ATGGATTTTACTACATTACAAGCTAATAAAAGTGATGTT
CCCCTAGATATATGCAGTTCCATTTGCAAATATCCTGAT
TATCTAAAAATGGTTTCTGAGCCATATGGAGATATGTTA
TTTTTTTATCTACGTAGGGAGCAAATGTTTGTGAGACAT
TTATTTAATAGGGCTGGAACTGTAGGTGAAACAGTACCT
GCAGACCTATATATTAAGGGTACCACTGGCACATTGCCT
AGTACTAGTTATTTTCCTACTCCTAGTGGCTCTATGGTAA
CCTCCGATGCACAAATATTTAATAAACCATATTGGTTGC
AACGTGCACAAGGCCATAATAATGGTATTTGTTGGAGTA
ACCAATTGTTTGTTACTGTAGTTGATACAACCCGTAGTA
CAAATATGTCTGTGTGTTCTGCTGTGTCTTCTAGTGACAG
TACATATAAAAACGACAATTTTAAGGAATATTTAAGGCA
TGGTGAAGAATATGACCTGCAGTTTATTTTTCAGTTATG
TAAAATAACACTAACAGCAGATGTTATGACATATATTCA
TAGTATGAACCCGTCCATTTTAGAGGATTGGAATTTTGG
CCTTACACCACCGCCTTCTGGTACCTTAGAGGACACATA
TCGCTATGTAACATCACAGGCTGTAACTTGTCAAAAACC
CAGTGCACCAAAACCTAAAGATGATCCATTAAAAAATT
ATACTTTTTGGGAGGTTGATTTAAAGGAAAAGTTTTCTG
CAGACTTAGATCAATTTCCGTTGGGCCGTAAATTTTTGTT
ACAAGCAGGACTAAAGGCCAGGCCTAATTTTAGATTAG
GCAAGCGTGCAGCTCCAGCATCTACATCTAAAAAATCTT CTACTAAACGTAGAAAAGTAAAAAGT
HPV39_L1_DX ATGGCTATGTGGCGGTCTAGTGACAGCATGGTGTATTTG 8
CCTCCACCTTCTGTGGCGAAGGTTGTCAATACTGATGAT
TATGTTACACGCACAGGCATATATTATTATGCTGGCAGC
TCCAGATTATTAACAGTAGGACATCCATATTTTAAAGTG
GGTATGAATGGTGGTCGCAAGCAGGACATTCCAAAGGT
GTCTGCATATCAATATAGGGTATTTCGCGTGACATTGCC
CGATCCTAATAAATTCAGTATTCCAGATGCATCCTTATA
TAATCCAGAAACACAACGTTTAGTATGGGCTTGTGTAGG
GGTGGAGGTGGGCAGGGGCCAGCCATTGGGTGTTGGTA
TTAGTGGACACCCATTATATAATAGACAGGATGATACTG
AAAACTCACCATTTTCATCAACCACCAATAAGGACAGTA
GGGATAATGTGTCTGTGGATTATAAACAGACACAGTTGT
GCATTATAGGCTGTGTTCCCGCCATTGGGGAGCACTGGG
GTAAGGGAAAGGCATGCAAGCCCAATAATGTATCTACG
GGGGACTGTCCTCCTTTGGAACTAGTAAACACCCCTATT
GAGGATGGTGATATGATTGATACTGGCTATGGAGCTATG
GACTTTGGTGCATTGCAGGAAACCAAAAGTGAGGTGCC
TTTAGATATTTGTCAATCCATTTGTAAATATCCTGATTAT
TTGCAAATGTCTGCAGATGTGTATGGGGACAGTATGTTC
TTCTGTTTACGTAGGGAACAACTGTTTGCAAGACATTTT
TGGAATCGTGGTGGTATGGTGGGTGACGCCATTCCTGCC
CAATTGTATATTAAGGGCACAGATATACGTGCAAACCCC
GGTAGTTCTGTATACTGCCCCTCTCCCAGCGGTTCCATG
GTAACCTCTGATTCCCAGTTATTTAATAAGCCTTATTGGC
TACATAAGGCCCAGGGCCACAACAATGGTATATGTTGG
CATAATCAATTATTTCTTACTGTTGTGGACACTACCCGTA
GTACCAACTTTACATTATCTACCTCTATAGAGTCTTCCAT
ACCTTCTACATATGATCCTTCTAAGTTTAAGGAATATAC
CAGGCACGTGGAGGAGTATGATTTACAGTTTATATTTCA
ACTGTGTACTGTCACATTAACAACTGATGTTATGTCTTAT
ATTCACACTATGAATTCCTCTATATTGGACAATTGGAAT
TTTGCTGTAGCTCCTCCACCATCTGCCAGTTTGGTAGAC
ACTTACAGATACCTACAGTCTGCAGCCATTACATGTCAA
AAGGATGCTCCAGCACCTGAAAAGAAAGATCCATATGA
CGGTCTAAAGTTTTGGAATGTTGACTTAAGGGAAAAGTT
TAGTTTGGAACTTGATCAATTCCCTTTGGGACGTAAATT
TTTGTTGCAGGCCAGGGTCCGCAGGCGCCCTACTATAGG
TCCCCGAAAGCGGCCTGCTGCATCCACTTCCTCGTCCTC
AGCTACTAAACACAAACGTAAACGTGTGTCTAAA HPV45_L1_DX
ATGGCTTTGTGGCGGCCTAGTGACAGTACGGTATATCTT 9
CCACCACCTTCTGTGGCCAGAGTTGTCAGCACTGATGAT
TATGTGTCTCGCACAAGCATATTTTATCATGCAGGCAGT
TCCCGATTATTAACTGTAGGCAATCCATATTTTAGGGTT
GTACCTAATGGTGCAGGTAATAAACAGGCTGTTCCTAAG
GTATCCGCATATCAGTATAGGGTGTTTAGAGTAGCTTTA
CCCGATCCTAATAAATTTGGATTACCTGATTCTACTATAT
ATAATCCTGAAACACAACGTTTGGTTTGGGCATGTGTAG
GTATGGAAATTGGTCGTGGGCAGCCTTTAGGTATTGGCC
TAAGTGGCCATCCATTTTATAATAAATTGGATGATACAG
AAAGTGCTCATGCAGCTACAGCTGTTATTACGCAGGATG
TTAGGGATAATGTGTCAGTTGATTATAAGCAAACACAGC
TGTGTATTTTAGGTTGTGTACCTGCTATTGGTGAGCACTG
GGCCAAGGGCACACTTTGTAAACCTGCACAATTGCAACC
TGGTGACTGTCCTCCTTTGGAACTTAAAAACACCATTAT
TGAGGATGGTGATATGGTGGATACAGGTTATGGGGCAA
TGGATTTTAGTACATTGCAGGATACAAAGTGCGAGGTTC
CATTAGACATTTGTCAATCCATCTGTAAATATCCAGATT
ATTTGCAAATGTCTGCTGATCCCTATGGGGATTCTATGTT
TTTTTGCCTACGCCGTGAACAACTGTTTGCAAGACATTTT
TGGAATAGGGCAGGTGTTATGGGTGACACAGTACCTAC
GGACCTATATATTAAAGGCACTAGCGCTAATATGCGTGA
AACCCCTGGCAGTTGTGTGTATTCCCCTTCTCCCAGTGG
CTCTATTATTACTTCTGATTCTCAATTATTTAATAAGCCA
TATTGGTTACATAAGGCCCAGGGCCATAACAATGGTATT
TGTTGGCATAATCAGTTGTTTGTTACTGTAGTGGACACT
ACCCGCAGTACTAATTTAACATTATGTGCCTCTACACAA
AATCCTGTGCCAAGTACATATGACCCTACTAAGTTTAAG
CAGTATAGTAGACATGTGGAGGAATATGATTTACAGTTT
ATTTTTCAGTTGTGCACTATTACTCTCACTGCAGAGGTTA
TGTCATATATCCATAGTATGAATAGTAGTATATTAGAAA
ATTGGAATTTTGGTGTCCCTCCACCACCTACTACAAGTTT
GGTGGATACATATCGTTTTGTGCAATCAGTTGCTGTTAC
CTGTCAAAAGGATACTACACCTCCAGAAAAGCAGGATC
CATATGATAAATTAAAGTTTTGGACTGTTGACCTAAAGG
AAAAATTTTCCTCCGATTTGGATCAATATCCCCTTGGTC
GAAAGTTTTTAGTTCAGGCTGGGTTACGTCGTAGGCCTA
CCATAGGACCTCGTAAGCGTCCTGCTGCTTCCACGTCTA
CTGCATCTACTGCATCTAGGCCTGCCAAACGTGTACGTA TACGTAGTAAGAAA HPV51_L1_DX
ATGGCATTGTGGCGCACTAATGACAGCAAGGTGTATTTG 10
CCACCTGCACCTGTGTCTCGAATTGTGAATACAGAAGAA
TATATCACACGCACCGGCATATATTACTATGCAGGCAGT
TCCAGACTAATAACATTAGGACATCCCTATTTTCCAATA
CCTAAAACCTCAACGCGTGCTGCTATTCCTAAAGTATCT
GCATTTCAATACAGGGTATTTAGGGTACAGTTACCAGAT
CCTAACAAGTTTGGACTCCCGGATCCAAATTTATATAAT
CCAGACACAGATAGGTTGGTGTGGGGTTGTGTGGGCGTT
GAGGTGGGCAGAGGACAGCCCCTTGGTGTTGGCCTTAGT
GGTCATCCCTTATTTAATAAATATGATGACACAGAAAAT
TCACGCATAGCAAATGGCAATGCACAACAAGATGTTAG
AGATAACACATCTGTTGACAACAAACAGACTCAGTTATG
TATAATAGGCTGTGCTCCACCTATTGGGGAACACTGGGG
TATTGGCACTACATGCAAAAACACACCTGTACCTCCAGG
AGACTGCCCCCCCCTGGAACTTGTATCCTCTGTCATTCA
GGATGGCGATATGATTGATACAGGGTTTGGAGCTATGG
ATTTCGCTGCCCTACAGGCCACCAAATCAGACGTCCCTT
TGGATATTTCACAGTCTGTTTGTAAATATCCTGATTATTT
AAAAATGTCTGCAGACACATATGGTAATTCCATGTTTTT
TCATTTACGCAGGGAGCAAATCTTTGCTAGGCACTATTA
TAATAAACTTGTAGGTGTTGGGGAAGACATTCCTAACGA
TTATTATATTAAGGGTAGTGGTAATGGCCGTGACCCTAT
AGAAAGTTATATATACTCTGCTACTCCCAGTGGGTCTAT
GATAACATCTGATTCTCAAATTTTTAATAAGCCTTATTG
GCTCCACCGTGCGCAGGGTCACAATAATGGCATTTGCTG
GAACAATCAGCTTTTTATTACCTGTGTTGATACTACCAG
AAGTACAAATTTAACTATTAGCACTGCCACTGCTGCGGT
TTCCCCAACATTTACTCCAAGTAACTTTAAGCAATATAT
TAGGCATGGGGAAGAGTATGAATTGCAATTTATTTTTCA
ATTATGTAAAATTACTCTGACTACAGAGGTAATGGCTTA
TTTACACACAATGGATCCTACCATTCTTGAACAGTGGAA
TTTTGGATTAACATTACCTCCGTCTGCTAGTTTGGAGGAT
GCATATAGGTTTGTTAGAAATGCAGCTACTAGCTGTCAA
AAGGACACCCCTCCACAGGCTAAGCCAGATCCTTTGGCC
AAATATAAATTTTGGGATGTTGATTTAAAGGAACGATTT
TCTTTAGATTTAGACCAATTTGCATTGGGTCGCAAGTTTT
TGTTGCAGGTTGGCGTACAACGCAAGCCCAGACCAGGC
CTTAAACGCCCGGCCTCATCGGCATCCTCTTCCTCTTCCT
CTTCAGCCAAACGTAAACGTGTTAAAAAG HPV52_L1_DX
ATGTCCGTGTGGCGGCCTAGTGAGGCCACTGTGTACCTG 11
CCTCCTGTACCTGTCTCTAAGGTTGTAAGCACTGATGAG
TATGTGTCTCGCACAAGCATCTATTATTATGCAGGCAGT
TCTCGATTACTAACAGTAGGACATCCCTATTTTTCTATTA
AAAACACCAGTAGTGGTAATGGTAAAAAAGTTTTAGTTC
CCAAGGTGTCTGGCCTGCAATACAGGGTATTTAGAATTA
AATTGCCGGACCCTAATAAATTTGGTTTTCCAGATACAT
CTTTTTATAACCCAGAAACCCAAAGGTTGGTGTGGGCCT
GTACAGGCTTGGAAATTGGTAGGGGACAGCCTTTAGGT
GTGGGTATTAGTGGGCATCCTTTATTAAACAAGTTTGAT
GATACTGAAACCAGTAACAAATATGCTGGTAAACCTGG
TATAGATAATAGGGAATGTTTATCTATGGATTATAAGCA
GACTCAGTTATGCATTTTAGGATGCAAACCTCCTATAGG
TGAACATTGGGGTAAGGGAACCCCTTGTAATAATAATTC
AGGAAATCCTGGGGATTGTCCTCCCCTACAGCTCATTAA
CAGTGTAATACAGGATGGGGACATGGTAGATACAGGAT
TTGGTTGCATGGATTTTAATACCTTGCAAGCTAGTAAAA
GTGATGTGCCCATTGATATATGTAGCAGTGTATGTAAGT
ATCCAGATTATTTGCAAATGGCTAGCGAGCCATATGGTG
ACAGTTTGTTCTTTTTTCTTAGACGTGAGCAAATGTTTGT
TAGACACTTTTTTAATAGGGCCGGTACCTTAGGTGACCC
TGTGCCAGGTGATTTATATATACAAGGGTCTAACTCTGG
CAATACTGCCACTGTACAAAGCAGTGCTTTTTTTCCTACT
CCTAGTGGTTCTATGGTAACCTCAGAATCCCAATTATTT
AATAAACCGTACTGGTTACAACGTGCGCAGGGCCACAA
TAATGGCATATGTTGGGGCAATCAGTTGTTTGTCACAGT
TGTGGATACCACTCGTAGCACTAACATGACTTTATGTGC
TGAGGTTAAAAAGGAAAGCACATATAAAAATGAAAATT
TTAAGGAATACCTTCGTCATGGCGAGGAATTTGATTTAC
AGTTTATTTTTCAGTTGTGCAAAATTACATTAACAGCTG
ATGTTATGACATACATTCATAAGATGGATGCCACTATTT
TAGAGGACTGGCAATTTGGCCTTACCCCACCACCGTCTG
CATCTTTGGAGGACACATACAGATTTGTCACTTCTACTG
CTATAACTTGTCAAAAAAACACACCACCTAAAGGAAAG
GAAGATCCTTTAAAGGACTATATGTTTTGGGAGGTGGAT
TTAAAAGAAAAGTTTTCTGCAGATTTAGATCAGTTTCCT
TTAGGTAGGAAGTTTTTGTTACAGGCAGGGCTACAGGCT
AGGCCCAAACTAAAACGCCCTGCATCATCGGCCCCACGT
ACCTCCACAAAGAAGAAAAAGGTTAAAAGG HPV56_L1_DX
ATGGCGACGTGGCGGCCTAGTGAAAATAAGGTGTATCT 12
ACCTCCAACACCTGTTTCAAAGGTTGTGGCAACGGATTC
CTATGTAAAACGCACTAGTATATTTTATCATGCAGGCAG
TTCACGATTGCTTGCCGTAGGACATCCCTATTACTCTGTG
ACTAAGGACAATACCAAAACAAACATTCCCAAAGTTAG
TGCATATCAATATAGGGTATTTAGGGTACGGTTGCCCGA
CCCTAATAAGTTTGGGCTTCCAGATACTAATATTTATAA
TCCGGACCAGGAACGGTTAGTGTGGGCATGTGTAGGTTT
GGAGGTAGGCCGCGGACAGCCTTTAGGTGCTGGGCTAA
GTGGCCATCCATTGTTTAATAGGCTGGATGATACTGAAA
GTTCCAATTTAGCAAATAATAATGTTATAGAAGATAGTA
GGGACAATATATCAGTTGATGGCAAGCAAACACAGTTG
TGTATTGTTGGATGTACTCCCGCTATGGGTGAACATTGG
ACTAAAGGTGCTGTGTGTAAGTCCACACAAGTTACCACA
GGGGACTGCCCGCCTCTTGCATTAATTAATACACCTATA
GAGGATGGGGACATGATAGACACAGGATTTGGCGCTAT
GGACTTTAAGGTGTTGCAGGAATCTAAGGCTGAGGTACC
TTTAGACATTGTACAATCCACCTGTAAATATCCTGACTA
TTTAAAAATGTCTGCAGATGCCTATGGTGATTCTATGTG
GTTTTACTTACGCAGGGAACAATTATTTGCCAGACATTA
TTTTAATAGGGCTGGTAAAGTTGGGGAAACAATACCTGC
AGAGTTATATTTAAAGGGTAGCAATGGTAGAGAACCCC
CTCCGAGTTCTGTATATGTTGCTACGCCTAGTGGGTCTAT
GATTACGTCTGAGGCACAGTTATTTAATAAACCTTATTG
GTTGCAACGTGCCCAAGGCCATAATAATGGCATTTGCTG
GGGTAATCAATTATTTGTTACTGTAGTAGATACTACTAG
AAGTACTAACATGACTATTAGTACTGCTACAGAACAGCT
CAGTAAATATGATGCACGAAAAATTAATCAGTACCTTAG
ACATGTGGAGGAATATGAATTACAATTTGTTTTTCAATT
ATGCAAAATTACTTTGTCTGCAGAGGTTATGGCATATTT
ACATAATATGAATGCTAACCTACTGGAGGACTGGAATAT
TGGGTTATCCCCGCCAGTGGCCACCAGCCTAGAAGATAA
ATATAGATATGTTAGAAGCACAGCTATAACATGTCAACG
GGAACAGCCACCAACAGAAAAACAGGACCCATTAGCTA
AATATAAATTTTGGGATGTTAACTTACAGGACAGTTTTT
CTACAGACCTGGATCAATTTCCACTGGGTAGAAAATTTT
TAATGCAACTGGGCACTAGGTCAAAGCCTGCTGTAGCTA
CCTCTAAAAAGCGATCTGCTCCTACCTCCACCTCTACAC CAGCAAAACGTAAAAGGCGG
HPV58_L1_DX ATGTCCGTGTGGCGGCCTAGTGAGGCCACTGTGTACCTG 13
CCTCCTGTGCCTGTGTCTAAGGTTGTAAGCACTGATGAA
TATGTGTCACGCACAAGCATTTATTATTATGCTGGCAGT
TCCAGACTTTTGGCTGTTGGCAATCCATATTTTTCCATCA
AAAGTCCCAATAACAATAAAAAAGTATTAGTTCCCAAG
GTATCAGGCTTACAGTATAGGGTCTTTAGGGTGCGTTTA
CCTGATCCCAATAAATTTGGTTTTCCTGATACATCTTTTT
ATAACCCTGATACACAACGTTTGGTCTGGGCATGTGTAG
GCCTTGAAATAGGTAGGGGACAGCCATTGGGTGTTGGC
GTAAGTGGTCATCCTTATTTAAATAAATTTGATGACACT
GAAACCAGTAACAGATATCCCGCACAGCCAGGGTCTGA
TAACAGGGAATGCTTATCTATGGATTATAAACAAACACA
ATTATGTTTAATTGGCTGTAAACCTCCCACTGGTGAGCA
TTGGGGTAAAGGTGTTGCCTGTAACAATAATGCAGCTGC
TACTGATTGTCCTCCATTGGAACTTTTTAATTCTATTATT
GAGGATGGTGACATGGTAGATACAGGGTTTGGATGCAT
GGACTTTGGTACATTGCAGGCTAATAAAAGTGATGTGCC
TATTGATATTTGTAACAGTACATGCAAATATCCAGATTA
TTTAAAAATGGCCAGTGAACCTTATGGGGATAGTTTGTT
CTTTTTTCTTAGACGTGAGCAGATGTTTGTTAGACACTTT
TTTAATAGGGCTGGAAAACTTGGCGAGGCTGTCCCGGAT
GACCTTTATATTAAAGGGTCCGGTAATACTGCAGTTATC
CAAAGTAGTGCATTTTTTCCAACTCCTAGTGGCTCTATA
GTTACCTCAGAATCACAATTATTTAATAAGCCTTATTGG
CTACAGCGTGCACAAGGTCATAACAATGGCATTTGCTGG
GGCAATCAGTTATTTGTTACCGTGGTTGATACCACTCGT
AGCACTAATATGACATTATGCACTGAAGTAACTAAGGA
AGGTACATATAAAAATGATAATTTTAAGGAATATGTACG
TCATGTTGAAGAATATGACCTACAGTTTGTTTTTCAGCTT
TGCAAAATTACACTAACTGCAGAGATAATGACATATATA
CATACTATGGATTCCAATATTTTGGAGGACTGGCAATTT
GGTTTAACACCTCCTCCGTCTGCCAGTTTACAGGACACA
TATAGATTTGTTACCTCCCAGGCTATTACTTGCCAAAAA
ACAGCACCCCCTAAAGAAAAGGAAGATCCATTAAATAA
ATATACTTTTTGGGAGGTTAACTTAAAGGAAAAGTTTTC
TGCAGATCTTGATCAGTTTCCTTTGGGACGAAAGTTTTT
ATTACAATCAGGCCTTAAAGCAAAGCCCAGACTAAAAC
GTTCGGCCCCTACTACCCGTGCACCATCCACCAAACGCA AAAAGGTTAAAAAA HPV59_L1_DX
ATGGCTCTATGGCGTTCTAGTGACAACAAGGTGTATCTA 14
CCTCCACCTTCGGTAGCTAAGGTTGTCAGCACTGATGAG
TATGTCACCCGTACCAGTATTTTCTACCACGCAGGCAGT
TCCAGACTTCTTACAGTTGGACATCCATATTTTAAAGTA
CCTAAAGGTGGTAATGGTAGACAGGATGTTCCTAAGGT
GTCTGCATATCAATACAGAGTATTTAGGGTTAAGTTACC
TGATCCCAATAAATTTGGCCTTCCAGATAACACAGTATA
TGATCCTAACTCTCAACGCTTGGTCTGGGCCTGTGTAGG
TGTTGAAATCGGTCGGGGCCAACCTTTAGGGGTAGGACT
CAGTGGTCATCCATTATATAATAAATTGGATGACACTGA
AAACTCTCATGTAGCATCTGCTGTTGATACCAAAGATAC
ACGTGATAATGTATCTGTGGATTATAAACAAACTCAGCT
GTGTATTATTGGCTGTGTACCTGCCATTGGAGAACACTG
GACAAAGGGCACTGCTTGTAAGCCTACTACTGTGGTTCA
GGGCGATTGTCCTCCACTAGAATTAATAAATACACCAAT
TGAAGATGGTGATATGGTAGACACAGGATATGGGGCTA
TGGACTTTAAATTGTTGCAGGATAACAAAAGTGAAGTAC
CATTGGATATTTGTCAGTCTATTTGTAAATATCCTGATTA
TTTACAAATGTCAGCAGATGCTTATGGAGACAGTATGTT
TTTTTGTTTAAGGCGAGAACAGGTTTTTGCCAGACATTTT
TGGAATAGATCTGGTACTATGGGTGATCAACTTCCTGAA
TCACTATATATTAAAGGTACTGACATACGTGCCAACCCA
GGCAGTTATTTATATTCCCCTTCCCCAAGTGGGTCTGTG
GTTACTTCTGATTCACAATTATTTAATAAACCATATTGGC
TGCACAAGGCTCAGGGTTTAAACAATGGTATATGTTGGC
ACAATCAATTGTTTTTAACAGTTGTAGATACTACTCGCA
GCACCAATCTTTCTGTGTGTGCTTCTACTACTTCTTCTAT
TCCTAATGTATACACACCTACCAGTTTTAAAGAATATGC
CAGACATGTGGAGGAATTTGATTTGCAGTTTATATTTCA
GCTGTGTAAAATAACATTAACTACAGAGGTAATGTCATA
CATTCATAATATGAATACCACTATTTTGGAGGATTGGAA
TTTTGGTGTTACACCACCTCCTACTGCTAGTTTAGTTGAC
ACATACCGTTTTGTTCAATCTGCTGCTGTAACTTGTCAAA
AGGACACCGCACCGCCAGTTAAACAGGACCCTTATGAC
AAACTAAAGTTTTGGCCTGTAGATCTTAAGGAAAGGTTT
TCTGCAGATCTTGATCAGTTTCCTTTGGGACGTAAATTTT
TATTGCAATTAGGAGCTAGACCTAAGCCCACTATAGGCC
CACGCAAACGTGCAGCGCCTGCCCCTACCTCTACCCCAT
CACCAAAACGTGTTAAGCGTCGCAAGTCTTCCAGAAAA HPV68_L1_DX
ATGGCATTGTGGCGAGCTAGCGACAACATGGTGTATTTG 15
CCTCCCCCCTCAGTGGCGAAGGTTGTCAATACAGATGAT
TATGTGACACGCACTGGCATGTATTACTATGCTGGTACA
TCTAGGTTATTAACTGTAGGCCATCCATATTTTAAGGTTC
CTATGTCTGGGGGCCGCAAGCAGGGCATTCCTAAGGTGT
CTGCATATCAATACAGAGTGTTTAGGGTTACCTTACCTG
ATCCTAATAAATTTAGTGTTCCTGAGTCTACATTATATA
ATCCAGATACACAGCGCATGGTATGGGCCTGTGTTGGTG
TTGAAATAGGTAGGGGGCAGCCATTGGGCGTTGGCCTTA
GTGGGCATCCACTATATAATAGGCTGGATGATACTGAAA
ATTCCCCGTTTTCCTCTAATAAAAATCCTAAAGATAGTA
GGGACAATGTTGCAGTGGACTGTAAACAAACACAGCTG
TGTATTATAGGCTGTGTTCCTGCTATTGGAGAGCACTGG
GCCAAAGGTAAATCTTGTAAGCCTACCAATGTACAACA
AGGGGACTGTCCCCCATTGGAATTGGTAAATACTCCTAT
TGAGGATGGCGATATGATTGATACAGGATATGGTGCTAT
GGACTTTGGTACATTACAAGAAACGAAAAGCGAGGTAC
CTTTGGATATATGTCAATCTGTTTGCAAATATCCTGACTA
TTTGCAAATGTCTGCAGATGTGTATGGAGACAGTATGTT
TTTTTGTTTACGTAGGGAACAGTTATTTGCCAGGCATTTT
TGGAATAGGGGAGGCATGGTAGGGGACACTATTCCCAC
TGACATGTATATTAAGGGCACTGACATTCGTGAAACTCC
TAGTAGTTATGTGTATGCCCCCTCGCCTAGCGGGTCTAT
GGTGTCCTCTGACTCCCAGTTATTTAACAAGCCCTATTG
GCTGCACAAGGCACAGGGACACAACAATGGTATTTGTT
GGCATAATCAATTATTTCTTACCGTTGTGGATACAACGC
GCAGTACTAATTTTACATTGTCCACTACTACAGACTCTA
CTGTACCAGCTGTGTATGATTCTAATAAATTTAAGGAAT
ATGTTAGGCATGTTGAGGAATATGATTTGCAGTTTATAT
TTCAGTTGTGTACTATAACATTATCCACTGACGTAATGT
CATATATACATACTATGAATCCTGCTATTTTGGATGATT
GGAATTTTGGTGTTGCCCCTCCACCATCTGCTAGTCTTGT
AGATACATACCGCTACCTACAATCAGCAGCAATTACATG
TCAAAAGGACGCCCCTGCACCTGTTAAAAAAGATCCCTA
TGATGGTCTTAACTTTTGGAATGTGGATTTAAAGGAAAA
GTTTAGTTCTGAACTGGACCAATTCCCATTAGGACGCAA
ATTTCTGTTACAGGCAGGTGTTCGCAGACGGCCCACCAT
AGGCCCTCGTAAACGCACTGCCACTGCAGCTACCACATC
TACCTCTAAACACAAACGTAAACGTGTGTCAAAA HPV73_L1_DX
ATGTGGCGACCTACTGATGCAAAGGTATACCTGCCCCCT 16
GTGTCTGTGTCTAAGGTTGTAAGCACAGATGAATATGTA
ACAAGAACAAATATATATTATTATGCAGGTAGCACACGT
TTGTTGGCTGTGGGACACCCATATTTTCCTATCAAGGAT
TCTCAAAAACGTAAAACCATAGTTCCTAAAGTTTCAGGT
TTGCAATACAGGGTGTTTAGGCTTCGTTTACCAGATCCT
AATAAATTTGGATTTCCAGATGCATCCTTTTATAATCCTG
ATAAGGAGCGCCTAGTATGGGCCTGTTCTGGTGTGGAGG
TTGGACGTGGACAACCCTTAGGTATAGGTACTAGTGGCA
ATCCATTTATGAATAAATTAGATGATACTGAAAATGCTC
CTAAATACATTGCTGGACAAAATACAGATGGTAGAGAA
TGTATGTCAGTGGATTATAAACAAACACAGTTGTGTATT
TTAGGTTGTAGGCCTCCCTTAGGGGAACATTGGGGTCCA
GGCACGCCATGTACTTCACAAACTGTTAATACTGGTGAT
TGTCCCCCACTGGAATTAAAGAACACCCCTATACAGGAT
GGTGATATGATAGATGTTGGCTTTGGAGCCATGGATTTT
AAAGCTTTACAAGCAAATAAAAGTGATGTACCTATTGAT
ATTTCTAACACTACCTGTAAATACCCAGATTATTTAGGC
ATGGCTGCTGATCCCTATGGTGATTCCATGTGGTTTTATC
TTCGTAGGGAACAAATGTTTGTTCGACACTTATTTAACA
GGGCTGGTGATACCGGTGATAAAATCCCAGATGACCTA
ATGATTAAAGGCACAGGCAATACTGCAACACCATCCAG
TTGTGTTTTTTATCCTACACCTAGTGGTTCCATGGTTTCT
TCAGATGCACAGTTGTTTAATAAACCTTATTGGTTGCAA
AAGGCACAGGGACAAAATAATGGTATTTGTTGGCATAA
TCAATTATTTTTAACTGTTGTAGATACTACTAGAAGCAC
TAATTTTTCTGTATGTGTAGGTACACAGGCTAGTAGCTC
TACTACAACGTATGCCAACTCTAATTTTAAGGAATATTT
AAGACATGCAGAAGAGTTTGACTTACAGTTTGTTTTTCA
GTTATGTAAAATTAGTTTAACCACTGAGGTGATGACATA
TATCCATTCTATGAATTCTACTATATTGGAAGAGTGGAA
TTTTGGTCTTACCCCACCACCGTCAGGTACTTTAGAGGA
AACATATAGATATGTAACATCACAGGCTATTAGTTGCCA
ACGTCCTCAACCTCCTAAAGAAACAGAGGACCCATATG
CCAAGCTATCCTTTTGGGATGTAGATCTTAAGGAAAAGT
TTTCTGCAGAATTAGACCAGTTTCCTTTGGGAAGAAAAT
TTTTATTACAACTTGGTATGCGTGCACGTCCTAAGTTAC
AAGCTTCTAAACGTTCTGCATCTGCTACCACAAGTGCCA
CACCTAAGAAAAAACGTGCTAAACGTATT HPV82_L1_DX
ATGGCTTTGTGGCGTACTAATGACAGCAAAGTGTATTTA 17
CCACCTGCACCAGTGTCACGCATTGTCAACACAGAAGA
ATATATAACCCGCACCGGCATATATTATTATGCAGGCAG
TTCCAGACTTATTACCTTAGGACATCCATATTTTTCAATA
CCCAAAACCAATACACGTGCTGAAATACCTAAGGTATCT
GCCTTTCAGTATAGGGTGTTTAGGGTACAGTTACCTGAC
CCCAACAAATTTGGTCTTCCTGATCCTAATTTGTTTAATC
CAGACACAGATCGTTTGGTGTGGGGATGTGTTGGTGTTG
AAGTAGGTAGGGGTCAGCCGTTAGGTGTTGGCCTTAGTG
GTCATCCTTTATTTAATAAGTATGATGATACTGAAAACT
CTAGGTTTGCCAATGGCAACGACCAACAGGATGTTAGG
GACAACATATCTGTGGACAACAAACAAACTCAGTTATG
CATTATAGGCTGCGCTCCTCCTATTGGGGAACACTGGGC
CACAGGTACCACATGTAAAAACGTACCTGTACCTCAGG
GTGACTGTCCACCTTTGGAACTTGTGTCTACTGTCATTGA
GGATGGCGATATGGTGGACACTGGTTTTGGGGCCATGG
ATTTTGCTAATTTACAAGCTACTAAATCAGATGTTCCATT
GGATATTGCTCAGTCTGTGTGTAAATACCCTGATTACTT
AAAAATGTCAGCAGATACATATGGCAATTCTATGTTTTT
TCATTTACGCAGGGAGCAAATATTTGCTAGGCATTACTA
TAATAAGGCTGGTGTGGTTGGTGATGCCATTCCAGACAA
GGCTTATATTAAGGGTACTGGTGCTGGCCGCGACCCTAT
TAGTAGTTATATTTATTCAGCTACTCCCAGTGGTTCTATG
ATAACCTCTGATTCTCAGATTTTTAATAAGCCTTATTGGT
TGCATCGCGCCCAGGGCCACAATAATGGCATTTGCTGGA
ATAATCAGCTTTTTATTACTTGTGTTGACACTACTAAAA
GTACCAATTTAACCATTAGCACTGCTGTTACTCCATCTGT
TGCACAAACATTTACTCCAGCAAACTTTAAGCAGTACAT
TAGGCATGGGGAAGAATATGAATTGCAATTTATATTTCA
ATTGTGTAAAATCACTTTAACTACTGAAATTATGGCTTA
CCTGCACACCATGGATTCTACAATTTTAGAACAGTGGAA
TTTTGGATTAACATTGCCCCCCTCCGCTAGTTTGGAGGA
TGCCTATCGATTTGTAAAAAATGCAGCAACATCCTGTCA
CAAGGACAGTCCTCCACAGGCTAAAGAAGACCCTTTGG
CAAAATATAAATTTTGGAATGTAGACCTTAAGGAACGCT
TTTCTTTGGATTTGGATCAGTTTGCATTGGGTCGCAAGTT
TTTATTACAAATCGGTGCCCAACGCAAACCCAGACCAGG
CCTTAAAAGGCCTGCCCCATCCTCTTCCGCTTCCTCGTCT GCCAAACGTAAAAGGGTTAAAAAA
IgK_HPV18_E7_Rb_mut ATGGAGACCCCCGCCCAGCTGCTGTTCCTGCTGCTGCTG 18
TGGCTGCCCGACACCACCGGCCACGGCCCCAAGGCCAC
CCTGCAGGACATCGTGCTGCACCTGGAGCCCCAGAACG
AGATCCCCGTGGACCTGCTGGGCCACGGCCAGCTGAGC
GACAGCGAGGAGGAGAACGACGAGATCGACGGCGTGA
ACCACCAGCACCTGCCCGCCAGAAGAGCCGAGCCCCAG
AGACACACCATGCTGTGCATGTGCTGCAAGTGCGAGGC
CAGAATCAAGCTGGTGGTGGAGAGCAGCGCCGACGACC
TGAGAGCCTTCCAGCAGCTGTTCCTGAACACCCTGAGCT
TCGTGTGCCCCTGGTGCGCCAGCCAGCAG HPV18_E7_Rb_mut
ATGCACGGCCCCAAGGCCACCCTGCAGGACATCGTGCT 19
GCACCTGGAGCCCCAGAACGAGATCCCCGTGGACCTGC
TGGGCCACGGCCAGCTGAGCGACAGCGAGGAGGAGAAC
GACGAGATCGACGGCGTGAACCACCAGCACCTGCCCGC
CAGAAGAGCCGAGCCCCAGAGACACACCATGCTGTGCA
TGTGCTGCAAGTGCGAGGCCAGAATCAAGCTGGTGGTG
GAGAGCAGCGCCGACGACCTGAGAGCCTTCCAGCAGCT
GTTCCTGAACACCCTGAGCTTCGTGTGCCCCTGGTGCGC CAGCCAGCAG
IgK_HPV16_E7_Rb_mut ATGGAGACCCCCGCCCAGCTGCTGTTCCTGCTGCTGCTG 20
TGGCTGCCCGACACCACCGGCCACGGCGACACCCCCAC
CCTGCACGAGTACATGCTGGACCTGCAGCCCGAGACCA
CCGACCTGTACGGCTACGGCCAGCTGAACGACAGCAGC
GAGGAGGAGGACGAGATCGACGGCCCCGCCGGCCAGGC
CGAGCCCGACAGAGCCCACTACAACATCGTGACCTTCTG
CTGCAAGTGCGACAGCACCCTGAGACTGTGCGTGCAGA
GCACCCACGTGGACATCAGAACCCTGGAGGACCTGCTG
ATGGGCACCCTGGGCATCGTGTGCCCCATCTGCAGCCAG AAGCCC HPV16_E7_Rb_mut
ATGCACGGCGACACCCCCACCCTGCACGAGTACATGCTG 21
GACCTGCAGCCCGAGACCACCGACCTGTACGGCTACGG
CCAGCTGAACGACAGCAGCGAGGAGGAGGACGAGATCG
ACGGCCCCGCCGGCCAGGCCGAGCCCGACAGAGCCCAC
TACAACATCGTGACCTTCTGCTGCAAGTGCGACAGCACC
CTGAGACTGTGCGTGCAGAGCACCCACGTGGACATCAG
AACCCTGGAGGACCTGCTGATGGGCACCCTGGGCATCGT GTGCCCCATCTGCAGCCAGAAGCCC
IgK_HPV18_E6_p53_mutdel ATGGAGACCCCCGCCCAGCTGCTGTTCCTGCTGCTGCTG 22
TGGCTGCCCGACACCACCGGCGCCAGATTCGAGGACCC
CACCAGAAGCGGCTACAAGCTGCCCGACCTGTGCACCG
AGCTGAACACCAGCCTGCAGGACATCGAGATCACCTGC
GTGTACTGCAAGACCGTGCTGGAGCTGACCGAGGTGTTC
GAGAAGGACCTGTTCGTGGTGTACAGAGACAGCATCCC
CCACGCCGCCTGCCACAAGTGCATCGACTTCTACAGCAG
AATCAGAGAGCTGAGACACTACAGCGACAGCGTGTACG
GCGACACCCTGGAGAAGCTGACCAACACCGGCCTGTAC
AACCTGCTGATCAGATGCCTGAGATGCCAGAAGCCCCTG
CTGAGACACCTGAACGAGAAGAGAAGATTCCACAACAT
CGCCGGCCACTACAGAGGCCAGTGCCACAGCTGCTGCA
ACAGAGCCAGACAGGAGAGACTGCAGAGAAGAAGAGA GACCCAGGTG
HPV18_E6_p53_mutdel ATGGCCAGATTCGAGGACCCCACCAGAAGCGGCTACAA 23
GCTGCCCGACCTGTGCACCGAGCTGAACACCAGCCTGCA
GGACATCGAGATCACCTGCGTGTACTGCAAGACCGTGCT
GGAGCTGACCGAGGTGTTCGAGAAGGACCTGTTCGTGG
TGTACAGAGACAGCATCCCCCACGCCGCCTGCCACAAGT
GCATCGACTTCTACAGCAGAATCAGAGAGCTGAGACAC
TACAGCGACAGCGTGTACGGCGACACCCTGGAGAAGCT
GACCAACACCGGCCTGTACAACCTGCTGATCAGATGCCT
GAGATGCCAGAAGCCCCTGCTGAGACACCTGAACGAGA
AGAGAAGATTCCACAACATCGCCGGCCACTACAGAGGC
CAGTGCCACAGCTGCTGCAACAGAGCCAGACAGGAGAG ACTGCAGAGAAGAAGAGAGACCCAGGTG
IgK_HPV16_E6_p53_mutdel ATGGAGACCCCCGCCCAGCTGCTGTTCCTGCTGCTGCTG 24
TGGCTGCCCGACACCACCGGCCACCAGAAGAGAACCGC
CATGTTCCAGGACCCCCAGGAGAGCGGCAGAAAGCTGC
CCCAGCTGTGCACCGAGCTGCAGACCACCATCCACGAC
ATCATCCTGGAGTGCGTGTACTGCAAGCAGCAGCTGCTG
AGAAGAGAGGTGTACGACAGAGACCTGTGCATCGTGTA
CAGAGACGGCAACCCCTACGCCGTGTGCGACAAGTGCC
TGAAGTTCTACAGCAAGATCAGCGAGTACAGACACTAC
TGCTACAGCCTGTACGGCACCACCCTGGAGCAGCAGTAC
AACAAGCCCCTGTGCGACCTGCTGATCAGATGCATCAAC
TGCCAGAAGCCCCTGCAGAGACACCTGGACAAGAAGCA
GAGATTCCACAACATCAGAGGCAGATGGACCGGCAGAT
GCATGAGCTGCTGCAGAAGCAGCAGAACCAGAAGAGAG ACCCAGCTG
HPV16_E6_p53_mutdel ATGCACCAGAAGAGAACCGCCATGTTCCAGGACCCCCA 463
GGAGAGCGGCAGAAAGCTGCCCCAGCTGTGCACCGAGC
TGCAGACCACCATCCACGACATCATCCTGGAGTGCGTGT
ACTGCAAGCAGCAGCTGCTGAGAAGAGAGGTGTACGAC
AGAGACCTGTGCATCGTGTACAGAGACGGCAACCCCTA
CGCCGTGTGCGACAAGTGCCTGAAGTTCTACAGCAAGAT
CAGCGAGTACAGACACTACTGCTACAGCCTGTACGGCA
CCACCCTGGAGCAGCAGTACAACAAGCCCCTGTGCGAC
CTGCTGATCAGATGCATCAACTGCCAGAAGCCCCTGCAG
AGACACCTGGACAAGAAGCAGAGATTCCACAACATCAG
AGGCAGATGGACCGGCAGATGCATGAGCTGCTGCAGAA
GCAGCAGAACCAGAAGAGAGACCCAGCTG HPV18_E7
ATGCATGGACCTAAGGCAACATTGCAAGACATTGTATTG 25
CATTTAGAGCCCCAAAATGAAATTCCGGTTGACCTTCTA
TGTCACGAGCAATTAAGCGACTCAGAGGAAGAAAACGA
TGAAATAGATGGAGTTAATCATCAACATTTACCAGCCCG
ACGAGCCGAACCACAACGTCACACAATGTTGTGTATGTG
TTGTAAGTGTGAAGCCAGAATTGAGCTAGTAGTAGAAA
GCTCAGCAGACGACCTTCGAGCATTCCAGCAGCTGTTTC
TGAACACCCTGTCCTTTGTGTGTCCGTGGTGTGCATCCC AGCAG HPV16_E7
ATGCATGGAGATACACCTACATTGCATGAATATATGTTA 26
GATTTGCAACCAGAGACAACTGATCTCTACTGTTATGAG
CAATTAAATGACAGCTCAGAGGAGGAGGATGAAATAGA
TGGTCCAGCTGGACAAGCAGAACCGGACAGAGCCCATT
ACAATATTGTAACCTTTTGTTGCAAGTGTGACTCTACGC
TTCGGTTGTGCGTACAAAGCACACACGTAGACATTCGTA
CTTTGGAAGACCTGTTAATGGGCACACTAGGAATTGTGT GCCCCATCTGTTCTCAGAAACCA
HPV18_E6 ATGGCGCGCTTTGAGGATCCAACACGGCGACCCTACAA 27
GCTACCTGATCTGTGCACGGAACTGAACACTTCACTGCA
AGACATAGAAATAACCTGTGTATATTGCAAGACAGTATT
GGAACTTACAGAGGTATTTGAATTTGCATTTAAAGATTT
ATTTGTGGTGTATAGAGACAGTATACCCCATGCTGCATG
CCATAAATGTATAGATTTTTATTCCAGAATTAGAGAATT
AAGACATTATTCAGACTCTGTGTATGGAGACACATTGGA
AAAACTAACTAACACTGGGTTATACAATTTATTAATAAG
GTGCCTGCGGTGCCAGAAACCGTTGAATCCAGCAGAAA
AACTTAGACACCTTAATGAAAAACGACGATTTCACAAC
ATAGCTGGGCACTATAGAGGCCAGTGCCATTCGTGCTGC
AACCGAGCACGACAGGAACGACTCCAACGACGCAGAGA AACACAAGTA HPV16_E6
ATGCACCAAAAGAGAACTGCAATGTTTCAGGACCCACA 28
GGAGCGACCCAGAAAGTTACCACAGTTATGCACAGAGC
TGCAAACAACTATACATGATATAATATTAGAATGTGTGT
ACTGCAAGCAACAGTTACTGCGACGTGAGGTATATGACT
TTGCTTTTCGGGATTTATGCATAGTATATAGAGATGGGA
ATCCATATGCTGTATGTGATAAATGTTTAAAGTTTTATTC
TAAAATTAGTGAGTATAGACATTATTGTTATAGTTTGTA
TGGAACAACATTAGAACAGCAATACAACAAACCGTTGT
GTGATTTGTTAATTAGGTGTATTAACTGTCAAAAGCCAC
TGTGTCCTGAAGAAAAGCAAAGACATCTGGACAAAAAG
CAAAGATTCCATAATATAAGGGGTCGGTGGACCGGTCG
ATGTATGTCTTGTTGCAGATCATCAAGAACACGTAGAGA AACCCAGCTG mGMCSF
ATGTGGCTTCAAAATCTCTTGTTTCTTGGAATCGTCGTGT 29
ACAGCCTGTCAGCCCCAACTAGATCGCCTATCACTGTGA
CGCGCCCGTGGAAGCACGTGGAAGCCATCAAGGAGGCT
CTGAATCTGCTCGACGATATGCCAGTGACCCTGAACGAG
GAAGTCGAAGTGGTGTCCAACGAATTTTCCTTCAAAAAG
TTGACCTGTGTTCAGACCCGGCTGAAGATTTTCGAGCAG
GGCCTCAGGGGAAACTTCACCAAACTGAAGGGTGCACT
GAACATGACCGCCAGCTACTACCAGACCTATTGCCCTCC
GACTCCGGAAACTGATTGCGAGACTCAAGTCACCACCTA
CGCGGACTTCATCGACTCGCTCAAGACGTTCCTGACTGA
CATCCCCTTCGAGTGCAAGAAGCCGGGGCAGAAA hGMCSF
ATGTGGCTACAGTCTCTCCTGCTCCTGGGAACCGTGGCT 30
TGCAGCATATCAGCGCCTGCCAGGAGCCCCAGCCCATCT
ACCCAGCCATGGGAGCACGTAAACGCCATACAGGAAGC
CCGGCGGCTGCTTAATCTATCCCGCGATACAGCAGCCGA
AATGAACGAAACCGTGGAGGTCATCAGTGAGATGTTTG
ATCTACAAGAGCCTACTTGCTTACAAACCCGCCTAGAGC
TTTACAAGCAAGGCCTCCGGGGCTCTCTCACAAAGCTGA
AAGGTCCATTAACTATGATGGCCTCCCACTATAAACAGC
ACTGCCCACCTACACCAGAGACCTCCTGTGCCACCCAGA
TTATAACCTTCGAAAGCTTTAAGGAGAATTTAAAGGATT
TCCTCCTGGTCATCCCCTTCGACTGCTGGGAACCAGTCC AG hMPV mRNA Sequences
HPV6_L1 AUGUGGCGGCCUAGCGACAGCACAGUAUAUGUGCCUC 431
CUCCUAACCCUGUAUCCAAAGUUGUUGCCACGGAUGC
UUAUGUUACUCGCACCAACAUAUUUUAUCAUGCCAGC
AGUUCCAGACUUCUUGCAGUGGGACAUCCUUAUUUUU
CCAUAAAACGGGCUAACAAAACUGUUGUGCCAAAGGU
GUCAGGAUAUCAAUACAGGGUAUUUAAGGUGGUGUUA
CCAGAUCCUAACAAAUUUGCAUUGCCUGACUCGUCUC
UUUUCGAUCCCACAACACAACGUUUAGUAUGGGCAUG
CACAGGCCUAGAGGUGGGCAGGGGACAGCCAUUAGGU
GUGGGUGUAAGUGGACAUCCUUUCCUAAAUAAAUAUG
AUGAUGUUGAAAAUUCAGGGAGUGGUGGUAACCCUGG
ACAGGAUAACAGGGUUAAUGUAGGUAUGGAUUAUAAA
CAAACACAAUUAUGCAUGGUUGGAUGUGCCCCCCCUU
UGGGCGAGCAUUGGGGUAAAGGUAAACAGUGUACUAA
UACACCUGUACAGGCUGGUGACUGCCCGCCCUUAGAAC
UUAUUACCAGUGUUAUACAGGAUGGCGAUAUGGUUGA
CACAGGCUUUGGUGCUAUGAAUUUUGCUGAUUUGCAG
ACCAAUAAAUCAGAUGUUCCUAUUGACAUAUGUGGCA
CUACAUGUAAAUAUCCAGAUUAUUUACAAAUGGCUGC
AGACCCAUAUGGUGAUAGAUUAUUUUUUUUUCUACGG
AAGGAACAAAUGUUUGCCAGACAUUUUUUUAACAGGG
CUGGCGAGGUGGGGGAACCUGUGCCUGAUACACUUAU
AAUUAAGGGUAGUGGAAAUCGCACGUCUGUAGGGAGU
AGUAUAUAUGUUAACACCCCGAGCGGCUCUUUGGUGU
CCUCUGAGGCACAAUUGUUUAAUAAGCCAUAUUGGCU
ACAAAAAGCCCAGGGACAUAACAAUGGUAUUUGUUGG
GGUAAUCAACUGUUUGUUACUGUGGUAGAUACCACAC
GCAGUACCAACAUGACAUUAUGUGCAUCCGUAACUAC
AUCUUCCACAUACACCAAUUCUGAUUAUAAAGAGUAC
AUGCGUCAUGUGGAAGAGUAUGAUUUACAAUUUAUUU
UUCAAUUAUGUAGCAUUACAUUGUCUGCUGAAGUAAU
GGCCUAUAUUCACACAAUGAAUCCCUCUGUUUUGGAA
GACUGGAACUUUGGGUUAUCGCCUCCCCCAAAUGGUA
CAUUAGAAGAUACCUAUAGGUAUGUGCAGUCACAGGC
CAUUACCUGUCAAAAGCCCACUCCUGAAAAGGAAAAG
CCAGAUCCCUAUAAGAACCUUAGUUUUUGGGAGGUUA
AUUUAAAAGAAAAGUUUUCUAGUGAAUUGGAUCAGUA
UCCUUUGGGACGCAAGUUUUUGUUACAAAGUGGAUAU
AGGGGACGGUCCUCUAUUCGUACAGGUGUUAAGCGCC
CUGCUGUUUCCAAAGCCUCUGCUGCCCCUAAACGUAAG CGCGCCAAAACUAAAAGG HPV11_L1
AUGUGGCGGCCUAGCGACAGCACAGUAUAUGUGCCUC 432
CUCCCAACCCUGUAUCCAAGGUUGUUGCCACGGAUGCG
UAUGUUAAACGCACCAACAUAUUUUAUCAUGCCAGCA
GUUCCAGACUCCUUGCUGUGGGACAUCCAUAUUACUC
UAUCAAAAAAGUUAACAAAACAGUUGUACCAAAGGUG
UCUGGAUAUCAAUAUAGAGUGUUUAAGGUAGUGUUGC
CAGAUCCUAACAAGUUUGCAUUACCUGAUUCAUCCCU
GUUUGACCCCACUACACAGCGUUUAGUAUGGGCGUGC
ACAGGGUUGGAGGUAGGCAGGGGUCAACCUUUAGGCG
UUGGUGUUAGUGGGCAUCCAUUGCUAAACAAAUAUGA
UGAUGUAGAAAAUAGUGGUGGGUAUGGUGGUAAUCCU
GGUCAGGAUAAUAGGGUUAAUGUAGGUAUGGAUUAUA
AACAAACCCAGCUAUGUAUGGUGGGCUGUGCUCCACC
GUUAGGUGAACAUUGGGGUAAGGGUACACAAUGUUCA
AAUACCUCUGUACAAAAUGGUGACUGCCCCCCGUUGG
AACUUAUUACCAGUGUUAUACAGGAUGGGGACAUGGU
UGAUACAGGCUUUGGUGCUAUGAAUUUUGCAGACUUA
CAAACCAAUAAAUCGGAUGUUCCCCUUGAUAUUUGUG
GAACUGUCUGCAAAUAUCCUGAUUAUUUGCAAAUGGC
UGCAGACCCUUAUGGUGAUAGGUUGUUUUUUUAUUUG
CGAAAGGAACAAAUGUUUGCUAGACACUUUUUUAAUA
GGGCCGGUACUGUGGGGGAACCUGUGCCUGAUGACCU
GUUGGUAAAAGGGGGUAAUAACAGAUCAUCUGUAGCU
AGUAGUAUUUAUGUACAUACACCUAGUGGCUCAUUGG
UGUCUUCAGAGGCUCAAUUAUUUAAUAAACCAUAUUG
GCUUCAAAAGGCUCAGGGACAUAACAAUGGUAUUUGC
UGGGGAAACCACUUGUUUGUUACUGUGGUAGAUACCA
CACGCAGUACAAAUAUGACACUAUGUGCAUCUGUGUC
UAAAUCUGCUACAUACACUAAUUCAGAUUAUAAGGAA
UACAUGCGCCAUGUGGAGGAGUUUGAUUUACAGUUUA
UUUUUCAAUUGUGUAGCAUUACAUUAUCUGCAGAAGU
CAUGGCCUAUAUACACACAAUGAAUCCUUCUGUUUUG
GAGGACUGGAACUUUGGUUUAUCGCCUCCACCAAAUG
GUACACUGGAGGAUACUUAUAGAUAUGUACAGUCACA
GGCCAUUACCUGUCAGAAACCCACACCUGAAAAAGAA
AAACAGGAUCCCUAUAAGGAUAUGAGUUUUUGGGAGG
UUAACUUAAAAGAAAAGUUUUCAAGUGAAUUAGAUCA
GUUUCCCCUUGGACGUAAGUUUUUAUUGCAAAGUGGA
UAUCGAGGACGGACGUCUGCUCGUACAGGUAUAAAGC
GCCCAGCUGUGUCUAAGCCCUCUACAGCCCCCAAACGA AAACGUACCAAAACCAAAAAG
HPV16_L1 AUGUCUCUUUGGCUGCCUAGUGAGGCCACUGUCUACU 433
UGCCUCCUGUCCCAGUAUCUAAGGUUGUAAGCACGGA
UGAAUAUGUUGCACGCACAAACAUAUAUUAUCAUGCA
GGAACAUCCAGACUACUUGCAGUUGGACAUCCCUAUU
UUCCUAUUAAAAAACCUAACAAUAACAAAAUAUUAGU
UCCUAAAGUAUCAGGAUUACAAUACAGGGUAUUUAGA
AUACAUUUACCUGACCCCAAUAAGUUUGGUUUUCCUG
ACACCUCAUUUUAUAAUCCAGAUACACAGCGGCUGGU
UUGGGCCUGUGUAGGUGUUGAGGUAGGUCGUGGUCAG
CCAUUAGGUGUGGGCAUUAGUGGCCAUCCUUUAUUAA
AUAAAUUGGAUGACACAGAAAAUGCUAGUGCUUAUGC
AGCAAAUGCAGGUGUGGAUAAUAGAGAAUGUAUAUCU
AUGGAUUACAAACAAACACAAUUGUGUUUAAUUGGUU
GCAAACCACCUAUAGGGGAACACUGGGGCAAAGGAUC
CCCAUGUACCAAUGUUGCAGUAAAUCCAGGUGAUUGU
CCACCAUUAGAGUUAAUAAACACAGUUAUUCAGGAUG
GUGAUAUGGUUGAUACUGGCUUUGGUGCUAUGGACUU
UACUACAUUACAGGCUAACAAAAGUGAAGUUCCACUG
GAUAUUUGUACAUCUAUUUGCAAAUAUCCAGAUUAUA
UUAAAAUGGUGUCAGAACCAUAUGGCGACAGCUUAUU
UUUUUAUUUACGAAGGGAACAAAUGUUUGUUAGACAU
UUAUUUAAUAGGGCUGGUACUGUUGGUGAAAAUGUAC
CAGACGAUUUAUACAUUAAAGGCUCUGGGUCUACUGC
AAAUUUAGCCAGUUCAAAUUAUUUUCCUACACCUAGU
GGUUCUAUGGUUACCUCUGAUGCCCAAAUAUUCAAUA
AACCUUAUUGGUUACAACGAGCACAGGGCCACAAUAA
UGGCAUUUGUUGGGGUAACCAACUAUUUGUUACUGUU
GUUGAUACUACACGCAGUACAAAUAUGUCAUUAUGUG
CUGCCAUAUCUACUUCAGAAACUACAUAUAAAAAUAC
UAACUUUAAGGAGUACCUACGACAUGGGGAGGAAUAU
GAUUUACAGUUUAUUUUUCAACUGUGCAAAAUAACCU
UAACUGCAGACGUUAUGACAUACAUACAUUCUAUGAA
UUCCACUAUUUUGGAGGACUGGAAUUUUGGUCUACAA
CCUCCCCCAGGAGGCACACUAGAAGAUACUUAUAGGU
UUGUAACAUCCCAGGCAAUUGCUUGUCAAAAACAUAC
ACCUCCAGCACCUAAAGAAGAUCCCCUUAAAAAAUAC
ACUUUUUGGGAAGUAAAUUUAAAGGAAAAGUUUUCUG
CAGACCUAGAUCAGUUUCCUUUAGGACGCAAAUUUUU
ACUACAAGCAGGAUUGAAGGCCAAACCAAAAUUUACA
UUAGGAAAACGAAAAGCUACACCCACCACCUCAUCUAC
CUCUACAACUGCUAAACGCAAAAAACGUAAGCUG HPV18_L1
AUGGCUUUGUGGCGGCCUAGUGACAAUACCGUAUAUC 434
UUCCACCUCCUUCUGUGGCAAGAGUUGUAAAUACCGA
UGAUUAUGUGACUCGCACAAGCAUAUUUUAUCAUGCU
GGCAGCUCCAGAUUAUUAACUGUUGGUAAUCCAUAUU
UUAGGGUUCCUGCAGGUGGUGGCAAUAAGCAGGAUAU
UCCUAAGGUUUCUGCAUACCAAUAUAGAGUAUUUAGG
GUGCAGUUACCUGACCCAAAUAAAUUUGGUUUACCUG
AUACUAGUAUUUAUAAUCCUGAAACACAACGUUUAGU
GUGGGCCUGUGCUGGAGUGGAAAUUGGCCGUGGUCAG
CCUUUAGGUGUUGGCCUUAGUGGGCAUCCAUUUUAUA
AUAAAUUAGAUGACACUGAAAGUUCCCAUGCCGCCAC
GUCUAAUGUUUCUGAGGACGUUAGGGACAAUGUGUCU
GUAGAUUAUAAGCAGACACAGUUAUGUAUUUUGGGCU
GUGCCCCUGCUAUUGGGGAACACUGGGCUAAAGGCAC
UGCUUGUAAAUCGCGUCCUUUAUCACAGGGCGAUUGC
CCCCCUUUAGAACUUAAAAACACAGUUUUGGAAGAUG
GUGAUAUGGUAGAUACUGGAUAUGGUGCCAUGGACUU
UAGUACAUUGCAAGAUACUAAAUGUGAGGUACCAUUG
GAUAUUUGUCAGUCUAUUUGUAAAUAUCCUGAUUAUU
UACAAAUGUCUGCAGAUCCUUAUGGGGAUUCCAUGUU
UUUUUGCUUACGGCGUGAGCAGCUUUUUGCUAGGCAU
UUUUGGAAUAGAGCAGGUACUAUGGGUGACACUGUGC
CUCAAUCCUUAUAUAUUAAAGGCACAGGUAUGCGUGC
UUCACCUGGCAGCUGUGUGUAUUCUCCCUCUCCAAGU
GGCUCUAUUGUUACCUCUGACUCCCAGUUGUUUAAUA
AACCAUAUUGGUUACAUAAGGCACAGGGUCAUAACAA
UGGUGUUUGCUGGCAUAAUCAAUUAUUUGUUACUGUG
GUAGAUACCACUCGCAGUACCAAUUUAACAAUAUGUG
CUUCUACACAGUCUCCUGUACCUGGGCAAUAUGAUGC
UACCAAAUUUAAGCAGUAUAGCAGACAUGUUGAGGAA
UAUGAUUUGCAGUUUAUUUUUCAGUUGUGUACUAUUA
CUUUAACUGCAGAUGUUAUGUCCUAUAUUCAUAGUAU
GAAUAGCAGUAUUUUAGAGGAUUGGAACUUUGGUGUU
CCCCCCCCGCCAACUACUAGUUUGGUGGAUACAUAUCG
UUUUGUACAAUCUGUUGCUAUUACCUGUCAAAAGGAU
GCUGCACCGGCUGAAAAUAAGGAUCCCUAUGAUAAGU
UAAAGUUUUGGAAUGUGGAUUUAAAGGAAAAGUUUUC
UUUAGACUUAGAUCAAUAUCCCCUUGGACGUAAAUUU
UUGGUUCAGGCUGGAUUGCGUCGCAAGCCCACCAUAG
GCCCUCGCAAACGUUCUGCUCCAUCUGCCACUACGUCU
UCUAAACCUGCCAAGCGUGUGCGUGUACGUGCCAGGA AG HPV31_L1
AUGUCUCUGUGGCGGCCUAGCGAGGCUACUGUCUACU 435
UACCACCUGUCCCAGUGUCUAAAGUUGUAAGCACGGA
UGAAUAUGUAACACGAACCAACAUAUAUUAUCACGCA
GGCAGUGCUAGGCUGCUUACAGUAGGCCAUCCAUAUU
AUUCCAUACCUAAAUCUGACAAUCCUAAAAAAAUAGU
UGUACCAAAGGUGUCAGGAUUACAAUAUAGGGUAUUU
AGGGUUCGUUUACCAGAUCCAAACAAAUUUGGAUUUC
CUGAUACAUCUUUUUAUAAUCCUGAAACUCAACGCUU
AGUUUGGGCCUGUGUUGGUUUAGAGGUAGGUCGCGGG
CAGCCAUUAGGUGUAGGUAUUAGUGGUCAUCCAUUAU
UAAAUAAAUUUGAUGACACUGAAAACUCUAAUAGAUA
UGCCGGUGGUCCUGGCACUGAUAAUAGGGAAUGUAUA
UCAAUGGAUUAUAAACAAACACAACUGUGUUUACUUG
GUUGCAAACCACCUAUUGGAGAGCAUUGGGGUAAAGG
UAGUCCUUGUAGUAACAAUGCUAUUACCCCUGGUGAU
UGUCCUCCAUUAGAAUUAAAAAAUUCAGUUAUACAAG
AUGGGGAUAUGGUUGAUACAGGCUUUGGAGCUAUGGA
UUUUACUGCUUUACAAGACACUAAAAGUAAUGUUCCU
UUGGACAUUUGUAAUUCUAUUUGUAAAUAUCCAGAUU
AUCUUAAAAUGGUUGCUGAGCCAUAUGGCGAUACAUU
AUUUUUUUAUUUACGUAGGGAACAAAUGUUUGUAAGG
CAUUUUUUUAAUAGAUCAGGCACGGUUGGUGAAUCGG
UCCCUACUGACUUAUAUAUUAAAGGCUCCGGUUCAAC
AGCUACUUUAGCUAACAGUACAUACUUUCCUACACCU
AGCGGCUCCAUGGUUACUUCAGAUGCACAAAUUUUUA
AUAAACCAUAUUGGAUGCAACGUGCUCAGGGACACAA
UAAUGGUAUUUGUUGGGGCAAUCAGUUAUUUGUUACU
GUGGUAGAUACCACACGUAGUACCAAUAUGUCUGUUU
GUGCUGCAAUUGCAAACAGUGAUACUACAUUUAAAAG
UAGUAAUUUUAAAGAGUAUUUAAGACAUGGUGAGGAA
UUUGAUUUACAAUUUAUAUUUCAGUUAUGCAAAAUAA
CAUUAUCUGCAGACAUAAUGACAUAUAUUCACAGUAU
GAAUCCUGCUAUUUUGGAAGAUUGGAAUUUUGGAUUG
ACCACACCUCCCUCAGGUUCUUUGGAGGAUACCUAUA
GGUUUGUCACCUCACAGGCCAUUACAUGUCAAAAAAC
UGCCCCCCAAAAGCCCAAGGAAGAUCCAUUUAAAGAU
UAUGUAUUUUGGGAGGUUAAUUUAAAAGAAAAGUUUU
CUGCAGAUUUAGAUCAGUUUCCACUGGGUCGCAAAUU
UUUAUUACAGGCAGGAUAUAGGGCACGUCCUAAAUUU
AAAGCAGGUAAACGUAGUGCACCCUCAGCAUCUACCA
CUACACCAGCAAAACGUAAAAAAACUAAAAAG HPV33_L1
AUGUCCGUGUGGCGGCCUAGUGAGGCCACAGUGUACC 436
UGCCUCCUGUACCUGUAUCUAAAGUUGUCAGCACUGA
UGAAUAUGUGUCUCGCACAAGCAUUUAUUAUUAUGCU
GGUAGUUCCAGACUUCUUGCUGUUGGCCAUCCAUAUU
UUUCUAUUAAAAAUCCUACUAACGCUAAAAAAUUAUU
GGUACCCAAAGUAUCAGGCUUGCAAUAUAGGGUUUUU
AGGGUCCGUUUACCAGAUCCUAAUAAAUUUGGAUUUC
CUGACACCUCCUUUUAUAACCCUGAUACACAACGAUU
AGUAUGGGCAUGUGUAGGCCUUGAAAUAGGUAGAGGG
CAGCCAUUAGGCGUUGGCAUAAGUGGUCAUCCUUUAU
UAAACAAAUUUGAUGACACUGAAACCGGUAACAAGUA
UCCUGGACAACCGGGUGCUGAUAAUAGGGAAUGUUUA
UCCAUGGAUUAUAAACAAACACAGUUAUGUUUACUUG
GAUGUAAGCCUCCAACAGGGGAACAUUGGGGUAAAGG
UGUUGCUUGUACUAAUGCAGCACCUGCCAAUGAUUGU
CCACCUUUAGAACUUAUAAAUACUAUUAUUGAGGAUG
GUGAUAUGGUGGACACAGGAUUUGGUUGCAUGGAUUU
UAAAACAUUGCAGGCUAAUAAAAGUGAUGUUCCUAUU
GAUAUUUGUGGCAGUACAUGCAAAUAUCCAGAUUAUU
UAAAAAUGACUAGUGAGCCUUAUGGUGAUAGUUUAUU
UUUCUUUCUUCGACGUGAACAAAUGUUUGUAAGACAC
UUUUUUAAUAGGGCUGGUACAUUAGGAGAGGCUGUUC
CCGAUGACCUGUACAUUAAAGGUUCAGGAACUACUGC
CUCUAUUCAAAGCAGUGCUUUUUUUCCCACUCCUAGU
GGAUCAAUGGUUACUUCCGAAUCUCAGUUAUUUAAUA
AGCCAUAUUGGCUACAACGUGCACAAGGUCAUAAUAA
UGGUAUUUGUUGGGGCAAUCAGGUAUUUGUUACUGUG
GUAGAUACCACUCGCAGUACUAAUAUGACUUUAUGCA
CACAAGUAACUAGUGACAGUACAUAUAAAAAUGAAAA
UUUUAAAGAAUAUAUAAGACAUGUUGAAGAAUAUGAU
CUACAGUUUGUUUUUCAACUAUGCAAAGUUACCUUAA
CUGCAGAAGUUAUGACAUAUAUUCAUGCUAUGAAUCC
AGAUAUUUUAGAAGAUUGGCAAUUUGGUUUAACACCU
CCUCCAUCUGCUAGUUUACAGGAUACCUAUAGGUUUG
UUACCUCUCAGGCUAUUACGUGUCAAAAAACAGUACC
UCCAAAGGAAAAGGAAGACCCCUUAGGUAAAUAUACA
UUUUGGGAAGUGGAUUUAAAGGAAAAAUUUUCAGCAG
AUUUAGAUCAGUUUCCUUUGGGACGCAAGUUUUUAUU
ACAGGCAGGUCUUAAAGCAAAACCUAAACUUAAACGU
GCAGCCCCCACAUCCACCCGCACAUCGUCUGCAAAACG CAAAAAGGUUAAAAAA HPV35_L1_DX
AUGUCUCUGUGGCGGUCUAACGAAGCCACUGUCUACC 437
UGCCUCCAGUGUCAGUGUCUAAGGUUGUUAGCACUGA
UGAAUAUGUAACACGCACAAACAUCUACUAUCAUGCA
GGCAGUUCUAGGCUAUUAGCUGUGGGUCACCCAUACU
AUGCUAUUAAAAAACAAGAUUCUAAUAAAAUAGCAGU
ACCCAAGGUAUCUGGUUUGCAAUACAGAGUAUUUAGA
GUAAAAUUACCAGAUCCUAAUAAGUUUGGAUUUCCAG
ACACAUCAUUUUAUGAUCCUGCCUCCCAGCGUUUGGU
UUGGGCCUGUACAGGAGUUGAAGUAGGUCGUGGUCAG
CCAUUGGGUGUAGGUAUUAGUGGUCAUCCUUUACUCA
AUAAAUUGGAUGAUACUGAAAAUUCUAAUAAAUAUGU
UGGUAACUCUGGUACAGAUAACAGGGAAUGCAUUUCU
AUGGAUUAUAAACAAACACAAUUGUGUUUAAUAGGUU
GUAGGCCUCCUAUAGGUGAACAUUGGGGAAAAGGCAC
ACCUUGUAAUGCUAACCAGGUAAAAGCAGGAGAAUGU
CCUCCUUUGGAGUUACUAAACACUGUACUACAAGACG
GGGACAUGGUAGACACAGGAUUUGGUGCAAUGGAUUU
UACUACAUUACAAGCUAAUAAAAGUGAUGUUCCCCUA
GAUAUAUGCAGUUCCAUUUGCAAAUAUCCUGAUUAUC
UAAAAAUGGUUUCUGAGCCAUAUGGAGAUAUGUUAUU
UUUUUAUCUACGUAGGGAGCAAAUGUUUGUGAGACAU
UUAUUUAAUAGGGCUGGAACUGUAGGUGAAACAGUAC
CUGCAGACCUAUAUAUUAAGGGUACCACUGGCACAUU
GCCUAGUACUAGUUAUUUUCCUACUCCUAGUGGCUCU
AUGGUAACCUCCGAUGCACAAAUAUUUAAUAAACCAU
AUUGGUUGCAACGUGCACAAGGCCAUAAUAAUGGUAU
UUGUUGGAGUAACCAAUUGUUUGUUACUGUAGUUGAU
ACAACCCGUAGUACAAAUAUGUCUGUGUGUUCUGCUG
UGUCUUCUAGUGACAGUACAUAUAAAAACGACAAUUU
UAAGGAAUAUUUAAGGCAUGGUGAAGAAUAUGACCUG
CAGUUUAUUUUUCAGUUAUGUAAAAUAACACUAACAG
CAGAUGUUAUGACAUAUAUUCAUAGUAUGAACCCGUC
CAUUUUAGAGGAUUGGAAUUUUGGCCUUACACCACCG
CCUUCUGGUACCUUAGAGGACACAUAUCGCUAUGUAA
CAUCACAGGCUGUAACUUGUCAAAAACCCAGUGCACC
AAAACCUAAAGAUGAUCCAUUAAAAAAUUAUACUUUU
UGGGAGGUUGAUUUAAAGGAAAAGUUUUCUGCAGACU
UAGAUCAAUUUCCGUUGGGCCGUAAAUUUUUGUUACA
AGCAGGACUAAAGGCCAGGCCUAAUUUUAGAUUAGGC
AAGCGUGCAGCUCCAGCAUCUACAUCUAAAAAAUCUU CUACUAAACGUAGAAAAGUAAAAAGU
HPV39_L1_DX AUGGCUAUGUGGCGGUCUAGUGACAGCAUGGUGUAUU 438
UGCCUCCACCUUCUGUGGCGAAGGUUGUCAAUACUGA
UGAUUAUGUUACACGCACAGGCAUAUAUUAUUAUGCU
GGCAGCUCCAGAUUAUUAACAGUAGGACAUCCAUAUU
UUAAAGUGGGUAUGAAUGGUGGUCGCAAGCAGGACAU
UCCAAAGGUGUCUGCAUAUCAAUAUAGGGUAUUUCGC
GUGACAUUGCCCGAUCCUAAUAAAUUCAGUAUUCCAG
AUGCAUCCUUAUAUAAUCCAGAAACACAACGUUUAGU
AUGGGCUUGUGUAGGGGUGGAGGUGGGCAGGGGCCAG
CCAUUGGGUGUUGGUAUUAGUGGACACCCAUUAUAUA
AUAGACAGGAUGAUACUGAAAACUCACCAUUUUCAUC
AACCACCAAUAAGGACAGUAGGGAUAAUGUGUCUGUG
GAUUAUAAACAGACACAGUUGUGCAUUAUAGGCUGUG
UUCCCGCCAUUGGGGAGCACUGGGGUAAGGGAAAGGC
AUGCAAGCCCAAUAAUGUAUCUACGGGGGACUGUCCU
CCUUUGGAACUAGUAAACACCCCUAUUGAGGAUGGUG
AUAUGAUUGAUACUGGCUAUGGAGCUAUGGACUUUGG
UGCAUUGCAGGAAACCAAAAGUGAGGUGCCUUUAGAU
AUUUGUCAAUCCAUUUGUAAAUAUCCUGAUUAUUUGC
AAAUGUCUGCAGAUGUGUAUGGGGACAGUAUGUUCUU
CUGUUUACGUAGGGAACAACUGUUUGCAAGACAUUUU
UGGAAUCGUGGUGGUAUGGUGGGUGACGCCAUUCCUG
CCCAAUUGUAUAUUAAGGGCACAGAUAUACGUGCAAA
CCCCGGUAGUUCUGUAUACUGCCCCUCUCCCAGCGGUU
CCAUGGUAACCUCUGAUUCCCAGUUAUUUAAUAAGCC
UUAUUGGCUACAUAAGGCCCAGGGCCACAACAAUGGU
AUAUGUUGGCAUAAUCAAUUAUUUCUUACUGUUGUGG
ACACUACCCGUAGUACCAACUUUACAUUAUCUACCUCU
AUAGAGUCUUCCAUACCUUCUACAUAUGAUCCUUCUA
AGUUUAAGGAAUAUACCAGGCACGUGGAGGAGUAUGA
UUUACAGUUUAUAUUUCAACUGUGUACUGUCACAUUA
ACAACUGAUGUUAUGUCUUAUAUUCACACUAUGAAUU
CCUCUAUAUUGGACAAUUGGAAUUUUGCUGUAGCUCC
UCCACCAUCUGCCAGUUUGGUAGACACUUACAGAUAC
CUACAGUCUGCAGCCAUUACAUGUCAAAAGGAUGCUC
CAGCACCUGAAAAGAAAGAUCCAUAUGACGGUCUAAA
GUUUUGGAAUGUUGACUUAAGGGAAAAGUUUAGUUUG
GAACUUGAUCAAUUCCCUUUGGGACGUAAAUUUUUGU
UGCAGGCCAGGGUCCGCAGGCGCCCUACUAUAGGUCCC
CGAAAGCGGCCUGCUGCAUCCACUUCCUCGUCCUCAGC
UACUAAACACAAACGUAAACGUGUGUCUAAA HPV45_L1_DX
AUGGCUUUGUGGCGGCCUAGUGACAGUACGGUAUAUC 439
UUCCACCACCUUCUGUGGCCAGAGUUGUCAGCACUGA
UGAUUAUGUGUCUCGCACAAGCAUAUUUUAUCAUGCA
GGCAGUUCCCGAUUAUUAACUGUAGGCAAUCCAUAUU
UUAGGGUUGUACCUAAUGGUGCAGGUAAUAAACAGGC
UGUUCCUAAGGUAUCCGCAUAUCAGUAUAGGGUGUUU
AGAGUAGCUUUACCCGAUCCUAAUAAAUUUGGAUUAC
CUGAUUCUACUAUAUAUAAUCCUGAAACACAACGUUU
GGUUUGGGCAUGUGUAGGUAUGGAAAUUGGUCGUGGG
CAGCCUUUAGGUAUUGGCCUAAGUGGCCAUCCAUUUU
AUAAUAAAUUGGAUGAUACAGAAAGUGCUCAUGCAGC
UACAGCUGUUAUUACGCAGGAUGUUAGGGAUAAUGUG
UCAGUUGAUUAUAAGCAAACACAGCUGUGUAUUUUAG
GUUGUGUACCUGCUAUUGGUGAGCACUGGGCCAAGGG
CACACUUUGUAAACCUGCACAAUUGCAACCUGGUGAC
UGUCCUCCUUUGGAACUUAAAAACACCAUUAUUGAGG
AUGGUGAUAUGGUGGAUACAGGUUAUGGGGCAAUGGA
UUUUAGUACAUUGCAGGAUACAAAGUGCGAGGUUCCA
UUAGACAUUUGUCAAUCCAUCUGUAAAUAUCCAGAUU
AUUUGCAAAUGUCUGCUGAUCCCUAUGGGGAUUCUAU
GUUUUUUUGCCUACGCCGUGAACAACUGUUUGCAAGA
CAUUUUUGGAAUAGGGCAGGUGUUAUGGGUGACACAG
UACCUACGGACCUAUAUAUUAAAGGCACUAGCGCUAA
UAUGCGUGAAACCCCUGGCAGUUGUGUGUAUUCCCCU
UCUCCCAGUGGCUCUAUUAUUACUUCUGAUUCUCAAU
UAUUUAAUAAGCCAUAUUGGUUACAUAAGGCCCAGGG
CCAUAACAAUGGUAUUUGUUGGCAUAAUCAGUUGUUU
GUUACUGUAGUGGACACUACCCGCAGUACUAAUUUAA
CAUUAUGUGCCUCUACACAAAAUCCUGUGCCAAGUAC
AUAUGACCCUACUAAGUUUAAGCAGUAUAGUAGACAU
GUGGAGGAAUAUGAUUUACAGUUUAUUUUUCAGUUGU
GCACUAUUACUCUCACUGCAGAGGUUAUGUCAUAUAU
CCAUAGUAUGAAUAGUAGUAUAUUAGAAAAUUGGAAU
UUUGGUGUCCCUCCACCACCUACUACAAGUUUGGUGG
AUACAUAUCGUUUUGUGCAAUCAGUUGCUGUUACCUG
UCAAAAGGAUACUACACCUCCAGAAAAGCAGGAUCCA
UAUGAUAAAUUAAAGUUUUGGACUGUUGACCUAAAGG
AAAAAUUUUCCUCCGAUUUGGAUCAAUAUCCCCUUGG
UCGAAAGUUUUUAGUUCAGGCUGGGUUACGUCGUAGG
CCUACCAUAGGACCUCGUAAGCGUCCUGCUGCUUCCAC
GUCUACUGCAUCUACUGCAUCUAGGCCUGCCAAACGU GUACGUAUACGUAGUAAGAAA
HPV51_L1_DX AUGGCAUUGUGGCGCACUAAUGACAGCAAGGUGUAUU 440
UGCCACCUGCACCUGUGUCUCGAAUUGUGAAUACAGA
AGAAUAUAUCACACGCACCGGCAUAUAUUACUAUGCA
GGCAGUUCCAGACUAAUAACAUUAGGACAUCCCUAUU
UUCCAAUACCUAAAACCUCAACGCGUGCUGCUAUUCCU
AAAGUAUCUGCAUUUCAAUACAGGGUAUUUAGGGUAC
AGUUACCAGAUCCUAACAAGUUUGGACUCCCGGAUCC
AAAUUUAUAUAAUCCAGACACAGAUAGGUUGGUGUGG
GGUUGUGUGGGCGUUGAGGUGGGCAGAGGACAGCCCC
UUGGUGUUGGCCUUAGUGGUCAUCCCUUAUUUAAUAA
AUAUGAUGACACAGAAAAUUCACGCAUAGCAAAUGGC
AAUGCACAACAAGAUGUUAGAGAUAACACAUCUGUUG
ACAACAAACAGACUCAGUUAUGUAUAAUAGGCUGUGC
UCCACCUAUUGGGGAACACUGGGGUAUUGGCACUACA
UGCAAAAACACACCUGUACCUCCAGGAGACUGCCCCCC
CCUGGAACUUGUAUCCUCUGUCAUUCAGGAUGGCGAU
AUGAUUGAUACAGGGUUUGGAGCUAUGGAUUUCGCUG
CCCUACAGGCCACCAAAUCAGACGUCCCUUUGGAUAUU
UCACAGUCUGUUUGUAAAUAUCCUGAUUAUUUAAAAA
UGUCUGCAGACACAUAUGGUAAUUCCAUGUUUUUUCA
UUUACGCAGGGAGCAAAUCUUUGCUAGGCACUAUUAU
AAUAAACUUGUAGGUGUUGGGGAAGACAUUCCUAACG
AUUAUUAUAUUAAGGGUAGUGGUAAUGGCCGUGACCC
UAUAGAAAGUUAUAUAUACUCUGCUACUCCCAGUGGG
UCUAUGAUAACAUCUGAUUCUCAAAUUUUUAAUAAGC
CUUAUUGGCUCCACCGUGCGCAGGGUCACAAUAAUGG
CAUUUGCUGGAACAAUCAGCUUUUUAUUACCUGUGUU
GAUACUACCAGAAGUACAAAUUUAACUAUUAGCACUG
CCACUGCUGCGGUUUCCCCAACAUUUACUCCAAGUAAC
UUUAAGCAAUAUAUUAGGCAUGGGGAAGAGUAUGAAU
UGCAAUUUAUUUUUCAAUUAUGUAAAAUUACUCUGAC
UACAGAGGUAAUGGCUUAUUUACACACAAUGGAUCCU
ACCAUUCUUGAACAGUGGAAUUUUGGAUUAACAUUAC
CUCCGUCUGCUAGUUUGGAGGAUGCAUAUAGGUUUGU
UAGAAAUGCAGCUACUAGCUGUCAAAAGGACACCCCU
CCACAGGCUAAGCCAGAUCCUUUGGCCAAAUAUAAAU
UUUGGGAUGUUGAUUUAAAGGAACGAUUUUCUUUAGA
UUUAGACCAAUUUGCAUUGGGUCGCAAGUUUUUGUUG
CAGGUUGGCGUACAACGCAAGCCCAGACCAGGCCUUA
AACGCCCGGCCUCAUCGGCAUCCUCUUCCUCUUCCUCU UCAGCCAAACGUAAACGUGUUAAAAAG
HPV52_L1_DX AUGUCCGUGUGGCGGCCUAGUGAGGCCACUGUGUACC 441
UGCCUCCUGUACCUGUCUCUAAGGUUGUAAGCACUGA
UGAGUAUGUGUCUCGCACAAGCAUCUAUUAUUAUGCA
GGCAGUUCUCGAUUACUAACAGUAGGACAUCCCUAUU
UUUCUAUUAAAAACACCAGUAGUGGUAAUGGUAAAAA
AGUUUUAGUUCCCAAGGUGUCUGGCCUGCAAUACAGG
GUAUUUAGAAUUAAAUUGCCGGACCCUAAUAAAUUUG
GUUUUCCAGAUACAUCUUUUUAUAACCCAGAAACCCA
AAGGUUGGUGUGGGCCUGUACAGGCUUGGAAAUUGGU
AGGGGACAGCCUUUAGGUGUGGGUAUUAGUGGGCAUC
CUUUAUUAAACAAGUUUGAUGAUACUGAAACCAGUAA
CAAAUAUGCUGGUAAACCUGGUAUAGAUAAUAGGGAA
UGUUUAUCUAUGGAUUAUAAGCAGACUCAGUUAUGCA
UUUUAGGAUGCAAACCUCCUAUAGGUGAACAUUGGGG
UAAGGGAACCCCUUGUAAUAAUAAUUCAGGAAAUCCU
GGGGAUUGUCCUCCCCUACAGCUCAUUAACAGUGUAA
UACAGGAUGGGGACAUGGUAGAUACAGGAUUUGGUUG
CAUGGAUUUUAAUACCUUGCAAGCUAGUAAAAGUGAU
GUGCCCAUUGAUAUAUGUAGCAGUGUAUGUAAGUAUC
CAGAUUAUUUGCAAAUGGCUAGCGAGCCAUAUGGUGA
CAGUUUGUUCUUUUUUCUUAGACGUGAGCAAAUGUUU
GUUAGACACUUUUUUAAUAGGGCCGGUACCUUAGGUG
ACCCUGUGCCAGGUGAUUUAUAUAUACAAGGGUCUAA
CUCUGGCAAUACUGCCACUGUACAAAGCAGUGCUUUU
UUUCCUACUCCUAGUGGUUCUAUGGUAACCUCAGAAU
CCCAAUUAUUUAAUAAACCGUACUGGUUACAACGUGC
GCAGGGCCACAAUAAUGGCAUAUGUUGGGGCAAUCAG
UUGUUUGUCACAGUUGUGGAUACCACUCGUAGCACUA
ACAUGACUUUAUGUGCUGAGGUUAAAAAGGAAAGCAC
AUAUAAAAAUGAAAAUUUUAAGGAAUACCUUCGUCAU
GGCGAGGAAUUUGAUUUACAGUUUAUUUUUCAGUUGU
GCAAAAUUACAUUAACAGCUGAUGUUAUGACAUACAU
UCAUAAGAUGGAUGCCACUAUUUUAGAGGACUGGCAA
UUUGGCCUUACCCCACCACCGUCUGCAUCUUUGGAGGA
CACAUACAGAUUUGUCACUUCUACUGCUAUAACUUGU
CAAAAAAACACACCACCUAAAGGAAAGGAAGAUCCUU
UAAAGGACUAUAUGUUUUGGGAGGUGGAUUUAAAAGA
AAAGUUUUCUGCAGAUUUAGAUCAGUUUCCUUUAGGU
AGGAAGUUUUUGUUACAGGCAGGGCUACAGGCUAGGC
CCAAACUAAAACGCCCUGCAUCAUCGGCCCCACGUACC UCCACAAAGAAGAAAAAGGUUAAAAGG
HPV56_L1_DX AUGGCGACGUGGCGGCCUAGUGAAAAUAAGGUGUAUC 442
UACCUCCAACACCUGUUUCAAAGGUUGUGGCAACGGA
UUCCUAUGUAAAACGCACUAGUAUAUUUUAUCAUGCA
GGCAGUUCACGAUUGCUUGCCGUAGGACAUCCCUAUU
ACUCUGUGACUAAGGACAAUACCAAAACAAACAUUCC
CAAAGUUAGUGCAUAUCAAUAUAGGGUAUUUAGGGUA
CGGUUGCCCGACCCUAAUAAGUUUGGGCUUCCAGAUA
CUAAUAUUUAUAAUCCGGACCAGGAACGGUUAGUGUG
GGCAUGUGUAGGUUUGGAGGUAGGCCGCGGACAGCCU
UUAGGUGCUGGGCUAAGUGGCCAUCCAUUGUUUAAUA
GGCUGGAUGAUACUGAAAGUUCCAAUUUAGCAAAUAA
UAAUGUUAUAGAAGAUAGUAGGGACAAUAUAUCAGUU
GAUGGCAAGCAAACACAGUUGUGUAUUGUUGGAUGUA
CUCCCGCUAUGGGUGAACAUUGGACUAAAGGUGCUGU
GUGUAAGUCCACACAAGUUACCACAGGGGACUGCCCG
CCUCUUGCAUUAAUUAAUACACCUAUAGAGGAUGGGG
ACAUGAUAGACACAGGAUUUGGCGCUAUGGACUUUAA
GGUGUUGCAGGAAUCUAAGGCUGAGGUACCUUUAGAC
AUUGUACAAUCCACCUGUAAAUAUCCUGACUAUUUAA
AAAUGUCUGCAGAUGCCUAUGGUGAUUCUAUGUGGUU
UUACUUACGCAGGGAACAAUUAUUUGCCAGACAUUAU
UUUAAUAGGGCUGGUAAAGUUGGGGAAACAAUACCUG
CAGAGUUAUAUUUAAAGGGUAGCAAUGGUAGAGAACC
CCCUCCGAGUUCUGUAUAUGUUGCUACGCCUAGUGGG
UCUAUGAUUACGUCUGAGGCACAGUUAUUUAAUAAAC
CUUAUUGGUUGCAACGUGCCCAAGGCCAUAAUAAUGG
CAUUUGCUGGGGUAAUCAAUUAUUUGUUACUGUAGUA
GAUACUACUAGAAGUACUAACAUGACUAUUAGUACUG
CUACAGAACAGCUCAGUAAAUAUGAUGCACGAAAAAU
UAAUCAGUACCUUAGACAUGUGGAGGAAUAUGAAUUA
CAAUUUGUUUUUCAAUUAUGCAAAAUUACUUUGUCUG
CAGAGGUUAUGGCAUAUUUACAUAAUAUGAAUGCUAA
CCUACUGGAGGACUGGAAUAUUGGGUUAUCCCCGCCA
GUGGCCACCAGCCUAGAAGAUAAAUAUAGAUAUGUUA
GAAGCACAGCUAUAACAUGUCAACGGGAACAGCCACC
AACAGAAAAACAGGACCCAUUAGCUAAAUAUAAAUUU
UGGGAUGUUAACUUACAGGACAGUUUUUCUACAGACC
UGGAUCAAUUUCCACUGGGUAGAAAAUUUUUAAUGCA
ACUGGGCACUAGGUCAAAGCCUGCUGUAGCUACCUCU
AAAAAGCGAUCUGCUCCUACCUCCACCUCUACACCAGC AAAACGUAAAAGGCGG HPV58_L1_DX
AUGUCCGUGUGGCGGCCUAGUGAGGCCACUGUGUACC 443
UGCCUCCUGUGCCUGUGUCUAAGGUUGUAAGCACUGA
UGAAUAUGUGUCACGCACAAGCAUUUAUUAUUAUGCU
GGCAGUUCCAGACUUUUGGCUGUUGGCAAUCCAUAUU
UUUCCAUCAAAAGUCCCAAUAACAAUAAAAAAGUAUU
AGUUCCCAAGGUAUCAGGCUUACAGUAUAGGGUCUUU
AGGGUGCGUUUACCUGAUCCCAAUAAAUUUGGUUUUC
CUGAUACAUCUUUUUAUAACCCUGAUACACAACGUUU
GGUCUGGGCAUGUGUAGGCCUUGAAAUAGGUAGGGGA
CAGCCAUUGGGUGUUGGCGUAAGUGGUCAUCCUUAUU
UAAAUAAAUUUGAUGACACUGAAACCAGUAACAGAUA
UCCCGCACAGCCAGGGUCUGAUAACAGGGAAUGCUUA
UCUAUGGAUUAUAAACAAACACAAUUAUGUUUAAUUG
GCUGUAAACCUCCCACUGGUGAGCAUUGGGGUAAAGG
UGUUGCCUGUAACAAUAAUGCAGCUGCUACUGAUUGU
CCUCCAUUGGAACUUUUUAAUUCUAUUAUUGAGGAUG
GUGACAUGGUAGAUACAGGGUUUGGAUGCAUGGACUU
UGGUACAUUGCAGGCUAAUAAAAGUGAUGUGCCUAUU
GAUAUUUGUAACAGUACAUGCAAAUAUCCAGAUUAUU
UAAAAAUGGCCAGUGAACCUUAUGGGGAUAGUUUGUU
CUUUUUUCUUAGACGUGAGCAGAUGUUUGUUAGACAC
UUUUUUAAUAGGGCUGGAAAACUUGGCGAGGCUGUCC
CGGAUGACCUUUAUAUUAAAGGGUCCGGUAAUACUGC
AGUUAUCCAAAGUAGUGCAUUUUUUCCAACUCCUAGU
GGCUCUAUAGUUACCUCAGAAUCACAAUUAUUUAAUA
AGCCUUAUUGGCUACAGCGUGCACAAGGUCAUAACAA
UGGCAUUUGCUGGGGCAAUCAGUUAUUUGUUACCGUG
GUUGAUACCACUCGUAGCACUAAUAUGACAUUAUGCA
CUGAAGUAACUAAGGAAGGUACAUAUAAAAAUGAUAA
UUUUAAGGAAUAUGUACGUCAUGUUGAAGAAUAUGAC
CUACAGUUUGUUUUUCAGCUUUGCAAAAUUACACUAA
CUGCAGAGAUAAUGACAUAUAUACAUACUAUGGAUUC
CAAUAUUUUGGAGGACUGGCAAUUUGGUUUAACACCU
CCUCCGUCUGCCAGUUUACAGGACACAUAUAGAUUUG
UUACCUCCCAGGCUAUUACUUGCCAAAAAACAGCACCC
CCUAAAGAAAAGGAAGAUCCAUUAAAUAAAUAUACUU
UUUGGGAGGUUAACUUAAAGGAAAAGUUUUCUGCAGA
UCUUGAUCAGUUUCCUUUGGGACGAAAGUUUUUAUUA
CAAUCAGGCCUUAAAGCAAAGCCCAGACUAAAACGUU
CGGCCCCUACUACCCGUGCACCAUCCACCAAACGCAAA AAGGUUAAAAAA HPV59_L1_DX
AUGGCUCUAUGGCGUUCUAGUGACAACAAGGUGUAUC 444
UACCUCCACCUUCGGUAGCUAAGGUUGUCAGCACUGA
UGAGUAUGUCACCCGUACCAGUAUUUUCUACCACGCA
GGCAGUUCCAGACUUCUUACAGUUGGACAUCCAUAUU
UUAAAGUACCUAAAGGUGGUAAUGGUAGACAGGAUGU
UCCUAAGGUGUCUGCAUAUCAAUACAGAGUAUUUAGG
GUUAAGUUACCUGAUCCCAAUAAAUUUGGCCUUCCAG
AUAACACAGUAUAUGAUCCUAACUCUCAACGCUUGGU
CUGGGCCUGUGUAGGUGUUGAAAUCGGUCGGGGCCAA
CCUUUAGGGGUAGGACUCAGUGGUCAUCCAUUAUAUA
AUAAAUUGGAUGACACUGAAAACUCUCAUGUAGCAUC
UGCUGUUGAUACCAAAGAUACACGUGAUAAUGUAUCU
GUGGAUUAUAAACAAACUCAGCUGUGUAUUAUUGGCU
GUGUACCUGCCAUUGGAGAACACUGGACAAAGGGCAC
UGCUUGUAAGCCUACUACUGUGGUUCAGGGCGAUUGU
CCUCCACUAGAAUUAAUAAAUACACCAAUUGAAGAUG
GUGAUAUGGUAGACACAGGAUAUGGGGCUAUGGACUU
UAAAUUGUUGCAGGAUAACAAAAGUGAAGUACCAUUG
GAUAUUUGUCAGUCUAUUUGUAAAUAUCCUGAUUAUU
UACAAAUGUCAGCAGAUGCUUAUGGAGACAGUAUGUU
UUUUUGUUUAAGGCGAGAACAGGUUUUUGCCAGACAU
UUUUGGAAUAGAUCUGGUACUAUGGGUGAUCAACUUC
CUGAAUCACUAUAUAUUAAAGGUACUGACAUACGUGC
CAACCCAGGCAGUUAUUUAUAUUCCCCUUCCCCAAGUG
GGUCUGUGGUUACUUCUGAUUCACAAUUAUUUAAUAA
ACCAUAUUGGCUGCACAAGGCUCAGGGUUUAAACAAU
GGUAUAUGUUGGCACAAUCAAUUGUUUUUAACAGUUG
UAGAUACUACUCGCAGCACCAAUCUUUCUGUGUGUGC
UUCUACUACUUCUUCUAUUCCUAAUGUAUACACACCU
ACCAGUUUUAAAGAAUAUGCCAGACAUGUGGAGGAAU
UUGAUUUGCAGUUUAUAUUUCAGCUGUGUAAAAUAAC
AUUAACUACAGAGGUAAUGUCAUACAUUCAUAAUAUG
AAUACCACUAUUUUGGAGGAUUGGAAUUUUGGUGUUA
CACCACCUCCUACUGCUAGUUUAGUUGACACAUACCGU
UUUGUUCAAUCUGCUGCUGUAACUUGUCAAAAGGACA
CCGCACCGCCAGUUAAACAGGACCCUUAUGACAAACUA
AAGUUUUGGCCUGUAGAUCUUAAGGAAAGGUUUUCUG
CAGAUCUUGAUCAGUUUCCUUUGGGACGUAAAUUUUU
AUUGCAAUUAGGAGCUAGACCUAAGCCCACUAUAGGC
CCACGCAAACGUGCAGCGCCUGCCCCUACCUCUACCCC
AUCACCAAAACGUGUUAAGCGUCGCAAGUCUUCCAGA AAA HPV68_L1_DX
AUGGCAUUGUGGCGAGCUAGCGACAACAUGGUGUAUU 445
UGCCUCCCCCCUCAGUGGCGAAGGUUGUCAAUACAGA
UGAUUAUGUGACACGCACUGGCAUGUAUUACUAUGCU
GGUACAUCUAGGUUAUUAACUGUAGGCCAUCCAUAUU
UUAAGGUUCCUAUGUCUGGGGGCCGCAAGCAGGGCAU
UCCUAAGGUGUCUGCAUAUCAAUACAGAGUGUUUAGG
GUUACCUUACCUGAUCCUAAUAAAUUUAGUGUUCCUG
AGUCUACAUUAUAUAAUCCAGAUACACAGCGCAUGGU
AUGGGCCUGUGUUGGUGUUGAAAUAGGUAGGGGGCAG
CCAUUGGGCGUUGGCCUUAGUGGGCAUCCACUAUAUA
AUAGGCUGGAUGAUACUGAAAAUUCCCCGUUUUCCUC
UAAUAAAAAUCCUAAAGAUAGUAGGGACAAUGUUGCA
GUGGACUGUAAACAAACACAGCUGUGUAUUAUAGGCU
GUGUUCCUGCUAUUGGAGAGCACUGGGCCAAAGGUAA
AUCUUGUAAGCCUACCAAUGUACAACAAGGGGACUGU
CCCCCAUUGGAAUUGGUAAAUACUCCUAUUGAGGAUG
GCGAUAUGAUUGAUACAGGAUAUGGUGCUAUGGACUU
UGGUACAUUACAAGAAACGAAAAGCGAGGUACCUUUG
GAUAUAUGUCAAUCUGUUUGCAAAUAUCCUGACUAUU
UGCAAAUGUCUGCAGAUGUGUAUGGAGACAGUAUGUU
UUUUUGUUUACGUAGGGAACAGUUAUUUGCCAGGCAU
UUUUGGAAUAGGGGAGGCAUGGUAGGGGACACUAUUC
CCACUGACAUGUAUAUUAAGGGCACUGACAUUCGUGA
AACUCCUAGUAGUUAUGUGUAUGCCCCCUCGCCUAGC
GGGUCUAUGGUGUCCUCUGACUCCCAGUUAUUUAACA
AGCCCUAUUGGCUGCACAAGGCACAGGGACACAACAA
UGGUAUUUGUUGGCAUAAUCAAUUAUUUCUUACCGUU
GUGGAUACAACGCGCAGUACUAAUUUUACAUUGUCCA
CUACUACAGACUCUACUGUACCAGCUGUGUAUGAUUC
UAAUAAAUUUAAGGAAUAUGUUAGGCAUGUUGAGGAA
UAUGAUUUGCAGUUUAUAUUUCAGUUGUGUACUAUAA
CAUUAUCCACUGACGUAAUGUCAUAUAUACAUACUAU
GAAUCCUGCUAUUUUGGAUGAUUGGAAUUUUGGUGUU
GCCCCUCCACCAUCUGCUAGUCUUGUAGAUACAUACCG
CUACCUACAAUCAGCAGCAAUUACAUGUCAAAAGGAC
GCCCCUGCACCUGUUAAAAAAGAUCCCUAUGAUGGUC
UUAACUUUUGGAAUGUGGAUUUAAAGGAAAAGUUUAG
UUCUGAACUGGACCAAUUCCCAUUAGGACGCAAAUUU
CUGUUACAGGCAGGUGUUCGCAGACGGCCCACCAUAG
GCCCUCGUAAACGCACUGCCACUGCAGCUACCACAUCU
ACCUCUAAACACAAACGUAAACGUGUGUCAAAA HPV73_L1_DX
AUGUGGCGACCUACUGAUGCAAAGGUAUACCUGCCCC 446
CUGUGUCUGUGUCUAAGGUUGUAAGCACAGAUGAAUA
UGUAACAAGAACAAAUAUAUAUUAUUAUGCAGGUAGC
ACACGUUUGUUGGCUGUGGGACACCCAUAUUUUCCUA
UCAAGGAUUCUCAAAAACGUAAAACCAUAGUUCCUAA
AGUUUCAGGUUUGCAAUACAGGGUGUUUAGGCUUCGU
UUACCAGAUCCUAAUAAAUUUGGAUUUCCAGAUGCAU
CCUUUUAUAAUCCUGAUAAGGAGCGCCUAGUAUGGGC
CUGUUCUGGUGUGGAGGUUGGACGUGGACAACCCUUA
GGUAUAGGUACUAGUGGCAAUCCAUUUAUGAAUAAAU
UAGAUGAUACUGAAAAUGCUCCUAAAUACAUUGCUGG
ACAAAAUACAGAUGGUAGAGAAUGUAUGUCAGUGGAU
UAUAAACAAACACAGUUGUGUAUUUUAGGUUGUAGGC
CUCCCUUAGGGGAACAUUGGGGUCCAGGCACGCCAUG
UACUUCACAAACUGUUAAUACUGGUGAUUGUCCCCCA
CUGGAAUUAAAGAACACCCCUAUACAGGAUGGUGAUA
UGAUAGAUGUUGGCUUUGGAGCCAUGGAUUUUAAAGC
UUUACAAGCAAAUAAAAGUGAUGUACCUAUUGAUAUU
UCUAACACUACCUGUAAAUACCCAGAUUAUUUAGGCA
UGGCUGCUGAUCCCUAUGGUGAUUCCAUGUGGUUUUA
UCUUCGUAGGGAACAAAUGUUUGUUCGACACUUAUUU
AACAGGGCUGGUGAUACCGGUGAUAAAAUCCCAGAUG
ACCUAAUGAUUAAAGGCACAGGCAAUACUGCAACACC
AUCCAGUUGUGUUUUUUAUCCUACACCUAGUGGUUCC
AUGGUUUCUUCAGAUGCACAGUUGUUUAAUAAACCUU
AUUGGUUGCAAAAGGCACAGGGACAAAAUAAUGGUAU
UUGUUGGCAUAAUCAAUUAUUUUUAACUGUUGUAGAU
ACUACUAGAAGCACUAAUUUUUCUGUAUGUGUAGGUA
CACAGGCUAGUAGCUCUACUACAACGUAUGCCAACUC
UAAUUUUAAGGAAUAUUUAAGACAUGCAGAAGAGUUU
GACUUACAGUUUGUUUUUCAGUUAUGUAAAAUUAGUU
UAACCACUGAGGUGAUGACAUAUAUCCAUUCUAUGAA
UUCUACUAUAUUGGAAGAGUGGAAUUUUGGUCUUACC
CCACCACCGUCAGGUACUUUAGAGGAAACAUAUAGAU
AUGUAACAUCACAGGCUAUUAGUUGCCAACGUCCUCA
ACCUCCUAAAGAAACAGAGGACCCAUAUGCCAAGCUA
UCCUUUUGGGAUGUAGAUCUUAAGGAAAAGUUUUCUG
CAGAAUUAGACCAGUUUCCUUUGGGAAGAAAAUUUUU
AUUACAACUUGGUAUGCGUGCACGUCCUAAGUUACAA
GCUUCUAAACGUUCUGCAUCUGCUACCACAAGUGCCAC ACCUAAGAAAAAACGUGCUAAACGUAUU
HPV82_L1_DX AUGGCUUUGUGGCGUACUAAUGACAGCAAAGUGUAUU 447
UACCACCUGCACCAGUGUCACGCAUUGUCAACACAGAA
GAAUAUAUAACCCGCACCGGCAUAUAUUAUUAUGCAG
GCAGUUCCAGACUUAUUACCUUAGGACAUCCAUAUUU
UUCAAUACCCAAAACCAAUACACGUGCUGAAAUACCU
AAGGUAUCUGCCUUUCAGUAUAGGGUGUUUAGGGUAC
AGUUACCUGACCCCAACAAAUUUGGUCUUCCUGAUCC
UAAUUUGUUUAAUCCAGACACAGAUCGUUUGGUGUGG
GGAUGUGUUGGUGUUGAAGUAGGUAGGGGUCAGCCGU
UAGGUGUUGGCCUUAGUGGUCAUCCUUUAUUUAAUAA
GUAUGAUGAUACUGAAAACUCUAGGUUUGCCAAUGGC
AACGACCAACAGGAUGUUAGGGACAACAUAUCUGUGG
ACAACAAACAAACUCAGUUAUGCAUUAUAGGCUGCGC
UCCUCCUAUUGGGGAACACUGGGCCACAGGUACCACA
UGUAAAAACGUACCUGUACCUCAGGGUGACUGUCCAC
CUUUGGAACUUGUGUCUACUGUCAUUGAGGAUGGCGA
UAUGGUGGACACUGGUUUUGGGGCCAUGGAUUUUGCU
AAUUUACAAGCUACUAAAUCAGAUGUUCCAUUGGAUA
UUGCUCAGUCUGUGUGUAAAUACCCUGAUUACUUAAA
AAUGUCAGCAGAUACAUAUGGCAAUUCUAUGUUUUUU
CAUUUACGCAGGGAGCAAAUAUUUGCUAGGCAUUACU
AUAAUAAGGCUGGUGUGGUUGGUGAUGCCAUUCCAGA
CAAGGCUUAUAUUAAGGGUACUGGUGCUGGCCGCGAC
CCUAUUAGUAGUUAUAUUUAUUCAGCUACUCCCAGUG
GUUCUAUGAUAACCUCUGAUUCUCAGAUUUUUAAUAA
GCCUUAUUGGUUGCAUCGCGCCCAGGGCCACAAUAAU
GGCAUUUGCUGGAAUAAUCAGCUUUUUAUUACUUGUG
UUGACACUACUAAAAGUACCAAUUUAACCAUUAGCAC
UGCUGUUACUCCAUCUGUUGCACAAACAUUUACUCCA
GCAAACUUUAAGCAGUACAUUAGGCAUGGGGAAGAAU
AUGAAUUGCAAUUUAUAUUUCAAUUGUGUAAAAUCAC
UUUAACUACUGAAAUUAUGGCUUACCUGCACACCAUG
GAUUCUACAAUUUUAGAACAGUGGAAUUUUGGAUUAA
CAUUGCCCCCCUCCGCUAGUUUGGAGGAUGCCUAUCGA
UUUGUAAAAAAUGCAGCAACAUCCUGUCACAAGGACA
GUCCUCCACAGGCUAAAGAAGACCCUUUGGCAAAAUA
UAAAUUUUGGAAUGUAGACCUUAAGGAACGCUUUUCU
UUGGAUUUGGAUCAGUUUGCAUUGGGUCGCAAGUUUU
UAUUACAAAUCGGUGCCCAACGCAAACCCAGACCAGGC
CUUAAAAGGCCUGCCCCAUCCUCUUCCGCUUCCUCGUC UGCCAAACGUAAAAGGGUUAAAAAA
IgK_HPV18_E7_Rb_mut AUGGAGACCCCCGCCCAGCUGCUGUUCCUGCUGCUGCU 448
GUGGCUGCCCGACACCACCGGCCACGGCCCCAAGGCCA
CCCUGCAGGACAUCGUGCUGCACCUGGAGCCCCAGAAC
GAGAUCCCCGUGGACCUGCUGGGCCACGGCCAGCUGAG
CGACAGCGAGGAGGAGAACGACGAGAUCGACGGCGUG
AACCACCAGCACCUGCCCGCCAGAAGAGCCGAGCCCCA
GAGACACACCAUGCUGUGCAUGUGCUGCAAGUGCGAG
GCCAGAAUCAAGCUGGUGGUGGAGAGCAGCGCCGACG
ACCUGAGAGCCUUCCAGCAGCUGUUCCUGAACACCCUG
AGCUUCGUGUGCCCCUGGUGCGCCAGCCAGCAG HPV18_E7_Rb_mut
AUGCACGGCCCCAAGGCCACCCUGCAGGACAUCGUGCU 449
GCACCUGGAGCCCCAGAACGAGAUCCCCGUGGACCUGC
UGGGCCACGGCCAGCUGAGCGACAGCGAGGAGGAGAA
CGACGAGAUCGACGGCGUGAACCACCAGCACCUGCCCG
CCAGAAGAGCCGAGCCCCAGAGACACACCAUGCUGUGC
AUGUGCUGCAAGUGCGAGGCCAGAAUCAAGCUGGUGG
UGGAGAGCAGCGCCGACGACCUGAGAGCCUUCCAGCA
GCUGUUCCUGAACACCCUGAGCUUCGUGUGCCCCUGGU GCGCCAGCCAGCAG
IgK_HPV16_E7_Rb_mut AUGGAGACCCCCGCCCAGCUGCUGUUCCUGCUGCUGCU 450
GUGGCUGCCCGACACCACCGGCCACGGCGACACCCCCA
CCCUGCACGAGUACAUGCUGGACCUGCAGCCCGAGACC
ACCGACCUGUACGGCUACGGCCAGCUGAACGACAGCAG
CGAGGAGGAGGACGAGAUCGACGGCCCCGCCGGCCAG
GCCGAGCCCGACAGAGCCCACUACAACAUCGUGACCUU
CUGCUGCAAGUGCGACAGCACCCUGAGACUGUGCGUG
CAGAGCACCCACGUGGACAUCAGAACCCUGGAGGACCU
GCUGAUGGGCACCCUGGGCAUCGUGUGCCCCAUCUGCA GCCAGAAGCCC HPV16_E7_Rb_mut
AUGCACGGCGACACCCCCACCCUGCACGAGUACAUGCU 451
GGACCUGCAGCCCGAGACCACCGACCUGUACGGCUACG
GCCAGCUGAACGACAGCAGCGAGGAGGAGGACGAGAU
CGACGGCCCCGCCGGCCAGGCCGAGCCCGACAGAGCCC
ACUACAACAUCGUGACCUUCUGCUGCAAGUGCGACAG
CACCCUGAGACUGUGCGUGCAGAGCACCCACGUGGACA
UCAGAACCCUGGAGGACCUGCUGAUGGGCACCCUGGG
CAUCGUGUGCCCCAUCUGCAGCCAGAAGCCC IgK_HPV18_E6_p53_mutdel
AUGGAGACCCCCGCCCAGCUGCUGUUCCUGCUGCUGCU 452
GUGGCUGCCCGACACCACCGGCGCCAGAUUCGAGGACC
CCACCAGAAGCGGCUACAAGCUGCCCGACCUGUGCACC
GAGCUGAACACCAGCCUGCAGGACAUCGAGAUCACCU
GCGUGUACUGCAAGACCGUGCUGGAGCUGACCGAGGU
GUUCGAGAAGGACCUGUUCGUGGUGUACAGAGACAGC
AUCCCCCACGCCGCCUGCCACAAGUGCAUCGACUUCUA
CAGCAGAAUCAGAGAGCUGAGACACUACAGCGACAGC
GUGUACGGCGACACCCUGGAGAAGCUGACCAACACCG
GCCUGUACAACCUGCUGAUCAGAUGCCUGAGAUGCCA
GAAGCCCCUGCUGAGACACCUGAACGAGAAGAGAAGA
UUCCACAACAUCGCCGGCCACUACAGAGGCCAGUGCCA
CAGCUGCUGCAACAGAGCCAGACAGGAGAGACUGCAG AGAAGAAGAGAGACCCAGGUG
HPV18_E6_p53_mutdel AUGGCCAGAUUCGAGGACCCCACCAGAAGCGGCUACA 453
AGCUGCCCGACCUGUGCACCGAGCUGAACACCAGCCUG
CAGGACAUCGAGAUCACCUGCGUGUACUGCAAGACCG
UGCUGGAGCUGACCGAGGUGUUCGAGAAGGACCUGUU
CGUGGUGUACAGAGACAGCAUCCCCCACGCCGCCUGCC
ACAAGUGCAUCGACUUCUACAGCAGAAUCAGAGAGCU
GAGACACUACAGCGACAGCGUGUACGGCGACACCCUG
GAGAAGCUGACCAACACCGGCCUGUACAACCUGCUGA
UCAGAUGCCUGAGAUGCCAGAAGCCCCUGCUGAGACA
CCUGAACGAGAAGAGAAGAUUCCACAACAUCGCCGGC
CACUACAGAGGCCAGUGCCACAGCUGCUGCAACAGAGC
CAGACAGGAGAGACUGCAGAGAAGAAGAGAGACCCAG GUG IgK_HPV16_E6_p53_mutdel
AUGGAGACCCCCGCCCAGCUGCUGUUCCUGCUGCUGCU 454
GUGGCUGCCCGACACCACCGGCCACCAGAAGAGAACCG
CCAUGUUCCAGGACCCCCAGGAGAGCGGCAGAAAGCU
GCCCCAGCUGUGCACCGAGCUGCAGACCACCAUCCACG
ACAUCAUCCUGGAGUGCGUGUACUGCAAGCAGCAGCU
GCUGAGAAGAGAGGUGUACGACAGAGACCUGUGCAUC
GUGUACAGAGACGGCAACCCCUACGCCGUGUGCGACA
AGUGCCUGAAGUUCUACAGCAAGAUCAGCGAGUACAG
ACACUACUGCUACAGCCUGUACGGCACCACCCUGGAGC
AGCAGUACAACAAGCCCCUGUGCGACCUGCUGAUCAG
AUGCAUCAACUGCCAGAAGCCCCUGCAGAGACACCUGG
ACAAGAAGCAGAGAUUCCACAACAUCAGAGGCAGAUG
GACCGGCAGAUGCAUGAGCUGCUGCAGAAGCAGCAGA ACCAGAAGAGAGACCCAGCUG
HPV16_E6_p53_mutdel AUGCACCAGAAGAGAACCGCCAUGUUCCAGGACCCCCA 455
GGAGAGCGGCAGAAAGCUGCCCCAGCUGUGCACCGAG
CUGCAGACCACCAUCCACGACAUCAUCCUGGAGUGCGU
GUACUGCAAGCAGCAGCUGCUGAGAAGAGAGGUGUAC
GACAGAGACCUGUGCAUCGUGUACAGAGACGGCAACC
CCUACGCCGUGUGCGACAAGUGCCUGAAGUUCUACAG
CAAGAUCAGCGAGUACAGACACUACUGCUACAGCCUG
UACGGCACCACCCUGGAGCAGCAGUACAACAAGCCCCU
GUGCGACCUGCUGAUCAGAUGCAUCAACUGCCAGAAG
CCCCUGCAGAGACACCUGGACAAGAAGCAGAGAUUCC
ACAACAUCAGAGGCAGAUGGACCGGCAGAUGCAUGAG
CUGCUGCAGAAGCAGCAGAACCAGAAGAGAGACCCAG CUG HPV18_E7
AUGCAUGGACCUAAGGCAACAUUGCAAGACAUUGUAU 456
UGCAUUUAGAGCCCCAAAAUGAAAUUCCGGUUGACCU
UCUAUGUCACGAGCAAUUAAGCGACUCAGAGGAAGAA
AACGAUGAAAUAGAUGGAGUUAAUCAUCAACAUUUAC
CAGCCCGACGAGCCGAACCACAACGUCACACAAUGUUG
UGUAUGUGUUGUAAGUGUGAAGCCAGAAUUGAGCUAG
UAGUAGAAAGCUCAGCAGACGACCUUCGAGCAUUCCA
GCAGCUGUUUCUGAACACCCUGUCCUUUGUGUGUCCG UGGUGUGCAUCCCAGCAG HPV16_E7
AUGCAUGGAGAUACACCUACAUUGCAUGAAUAUAUGU 457
UAGAUUUGCAACCAGAGACAACUGAUCUCUACUGUUA
UGAGCAAUUAAAUGACAGCUCAGAGGAGGAGGAUGAA
AUAGAUGGUCCAGCUGGACAAGCAGAACCGGACAGAG
CCCAUUACAAUAUUGUAACCUUUUGUUGCAAGUGUGA
CUCUACGCUUCGGUUGUGCGUACAAAGCACACACGUA
GACAUUCGUACUUUGGAAGACCUGUUAAUGGGCACAC
UAGGAAUUGUGUGCCCCAUCUGUUCUCAGAAACCA HPV18_E6
AUGGCGCGCUUUGAGGAUCCAACACGGCGACCCUACA 458
AGCUACCUGAUCUGUGCACGGAACUGAACACUUCACU
GCAAGACAUAGAAAUAACCUGUGUAUAUUGCAAGACA
GUAUUGGAACUUACAGAGGUAUUUGAAUUUGCAUUUA
AAGAUUUAUUUGUGGUGUAUAGAGACAGUAUACCCCA
UGCUGCAUGCCAUAAAUGUAUAGAUUUUUAUUCCAGA
AUUAGAGAAUUAAGACAUUAUUCAGACUCUGUGUAUG
GAGACACAUUGGAAAAACUAACUAACACUGGGUUAUA
CAAUUUAUUAAUAAGGUGCCUGCGGUGCCAGAAACCG
UUGAAUCCAGCAGAAAAACUUAGACACCUUAAUGAAA
AACGACGAUUUCACAACAUAGCUGGGCACUAUAGAGG
CCAGUGCCAUUCGUGCUGCAACCGAGCACGACAGGAAC
GACUCCAACGACGCAGAGAAACACAAGUA HPV16_E6
AUGCACCAAAAGAGAACUGCAAUGUUUCAGGACCCAC 459
AGGAGCGACCCAGAAAGUUACCACAGUUAUGCACAGA
GCUGCAAACAACUAUACAUGAUAUAAUAUUAGAAUGU
GUGUACUGCAAGCAACAGUUACUGCGACGUGAGGUAU
AUGACUUUGCUUUUCGGGAUUUAUGCAUAGUAUAUAG
AGAUGGGAAUCCAUAUGCUGUAUGUGAUAAAUGUUUA
AAGUUUUAUUCUAAAAUUAGUGAGUAUAGACAUUAUU
GUUAUAGUUUGUAUGGAACAACAUUAGAACAGCAAUA
CAACAAACCGUUGUGUGAUUUGUUAAUUAGGUGUAUU
AACUGUCAAAAGCCACUGUGUCCUGAAGAAAAGCAAA
GACAUCUGGACAAAAAGCAAAGAUUCCAUAAUAUAAG
GGGUCGGUGGACCGGUCGAUGUAUGUCUUGUUGCAGA
UCAUCAAGAACACGUAGAGAAACCCAGCUG mGMCSF
AUGUGGCUUCAAAAUCUCUUGUUUCUUGGAAUCGUCG 460
UGUACAGCCUGUCAGCCCCAACUAGAUCGCCUAUCACU
GUGACGCGCCCGUGGAAGCACGUGGAAGCCAUCAAGG
AGGCUCUGAAUCUGCUCGACGAUAUGCCAGUGACCCU
GAACGAGGAAGUCGAAGUGGUGUCCAACGAAUUUUCC
UUCAAAAAGUUGACCUGUGUUCAGACCCGGCUGAAGA
UUUUCGAGCAGGGCCUCAGGGGAAACUUCACCAAACU
GAAGGGUGCACUGAACAUGACCGCCAGCUACUACCAG
ACCUAUUGCCCUCCGACUCCGGAAACUGAUUGCGAGAC
UCAAGUCACCACCUACGCGGACUUCAUCGACUCGCUCA
AGACGUUCCUGACUGACAUCCCCUUCGAGUGCAAGAA GCCGGGGCAGAAA hGMCSF
AUGUGGCUACAGUCUCUCCUGCUCCUGGGAACCGUGG 461
CUUGCAGCAUAUCAGCGCCUGCCAGGAGCCCCAGCCCA
UCUACCCAGCCAUGGGAGCACGUAAACGCCAUACAGG
AAGCCCGGCGGCUGCUUAAUCUAUCCCGCGAUACAGCA
GCCGAAAUGAACGAAACCGUGGAGGUCAUCAGUGAGA
UGUUUGAUCUACAAGAGCCUACUUGCUUACAAACCCG
CCUAGAGCUUUACAAGCAAGGCCUCCGGGGCUCUCUCA
CAAAGCUGAAAGGUCCAUUAACUAUGAUGGCCUCCCA
CUAUAAACAGCACUGCCCACCUACACCAGAGACCUCCU
GUGCCACCCAGAUUAUAACCUUCGAAAGCUUUAAGGA
GAAUUUAAAGGAUUUCCUCCUGGUCAUCCCCUUCGAC UGCUGGGAACCAGUCCAG
TABLE-US-00003 TABLE 2 HPV Amino Acid Sequences SEQ ID Description
Sequence NO: HPV6_L1 MWRPSDSTVYVPPPNPVSKVVATDAYVTRTNIFYHASSSR 31
LLAVGHPYFSIKRANKTVVPKVSGYQYRVFKVVLPDPNKF
ALPDSSLFDPTTQRLVWACTGLEVGRGQPLGVGVSGHPFL
NKYDDVENSGSGGNPGQDNRVNVGMDYKQTQLCMVGC
APPLGEHWGKGKQCTNTPVQAGDCPPLELITSVIQDGDMV
DTGFGAMNFADLQTNKSDVPIDICGTTCKYPDYLQMAADP
YGDRLFFFLRKEQMFARHFFNRAGEVGEPVPDTLIIKGSGN
RTSVGSSIYVNTPSGSLVSSEAQLFNKPYWLQKAQGHNNGI
CWGNQLFVTVVDTTRSTNMTLCASVTTSSTYTNSDYKEY
MRHVEEYDLQFIFQLCSITLSAEVMAYIHTMNPSVLEDWN
FGLSPPPNGTLEDTYRYVQSQAITCQKPTPEKEKPDPYKNL
SFWEVNLKEKFSSELDQYPLGRKFLLQSGYRGRSSIRTGVK RPAVSKASAAPKRKRAKTKR
HPV11_L1 MWRPSDSTVYVPPPNPVSKVVATDAYVKRTNIFYHASSSR 32
LLAVGHPYYSIKKVNKTVVPKVSGYQYRVFKVVLPDPNKF
ALPDSSLFDPTTQRLVWACTGLEVGRGQPLGVGVSGHPLL
NKYDDVENSGGYGGNPGQDNRVNVGMDYKQTQLCMVG
CAPPLGEHWGKGTQCSNTSVQNGDCPPLELITSVIQDGDM
VDTGFGAMNFADLQTNKSDVPLDICGTVCKYPDYLQMAA
DPYGDRLFFYLRKEQMFARHFFNRAGTVGEPVPDDLLVKG
GNNRSSVASSIYVHTPSGSLVSSEAQLFNKPYWLQKAQGH
NNGICWGNHLFVTVVDTTRSTNMTLCASVSKSATYTNSDY
KEYMRHVEEFDLQFIFQLCSITLSAEVMAYIHTMNPSVLED
WNFGLSPPPNGTLEDTYRYVQSQAITCQKPTPEKEKQDPY
KDMSFWEVNLKEKFSSELDQFPLGRKFLLQSGYRGRTSAR TGIKRPAVSKPSTAPKRKRTKTKK
HPV16_L1 MSLWLPSEATVYLPPVPVSKVVSTDEYVARTNIYYHAGTS 33
RLLAVGHPYFPIKKPNNNKILVPKVSGLQYRVFRIHLPDPN
KFGFPDTSFYNPDTQRLVWACVGVEVGRGQPLGVGISGHP
LLNKLDDTENASAYAANAGVDNRECISMDYKQTQLCLIGC
KPPIGEHWGKGSPCTNVAVNPGDCPPLELINTVIQDGDMV
DTGFGAMDFTTLQANKSEVPLDICTSICKYPDYIKMVSEPY
GDSLFFYLRREQMFVRHLFNRAGTVGENVPDDLYIKGSGS
TANLASSNYFPTPSGSMVTSDAQIFNKPYWLQRAQGHNNG
ICWGNQLFVTVVDTTRSTNMSLCAAISTSETTYKNTNFKEY
LRHGEEYDLQFIFQLCKITLTADVMTYIHSMNSTILEDWNF
GLQPPPGGTLEDTYRFVTSQAIACQKHTPPAPKEDPLKKYT
FWEVNLKEKFSADLDQFPLGRKFLLQAGLKAKPKFTLGKR KATPTTSSTSTTAKRKKRKL
HPV18_L1 MALWRPSDNTVYLPPPSVARVVNTDDYVTRTSIFYHAGSS 34
RLLTVGNPYFRVPAGGGNKQDIPKVSAYQYRVFRVQLPDP
NKFGLPDTSIYNPETQRLVWACAGVEIGRGQPLGVGLSGH
PFYNKLDDTESSHAATSNVSEDVRDNVSVDYKQTQLCILG
CAPAIGEHWAKGTACKSRPLSQGDCPPLELKNTVLEDGDM
VDTGYGAMDFSTLQDTKCEVPLDICQSICKYPDYLQMSAD
PYGDSMFFCLRREQLFARHFWNRAGTMGDTVPQSLYIKGT
GMRASPGSCVYSPSPSGSIVTSDSQLFNKPYWLHKAQGHN
NGVCWHNQLFVTVVDTTRSTNLTICASTQSPVPGQYDATK
FKQYSRHVEEYDLQFIFQLCTITLTADVMSYIHSMNSSILED
WNFGVPPPPTTSLVDTYRFVQSVAITCQKDAAPAENKDPY
DKLKFWNVDLKEKFSLDLDQYPLGRKFLVQAGLRRKPTIG PRKRSAPSATTSSKPAKRVRVRARK
HPV31_L1 MSLWRPSEATVYLPPVPVSKVVSTDEYVTRTNIYYHAGSA 35
RLLTVGHPYYSIPKSDNPKKIVVPKVSGLQYRVFRVRLPDP
NKFGFPDTSFYNPETQRLVWACVGLEVGRGQPLGVGISGH
PLLNKFDDTENSNRYAGGPGTDNRECISMDYKQTQLCLLG
CKPPIGEHWGKGSPCSNNAITPGDCPPLELKNSVIQDGDMV
DTGFGAMDFTALQDTKSNVPLDICNSICKYPDYLKMVAEP
YGDTLFFYLRREQMFVRHFFNRSGTVGESVPTDLYIKGSGS
TATLANSTYFPTPSGSMVTSDAQIFNKPYWMQRAQGHNN
GICWGNQLFVTVVDTTRSTNMSVCAAIANSDTTFKSSNFK
EYLRHGEEFDLQFIFQLCKITLSADIMTYIHSMNPAILEDWN
FGLTTPPSGSLEDTYRFVTSQAITCQKTAPQKPKEDPFKDY
VFWEVNLKEKFSADLDQFPLGRKFLLQAGYRARPKFKAG KRSAPSASTTTPAKRKKTKK
HPV33_L1 MSVWRPSEATVYLPPVPVSKVVSTDEYVSRTSIYYYAGSS 36
RLLAVGHPYFSIKNPTNAKKLLVPKVSGLQYRVFRVRLPDP
NKFGFPDTSFYNPDTQRLVWACVGLEIGRGQPLGVGISGHP
LLNKFDDTETGNKYPGQPGADNRECLSMDYKQTQLCLLG
CKPPTGEHWGKGVACTNAAPANDCPPLELINTIIEDGDMV
DTGFGCMDFKTLQANKSDVPIDICGSTCKYPDYLKMTSEP
YGDSLFFFLRREQMFVRHFFNRAGTLGEAVPDDLYIKGSG
TTASIQSSAFFPTPSGSMVTSESQLFNKPYWLQRAQGHNNG
ICWGNQVFVTVVDTTRSTNMTLCTQVTSDSTYKNENFKEY
IRHVEEYDLQFVFQLCKVTLTAEVMTYIHAMNPDILEDWQ
FGLTPPPSASLQDTYRFVTSQAITCQKTVPPKEKEDPLGKY
TFWEVDLKEKFSADLDQFPLGRKFLLQAGLKAKPKLKRAA PTSTRTSSAKRKKVKK
HPV35_L1_DX MSLWRSNEATVYLPPVSVSKVVSTDEYVTRTNIYYHAGSS 37
RLLAVGHPYYAIKKQDSNKIAVPKVSGLQYRVFRVKLPDP
NKFGFPDTSFYDPASQRLVWACTGVEVGRGQPLGVGISGH
PLLNKLDDTENSNKYVGNSGTDNRECISMDYKQTQLCLIG
CRPPIGEHWGKGTPCNANQVKAGECPPLELLNTVLQDGD
MVDTGFGAMDFTTLQANKSDVPLDICSSICKYPDYLKMVS
EPYGDMLFFYLRREQMFVRHLFNRAGTVGETVPADLYIKG
TTGTLPSTSYFPTPSGSMVTSDAQIFNKPYWLQRAQGHNN
GICWSNQLFVTVVDTTRSTNMSVCSAVSSSDSTYKNDNFK
EYLRHGEEYDLQFIFQLCKITLTADVMTYIHSMNPSILEDW
NFGLTPPPSGTLEDTYRYVTSQAVTCQKPSAPKPKDDPLKN
YTFWEVDLKEKFSADLDQFPLGRKFLLQAGLKARPNFRLG KRAAPASTSKKSSTKRRKVKS
HPV39_L1_DX MAMWRSSDSMVYLPPPSVAKVVNTDDYVTRTGIYYYAGS 38
SRLLTVGHPYFKVGMNGGRKQDIPKVSAYQYRVFRVTLPD
PNKFSIPDASLYNPETQRLVWACVGVEVGRGQPLGVGISG
HPLYNRQDDTENSPFSSTTNKDSRDNVSVDYKQTQLCIIGC
VPAIGEHWGKGKACKPNNVSTGDCPPLELVNTPIEDGDMI
DTGYGAMDFGALQETKSEVPLDICQSICKYPDYLQMSADV
YGDSMFFCLRREQLFARHFWNRGGMVGDAIPAQLYIKGT
DIRANPGSSVYCPSPSGSMVTSDSQLFNKPYWLHKAQGHN
NGICWHNQLFLTVVDTTRSTNFTLSTSIESSIPSTYDPSKFKE
YTRHVEEYDLQFIFQLCTVTLTTDVMSYIHTMNSSILDNWN
FAVAPPPSASLVDTYRYLQSAAITCQKDAPAPEKKDPYDG
LKFWNVDLREKFSLELDQFPLGRKFLLQARVRRRPTIGPRK RPAASTSSSSATKHKRKRVSK
HPV45_L1_DX MALWRPSDSTVYLPPPSVARVVSTDDYVSRTSIFYHAGSSR 39
LLTVGNPYFRVVPNGAGNKQAVPKVSAYQYRVFRVALPD
PNKFGLPDSTIYNPETQRLVWACVGMEIGRGQPLGIGLSGH
PFYNKLDDTESAHAATAVITQDVRDNVSVDYKQTQLCILG
CVPAIGEHWAKGTLCKPAQLQPGDCPPLELKNTIIEDGDM
VDTGYGAMDFSTLQDTKCEVPLDICQSICKYPDYLQMSAD
PYGDSMFFCLRREQLFARHFWNRAGVMGDTVPTDLYIKG
TSANMRETPGSCVYSPSPSGSIITSDSQLFNKPYWLHKAQG
HNNGICWHNQLFVTVVDTTRSTNLTLCASTQNPVPSTYDP
TKFKQYSRHVEEYDLQFIFQLCTITLTAEVMSYIHSMNSSIL
ENWNFGVPPPPTTSLVDTYRFVQSVAVTCQKDTTPPEKQD
PYDKLKFWTVDLKEKFSSDLDQYPLGRKFLVQAGLRRRPT
IGPRKRPAASTSTASTASRPAKRVRIRSKK HPV51_L1_DX
MALWRTNDSKVYLPPAPVSRIVNTEEYITRTGIYYYAGSSR 40
LITLGHPYFPIPKTSTRAAIPKVSAFQYRVFRVQLPDPNKFG
LPDPNLYNPDTDRLVWGCVGVEVGRGQPLGVGLSGHPLF
NKYDDTENSRIANGNAQQDVRDNTSVDNKQTQLCIIGCAP
PIGEHWGIGTTCKNTPVPPGDCPPLELVSSVIQDGDMIDTGF
GAMDFAALQATKSDVPLDISQSVCKYPDYLKMSADTYGN
SMFFHLRREQIFARHYYNKLVGVGEDIPNDYYIKGSGNGR
DPIESYIYSATPSGSMITSDSQIFNKPYWLHRAQGHNNGIC
WNNQLFITCVDTTRSTNLTISTATAAVSPTFTPSNFKQYIRH
GEEYELQFIFQLCKITLTTEVMAYLHTMDPTILEQWNFGLT
LPPSASLEDAYRFVRNAATSCQKDTPPQAKPDPLAKYKFW
DVDLKERFSLDLDQFALGRKFLLQVGVQRKPRPGLKRPAS SASSSSSSSAKRKRVKK
HPV52_L1_DX MSVWRPSEATVYLPPVPVSKVVSTDEYVSRTSIYYYAGSS 41
RLLTVGHPYFSIKNTSSGNGKKVLVPKVSGLQYRVFRIKLP
DPNKFGFPDTSFYNPETQRLVWACTGLEIGRGQPLGVGISG
HPLLNKFDDTETSNKYAGKPGIDNRECLSMDYKQTQLCIL
GCKPPIGEHWGKGTPCNNNSGNPGDCPPLQLINSVIQDGD
MVDTGFGCMDFNTLQASKSDVPIDICSSVCKYPDYLQMAS
EPYGDSLFFFLRREQMFVRHFFNRAGTLGDPVPGDLYIQGS
NSGNTATVQSSAFFPTPSGSMVTSESQLFNKPYWLQRAQG
HNNGICWGNQLFVTVVDTTRSTNMTLCAEVKKESTYKNE
NFKEYLRHGEEFDLQFIFQLCKITLTADVMTYIHKMDATIL
EDWQFGLTPPPSASLEDTYRFVTSTAITCQKNTPPKGKEDP
LKDYMFWEVDLKEKFSADLDQFPLGRKFLLQAGLQARPK LKRPASSAPRTSTKKKKVKR
HPV56_L1_DX MATWRPSENKVYLPPTPVSKVVATDSYVKRTSIFYHAGSS 42
RLLAVGHPYYSVTKDNTKTNIPKVSAYQYRVFRVRLPDPN
KFGLPDTNIYNPDQERLVWACVGLEVGRGQPLGAGLSGHP
LFNRLDDTESSNLANNNVIEDSRDNISVDGKQTQLCIVGCT
PAMGEHWTKGAVCKSTQVTTGDCPPLALINTPIEDGDMID
TGFGAMDFKVLQESKAEVPLDIVQSTCKYPDYLKMSADA
YGDSMWFYLRREQLFARHYFNRAGKVGETIPAELYLKGS
NGREPPPSSVYVATPSGSMITSEAQLFNKPYWLQRAQGHN
NGICWGNQLFVTVVDTTRSTNMTISTATEQLSKYDARKIN
QYLRHVEEYELQFVFQLCKITLSAEVMAYLHNMNANLLE
DWNIGLSPPVATSLEDKYRYVRSTAITCQREQPPTEKQDPL
AKYKFWDVNLQDSFSTDLDQFPLGRKFLMQLGTRSKPAV ATSKKRSAPTSTSTPAKRKRR
HPV58_L1_DX MSVWRPSEATVYLPPVPVSKVVSTDEYVSRTSIYYYAGSS 43
RLLAVGNPYFSIKSPNNNKKVLVPKVSGLQYRVFRVRLPD
PNKFGFPDTSFYNPDTQRLVWACVGLEIGRGQPLGVGVSG
HPYLNKFDDTETSNRYPAQPGSDNRECLSMDYKQTQLCLI
GCKPPTGEHWGKGVACNNNAAATDCPPLELFNSIIEDGDM
VDTGFGCMDFGTLQANKSDVPIDICNSTCKYPDYLKMASE
PYGDSLFFFLRREQMFVRHFFNRAGKLGEAVPDDLYIKGS
GNTAVIQSSAFFPTPSGSIVTSESQLFNKPYWLQRAQGHNN
GICWGNQLFVTVVDTTRSTNMTLCTEVTKEGTYKNDNFK
EYVRHVEEYDLQFVFQLCKITLTAEIMTYIHTMDSNILEDW
QFGLTPPPSASLQDTYRFVTSQAITCQKTAPPKEKEDPLNK
YTFWEVNLKEKFSADLDQFPLGRKFLLQSGLKAKPRLKRS APTTRAPSTKRKKVKK
HPV59_L1_DX MALWRSSDNKVYLPPPSVAKVVSTDEYVTRTSIFYHAGSS 44
RLLTVGHPYFKVPKGGNGRQDVPKVSAYQYRVFRVKLPD
PNKFGLPDNTVYDPNSQRLVWACVGVEIGRGQPLGVGLSG
HPLYNKLDDTENSHVASAVDTKDTRDNVSVDYKQTQLCII
GCVPAIGEHWTKGTACKPTTVVQGDCPPLELINTPIEDGDM
VDTGYGAMDFKLLQDNKSEVPLDICQSICKYPDYLQMSAD
AYGDSMFFCLRREQVFARHFWNRSGTMGDQLPESLYIKGT
DIRANPGSYLYSPSPSGSVVTSDSQLFNKPYWLHKAQGLN
NGICWHNQLFLTVVDTTRSTNLSVCASTTSSIPNVYTPTSFK
EYARHVEEFDLQFIFQLCKITLTTEVMSYIHNMNTTILEDW
NFGVTPPPTASLVDTYRFVQSAAVTCQKDTAPPVKQDPYD
KLKFWPVDLKERFSADLDQFPLGRKFLLQLGARPKPTIGPR KRAAPAPTSTPSPKRVKRRKSSRK
HPV68_L1_DX MALWRASDNMVYLPPPSVAKVVNTDDYVTRTGMYYYAG 45
TSRLLTVGHPYFKVPMSGGRKQGIPKVSAYQYRVFRVTLP
DPNKFSVPESTLYNPDTQRMVWACVGVEIGRGQPLGVGLS
GHPLYNRLDDTENSPFSSNKNPKDSRDNVAVDCKQTQLCII
GCVPAIGEHWAKGKSCKPTNVQQGDCPPLELVNTPIEDGD
MIDTGYGAMDFGTLQETKSEVPLDICQSVCKYPDYLQMSA
DVYGDSMFFCLRREQLFARHFWNRGGMVGDTIPTDMYIK
GTDIRETPSSYVYAPSPSGSMVSSDSQLFNKPYWLHKAQG
HNNGICWHNQLFLTVVDTTRSTNFTLSTTTDSTVPAVYDS
NKFKEYVRHVEEYDLQFIFQLCTITLSTDVMSYIHTMNPAI
LDDWNFGVAPPPSASLVDTYRYLQSAAITCQKDAPAPVKK
DPYDGLNFWNVDLKEKFSSELDQFPLGRKFLLQAGVRRRP TIGPRKRTATAATTSTSKHKRKRVSK
HPV73_L1_DX MWRPTDAKVYLPPVSVSKVVSTDEYVTRTNIYYYAGSTRL 46
LAVGHPYFPIKDSQKRKTIVPKVSGLQYRVFRLRLPDPNKF
GFPDASFYNPDKERLVWACSGVEVGRGQPLGIGTSGNPFM
NKLDDTENAPKYIAGQNTDGRECMSVDYKQTQLCILGCRP
PLGEHWGPGTPCTSQTVNTGDCPPLELKNTPIQDGDMIDV
GFGAMDFKALQANKSDVPIDISNTTCKYPDYLGMAADPY
GDSMWFYLRREQMFVRHLFNRAGDTGDKIPDDLMIKGTG
NTATPSSCVFYPTPSGSMVSSDAQLFNKPYWLQKAQGQNN
GICWHNQLFLTVVDTTRSTNFSVCVGTQASSSTTTYANSNF
KEYLRHAEEFDLQFVFQLCKISLTTEVMTYIHSMNSTILEE
WNFGLTPPPSGTLEETYRYVTSQAISCQRPQPPKETEDPYA
KLSFWDVDLKEKFSAELDQFPLGRKFLLQLGMRARPKLQA SKRSASATTSATPKKKRAKRI
HPV82_L1_DX MALWRTNDSKVYLPPAPVSRIVNTEEYITRTGIYYYAGSSR 47
LITLGHPYFSIPKTNTRAEIPKVSAFQYRVFRVQLPDPNKFG
LPDPNLFNPDTDRLVWGCVGVEVGRGQPLGVGLSGHPLFN
KYDDTENSRFANGNDQQDVRDNISVDNKQTQLCIIGCAPPI
GEHWATGTTCKNVPVPQGDCPPLELVSTVIEDGDMVDTGF
GAMDFANLQATKSDVPLDIAQSVCKYPDYLKMSADTYGN
SMFFHLRREQIFARHYYNKAGVVGDAIPDKAYIKGTGAGR
DPISSYIYSATPSGSMITSDSQIFNKPYWLHRAQGHNNGICW
NNQLFITCVDTTKSTNLTISTAVTPSVAQTFTPANFKQYIRH
GEEYELQFIFQLCKITLTTEIMAYLHTMDSTILEQWNFGLTL
PPSASLEDAYRFVKNAATSCHKDSPPQAKEDPLAKYKFWN
VDLKERFSLDLDQFALGRKFLLQIGAQRKPRPGLKRPAPSS SASSSAKRKRVKK
IgK_HPV18_E7_Rb_mut METPAQLLFLLLLWLPDTTGHGPKATLQDIVLHLEPQNEIP 48
VDLLGHGQLSDSEEENDEIDGVNHQHLPARRAEPQRHTML
CMCCKCEARIKLVVESSADDLRAFQQLFLNTLSFVCPWCA SQQ HPV18_E7_Rb_mut
MHGPKATLQDIVLHLEPQNEIPVDLLGHGQLSDSEEENDEI 49
DGVNHQHLPARRAEPQRHTMLCMCCKCEARIKLVVESSA DDLRAFQQLFLNTLSFVCPWCASQQ
IgK_HPV16_E7_Rb_mut METPAQLLFLLLLWLPDTTGHGDTPTLHEYMLDLQPETTD 50
LYGYGQLNDSSEEEDEIDGPAGQAEPDRAHYNIVTFCCKC
DSTLRLCVQSTHVDIRTLEDLLMGTLGIVCPICSQKP HPV16_E7_Rb_mut
MHGDTPTLHEYMLDLQPETTDLYGYGQLNDSSEEEDEIDG 51
PAGQAEPDRAHYNIVTFCCKCDSTLRLCVQSTHVDIRTLED LLMGTLGIVCPICSQKP
IgK_HPV18_E6_p53_mutdel METPAQLLFLLLLWLPDTTGARFEDPTRSGYKLPDLCTELN
52 TSLQDIEITCVYCKTVLELTEVFEKDLFVVYRDSIPHAACH
KCIDFYSRIRELRHYSDSVYGDTLEKLTNTGLYNLLIRCLRC
QKPLLRHLNEKRRFHNIAGHYRGQCHSCCNRARQERLQRR RETQV HPV18_E6_p53_mutdel
MARFEDPTRSGYKLPDLCTELNTSLQDIEITCVYCKTVLEL 53
TEVFEKDLFVVYRDSIPHAACHKCIDFYSRIRELRHYSDSV
YGDTLEKLTNTGLYNLLIRCLRCQKPLLRHLNEKRRFHNIA
GHYRGQCHSCCNRARQERLQRRRETQV IgK_HPV16_E6_p53_mutdel
METPAQLLFLLLLWLPDTTGHQKRTAMFQDPQESGRKLPQ 54
LCTELQTTIHDIILECVYCKQQLLRREVYDRDLCIVYRDGN
PYAVCDKCLKFYSKISEYRHYCYSLYGTTLEQQYNKPLCD
LLIRCINCQKPLQRHLDKKQRFHNIRGRWTGRCMSCCRSSR TRRETQL
HPV16_E6_p53_mutdel MHQKRTAMFQDPQESGRKLPQLCTELQTTIHDIILECVYCK 55
QQLLRREVYDRDLCIVYRDGNPYAVCDKCLKFYSKISEYR
HYCYSLYGTTLEQQYNKPLCDLLIRCINCQKPLQRHLDKK
QRFHNIRGRWTGRCMSCCRSSRTRRETQL HPV18_E7
MHGPKATLQDIVLHLEPQNEIPVDLLCHEQLSDSEEENDEI 56
DGVNHQHLPARRAEPQRHTMLCMCCKCEARIELVVESSA DDLRAFQQLFLNTLSFVCPWCASQQ
HPV16_E7 MHGDTPTLHEYMLDLQPETTDLYCYEQLNDSSEEEDEIDG 57
PAGQAEPDRAHYNIVTFCCKCDSTLRLCVQSTHVDIRTLED LLMGTLGIVCPICSQKP
HPV18_E6 MARFEDPTRRPYKLPDLCTELNTSLQDIEITCVYCKTVLEL 58
TEVFEFAFKDLFVVYRDSIPHAACHKCIDFYSRIRELRHYSD
SVYGDTLEKLTNTGLYNLLIRCLRCQKPLNPAEKLRHLNE
KRRFHNIAGHYRGQCHSCCNRARQERLQRRRETQV HPV16_E6
MHQKRTAMFQDPQERPRKLPQLCTELQTTIHDIILECVYCK 59
QQLLRREVYDFAFRDLCIVYRDGNPYAVCDKCLKFYSKIS
EYRHYCYSLYGTTLEQQYNKPLCDLLIRCINCQKPLCPEEK
QRHLDKKQRFHNIRGRWTGRCMSCCRSSRTRRETQL mGMCSF
MWLQNLLFLGIVVYSLSAPTRSPITVTRPWKHVEAIKEALN 60
LLDDMPVTLNEEVEVVSNEFSFKKLTCVQTRLKIFEQGLRG
NFTKLKGALNMTASYYQTYCPPTPETDCETQVTTYADFID SLKTFLTDIPFECKKPGQK hGMCSF
MWLQSLLLLGTVACSISAPARSPSPSTQPWEHVNAIQEARR 61
LLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLELYKQ
GLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESF KENLKDFLLVIPFDCWEPVQ
TABLE-US-00004 TABLE 3 HPV NCBI Accession Numbers (Amino Acid
Sequences) GenBank Type Virus Name Accession L1 hypothetical
protein HpV63gp7 NP_040902.1 [Human papillomavirus type 63] L1 L1
protein [Human papillomavirus type 204] AKG54930.1 L1 RecName: Full
= Major capsid protein L1 P27557.2 [Human papillomavirus type 41]
L1 hypothetical protein [Human papillomavirus type 41] NP_040294.1
L1 major capsid protein [Human papillomavirus type 138] AEM24620.1
L1 L1 protein [Human papillomavirus type 98] CAW42222.1 L1 RecName:
Full = Major capsid protein L1 P50790.1 L1 L1 [Human papillomavirus
type 16] AFS33363.1 L1 major capsid protein [Human papillomavirus
type 139] AEM24627.1 L1 L1 [Human papillomavirus type 16]
AFS33339.1 L1 L1 [Human papillomavirus type 16] AAV91659.1 L1 Chain
A, L1 Protein Of Human Papillomavirus 16 1DZL_A L1 L1 protein
[Human papillomavirus type 16] AGK28592.1 L1 late major capsid
protein [Human papillomavirus type 16] AAC09292.1 L1 major capsid
protein L1 [Human papillomavirus type 16] ACV53971.1 L1 L1 [Human
papillomavirus type 16] ACN91157.1 L1 HPV-16 L1 [synthetic
construct] AAY79402.1 L1 L1 [Human papillomavirus type 16]
AFS33347.1 L1 L1 protein [Human papillomavirus type 42] CCI11841.1
L1 L1 protein [Human papillomavirus type 42] CCI11834.1 L1 L1
[Human papillomavirus type 93] AAQ88285.1 L1 major capsid protein
L1 [Human papillomavirus type 16] ACV53973.1 L1 coat protein L1
[Cloning vector p119L1e] AAX54678.1 L1 late major capsid protein
[Human papillomavirus type 16] AAC61736.1 L1 L1 [Human
papillomavirus type 16] AAV91667.1 L1 major capsid protein L1
[Human papillomavirus type 16] AGC65525.1 L1 L1 [Human
papillomavirus type 16] AFS33350.1 L1 L1 protein [Human
papillomavirus type 16] AFP44558.1 L1 L1 protein [Human
papillomavirus type 16] AFP44198.1 L1 L1 protein [Human
papillomavirus type 42] CCI11844.1 L1 putative major capsid protein
L1 AAQ10410.1 [Human papillomavirus type 16] L1 L1 [Human
papillomavirus type 16] ALB35275.1 L1 RecName: Full = Major capsid
protein L1 P03101.2 L1 L1 [Human papillomavirus type 16] AIQ82817.1
L1 major capsid protein L1 [Human papillomavirus type 16]
ACV84004.1 L1 L1 capsid protein [Human papillomavirus type 16]
AAA92892.1 L1 L1 protein [Human papillomavirus type 16] AEZ01705.1
L1 L1 [Human papillomavirus type 16] AFS33335.1 L1 L1 protein
[Human papillomavirus type 16] AFP44382.1 L1 RecName: Full = Major
capsid protein L1 P27233.1 L1 putative major capsid protein L1
AAO15712.1 [Human papillomavirus type 16] L1 L1 protein [Human
papillomavirus type 16] AFP44630.1 L2 minor capsid protein L2
[Mupapillomavirus 1] NP_040308.1 L2 hypothetical protein HpV63gp6
NP_040901.1 [Human papillomavirus type 63] L2 L2 protein [Human
papillomavirus type 204] AKG54929.1 L2 late protein
[Lambdapapillomavirus 2] NP_056818.1 L2 L2 protein [Panthera leo
persica papillomavirus type 1] AAX86631.1 L2 L2 [Procyon lotor
papillomavirus 1] YP_249603.1 L2 L2 [Enhydra lutris papillomavirus
1] YP_009021868.1 L2 L2 [Canis familiaris papillomavirus 6]
YP_003204680.1 L2 L2 [Uncia uncia papillomavirus type 1] ABA61876.1
L2 L2 protein [Felis domesticus papillomavirus type 1] NP_848024.1
L2 L2 [Castor canadensis papillomavirus 1] YP_008992243.1 L2 L2
protein [Puma concolor papillomavirus type 1] AAX86624.1 L2 L2
protein [Crocuta crocuta papillomavirus 1] YP_006666519.1 L2 L2
protein [Lynx rufus papillomavirus type 1] AAX86617.1 L2 late
protein [Human papillomavirus type 9] NP_041865.1 L2 L2 [Macaca
fascicularis papillomavirus 2] YP_004646336.1 L2 L2 [Human
papillomavirus type 96] NP_932324.1 L2 minor capsid protein L2
ADH29817.1 [Human papillomavirus type 122] L2 putative L2 product
[Human papillomavirus type 150] CBK38951.1 L2 L2 protein [Human
papillomavirus type 98] CAW42221.1 L2 minor capsid protein [Human
papillomavirus type 5] NP_041371.1 L2 L2 protein [Human
papillomavirus type 75] CAA75453.1 L2 L2 protein [Human
papillomavirus type 104] CAW42255.1 L2 L2 protein [Human
papillomavirus FA75/KI88-03] ACC78261.1 L2 L2 [Human papillomavirus
type 5] AAY86491.1 L2 L2 protein [Human papillomavirus type 174]
CCV02863.1 L2 L2 protein [Human papillomavirus type 76] CAA75460.1
L2 RecName: Full = Minor capsid protein P50798.1 L2 [Human
papillomavirus type 24] L2 L2 [Human papillomavirus type 80]
CAA75475.1 L2 minor capsid protein [Human papillomavirus type 145]
AEM24668.1 L2 L2 protein [Human papillomavirus type 107] ABN79872.1
L2 L2 protein [Human papillomavirus type 111] ACC78275.1 L2 L2
[Human papillomavirus type 92] NP_775310.1 L2 RecName: Full = Minor
capsid protein P50795.1 L2 [Human papillomavirus type 21] L2
RecName: Full = Minor capsid protein P36749.1 L2 [Human
papillomavirus type 14] L2 minor capsid protein [Human
papillomavirus type 143] AEM24654.1 L2 late protein L2 [Human
papillomavirus type 115] ACZ58408.1 L2 RecName: Full = Minor capsid
protein Q80912.1 L2 [Human papillomavirus type 38] L2 putative L2
[uncultured Papillomavirus] AEY63592.1 L2 L2 protein [Human
papillomavirus type 49] NP_041836.1 L2 putative late L2 protein
[Rhinolophus ferrumequinum AHJ81406.1 papillomavirus type 1] L2
early protein L2 [Human papillomavirus type 36] AEA35083.1 L2
RecName: Full = Minor capsid protein P50794.1 L2 [Human
papillomavirus type 20] L2 L2 [Human papillomavirus type 5]
AFL02857.1 L2 RecName: Full = Minor capsid protein P26540.1 L2
[Human papillomavirus type 5b] L2 RecName: Full = Minor capsid
protein P50827.1 L2 [Human papillomavirus type 36] L2 L2 protein
[Human papillomavirus type 38b] AAY89823.2 L2 L2 [Human
papillomavirus type 93] AAQ88284.1 L2 RecName: Full = Minor capsid
protein P06419.1 L2 [Human papillomavirus type 8] L2 L2 protein
[Human papillomavirus type 113] CAW42275.1 L2 L2 protein [Human
papillomavirus type 159] CCJ27720.1 L2 RecName: Full = Minor capsid
protein P36752.1 L2 [Human papillomavirus type 19] L2 L2 [Human
papillomavirus type 38] AFL02871.1 L2 L2 [Human papillomavirus type
118] ACV30152.1 L2 early protein L2 [Human papillomavirus type 152]
AEA35077.1 L2 L2 [Macaca fascicularis papillomavirus type 1]
ABM67069.1 L2 L2 protein [Human papillomavirus type 105] CAW42266.1
L2 minor capsid protein L2 ADH29831.1 [Human papillomavirus type
124] L2 RecName: Full = Minor capsid protein P36750.1 L2 [Human
papillomavirus type 15] L2 L2 [Human papillomavirus RTRX7]
AAB61645.1 L2 L2 [Human papillomavirus type 17] AFL02864.1 L2
RecName: Full = Minor capsid protein P36748.1 L2 [Human
papillomavirus type 12] L2 L2 [Human papillomavirus type 110]
ACC78268.1 L2 RecName: Full = Minor capsid protein P36753.1 L2
[Human papillomavirus type 25] L2 L2 protein [Human papillomavirus
type 100] CAW42243.1 L2 L2 protein [Human papillomavirus type 99]
CAW42231.1 L2 RecName: Full = Minor capsid protein P22425.1 L2
[Human papillomavirus type 74] L2 L2 [Human papillomavirus type
120] AFJ32711.1 L2 putative L2 protein [Human papillomavirus type
120] CBI67303.1 L2 RecName: Full = Minor capsid protein Q80905.1 L2
[Human papillomavirus type 37] L2 RecName: Full = Minor capsid
protein P36751.1 L2 [Human papillomavirus type 17] L2 putative L2
product [Human papillomavirus type 151] CBK38958.1 L2 L2 [Colobus
guereza papillomavirus type 2] YP_004646342.1 L2 RecName: Full =
Minor capsid protein P50796.1 L2 [Human papillomavirus type 22] L2
minor capsid protein L2 [Kappapapillomavirus 1] NP_057847.1 L2
RecName: Full = Minor capsid protein P50797.1 L2 [Human
papillomavirus type 23] L2 L2 [Kappapapillomavirus 2] NP_077112.1
L2 L2 [Expression vector pBCGL2] ABM68360.1 L2 L2
[Kappapapillomavirus 2] CAB96168.1 L2 L2 [Kappapapillomavirus 2]
CAB96120.1 L2 L2 [Peromyscus papillomavirus type 1] AEM05820.1 L2
putative late L2 protein AHJ81394.1 [Eptesicus serotinus
papillomavirus type 2] L2 L2 [Kappapapillomavirus 2] AEG21068.1 L2
minor capsid protein YP_002427695.1 [Erinaceus europaeus
papillomavirus] L2 L2 [Human papillomavirus type 180] AGC93440.1 L2
L2 [Canis familiaris papillomavirus 2] YP_164634.1 L2 L2 [Human
papillomavirus type 134] YP_004169296.1 L2 L2 [Eidolon helvum
papillomavirus type 1] AGB34180.1 L2 L2 protein [Bovine
papillomavirus type 11] BAJ12077.1 L2 minor capsid protein [Human
papillomavirus type 139] AEM24626.1 L2 L2 [Human papillomavirus
type 173] AHC00355.1 L2 minor capsid protein L2 YP_003668030.1
[Human papillomavirus type 121] L2 unnamed protein product [Canine
papillomavirus 10] YP_004895385.1 L2 L2 [Human papillomavirus type
133] ADQ85974.1 L2 L2 protein [Bovine papillomavirus] AJG05911.1 L2
L2 [Human papillomavirus type 155] AEQ98810.1 L2 L2 protein
[Iotapapillomavirus 1] NP_042018.1 L2 minor capsid protein [Human
papillomavirus type 138] AEM24619.1 L2 putative L2 [Equus asinus
papillomavirus AA-2014] YP_009021885.1 L2 putative minor capsid
protein [Canine papillomavirus 3] YP_717905.1
TABLE-US-00005 TABLE 4 SEQ ID Description Sequence NO: Chlamydia
MOMP Nucleic Acid Sequences Chlamydia
ATGAAAAAACTCTTGAAATCGGTATTAGTATTTGCCGCT 62 trachomatis strain
TTGAGTTCTGCTTCCTCCTTGCAAGCTCTGCCTGTGGGGA C1 major outer
ATCCTGCTGAACCAAGCCTTATGATCGACGGAATTCTGT membrane protein
GGGAAGGTTTTGGCGGAGATCCTTGCGATCCTTGCACCA (ompA) gene,
CTTGGTGTGACGCTATCAGCATGCGTGTTGGTTACTACG complete cds;
GAGACTTTGTTTTCGACCGTGTTTTGAAAACTGATGTGA Accession No.
ATAAAGAATTTCAGATGGGAGCGGCGCCTACTACCAGC EU040363
GATGTAGTAGGCTTACAAAACGATCCAACAACAAACGT
TGCTCGTCCAAATCCCGCTTATGGCAAACACATGCAAGA
TGCTGAAATGTTTACGAACGCTGCTTACATGGCATTAAA
TATCTGGGATCGTTTTGATGTATTTTGTACATTGGGAGC
AACTACCGGTTATTTAAAAGGAAACTCTGCTTCCTTCAA
CTTAGTTGGATTATTCGGAACAAAAACACAATCTTCTAG
CTTTAATACAGCGAAGCTTATTCCTAACACTGCTTTGAA
TGAAGCTGTGGTTGAGCTTTATATAAACACTACCTTTGC
TTGGAGCGTAGGTGCTCGTGCAGCTCTCTGGGAATGTGG
GTGTGCAACGTTAGGAGCTTCTTTCCAATATGCTCAATC
TAAACCTAAAGTAGAAGAGTTAAATGTTCTTTGTAATGC
ATCCGAATTTACTATTAATAAGCCGAAAGGATATGTTGG
GGCGGAATTTCCACTTAATATTACCGCAGGAACAGAAG
CTGCGACAGGGACTAAGGATGCCTCTATTGACTACCATG
AGTGGCAAGCAAGTTTAGCCCTTTCTTACAGATTAAATA
TGTTCACTCCTTACATTGGAGTTAAATGGTCTAGAGTAA
GTTTTGATGCCGACACGATCCGTATCGCTCAGCCTAAAT
TGGCTGAAGCAATCTTGGATGTCACTACTCTAAACCCGA
CCATCGCTGGTAAAGGAAGTGTGGTCTCTGCCGGAACCG
ATAACGAACTGGCTGATACAATGCAAATCGTTTCCTTGC
AGTTGAACAAGATGAAATCTAGAAAATCTTGCGGTATTG
CAGTAGGAACGACTATTGTAGATGCAGACAAATACGCA
GTTACAGTTGAGGCTCGCTTGATCGATGAGAGAGCAGCT CACGTAAATGCACAATTCCGGTTCTAA
Chlamydia ATGAAAAAACTCTTGAAATCGGTATTAGTATTTGCCGCT 63 trachomatis
strain TTGAGTTCTGCTTCCTCCTTGCAAGCTCTGCCTGTGGGGA C2 major outer
ATCCTGCTGAACCAAGCCTTATGATCGACGGAATTCTGT membrane protein
GGGAAGGTTTTGGCGGAGATCCTTGCGATCCTTGCACCA (ompA) gene,
CTTGGTGTGACGCTATCAGCATGCGTGTTGGTTACTACG complete cds;
GAGACTTTGTTTTCGACCGTGTTTTGAAAACTGATGTGA Accession No.
ATAAAGAATTTCAGATGGGAGCGGCGCCTACTACCAGC EU040364
GATGTAGCAGGCTTACAAAACGATCCAACAACAAACGT
TGCTCGTCCAAATCCCGCTTATGGCAAACACATGCAAGA
TGCTGAAATGTTTACGAACGCTGCTTACATGGCATTAAA
TATCTGGGATCGTTTTGATGTATTTTGTACATTGGGAGC
AACTACCGGTTATTTAAAAGGAAACTCTGCTTCCTTCAA
CTTAGTTGGATTATTCGGAACAAAAACACAATCTTCTAG
CTTTAATACAGCGAAGCTTATTCCTAACACTGCTTTGAA
TGAAGCTGTGGTTGAGCTTTATATAAACACTACCTTTGC
TTGGAGCGTAGGTGCTCGTGCAGCTCTCTGGGAATGTGG
GTGTGCAACGTTAGGAGCTTCTTTCCAATATGCTCAATC
TAAACCTAAAGTAGAAGAGTTAAATGTTCTTTGTAATGC
ATCCGAATTTACTATTAATAAGCCGAAAGGATATGTTGG
GGCGGAATTTCCACTTAATATTACCGCAGGAACAGAAG
CTGCGACAGGGACTAAGGATGCCTCTATTGACTACCATG
AGTGGCAAGCAAGTTTAGCCCTTTCTTACAGATTAAATA
TGTTCACTCCTTACATTGGAGTTAAATGGTCTAGAGTAA
GTTTTGATGCCGACACGATCCGTATCGCTCAGCCTAAAT
TGGCTGAAGCAATCTTGGATGTCACTACTCTAAACCCGA
CCATCGCTGGTAAAGGAAGTGTGGTCTCTTCCGGAACCG
ATAACGAACTGGCTGATACAATGCAAATCGTTTCCTTGC
AGTTGAACAAGATGAAATCTAGAAAATCTTGCGGTATTG
CAGTAGGAACGACTATTGTAGATGCAGACAAATACGCA
GTTACAGTTGAGGCTCGCTTGATCGATGAGAGAGCAGCT
CACGTAAATGCACAATTCCGGTTCTAA; Chlamydia
ATGAAAAAACTCTTGAAATCGGTATTAGTATTTGCCGCT 64 trachomatis strain
TTGAGTTCTGCTTCCTCCTTGCAAGCTCTGCCTGTGGGGA C3 major outer
ATCCTGCTGAACCAAGCCTTATGATCGACGGAATTCTGT membrane protein
GGGAAGGTTTTGGCGGAGATCCTTGCGATCCTTGCACCA (ompA) gene,
CTTGGTGTGACGCTATCAGCATGCGTGTTGGTTACTACG complete cds;
GAGACTTTGTTTTCGACCGTGTTTTGAAAACTGATGTGA Accession No.
ATAAAGAATTTCAGATGGGAGCGGCGCCTACTACCAGC EU040365
GATGTAGTAGGCTTACAAAACGATCCAACAACAAACGT
TGCTCGTCCAAATCCCGCTTATGGCAAACACATGCAAGA
TGCTGAAATGTTTACGAACGCTGCTTACATGGCATTAAA
TATCTGGGATCGTTTTGATGTATTTTGTACATTGGGAGC
AACTACCGGTTATTTAAAAGGAAACTCTGCTTCCTTCAA
CTTAGTTGGATTATTCGGAACAAAAACACAATCTTCTAG
CTTTAATACAGCGAAGCTTATTCCTAACACTGCTTTGAA
TGAAGCTGTGGTTGAGCTTTATATAAACACTACCTTTGC
TTGGAGCGTAGGTGCTCGTGCAGCTCTCTGGGAATGTGG
GTGTGCAACGTTAGGAGCTTCTTTCCAATATGCTCAATC
TAAACCTAAAGTAGAAGAGTTAAATGTTCTTTGTAATGC
ATCCGAATTTACTATTAATAAGCCGAAAGGATATGTTGG
GGCGGAATTTCCACTTAATATTACCGCAGGAACAGAAG
CTGCGACAGGGACTAAGGATGCCTCTATTGACTACCATG
AGTGGCAAGCAAGTTTAGCCCTTTCTTACAGATTAAATA
TGTTCACTCCTTACATTGGAGTTAAATGGTCTAGAGTAA
GTTTTGATGCCGACACGATCCGTATCGCTCAGCCTAAAT
TGGCTGAAGCAATCTTGGATGTCACTACTCTAAACCCGA
CCATCGCTGGTAAAGGAAGTGTGGTCTCTTCCGGAACCG
ATAACGAACTGGCTGATACAATGCAAATCGTTTCCTTGC
AGTTGAACAAGATGAAATCTAGAAAATCTTGCGGTATTG
CAGTAGGAACGACTATTGTAGATGCAGACAAATACGCA
GTTACAGTTGAGGCTCGCTTGATCGATGAGAGAGCAGCT CACGTAAATGCACAATTCCGGTTCTAA
Chlamydia mRNA Sequences Chlamydia
AUGAAAAAACUCUUGAAAUCGGUAUUAGUAUUUGCCG 317 trachomatis strain
CUUUGAGUUCUGCUUCCUCCUUGCAAGCUCUGCCUGU C1 major outer
GGGGAAUCCUGCUGAACCAAGCCUUAUGAUCGACGGA membrane protein
AUUCUGUGGGAAGGUUUUGGCGGAGAUCCUUGCGAUC (ompA) gene,
CUUGCACCACUUGGUGUGACGCUAUCAGCAUGCGUGU complete cds;
UGGUUACUACGGAGACUUUGUUUUCGACCGUGUUUUG Accession No.
AAAACUGAUGUGAAUAAAGAAUUUCAGAUGGGAGCGG EU040363
CGCCUACUACCAGCGAUGUAGUAGGCUUACAAAACGA
UCCAACAACAAACGUUGCUCGUCCAAAUCCCGCUUAUG
GCAAACACAUGCAAGAUGCUGAAAUGUUUACGAACGC
UGCUUACAUGGCAUUAAAUAUCUGGGAUCGUUUUGAU
GUAUUUUGUACAUUGGGAGCAACUACCGGUUAUUUAA
AAGGAAACUCUGCUUCCUUCAACUUAGUUGGAUUAUU
CGGAACAAAAACACAAUCUUCUAGCUUUAAUACAGCG
AAGCUUAUUCCUAACACUGCUUUGAAUGAAGCUGUGG
UUGAGCUUUAUAUAAACACUACCUUUGCUUGGAGCGU
AGGUGCUCGUGCAGCUCUCUGGGAAUGUGGGUGUGCA
ACGUUAGGAGCUUCUUUCCAAUAUGCUCAAUCUAAAC
CUAAAGUAGAAGAGUUAAAUGUUCUUUGUAAUGCAUC
CGAAUUUACUAUUAAUAAGCCGAAAGGAUAUGUUGGG
GCGGAAUUUCCACUUAAUAUUACCGCAGGAACAGAAG
CUGCGACAGGGACUAAGGAUGCCUCUAUUGACUACCA
UGAGUGGCAAGCAAGUUUAGCCCUUUCUUACAGAUUA
AAUAUGUUCACUCCUUACAUUGGAGUUAAAUGGUCUA
GAGUAAGUUUUGAUGCCGACACGAUCCGUAUCGCUCA
GCCUAAAUUGGCUGAAGCAAUCUUGGAUGUCACUACU
CUAAACCCGACCAUCGCUGGUAAAGGAAGUGUGGUCU
CUGCCGGAACCGAUAACGAACUGGCUGAUACAAUGCA
AAUCGUUUCCUUGCAGUUGAACAAGAUGAAAUCUAGA
AAAUCUUGCGGUAUUGCAGUAGGAACGACUAUUGUAG
AUGCAGACAAAUACGCAGUUACAGUUGAGGCUCGCUU
GAUCGAUGAGAGAGCAGCUCACGUAAAUGCACAAUUC CGGUUCUAA Chlamydia
AUGAAAAAACUCUUGAAAUCGGUAUUAGUAUUUGCCG 318 trachomatis strain
CUUUGAGUUCUGCUUCCUCCUUGCAAGCUCUGCCUGU C2 major outer
GGGGAAUCCUGCUGAACCAAGCCUUAUGAUCGACGGA membrane protein
AUUCUGUGGGAAGGUUUUGGCGGAGAUCCUUGCGAUC (ompA) gene,
CUUGCACCACUUGGUGUGACGCUAUCAGCAUGCGUGU complete cds;
UGGUUACUACGGAGACUUUGUUUUCGACCGUGUUUUG Accession No.
AAAACUGAUGUGAAUAAAGAAUUUCAGAUGGGAGCGG EU040364
CGCCUACUACCAGCGAUGUAGCAGGCUUACAAAACGA
UCCAACAACAAACGUUGCUCGUCCAAAUCCCGCUUAUG
GCAAACACAUGCAAGAUGCUGAAAUGUUUACGAACGC
UGCUUACAUGGCAUUAAAUAUCUGGGAUCGUUUUGAU
GUAUUUUGUACAUUGGGAGCAACUACCGGUUAUUUAA
AAGGAAACUCUGCUUCCUUCAACUUAGUUGGAUUAUU
CGGAACAAAAACACAAUCUUCUAGCUUUAAUACAGCG
AAGCUUAUUCCUAACACUGCUUUGAAUGAAGCUGUGG
UUGAGCUUUAUAUAAACACUACCUUUGCUUGGAGCGU
AGGUGCUCGUGCAGCUCUCUGGGAAUGUGGGUGUGCA
ACGUUAGGAGCUUCUUUCCAAUAUGCUCAAUCUAAAC
CUAAAGUAGAAGAGUUAAAUGUUCUUUGUAAUGCAUC
CGAAUUUACUAUUAAUAAGCCGAAAGGAUAUGUUGGG
GCGGAAUUUCCACUUAAUAUUACCGCAGGAACAGAAG
CUGCGACAGGGACUAAGGAUGCCUCUAUUGACUACCA
UGAGUGGCAAGCAAGUUUAGCCCUUUCUUACAGAUUA
AAUAUGUUCACUCCUUACAUUGGAGUUAAAUGGUCUA
GAGUAAGUUUUGAUGCCGACACGAUCCGUAUCGCUCA
GCCUAAAUUGGCUGAAGCAAUCUUGGAUGUCACUACU
CUAAACCCGACCAUCGCUGGUAAAGGAAGUGUGGUCU
CUUCCGGAACCGAUAACGAACUGGCUGAUACAAUGCA
AAUCGUUUCCUUGCAGUUGAACAAGAUGAAAUCUAGA
AAAUCUUGCGGUAUUGCAGUAGGAACGACUAUUGUAG
AUGCAGACAAAUACGCAGUUACAGUUGAGGCUCGCUU
GAUCGAUGAGAGAGCAGCUCACGUAAAUGCACAAUUC CGGUUCUAA; Chlamydia
AUGAAAAAACUCUUGAAAUCGGUAUUAGUAUUUGCCG 319 trachomatis strain
CUUUGAGUUCUGCUUCCUCCUUGCAAGCUCUGCCUGU C3 major outer
GGGGAAUCCUGCUGAACCAAGCCUUAUGAUCGACGGA membrane protein
AUUCUGUGGGAAGGUUUUGGCGGAGAUCCUUGCGAUC (ompA) gene,
CUUGCACCACUUGGUGUGACGCUAUCAGCAUGCGUGU complete cds;
UGGUUACUACGGAGACUUUGUUUUCGACCGUGUUUUG Accession No.
AAAACUGAUGUGAAUAAAGAAUUUCAGAUGGGAGCGG EU040365
CGCCUACUACCAGCGAUGUAGUAGGCUUACAAAACGA
UCCAACAACAAACGUUGCUCGUCCAAAUCCCGCUUAUG
GCAAACACAUGCAAGAUGCUGAAAUGUUUACGAACGC
UGCUUACAUGGCAUUAAAUAUCUGGGAUCGUUUUGAU
GUAUUUUGUACAUUGGGAGCAACUACCGGUUAUUUAA
AAGGAAACUCUGCUUCCUUCAACUUAGUUGGAUUAUU
CGGAACAAAAACACAAUCUUCUAGCUUUAAUACAGCG
AAGCUUAUUCCUAACACUGCUUUGAAUGAAGCUGUGG
UUGAGCUUUAUAUAAACACUACCUUUGCUUGGAGCGU
AGGUGCUCGUGCAGCUCUCUGGGAAUGUGGGUGUGCA
ACGUUAGGAGCUUCUUUCCAAUAUGCUCAAUCUAAAC
CUAAAGUAGAAGAGUUAAAUGUUCUUUGUAAUGCAUC
CGAAUUUACUAUUAAUAAGCCGAAAGGAUAUGUUGGG
GCGGAAUUUCCACUUAAUAUUACCGCAGGAACAGAAG
CUGCGACAGGGACUAAGGAUGCCUCUAUUGACUACCA
UGAGUGGCAAGCAAGUUUAGCCCUUUCUUACAGAUUA
AAUAUGUUCACUCCUUACAUUGGAGUUAAAUGGUCUA
GAGUAAGUUUUGAUGCCGACACGAUCCGUAUCGCUCA
GCCUAAAUUGGCUGAAGCAAUCUUGGAUGUCACUACU
CUAAACCCGACCAUCGCUGGUAAAGGAAGUGUGGUCU
CUUCCGGAACCGAUAACGAACUGGCUGAUACAAUGCA
AAUCGUUUCCUUGCAGUUGAACAAGAUGAAAUCUAGA
AAAUCUUGCGGUAUUGCAGUAGGAACGACUAUUGUAG
AUGCAGACAAAUACGCAGUUACAGUUGAGGCUCGCUU
GAUCGAUGAGAGAGCAGCUCACGUAAAUGCACAAUUC CGGUUCUAA
TABLE-US-00006 TABLE 5 Chlamydia MOMP Amino Acid Sequences SEQ ID
Description Sequence NO:
sp|P13467|MOMP_Serovar_H_Chlamydia_trachomatis
MKKLLKSVLVFAALSSASSLQALPVGNPAEPSLMID 65
GILWEGFGGDPCDPCATWCDAISMRVGYYGDFVFD
RVLKTDVNKEFQMGAAPTTNDAADLQNDPKTNVA
RPNPAYGKHMQDAEMFTNAAYMALNIWDRFDVFC
TLGATTGYLKGNSASFNLVGLFGTKTKSSDFNTAKL
VPNIALNRAVVELYTDTTFAWSVGARAALWECGCA
TLGASFQYAQSKPKVEELNVLCNASEFTINKPKGYV
GAEFPLDITAGTEAATGTKDASIDYHEWQASLALSY
RLNMFTPYIGVKWSRVSFDADTIRIAQPKLAEAILDV
TTLNPTIAGKGTVVASGSDNDLADTMQIVSLQLNKM
KSRKSCGIAVGTTIVDADKYAVTVETRLIDERAAHV NAQFRF
sp|P16155|MOMP_Serovar_F_Chlamydia_trachomatis
MKKLLKSVLVFAALSSASSLQALPVGNPAEPSLMID 66
GILWEGFGGDPCDPCTTWCDAISMRMGYYGDFVFD
RVLKTDVNKEFEMGEALAGASGNTTSTLSKLVERTN
PAYGKHMQDAEMFTNAACMTLNIWDRFDVFCTLG
ATSGYLKGNSASFNLVGLFGDGVNATKPAADSIPNV
QLNQSVVELYTDTTFAWSVGARAALWECGCATLGA
SFQYAQSKPKIEELNVLCNAAEFTINKPKGYVGKEFP
LDLTAGTDAATGTKDASIDYHEWQASLSLSYRLNMF
TPYIGVKWSRASFDSDTIRIAQPRLVTPVVDITTLNPT
IAGCGSVAGANTEGQISDTMQIVSLQLNKMKSRKSC
GIAVGTTIVDADKYAVTVETRLIDERAAHVNAQFRF
sp|P17451|MOMP_Serovar_E_Chlamydia_trachomatis
MKKLLKSVLVFAALSSASSLQALPVGNPAEPSLMID 67
GILWEGFGGDPCDPCTTWCDAISMRMGYYGDFVFD
RVLKTDVNKEFQMGDKPTSTTGNATAPTTLTARENP
AYGRHMQDAEMFTNAACMALNIWDRFDVFCTLGA
SSGYLKGNSASFNLVGLFGDNENQSTVKTNSVPNMS
LDQSVVELYTDTAFSWSVGARAALWECGCATLGAS
FQYAQSKPKVEELNVLCNAAEFTINKPKGYVGQEFP
LALIAGTDAATGTKDASIDYHEWQASLALSYRLNMF
TPYIGVKWSRASFDADTIRIAQPKSATAIFDTTTLNPT
IAGAGDVKASAEGQLGDTMQIVSLQLNKMKSRKSC
GIAVGTTIVDADKYAVTVETRLIDERAAHVNAQFRF
sp|Q46409|MOMP_Serovar_D_Chlamydia_trachomatis_strain_D/
MKKLLKSVLVFAALSSASSLQALPVGNPAEPSLMID 68 UW-3/Cx
GILWEGFGGDPCDPCATWCDAISMRVGYYGDFVFD
RVLKTDVNKEFQMGAKPTTDTGNSAAPSTLTARENP
AYGRHMQDAEMFTNAACMALNIWDRFDVFCTLGA
TSGYLKGNSASFNLVGLFGDNENQKTVKAESVPNM
SFDQSVVELYTDTTFAWSVGARAALWECGCATLGA
SFQYAQSKPKVEELNVLCNAAEFTINKPKGYVGKEF
PLDLTAGTDAATGTKDASIDYHEWQASLALSYRLN
MFTPYIGVKWSRASFDADTIRIAQPKSATAIFDTTTL
NPTIAGAGDVKTGAEGQLGDTMQIVSLQLNKMKSR
KSCGIAVGTTIVDADKYAVTVETRLIDERAAHVNAQ FRF
gi|592971106|MOMP_Serovar_I_Chlamydia_trachomatis
MKKLLKSVLVFAALSSASSLQALPVGNPAEPSLMID 69
GILWEGFGGDPCDPCTTWCDAISMRMGYYGDFVFD
RVLKTDVNKEFQMGAAPTTKDVAGLENDPTTNVAR
PNPAYGKHMQDAEMFTNAAYMALNIWDRFDVFCT
LGATTGYLKGNSASFNLVGLFGTKTQSSNFNTAKLV
PNAALNQAVVELYTDTTFAWSVGARAALWECGCA
TLGASFQYAQSKPKVEELNVLCNASEFTINKPKGYV
GAEFPLDIIAGTEAATGTKDASIDYHEWQASLALSYR
LNMFTPYIGVKWSRVSFDADTIRIAQPKLAEAILDVT
TLNPTIAGKGTVVSSAENELADTMQIVSLQLNKMKS
RKSCGIAVGTTIVDADKYAVTVETRLIDERAAHVNA QFRF
gi|297140585||MOMP_Serovar_G_Chlamydia_trachomatis
MKKLLKSVLVFAALSSASSLQALPVGNPAEPSLMID 70
GILWEGFGGDPCDPCTTWCDAISMRMGYYGDFVFD
RVLKTDVNKEFEMGEALAGASGNTTSTLSKLVERTN
PAYGKHMQDAEMFTNAACMALNIWDRFDVFCTLG
ATSGYLRGNSASFNLVGLFGDGENATQPAATSIPNV
QLNQSVVELYTDTAFAWSVGARAALWECGCATLG
ASFQYAQSKPKVEELNVLCNAAEFTINKPKGYVGQE
FPLALTAGTDAATGTKDASIDYHEWQASLSLSYRLN
MFTPYIGVKWSRASFDSNTIRIAQPKLAKPVVDITTL
NPTIAGCGSVVAANAEGQISDTMQIVSLQLNKMKSR
KSCGIAVGTTIVDADKYAVTVETRLIDERAAHVNAQ FRF
gi|527133542|MOMP_Serovar_J_Chlamydia_trachomatis
MKKLLKSVLVFAALSSASSLQALPVGNPAEPSLMID 71
GILWEGFGGDPCDPCTTWCDAISMRMGYYGDFVFD
RVLKTDVNKEFQMGAAPTTSDVAGLQNDPTTNVAR
PNPAYGKHMQDAEMFTNAAYMALNIWDRFDVFCT
LGATTGYLKGNSASFNLVGLFGTKTQASSFNTANLF
PNTALNQAVVELYTDTTFAWSVGARAALWECGCAT
LGASFQYAQSKPKVEELNVLCNASEFTINKPKGYVG
AEFPLDITAGTEAATGTKDASIDYHEWQASLALSYR
LNMFTPYIGVKWSRVSFDADTIRIAQPKLAEAILDVT
TLNPTIAGKGTVVASGSENDLADTMQIVSLQLNKMK
SRKSCGIAVGTTIVDADKYAVTVETRLIDERAAHVN AQFRF
gi|440525609|MOMP_Serovar_K_Chlamydia_trachomatis
MKKLLKSVLVFAALSSASSLQALPVGNPAEPSLMID 72
GILWEGFGGDPCDPCTTWCDAISMRVGYYGDFVFD
RVLKTDVNKEFQMGAAPTTSDVEGLQNDPTTNVAR
PNPAYGKHMQDAEMFTNAAYMALNIWDRFDVFCT
LGATTGYLRGNSASFNLVGLFGTKTQYSKFNTANLV
PNTALDRAVVELYTDTTFAWSVGARAALWECGCAT
LGASFQYAQSKPKVEELNVLCNASEFTINKPKGYVG
VEFPLDITGTEAATGTKDASIDYHEWQASLALSYRL
NMFTPYIGVKWSRVSFDADTIRIAQPKLAEAILDVTT
LNPTIAGKGAVVSSGSDNELADTMQIVSLQLNKLKS
RKSCGIAVGTTIVDADKYAVTVETRLIDERAAHVNA QFRF
TABLE-US-00007 TABLE 6 NCBI Accession Numbers (Amino Acid
Sequences) GenBank Description Accession membrane protein
[Chlamydia trachomatis] WP_014736636.1 membrane protein [Chlamydia
trachomatis] WP_020967105.1 hypothetical protein [Chlamydia
trachomatis] WP_050866621.1 membrane protein [Chlamydia
trachomatis] WP_014541314.1 hypothetical protein [Chlamydia
trachomatis] WP_020915665.1 membrane protein [Chlamydia
trachomatis] WP_020966654.1 hypothetical protein [Chlamydia
trachomatis] WP_010725381.1 membrane protein [Chlamydia
trachomatis] WP_014541104.1 polymorphic membrane protein I
[Chlamydia trachomatis] AAQ74460.1 membrane protein [Chlamydia
trachomatis] WP_009873481.1 membrane protein [Chlamydia
trachomatis] WP_009872264.1 hypothetical protein [Chlamydia
trachomatis] WP_015505760.1 polymorphic membrane protein I
[Chlamydia trachomatis] AAQ74451.1 polymorphic membrane protein I
[Chlamydia trachomatis] AAQ74444.1 membrane protein [Chlamydia
trachomatis] WP_012728025.1 membrane protein [Chlamydia
trachomatis] WP_024067304.1 membrane protein [Chlamydia
trachomatis] WP_011324917.1 membrane protein [Chlamydia
trachomatis] WP_012728213.1 polymorphic outer membrane protein
[Chlamydia trachomatis] CRH27059.1 polymorphic membrane protein I
[Chlamydia trachomatis] AAO29993.1 polymorphic membrane protein I
[Chlamydia trachomatis] AAO29992.1 polymorphic membrane protein I
[Chlamydia trachomatis] AAO29987.1 polymorphic membrane protein I
[Chlamydia trachomatis] AAO29991.1 polymorphic membrane protein I
[Chlamydia trachomatis] AAO29988.1 polymorphic membrane protein I
[Chlamydia trachomatis] AAO29994.1 polymorphic membrane protein I
[Chlamydia trachomatis] AAO29990.1 polymorphic membrane protein I
[Chlamydia trachomatis] AAO29999.1 polymorphic membrane protein I
[Chlamydia trachomatis] AAO29989.1 polymorphic membrane protein I
[Chlamydia trachomatis] AAO29997.1 polymorphic membrane protein I
[Chlamydia trachomatis] AAO29998.1 polymorphic outer membrane
protein [Chlamydia trachomatis] CRH24400.1 Chlamydial polymorphic
outer membrane protein repeat CCP50073.1 [Chlamydia trachomatis
A/7249] polymorphic outer membrane protein [Chlamydia trachomatis]
CRI74229.1 polymorphic outer membrane protein [Chlamydia
trachomatis] CPR78550.1 polymorphic outer membrane protein
[Chlamydia trachomatis] CRH27024.1 polymorphic outer membrane
protein [Chlamydia trachomatis] CRH87199.1 membrane protein
[Chlamydia trachomatis] WP_009873248.1 PmpH [Chlamydia trachomatis]
ABY76804.1 hypothetical protein [Chlamydia trachomatis]
WP_010725378.1 Polymorphic outer membrane protein [Chlamydia
trachomatis D-EC] ADI51545.1 membrane protein [Chlamydia
trachomatis] WP_009872990.1 membrane protein [Chlamydia
trachomatis] WP_009872262.1 membrane protein [Chlamydia
trachomatis] WP_020967104.1 membrane protein [Chlamydia
trachomatis] WP_014541209.1 polymorphic membrane protein H
[Chlamydia trachomatis] AAX76608.1 membrane protein [Chlamydia
trachomatis] WP_014541103.1 polymorphic membrane protein H
[Chlamydia trachomatis] AAO30024.1 polymorphic membrane protein H
[Chlamydia trachomatis] AAO30025.1 polymorphic membrane protein H
[Chlamydia trachomatis] AAO30023.1 polymorphic membrane protein H
[Chlamydia trachomatis I/UW-12/UR] AAO30028.1 polymorphic membrane
protein H [Chlamydia trachomatis] AAO30029.1 Polymorphic outer
membrane protein [Chlamydia trachomatis A2497] AEP35781.1 membrane
protein [Chlamydia trachomatis] WP_011324915.1 membrane protein
[Chlamydia trachomatis] WP_009873479.1 hypothetical protein
[Chlamydia trachomatis] WP_015505933.1 hypothetical protein
[Chlamydia trachomatis] WP_015505759.1 hypothetical protein
[Chlamydia trachomatis] WP_015506646.1 Chlamydial polymorphic outer
membrane protein repeat CCP63815.1 [Chlamydia trachomatis L1/1
322/p2] membrane protein [Chlamydia trachomatis] WP_012263579.1
polymorphic membrane protein H [Chlamydia trachomatis] AAO30019.1
polymorphic membrane protein H [Chlamydia trachomatis] AAO30020.1
polymorphic membrane protein H [Chlamydia trachomatis] AAO30032.1
polymorphic membrane protein H [Chlamydia trachomatis] AAO30031.1
polymorphic membrane protein H [Chlamydia trachomatis] AAO30033.1
polymorphic membrane protein H [Chlamydia trachomatis] ABQ08057.1
Polymorphic outer membrane protein [Chlamydia trachomatis]
CRH60974.1 membrane protein [Chlamydia trachomatis] WP_009872260.1
PmpF [Chlamydia trachomatis] AAZ20335.1 membrane protein [Chlamydia
trachomatis] WP_020967102.1 hypothetical protein [Chlamydia
trachomatis] WP_022564835.1 membrane protein [Chlamydia
trachomatis] WP_014541101.1 membrane protein [Chlamydia
trachomatis] WP_014541207.1 PmpF [Chlamydia trachomatis] AAZ20334.1
PmpF [Chlamydia trachomatis] AAZ20333.1 membrane protein [Chlamydia
trachomatis] WP_024067300.1 membrane protein [Chlamydia
trachomatis] WP_011324913.1 membrane protein [Chlamydia
trachomatis] WP_009873477.1 membrane protein [Chlamydia
trachomatis] WP_012728023.1 polymorphic membrane protein F
[Chlamydia trachomatis] AAX76564.1 membrane protein [Chlamydia
trachomatis] WP_014316077.1 membrane protein [Chlamydia
trachomatis] WP_012263577.1 polymorphic membrane protein F
[Chlamydia trachomatis] AAX76565.1 membrane protein [Chlamydia
trachomatis] WP_012728212.1 PmpF [Chlamydia trachomatis] AAZ20337.1
polymorphic membrane protein F [Chlamydia trachomatis] AKG95439.1
membrane protein [Chlamydia suis] WP_035407888.1 polymorphic outer
membrane protein[Chlamydia trachomatis] CRH67080.1 Polymorphic
outer membrane protein [Chlamydia trachomatis D-EC] ADI51544.1
Polymorphic outer membrane protein [Chlamydia trachomatis]
CRH42293.1 hypothetical protein [Chlamydia trachomatis]
WP_050866642.1 polymorphic membrane protein G [Chlamydia
trachomatis] AAX76599.1 membrane protein [Chlamydia trachomatis]
WP_014541208.1 membrane protein [Chlamydia trachomatis]
WP_011324914.1 Polymorphic outer membrane protein [Chlamydia
trachomatis A2497] AEP35780.1 polymorphic membrane protein G
[Chlamydia trachomatis] AAX76596.1 Polymorphic outer membrane
protein [Chlamydia trachomatis] CRH57809.1 polymorphic membrane
protein G [Chlamydia trachomatis] AAX76587.1 membrane protein
[Chlamydia trachomatis] WP_020967103.1 membrane protein [Chlamydia
trachomatis] WP_012728024.1 polymorphic membrane protein G
[Chlamydia trachomatis] AAX76590.1 membrane protein [Chlamydia
trachomatis] WP_014541102.1 membrane protein [Chlamydia
trachomatis] WP_024067301.1 polymorphic membrane protein G
[Chlamydia trachomatis] AAX76592.1 Polymorphic outer membrane
protein [Chlamydia trachomatis] CRH45212.1 Chlamydial polymorphic
outer membrane protein repeat CCP55746.1 [Chlamydia trachomatis
E/SotonE4] hypothetical protein [Chlamydia trachomatis]
WP_015505758.1 hypothetical protein [Chlamydia trachomatis]
WP_015506645.1 polymorphic membrane protein G [Chlamydia
trachomatis] AAX76604.1 membrane protein [Chlamydia trachomatis]
WP_012263578.1 membrane protein [Chlamydia trachomatis]
WP_009873478.1 Polymorphic outer membrane protein [Chlamydia
trachomatis] CPR43068.1 Polymorphic outer membrane protein
[Chlamydia trachomatis] CRH24397.1 Chlamydial polymorphic outer
membrane protein repeat CCP63814.1 [Chlamydia trachomatis
L1/1322/p2] Polymorphic outer membrane protein [Chlamydia
trachomatis] CRH86260.1 Chlamydial polymorphic outer membrane
protein repeat CCP66483.1 [Chlamydia trachomatis] L2/25667R]
deubiquitinase [Chlamydia trachomatis] WP_009873246.1
deubiquitinase [Chlamydia trachomatis] WP_020967101.1
deubiquitinase [Chlamydia trachomatis] WP_014541312.1
deubiquitinase [Chlamydia trachomatis] WP_020967682.1
deubiquitinase [Chlamydia trachomatis] WP_009872987.1
deubiquitinase [Chlamydia trachomatis] WP_014541099.1 hypothetical
protein [Chlamydia trachomatis] ABX82376.1 membrane thiol protease
[Chlamydia trachomatis] AFU24067.1 membrane thiol protease
[Chlamydia trachomatis] CRH57812.1 deubiquitinase [Chlamydia
trachomatis] WP_014541784.1 deubiquitinase [Chlamydia trachomatis]
WP_020967726.1 deubiquitinase [Chlamydia trachomatis]
WP_014541837.1 deubiquitinase [Chlamydia trachomatis]
WP_012728210.1 membrane thiol protease [Chlamydia trachomatis]
AFU24069.1 deubiquitinase [Chlamydia trachomatis] WP_009872258.1
deubiquitinase [Chlamydia trachomatis] WP_014316076.1
deubiquitinase [Chlamydia trachomatis] WP_012728021.1
deubiquitinase [Chlamydia trachomatis] WP_024067298.1
deubiquitinase [Chlamydia trachomatis] WP_011324911.1 membrane
thiol protease [Chlamydia trachomatis] AFU24057.1 deubiquitinase
[Chlamydia trachomatis] WP_013984939.1 deubiquitinase [Chlamydia
trachomatis] WP_009873475.1 hypothetical protein [Chlamydia
trachomatis] WP_015506643.1 deubiquitinase [Chlamydia trachomatis]
WP_012263576.1 hypothetical protein [Chlamydia trachomatis]
WP_015505932.1 deubiquitinase [Chlamydia trachomatis]
WP_054088494.1 membrane thiol protease [Chlamydia trachomatis]
CQB85418.1
TABLE-US-00008 TABLE 7 Chlamydia mRNA Constructs (Amino Acids) mRNA
SEQ ID Name ORF Sequence (Amino Acid) NO: Cta1_E_EXT_noTM_nIgK
METPAQLLFLLLLWLPDTTGPPLPSSTQDNRSMDQQDSEEFLLQN 73
TLEDSEIISIPDTMNQIAIDTEKWFYLNKDCTNVGPISIVQLTAFLK
ECKHSPEKGIDPQELWVWKKGMPNWEKVKNIPELSGTVKDE Cta1_E_EXT_noTM_nIgK_cHis
METPAQLLFLLLLWLPDTTGPPLPSSTQDNRSMDQQDSEEFLLQN 74
TLEDSEIISIPDTMNQIAIDTEKWFYLNKDCTNVGPISIVQLTAFLK
ECKHSPEKGIDPQELWVWKKGMPNWEKVKNIPELSGTVKDEHH HHHH
Ct875_E_NGM_nFC_cHis METPAQLLFLLLLWLPDTTGEPKSCDKTHTCPPCPAPELLGGPSV
75 FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEV
HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA
LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY
PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSLSPGKMSIRGVGGNGNSRIPS
HNGDGSNRRSQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVD
VSSMIESTPTSGETTRASRGVLSRFQRGLVRIADKVRRAVQCAWS
SVSTSRSSATRAAESGSSSRTARGASSGYREYSPSAARGLRLMFT
DFWRTRVLRQTSPMAGVFGNLDVNEARLMAAYTSECADHLEAK
ELAGPDGVAAAREIAKRWEKRVRDLQDKGAARKLLNDPLGRRT
PNYQSKNPGEYTVGNSMFYDGPQVANLQNVDTGFWLDMQHLS
DVVLSREIQTGLRARATLEESMPMLENLEERFRRLQETCDAARTE
IEESGWTRESASRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSF
GEHVRVLCARVSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSP
EGASLAETLARFADDMGIERGADGTYDIPLVDDWRRGVPSIEGE
GSDSIYEIMMPIYEVMNMDLETRRSFAVQQGHYQDPRASDYDLP
RASDYDLPRSPYPTPPLPPRYQLQNMDVEAGFREAVYASFVAGM
YNYVVTQPQERIPNSQQVEGILRDMLTNGDQTFRDLMKRWNRE
VDREMSPILGYWKIKGLVQPTRLLLEYLEEKYEEHLYERDEGDK
WRNKKFELGLEFPNLPYYIDGDVKLTQSMAIIRYIADKHNMLGG
CPKERAEISMLEGAVLDIRYGVSRIAYSKDFETLKVDFLSKLPEML
KMFEDRLCHKTYLNGDHVTHPDFMLYDALDVVLYMDPMCLDA
FPKLVCFKKRIEAIPQIDKYLKSSKYIAWPLQGWQATFGGGDHPPK Ct875_E_nFC_cHis
METPAQLLFLLLLWLPDTTGEPKSCDKTHTCPPCPAPELLGGPSV 76
FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEV
HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA
LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY
PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSLSPGKMSIRGVGGNGNSRIPS
HNGDGSNRRSQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVD
VSSMIESTPTSGETTRASRGVLSRFQRGLVRIADKVRRAVQCAWS
SVSTSRSSATRAAESGSSSRTARGASSGYREYSPSAARGLRLMFT
DFWRTRVLRQTSPMAGVFGNLDVNEARLMAAYTSECADHLEAK
ELAGPDGVAAAREIAKRWEKRVRDLQDKGAARKLLNDPLGRRT
PNYQSKNPGEYTVGNSMFYDGPQVANLQNVDTGFWLDMSNLSD
VVLSREIQTGLRARATLEESMPMLENLEERFRRLQETCDAARTEI
EESGWTRESASRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSF
GEHVRVLCARVSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSP
EGASLAETLARFADDMGIERGADGTYDIPLVDDWRRGVPSIEGE
GSDSIYEIMMPIYEVMNMDLETRRSFAVQQGHYQDPRASDYDLP
RASDYDLPRSPYPTPPLPPRYQLQNMDVEAGFREAVYASFVAGM
YNYVVTQPQERIPNSQQVEGILRDMLTNGSQTFRDLMKRWNREV DREHHHHHH
Ct875_E_NGM_nFC METPAQLLFLLLLWLPDTTGEPKSCDKTHTCPPCPAPELLGGPSV 77
FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEV
HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA
LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY
PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSLSPGKMSIRGVGGNGNSRIPS
HNGDGSNRRSQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVD
VSSMIESTPTSGETTRASRGVLSRFQRGLVRIADKVRRAVQCAWS
SVSTSRSSATRAAESGSSSRTARGASSGYREYSPSAARGLRLMFT
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ELAGPDGVAAAREIAKRWEKRVRDLQDKGAARKLLNDPLGRRT
PNYQSKNPGEYTVGNSMFYDGPQVANLQNVDTGFWLDMQHLS
DVVLSREIQTGLRARATLEESMPMLENLEERFRRLQETCDAARTE
IEESGWTRESASRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSF
GEHVRVLCARVSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSP
EGASLAETLARFADDMGIERGADGTYDIPLVDDWRRGVPSIEGE
GSDSIYEIMMPIYEVMNMDLETRRSFAVQQGHYQDPRASDYDLP
RASDYDLPRSPYPTPPLPPRYQLQNMDVEAGFREAVYASFVAGM
YNYVVTQPQERIPNSQQVEGILRDMLTNGDQTFRDLMKRWNRE VDRE Ct875_E_nFC
METPAQLLFLLLLWLPDTTGEPKSCDKTHTCPPCPAPELLGGPSV 78
FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEV
HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA
LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY
PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSLSPGKMSIRGVGGNGNSRIPS
HNGDGSNRRSQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVD
VSSMIESTPTSGETTRASRGVLSRFQRGLVRIADKVRRAVQCAWS
SVSTSRSSATRAAESGSSSRTARGASSGYREYSPSAARGLRLMFT
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VVLSREIQTGLRARATLEESMPMLENLEERFRRLQETCDAARTEI
EESGWTRESASRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSF
GEHVRVLCARVSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSP
EGASLAETLARFADDMGIERGADGTYDIPLVDDWRRGVPSIEGE
GSDSIYEIMMPIYEVMNMDLETRRSFAVQQGHYQDPRASDYDLP
RASDYDLPRSPYPTPPLPPRYQLQNMDVEAGFREAVYASFVAGM
YNYVVTQPQERIPNSQQVEGILRDMLTNGSQTFRDLMKRWNREV DRE
Ct875_E_NGM_nIgK_nGst_cHis
METPAQLLFLLLLWLPDTTGMSPILGYWKIKGLVQPTRLLLEYLE 79
EKYEEHLYERDEGDKWRNKKFELGLEFPNLPYYIDGDVKLTQSM
AIIRYIADKHNMLGGCPKERAEISMLEGAVLDIRYGVSRIAYSKDF
ETLKVDFLSKLPEMLKMFEDRLCHKTYLNGDHVTHPDFMLYDA
LDVVLYMDPMCLDAFPKLVCFKKRIEAIPQIDKYLKSSKYIAWPL
QGWQATFGGGDHPPKMSIRGVGGNGNSRIPSHNGDGSNRRSQNT
KGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTSGETT
RASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATRAAE
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MAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAAAR
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ARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESASR
MEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCARVS
RGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLARFA
DDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPIYE
VMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSPYPT
PPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQERIPN
SQQVEGILRDMLTNGDQTFRDLMKRWNREVDREHHHHHH Ct875_E_nIgK_nGst_cHis
METPAQLLFLLLLWLPDTTGMSPILGYWKIKGLVQPTRLLLEYLE 80
EKYEEHLYERDEGDKWRNKKFELGLEFPNLPYYIDGDVKLTQSM
AIIRYIADKHNMLGGCPKERAEISMLEGAVLDIRYGVSRIAYSKDF
ETLKVDFLSKLPEMLKMFEDRLCHKTYLNGDHVTHPDFMLYDA
LDVVLYMDPMCLDAFPKLVCFKKRIEAIPQIDKYLKSSKYIAWPL
QGWQATFGGGDHPPKMSIRGVGGNGNSRIPSHNGDGSNRRSQNT
KGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTSGETT
RASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATRAAE
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MAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAAAR
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ARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESASR
MEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCARVS
RGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLARFA
DDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPIYE
VMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSPYPT
PPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQERIPN
SQQVEGILRDMLTNGSQTFRDLMKRWNREVDREHHHHHH Ct875_E_NGM_nIgK_nGst
METPAQLLFLLLLWLPDTTGMSPILGYWKIKGLVQPTRLLLEYLE 81
EKYEEHLYERDEGDKWRNKKFELGLEFPNLPYYIDGDVKLTQSM
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LDVVLYMDPMCLDAFPKLVCFKKRIEAIPQIDKYLKSSKYIAWPL
QGWQATFGGGDHPPKMSIRGVGGNGNSRIPSHNGDGSNRRSQNT
KGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTSGETT
RASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATRAAE
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MAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAAAR
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ARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESASR
MEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCARVS
RGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLARFA
DDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPIYE
VMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSPYPT
PPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQERIPN
SQQVEGILRDMLTNGDQTFRDLMKRWNREVDRE Ct875_E_nIgK_nGst
METPAQLLFLLLLWLPDTTGMSPILGYWKIKGLVQPTRLLLEYLE 82
EKYEEHLYERDEGDKWRNKKFELGLEFPNLPYYIDGDVKLTQSM
AIIRYIADKHNMLGGCPKERAEISMLEGAVLDIRYGVSRIAYSKDF
ETLKVDFLSKLPEMLKMFEDRLCHKTYLNGDHVTHPDFMLYDA
LDVVLYMDPMCLDAFPKLVCFKKRIEAIPQIDKYLKSSKYIAWPL
QGWQATFGGGDHPPKMSIRGVGGNGNSRIPSHNGDGSNRRSQNT
KGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTSGETT
RASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATRAAE
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MAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAAAR
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VGNSMFYDGPQVANLQNVDTGFWLDMSNLSDVVLSREIQTGLR
ARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESASR
MEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCARVS
RGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLARFA
DDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPIYE
VMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSPYPT
PPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQERIPN
SQQVEGILRDMLTNGSQTFRDLMKRWNREVDRE Ct875_E_574_NGM_nIgK_cHis
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 83
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
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LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPI
YEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSP
YPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQE
RIPNSQQVEGILRDMLTNGDHHHHHH Ct875_E_458_NGM_nIgK_cHis
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 84
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
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LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSHHHHHH Ct875_E_574_nIgK_cHis
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 85
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
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TSPMAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAA
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LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPI
YEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSP
YPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQE
RIPNSQQVEGILRDMLTNGSHHHHHH Ct875_E_458_nIgK_cHis
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 86
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
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LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSHHHHHH Ct875_E_574_NGM_nIgK
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 87
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
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LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPI
YEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSP
YPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQE RIPNSQQVEGILRDMLTNGD
Ct875_E_458_NGM_nIgK METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR
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YTVGNSMFYDGPQVANLQNVDTGFWLDMQHLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGS Ct875_E_574_nIgK
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 89
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
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TSPMAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAA
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YTVGNSMFYDGPQVANLQNVDTGFWLDMSNLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPI
YEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSP
YPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQE RIPNSQQVEGILRDMLTNGS
Ct875_E_458_nIgK METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 90
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
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YTVGNSMFYDGPQVANLQNVDTGFWLDMSNLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGS Ct875_E_1_574_NGM_nIgK_cHis
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 91
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
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TSPMAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAA
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YTVGNSMFYDGPQVANLQNVDTGFWLDMQHLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPI
YEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSP
YPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQE
RIPNSQQVEGILRDMLTNGDHHHHHH Ct875_E_NGM_nFc
METPAQLLFLLLLWLPDTTGEPKSCDKTHTCPPCPAPELLGGPSV 92
FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEV
HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA
LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY
PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSLSPGKMSIRGVGGNGNSRIPS
HNGDGSNRRSQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVD
VSSMIESTPTSGETTRASRGVLSRFQRGLVRIADKVRRAVQCAWS
SVSTSRSSATRAAESGSSSRTARGASSGYREYSPSAARGLRLMFT
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DVVLSREIQTGLRARATLEESMPMLENLEERFRRLQETCDAARTE
IEESGWTRESASRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSF
GEHVRVLCARVSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSP
EGASLAETLARFADDMGIERGADGTYDIPLVDDWRRGVPSIEGE
GSDSIYEIMMPIYEVMNMDLETRRSFAVQQGHYQDPRASDYDLP
RASDYDLPRSPYPTPPLPPRYQLQNMDVEAGFREAVYASFVAGM
YNYVVTQPQERIPNSQQVEGILRDMLTNGDQTFRDLMKRWNRE VDRE
Ct875_E_NGM_nFc_cHis METPAQLLFLLLLWLPDTTGEPKSCDKTHTCPPCPAPELLGGPSV
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HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA
LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY
PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSLSPGKMSIRGVGGNGNSRIPS
HNGDGSNRRSQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVD
VSSMIESTPTSGETTRASRGVLSRFQRGLVRIADKVRRAVQCAWS
SVSTSRSSATRAAESGSSSRTARGASSGYREYSPSAARGLRLMFT
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PNYQSKNPGEYTVGNSMFYDGPQVANLQNVDTGFWLDMQHLS
DVVLSREIQTGLRARATLEESMPMLENLEERFRRLQETCDAARTE
IEESGWTRESASRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSF
GEHVRVLCARVSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSP
EGASLAETLARFADDMGIERGADGTYDIPLVDDWRRGVPSIEGE
GSDSIYEIMMPIYEVMNMDLETRRSFAVQQGHYQDPRASDYDLP
RASDYDLPRSPYPTPPLPPRYQLQNMDVEAGFREAVYASFVAGM
YNYVVTQPQERIPNSQQVEGILRDMLTNGDQTFRDLMKRWNRE VDREHHHHHH
Ct875_E_1_574_NGM_nIgK_nGST
METPAQLLFLLLLWLPDTTGMSPILGYWKIKGLVQPTRLLLEYLE 94
EKYEEHLYERDEGDKWRNKKFELGLEFPNLPYYIDGDVKLTQSM
AIIRYIADKHNMLGGCPKERAEISMLEGAVLDIRYGVSRIAYSKDF
ETLKVDFLSKLPEMLKMFEDRLCHKTYLNGDHVTHPDFMLYDA
LDVVLYMDPMCLDAFPKLVCFKKRIEAIPQIDKYLKSSKYIAWPL
QGWQATFGGGDHPPKMSIRGVGGNGNSRIPSHNGDGSNRRSQNT
KGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTSGETT
RASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATRAAE
SGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQTSP
MAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAAAR
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VGNSMFYDGPQVANLQNVDTGFWLDMQHLSDVVLSREIQTGLR
ARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESASR
MEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCARVS
RGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLARFA
DDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPIYE
VMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSPYPT
PPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQERIPN SQQVEGILRDMLTNGD
Ct875_E_1_574_NGM_nIgK_nGST_cHis
METPAQLLFLLLLWLPDTTGMSPILGYWKIKGLVQPTRLLLEYLE 95
EKYEEHLYERDEGDKWRNKKFELGLEFPNLPYYIDGDVKLTQSM
AIIRYIADKHNMLGGCPKERAEISMLEGAVLDIRYGVSRIAYSKDF
ETLKVDFLSKLPEMLKMFEDRLCHKTYLNGDHVTHPDFMLYDA
LDVVLYMDPMCLDAFPKLVCFKKRIEAIPQIDKYLKSSKYIAWPL
QGWQATFGGGDHPPKMSIRGVGGNGNSRIPSHNGDGSNRRSQNT
KGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTSGETT
RASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATRAAE
SGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQTSP
MAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAAAR
EIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGEYT
VGNSMFYDGPQVANLQNVDTGFWLDMQHLSDVVLSREIQTGLR
ARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESASR
MEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCARVS
RGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLARFA
DDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPIYE
VMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSPYPT
PPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQERIPN SQQVEGILRDMLTNGDHHHHHH
Ct875_E_NGM_nIgK_nGST METPAQLLFLLLLWLPDTTGMSPILGYWKIKGLVQPTRLLLEYLE
96 EKYEEHLYERDEGDKWRNKKFELGLEFPNLPYYIDGDVKLTQSM
AIIRYIADKHNMLGGCPKERAEISMLEGAVLDIRYGVSRIAYSKDF
ETLKVDFLSKLPEMLKMFEDRLCHKTYLNGDHVTHPDFMLYDA
LDVVLYMDPMCLDAFPKLVCFKKRIEAIPQIDKYLKSSKYIAWPL
QGWQATFGGGDHPPKMSIRGVGGNGNSRIPSHNGDGSNRRSQNT
KGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTSGETT
RASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATRAAE
SGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQTSP
MAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAAAR
EIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGEYT
VGNSMFYDGPQVANLQNVDTGFWLDMQHLSDVVLSREIQTGLR
ARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESASR
MEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCARVS
RGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLARFA
DDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPIYE
VMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSPYPT
PPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQERIPN
SQQVEGILRDMLTNGDQTFRDLMKRWNREVDRE Ct875_E_NGM_nIgK_nGST_cHis
METPAQLLFLLLLWLPDTTGMSPILGYWKIKGLVQPTRLLLEYLE 97
EKYEEHLYERDEGDKWRNKKFELGLEFPNLPYYIDGDVKLTQSM
AIIRYIADKHNMLGGCPKERAEISMLEGAVLDIRYGVSRIAYSKDF
ETLKVDFLSKLPEMLKMFEDRLCHKTYLNGDHVTHPDFMLYDA
LDVVLYMDPMCLDAFPKLVCFKKRIEAIPQIDKYLKSSKYIAWPL
QGWQATFGGGDHPPKMSIRGVGGNGNSRIPSHNGDGSNRRSQNT
KGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTSGETT
RASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATRAAE
SGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQTSP
MAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAAAR
EIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGEYT
VGNSMFYDGPQVANLQNVDTGFWLDMQHLSDVVLSREIQTGLR
ARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESASR
MEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCARVS
RGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLARFA
DDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPIYE
VMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSPYPT
PPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQERIPN
SQQVEGILRDMLTNGDQTFRDLMKRWNREVDREHHHHHH Ct875_E_1_458_NGM_nIgK_nGST
METPAQLLFLLLLWLPDTTGMSPILGYWKIKGLVQPTRLLLEYLE 98
EKYEEHLYERDEGDKWRNKKFELGLEFPNLPYYIDGDVKLTQSM
AIIRYIADKHNMLGGCPKERAEISMLEGAVLDIRYGVSRIAYSKDF
ETLKVDFLSKLPEMLKMFEDRLCHKTYLNGDHVTHPDFMLYDA
LDVVLYMDPMCLDAFPKLVCFKKRIEAIPQIDKYLKSSKYIAWPL
QGWQATFGGGDHPPKMSIRGVGGNGNSRIPSHNGDGSNRRSQNT
KGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTSGETT
RASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATRAAE
SGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQTSP
MAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAAAR
EIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGEYT
VGNSMFYDGPQVANLQNVDTGFWLDMQHLSDVVLSREIQTGLR
ARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESASR
MEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCARVS
RGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLARFA
DDMGIERGADGTYDIPLVDDWRRGVPSIEGEGS Ct875_E_1_458_NGM_nIgK_nGST_cHis
METPAQLLFLLLLWLPDTTGMSPILGYWKIKGLVQPTRLLLEYLE 99
EKYEEHLYERDEGDKWRNKKFELGLEFPNLPYYIDGDVKLTQSM
AIIRYIADKHNMLGGCPKERAEISMLEGAVLDIRYGVSRIAYSKDF
ETLKVDFLSKLPEMLKMFEDRLCHKTYLNGDHVTHPDFMLYDA
LDVVLYMDPMCLDAFPKLVCFKKRIEAIPQIDKYLKSSKYIAWPL
QGWQATFGGGDHPPKMSIRGVGGNGNSRIPSHNGDGSNRRSQNT
KGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTSGETT
RASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATRAAE
SGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQTSP
MAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAAAR
EIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGEYT
VGNSMFYDGPQVANLQNVDTGFWLDMQHLSDVVLSREIQTGLR
ARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESASR
MEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCARVS
RGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLARFA
DDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSHHHHHH Ct875_E_1_458_NGM_nIgK
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 100
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
AAESGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQ
TSPMAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAA
AREIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGE
YTVGNSMFYDGPQVANLQNVDTGFWLDMQHLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGS Ct875_E_1_458_NGM_nIgK_cHis
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 101
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
AAESGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQ
TSPMAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAA
AREIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGE
YTVGNSMFYDGPQVANLQNVDTGFWLDMQHLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSHHHHHH Ct875_E_1_574_NGM_nIgK
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 102
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
AAESGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQ
TSPMAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAA
AREIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGE
YTVGNSMFYDGPQVANLQNVDTGFWLDMQHLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPI
YEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSP
YPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQE RIPNSQQVEGILRDMLTNGD
Ct875_E_1_574_nIgK_nGST
METPAQLLFLLLLWLPDTTGMSPILGYWKIKGLVQPTRLLLEYLE 103
EKYEEHLYERDEGDKWRNKKFELGLEFPNLPYYIDGDVKLTQSM
AIIRYIADKHNMLGGCPKERAEISMLEGAVLDIRYGVSRIAYSKDF
ETLKVDFLSKLPEMLKMFEDRLCHKTYLNGDHVTHPDFMLYDA
LDVVLYMDPMCLDAFPKLVCFKKRIEAIPQIDKYLKSSKYIAWPL
QGWQATFGGGDHPPKMSIRGVGGNGNSRIPSHNGDGSNRRSQNT
KGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTSGETT
RASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATRAAE
SGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQTSP
MAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAAAR
EIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGEYT
VGNSMFYDGPQVANLQNVDTGFWLDMSNLSDVVLSREIQTGLR
ARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESASR
MEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCARVS
RGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLARFA
DDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPIYE
VMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSPYPT
PPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQERIPN SQQVEGILRDMLTNGS
Ct875_E_1_574_nIgK_nGST_cHis
METPAQLLFLLLLWLPDTTGMSPILGYWKIKGLVQPTRLLLEYLE 104
EKYEEHLYERDEGDKWRNKKFELGLEFPNLPYYIDGDVKLTQSM
AIIRYIADKHNMLGGCPKERAEISMLEGAVLDIRYGVSRIAYSKDF
ETLKVDFLSKLPEMLKMFEDRLCHKTYLNGDHVTHPDFMLYDA
LDVVLYMDPMCLDAFPKLVCFKKRIEAIPQIDKYLKSSKYIAWPL
QGWQATFGGGDHPPKMSIRGVGGNGNSRIPSHNGDGSNRRSQNT
KGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTSGETT
RASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATRAAE
SGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQTSP
MAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAAAR
EIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGEYT
VGNSMFYDGPQVANLQNVDTGFWLDMSNLSDVVLSREIQTGLR
ARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESASR
MEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCARVS
RGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLARFA
DDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPIYE
VMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSPYPT
PPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQERIPN SQQVEGILRDMLTNGSHHHHHH
Ct875_E_nIgK_nGST METPAQLLFLLLLWLPDTTGMSPILGYWKIKGLVQPTRLLLEYLE 105
EKYEEHLYERDEGDKWRNKKFELGLEFPNLPYYIDGDVKLTQSM
AIIRYIADKHNMLGGCPKERAEISMLEGAVLDIRYGVSRIAYSKDF
ETLKVDFLSKLPEMLKMFEDRLCHKTYLNGDHVTHPDFMLYDA
LDVVLYMDPMCLDAFPKLVCFKKRIEAIPQIDKYLKSSKYIAWPL
QGWQATFGGGDHPPKMSIRGVGGNGNSRIPSHNGDGSNRRSQNT
KGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTSGETT
RASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATRAAE
SGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQTSP
MAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAAAR
EIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGEYT
VGNSMFYDGPQVANLQNVDTGFWLDMSNLSDVVLSREIQTGLR
ARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESASR
MEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCARVS
RGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLARFA
DDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPIYE
VMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSPYPT
PPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQERIPN
SQQVEGILRDMLTNGSQTFRDLMKRWNREVDRE Ct875_E_nIgK_nGST_cHis
METPAQLLFLLLLWLPDTTGMSPILGYWKIKGLVQPTRLLLEYLE 106
EKYEEHLYERDEGDKWRNKKFELGLEFPNLPYYIDGDVKLTQSM
AIIRYIADKHNMLGGCPKERAEISMLEGAVLDIRYGVSRIAYSKDF
ETLKVDFLSKLPEMLKMFEDRLCHKTYLNGDHVTHPDFMLYDA
LDVVLYMDPMCLDAFPKLVCFKKRIEAIPQIDKYLKSSKYIAWPL
QGWQATFGGGDHPPKMSIRGVGGNGNSRIPSHNGDGSNRRSQNT
KGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTSGETT
RASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATRAAE
SGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQTSP
MAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAAAR
EIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGEYT
VGNSMFYDGPQVANLQNVDTGFWLDMSNLSDVVLSREIQTGLR
ARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESASR
MEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCARVS
RGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLARFA
DDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPIYE
VMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSPYPT
PPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQERIPN
SQQVEGILRDMLTNGSQTFRDLMKRWNREVDREHHHHHH Ct875_E_nFc
METPAQLLFLLLLWLPDTTGEPKSCDKTHTCPPCPAPELLGGPSV 107
FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEV
HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA
LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY
PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSLSPGKMSIRGVGGNGNSRIPS
HNGDGSNRRSQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVD
VSSMIESTPTSGETTRASRGVLSRFQRGLVRIADKVRRAVQCAWS
SVSTSRSSATRAAESGSSSRTARGASSGYREYSPSAARGLRLMFT
DFWRTRVLRQTSPMAGVFGNLDVNEARLMAAYTSECADHLEAK
ELAGPDGVAAAREIAKRWEKRVRDLQDKGAARKLLNDPLGRRT
PNYQSKNPGEYTVGNSMFYDGPQVANLQNVDTGFWLDMSNLSD
VVLSREIQTGLRARATLEESMPMLENLEERFRRLQETCDAARTEI
EESGWTRESASRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSF
GEHVRVLCARVSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSP
EGASLAETLARFADDMGIERGADGTYDIPLVDDWRRGVPSIEGE
GSDSIYEIMMPIYEVMNMDLETRRSFAVQQGHYQDPRASDYDLP
RASDYDLPRSPYPTPPLPPRYQLQNMDVEAGFREAVYASFVAGM
YNYVVTQPQERIPNSQQVEGILRDMLTNGSQTFRDLMKRWNREV DRE Ct875_E_nFc_cHis
METPAQLLFLLLLWLPDTTGEPKSCDKTHTCPPCPAPELLGGPSV 108
FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEV
HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA
LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY
PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSLSPGKMSIRGVGGNGNSRIPS
HNGDGSNRRSQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVD
VSSMIESTPTSGETTRASRGVLSRFQRGLVRIADKVRRAVQCAWS
SVSTSRSSATRAAESGSSSRTARGASSGYREYSPSAARGLRLMFT
DFWRTRVLRQTSPMAGVFGNLDVNEARLMAAYTSECADHLEAK
ELAGPDGVAAAREIAKRWEKRVRDLQDKGAARKLLNDPLGRRT
PNYQSKNPGEYTVGNSMFYDGPQVANLQNVDTGFWLDMSNLSD
VVLSREIQTGLRARATLEESMPMLENLEERFRRLQETCDAARTEI
EESGWTRESASRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSF
GEHVRVLCARVSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSP
EGASLAETLARFADDMGIERGADGTYDIPLVDDWRRGVPSIEGE
GSDSIYEIMMPIYEVMNMDLETRRSFAVQQGHYQDPRASDYDLP
RASDYDLPRSPYPTPPLPPRYQLQNMDVEAGFREAVYASFVAGM
YNYVVTQPQERIPNSQQVEGILRDMLTNGSQTFRDLMKRWNREV DREHHHHHH
Ct043_E_NGM_nIgK_no4A METPAQLLFLLLLWLPDTTGMSRQNAEENLKNFAKELKLPDVAF
109 DQNNACILFVDGEFSLHLTYEEHSDRLYVYAPLLDGLPDNPQRKL
ALYEKLLEGSMLGGQMAGGGVGVATKEQLILMHCVLDMKYAE
TNLLKAFAQLFIETVVKWRTVCSDISAGREPTVDTMPQMPQGGG GGIQPPPAGIRA
Ct043_E_NGM_nIgK_cHis_no4A
METPAQLLFLLLLWLPDTTGMSRQNAEENLKNFAKELKLPDVAF 110
DQNNACILFVDGEFSLHLTYEEHSDRLYVYAPLLDGLPDNPQRKL
ALYEKLLEGSMLGGQMAGGGVGVATKEQLILMHCVLDMKYAE
TNLLKAFAQLFIETVVKWRTVCSDISAGREPTVDTMPQMPQGGG GGIQPPPAGIRAHHHHHH
Ct043_E_nIgK_no4A METPAQLLFLLLLWLPDTTGMSRQNAEENLKNFAKELKLPDVAF 111
DQNNTCILFVDGEFSLHLTYEEHSDRLYVYAPLLDGLPDNPQRKL
ALYEKLLEGSMLGGQMAGGGVGVATKEQLILMHCVLDMKYAE
TNLLKAFAQLFIETVVKWRTVCSDISAGREPTVDTMPQMPQGGG GGIQPPPAGIRA
Ct043_E_nIgK_cHis_no4A METPAQLLFLLLLWLPDTTGMSRQNAEENLKNFAKELKLPDVAF
112 DQNNTCILFVDGEFSLHLTYEEHSDRLYVYAPLLDGLPDNPQRKL
ALYEKLLEGSMLGGQMAGGGVGVATKEQLILMHCVLDMKYAE
TNLLKAFAQLFIETVVKWRTVCSDISAGREPTVDTMPQMPQGGG GGIQPPPAGIRAHHHHHH
Chlamydia_Ct812_pd_serovarD_nIgK_cHis_nopolyN
METPAQLLFLLLLWLPDTTGSCVDLHAGGQSVNELVYVGPQAVL 113
LLDQIRDLFVGSKDSQAEGQYRLIVGDPSSFQEKDADTLPGKVEQ
STLFSVTNPVVFQGVDQQDQVSSQGLICSFTSSNLDSPRDGESFLG
IAFVGDSSKAGITLTDVKASLSGAALYSTEDLIFEKIKGGLEFASCS
SLEQGGACAAQSILIHDCQGLQVKHCTTAVNAEGSSANDHLGFG
GGAFFVTGSLSGEKSLYMPAGDMVVANCDGAISFEGNSANFANG
GAIAASGKVLFVANDKKTSFIENRALSGGAIAASSDIAFQNCAEL
VFKGNCAIGTEDKGSLGGGAISSLGTVLLQGNHGITCDKNESASQ
GGAIFGKNCQISDNEGPVVFRDSTACLGGGAIAAQEIVSIQNNQA
GISFEGGKASFGGGIACGSFSSAGGASVLGTIDISKNLGAISFSRTL
CTTSDLGQMEYQGGGALFGENISLSENAGVLTFKDNIVKTFASNG
KILGGGAILATGKVEITNNSEGISFTGNARAPQALPTQEEFPLFSKK
EGRPLSSGYSGGGAILGREVAILHNAAVVFEQNRLQCSEEEATLL
GCCGGGAVHGMDSTSIVGNSSVRFGNNYAMGQGVSGGALLSKT
VQLAGNGSVDFSRNIASLGGGALQASEGNCELVDNGYVLFRDNR
GRVYGGAISCLRGDVVISGNKGRVEFKDNIATRLYVEETVEKVEE
VEPAPEQKDNNELSFLGRAEQSFITAANQALFASEDGDLSPESSIS
SEELAKRRECAGGAIFAKRVRIVDNQEAVVFSNNFSDIYGGAIFT
GSLREEDKLDGQIPEVLISGNAGDVVFSGNSSKRDEHLPHTGGGA
ICTQNLTISQNTGNVLFYNNVACSGGAVRIEDHGNVLLEAFGGDI
VFKGNSSFRAQGSDAIYFAGKESHITALNATEGHAIVFHDALVFE
NLEERKSAEVLLINSRENPGYTGSIRFLEAESKVPQCIHVQQGSLE
LLNGATLCSYGFKQDAGAKLVLAAGAKLKILDSGTPVQQGHAIS
KPEAEIESSSEPEGAHSLWIAKNAQTTVPMVDIHTISVDLASFSSSQ
QEGTVEAPQVIVPGGSYVRSGELNLELVNTTGTGYENHALLKNE
AKVPLMSFVASGDEASAEISNLSVSDLQIHVVTPEIEEDTYGHMG
DWSEAKIQDGTLVISWNPTGHHHHHH Chlamydia_Ct812_pd_serovarD_nIgK_nopolyN
METPAQLLFLLLLWLPDTTGSCVDLHAGGQSVNELVYVGPQAVL 114
LLDQIRDLFVGSKDSQAEGQYRLIVGDPSSFQEKDADTLPGKVEQ
STLFSVTNPVVFQGVDQQDQVSSQGLICSFTSSNLDSPRDGESFLG
IAFVGDSSKAGITLTDVKASLSGAALYSTEDLIFEKIKGGLEFASCS
SLEQGGACAAQSILIHDCQGLQVKHCTTAVNAEGSSANDHLGFG
GGAFFVTGSLSGEKSLYMPAGDMVVANCDGAISFEGNSANFANG
GAIAASGKVLFVANDKKTSFIENRALSGGAIAASSDIAFQNCAEL
VFKGNCAIGTEDKGSLGGGAISSLGTVLLQGNHGITCDKNESASQ
GGAIFGKNCQISDNEGPVVFRDSTACLGGGAIAAQEIVSIQNNQA
GISFEGGKASFGGGIACGSFSSAGGASVLGTIDISKNLGAISFSRTL
CTTSDLGQMEYQGGGALFGENISLSENAGVLTFKDNIVKTFASNG
KILGGGAILATGKVEITNNSEGISFTGNARAPQALPTQEEFPLFSKK
EGRPLSSGYSGGGAILGREVAILHNAAVVFEQNRLQCSEEEATLL
GCCGGGAVHGMDSTSIVGNSSVRFGNNYAMGQGVSGGALLSKT
VQLAGNGSVDFSRNIASLGGGALQASEGNCELVDNGYVLFRDNR
GRVYGGAISCLRGDVVISGNKGRVEFKDNIATRLYVEETVEKVEE
VEPAPEQKDNNELSFLGRAEQSFITAANQALFASEDGDLSPESSIS
SEELAKRRECAGGAIFAKRVRIVDNQEAVVFSNNFSDIYGGAIFT
GSLREEDKLDGQIPEVLISGNAGDVVFSGNSSKRDEHLPHTGGGA
ICTQNLTISQNTGNVLFYNNVACSGGAVRIEDHGNVLLEAFGGDI
VFKGNSSFRAQGSDAIYFAGKESHITALNATEGHAIVFHDALVFE
NLEERKSAEVLLINSRENPGYTGSIRFLEAESKVPQCIHVQQGSLE
LLNGATLCSYGFKQDAGAKLVLAAGAKLKILDSGTPVQQGHAIS
KPEAEIESSSEPEGAHSLWIAKNAQTTVPMVDIHTISVDLASFSSSQ
QEGTVEAPQVIVPGGSYVRSGELNLELVNTTGTGYENHALLKNE
AKVPLMSFVASGDEASAEISNLSVSDLQIHVVTPEIEEDTYGHMG DWSEAKIQDGTLVISWNPTG
Ct812pd_PmpD_D_NGM_nIgK_nopolyN
METPAQLLFLLLLWLPDTTGSCVDLHAGGQSVNELVYVGPQAVL 115
LLDQIRDLFVGSKDSQAEGQYRLIVGDPSSFQEKDADTLPGKVEQ
STLFSVTNPVVFQGVDQQDQVSSQGLICSFTSSNLDSPRDGESFLG
IAFVGDSSKAGITLTDVKASLSGAALYSTEDLIFEKIKGGLEFASCS
SLEQGGACAAQSILIHDCQGLQVKHCTTAVNAEGSSANDHLGFG
GGAFFVTGSLSGEKSLYMPAGDMVVANCDGAISFEGNSANFANG
GAIAASGKVLFVANDKKTSFIENRALSGGAIAASSDIAFQNCAEL
VFKGNCAIGTEDKGSLGGGAISSLGTVLLQGNHGITCDKNEAASQ
GGAIFGKNCQISDNEGPVVFRDSTACLGGGAIAAQEIVSIQNNQA
GISFEGGKASFGGGIACGSFSSAGGASVLGTIDISKNLGAISFSRTL
CTTSDLGQMEYQGGGALFGENIALSENAGVLTFKDNIVKTFASN
GKILGGGAILATGKVEITNNAEGISFTGNARAPQALPTQEEFPLFS
KKEGRPLSSGYSGGGAILGREVAILHNAAVVFEQNRLQCSEEEAT
LLGCCGGGAVHGMDSTSIVGNSAVRFGNNYAMGQGVSGGALLS
KTVQLAGNGAVDFSRNIASLGGGALQASEGNCELVDNGYVLFRD
NRGRVYGGAISCLRGDVVISGNKGRVEFKDNIATRLYVEETVEK
VEEVEPAPEQKDNNELSFLGRAEQSFITAANQALFASEDGDLSPES
SISSEELAKRRECAGGAIFAKRVRIVDNQEAVVFSNNFADIYGGAI
FTGSLREEDKLDGQIPEVLISGNAGDVVFSGNSAKRDEHLPHTGG
GAICTQNLAISQNTGNVLFYNNVACSGGAVRIEDHGNVLLEAFG
GDIVFKGNSAFRAQGSDAIYFAGKESHITALNAAEGHAIVFHDAL
VFENLEERKSAEVLLINSRENPGYTGSIRFLEAESKVPQCIHVQQG
SLELLNGATLCSYGFKQDAGAKLVLAAGAKLKILDSGTPVQQGH
AISKPEAEIESSSEPEGAHSLWIAKNAQTTVPMVDIHTISVDLASFS
SSQQEGTVEAPQVIVPGGSYVRSGELNLELVNTAGTGYENHALL
KNEAKVPLMSFVASGDEASAEISNLAVSDLQIHVVTPEIEEDTYG
HMGDWSEAKIQDGTLVISWNPAG Ct812pd_PmpD_D_NGM_nIgK_cHis_nopolyN
METPAQLLFLLLLWLPDTTGSCVDLHAGGQSVNELVYVGPQAVL 116
LLDQIRDLFVGSKDSQAEGQYRLIVGDPSSFQEKDADTLPGKVEQ
STLFSVTNPVVFQGVDQQDQVSSQGLICSFTSSNLDSPRDGESFLG
IAFVGDSSKAGITLTDVKASLSGAALYSTEDLIFEKIKGGLEFASCS
SLEQGGACAAQSILIHDCQGLQVKHCTTAVNAEGSSANDHLGFG
GGAFFVTGSLSGEKSLYMPAGDMVVANCDGAISFEGNSANFANG
GAIAASGKVLFVANDKKTSFIENRALSGGAIAASSDIAFQNCAEL
VFKGNCAIGTEDKGSLGGGAISSLGTVLLQGNHGITCDKNEAASQ
GGAIFGKNCQISDNEGPVVFRDSTACLGGGAIAAQEIVSIQNNQA
GISFEGGKASFGGGIACGSFSSAGGASVLGTIDISKNLGAISFSRTL
CTTSDLGQMEYQGGGALFGENIALSENAGVLTFKDNIVKTFASN
GKILGGGAILATGKVEITNNAEGISFTGNARAPQALPTQEEFPLFS
KKEGRPLSSGYSGGGAILGREVAILHNAAVVFEQNRLQCSEEEAT
LLGCCGGGAVHGMDSTSIVGNSAVRFGNNYAMGQGVSGGALLS
KTVQLAGNGAVDFSRNIASLGGGALQASEGNCELVDNGYVLFRD
NRGRVYGGAISCLRGDVVISGNKGRVEFKDNIATRLYVEETVEK
VEEVEPAPEQKDNNELSFLGRAEQSFITAANQALFASEDGDLSPES
SISSEELAKRRECAGGAIFAKRVRIVDNQEAVVFSNNFADIYGGAI
FTGSLREEDKLDGQIPEVLISGNAGDVVFSGNSAKRDEHLPHTGG
GAICTQNLAISQNTGNVLFYNNVACSGGAVRIEDHGNVLLEAFG
GDIVFKGNSAFRAQGSDAIYFAGKESHITALNAAEGHAIVFHDAL
VFENLEERKSAEVLLINSRENPGYTGSIRFLEAESKVPQCIHVQQG
SLELLNGATLCSYGFKQDAGAKLVLAAGAKLKILDSGTPVQQGH
AISKPEAEIESSSEPEGAHSLWIAKNAQTTVPMVDIHTISVDLASFS
SSQQEGTVEAPQVIVPGGSYVRSGELNLELVNTAGTGYENHALL
KNEAKVPLMSFVASGDEASAEISNLAVSDLQIHVVTPEIEEDTYG
HMGDWSEAKIQDGTLVISWNPAGHHHHHH Ct871pd_PmpG_D_NGM_nIgK
METPAQLLFLLLLWLPDTTGAEIMIPQGIYDGETLTVSFPYTVIGD 117
PSGTTVFSAGELTLKNLDNSIAALPLSCFGNLLGSFTVLGRGHSLT
FENIRTSTNGAALSDSANSGLFTIEGFKELSFSNCNSLLAVLPAATT
NSGSQTPTTTSTPSNGAIYSKTDLLLLNNEKFSFYSNLVSGDGGAI
DAKSLTVQGISKLCVFQENTAQADGGACQVVTSFSAMANEAPIA
FIANVAGVRGGGIAAVQDGQQGVSSSTSTEDPVVSFSRNTAVEFD
GNVARVGGGIYSYGNVAFLNNGKTLFLNNVASPVYIAAEQPTNG
QASNTADNYGDGGAIFCKNGAQAAGSNNAGSVSFDGEGVVFFSS
NVAAGKGGAIYAKKLSVANCGPVQFLGNIANDGGAIYLGESGEL
SLSADYGDIIFDGNLKRTAKENAADVNGVTVSSQAISMGSGGKIT
TLRAKAGHQILFNDPIEMANGNNQPAQSSEPLKINDGEGYTGDIV
FANGNSALYQNVAIEQGRIVLREKAKLSVNSLSQTGGSLYMEAG
STLDFVTPQPPQQPPAANQLITLSNLHLSLSSLLANNAVTNPPTNP
PAQDSHPAIIGSTTAGSVTISGPIFFEDLDDTAYDRYDWLGSNQKI
DVLKLQLGTQPSANAPSDLTLGNEMPKYGYQGSWKLAWDPNTA NNGPYTLKATWTKTG
Ct871pd_PmpG_D_NGM_nIgK_cHis
METPAQLLFLLLLWLPDTTGAEIMIPQGIYDGETLTVSFPYTVIGD 118
PSGTTVFSAGELTLKNLDNSIAALPLSCFGNLLGSFTVLGRGHSLT
FENIRTSTNGAALSDSANSGLFTIEGFKELSFSNCNSLLAVLPAATT
NSGSQTPTTTSTPSNGAIYSKTDLLLLNNEKFSFYSNLVSGDGGAI
DAKSLTVQGISKLCVFQENTAQADGGACQVVTSFSAMANEAPIA
FIANVAGVRGGGIAAVQDGQQGVSSSTSTEDPVVSFSRNTAVEFD
GNVARVGGGIYSYGNVAFLNNGKTLFLNNVASPVYIAAEQPTNG
QASNTADNYGDGGAIFCKNGAQAAGSNNAGSVSFDGEGVVFFSS
NVAAGKGGAIYAKKLSVANCGPVQFLGNIANDGGAIYLGESGEL
SLSADYGDIIFDGNLKRTAKENAADVNGVTVSSQAISMGSGGKIT
TLRAKAGHQILFNDPIEMANGNNQPAQSSEPLKINDGEGYTGDIV
FANGNSALYQNVAIEQGRIVLREKAKLSVNSLSQTGGSLYMEAG
STLDFVTPQPPQQPPAANQLITLSNLHLSLSSLLANNAVTNPPTNP
PAQDSHPAIIGSTTAGSVTISGPIFFEDLDDTAYDRYDWLGSNQKI
DVLKLQLGTQPSANAPSDLTLGNEMPKYGYQGSWKLAWDPNTA NNGPYTLKATWTKTGHHHHHH
Ct460_D_S16A_nIgK METPAQLLFLLLLWLPDTTGMSQNKNSAFMQPVNVAADLAAIV 119
GAGPMPRTEIIKKMWDYIKKNGLQDPTNKRNINPDDKLAKVFGT EKPIDMFQMTKMVSQHIIK
Ct460_D_S16A_nIgK_cHis METPAQLLFLLLLWLPDTTGMSQNKNSAFMQPVNVAADLAAIV
120 GAGPMPRTEIIKKMWDYIKKNGLQDPTNKRNINPDDKLAKVFGT
EKPIDMFQMTKMVSQHIIKHHHHHH Ct875_E_S274Q_N275H_S574D_nIgK
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 121
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
AAESGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQ
TSPMAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAA
AREIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGE
YTVGNSMFYDGPQVANLQNVDTGFWLDMQHLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPI
YEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSP
YPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQE
RIPNSQQVEGILRDMLTNGDQTFRDLMKRWNREVDRE
Ct875_E_S274Q_N275H_S574D_nIgK_cHis
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 122
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
AAESGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQ
TSPMAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAA
AREIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGE
YTVGNSMFYDGPQVANLQNVDTGFWLDMQHLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPI
YEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSP
YPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQE
RIPNSQQVEGILRDMLTNGDQTFRDLMKRWNREVDREHHHHHH
Ct622_E_S13N_S179A_S220N_nIgK
METPAQLLFLLLLWLPDTTGMESGPESVSSNQNSMNPIINGQIASN 123
SETKESTKASEASPSASSSVSSWSFLSSAKNALISLRDAILNKNSSP
TDSLSQLEASTSTSTVTRVAAKDYDEAKSNFDTAKSGLENAKTL
AEYETKMADLMAALQDMERLANSDPSNNHTEEVNNIKKALEAQ
KDTIDKLNKLVTLQNQNKALTEVLKTTDSADQIPAINSQLEINKN
SADQIIKDLERQNINYEAVLTNAGEVIKASSEAGIKLGQALQSIVD
AGDQSQAAVLQAQQNNSPDNIAATKELIDAAETKVNELKQEHTG
LTDSPLVKKAEEQISQAQKDIQEIKPSGSDIPIVGPSGSAASAGSAA
GALKSSNNSGRISLLLDDVDNEMAAIALQGFRSMIEQFNVNNPAT
AKELQAMEAQLTAMSDQLVGADGELPAEIQAIKDALAQALKQPS
ADGLATAMGQVAFAAAKVGGGSAGTAGTVQMNVKQLYKTAFS
STSSSSYAAALSDGYSAYKTLNSLYSESRSGVQSAISQTANPALSR
SVSRSGIESQGRSADASQRAAETIVRDSQTLGDVYSRLQVLDSLM
STIVSNPQANQEEIMQKLTASISKAPQFGYPAVQNSADSLQKFAA
QLEREFVDGERSLAESQENAFRKQPAFIQQVLVNIASLFSGYLS
Ct622_E_S13N_S179A_S220N_nIgK_cHis
METPAQLLFLLLLWLPDTTGMESGPESVSSNQNSMNPIINGQIASN 124
SETKESTKASEASPSASSSVSSWSFLSSAKNALISLRDAILNKNSSP
TDSLSQLEASTSTSTVTRVAAKDYDEAKSNFDTAKSGLENAKTL
AEYETKMADLMAALQDMERLANSDPSNNHTEEVNNIKKALEAQ
KDTIDKLNKLVTLQNQNKALTEVLKTTDSADQIPAINSQLEINKN
SADQIIKDLERQNINYEAVLTNAGEVIKASSEAGIKLGQALQSIVD
AGDQSQAAVLQAQQNNSPDNIAATKELIDAAETKVNELKQEHTG
LTDSPLVKKAEEQISQAQKDIQEIKPSGSDIPIVGPSGSAASAGSAA
GALKSSNNSGRISLLLDDVDNEMAAIALQGFRSMIEQFNVNNPAT
AKELQAMEAQLTAMSDQLVGADGELPAEIQAIKDALAQALKQPS
ADGLATAMGQVAFAAAKVGGGSAGTAGTVQMNVKQLYKTAFS
STSSSSYAAALSDGYSAYKTLNSLYSESRSGVQSAISQTANPALSR
SVSRSGIESQGRSADASQRAAETIVRDSQTLGDVYSRLQVLDSLM
STIVSNPQANQEEIMQKLTASISKAPQFGYPAVQNSADSLQKFAA
QLEREFVDGERSLAESQENAFRKQPAFIQQVLVNIASLFSGYLSHH HHHH
Cta1_E_noTM_nIgK_cHis METPAQLLFLLLLWLPDTTGPSSTQDNRSMDQQDSEEFLLQNTLE
125 DSEIISIPDTMNQIAIDTEKWFYLNKDCTNVGPISIVQLTAFLKECK
HSPEKGIDPQELWVWKKGMPNWEKVKNIPELSGTVKDEHHHHHH Cta1_E_noTM_nIgK
METPAQLLFLLLLWLPDTTGPSSTQDNRSMDQQDSEEFLLQNTLE 126
DSEIISIPDTMNQIAIDTEKWFYLNKDCTNVGPISIVQLTAFLKECK
HSPEKGIDPQELWVWKKGMPNWEKVKNIPELSGTVKDE Cta1_E_cHis
MNSGMFPFTFFLLYICLGMLTAYLANKKNRNLIGWFLAGMFFGIF 127
AIIFLLILPPLPSSTQDNRSMDQQDSEEFLLQNTLEDSEIISIPDTMN
QIAIDTEKWFYLNKDCTNVGPISIVQLTAFLKECKHSPEKGIDPQE
LWVWKKGMPNWEKVKNIPELSGTVKDEHHHHHH Cta1_E
MNSGMFPFTFFLLYICLGMLTAYLANKKNRNLIGWFLAGMFFGIF 128
AIIFLLILPPLPSSTQDNRSMDQQDSEEFLLQNTLEDSEIISIPDTMN
QIAIDTEKWFYLNKDCTNVGPISIVQLTAFLKECKHSPEKGIDPQE
LWVWKKGMPNWEKVKNIPELSGTVKDE Ct443_E_nIgK_cHis_mod
METPAQLLFLLLLWLPDTTGSGVLETSMAESLSTNVISLADTKAK 129
DNTSHKSKKARKNHSKETLVDRKEVAPVHESKATGPKQDSCFGR
MYTVKVNDDRNVEITQAVPEYATVGSPYPIEITATGKRDCVDVII
TQQLPCEAEFVRSDPATTPTADGKLVWKIDRLGQGEKSKITVWV
KPLKEGCCFTAATVCACPEIRSVTKCGQPAICVKQEGPENACLRC
PVVYKINVVNQGTAIARNVVVENPVPDGYAHSSGQRVLTFTLGD
MQPGEHRTITVEFCPLKRGRATNIATVSYCGGHKNTASVTTVINE
PCVQVSIAGADWSYVCKPVEYVISVSNPGDLVLRDVVVEDTLSP
GVTVLEAAGAQISCNKVVWTVKELNPGESLQYKVLVRAQTPGQ
FTNNVVVKSCSDCGTCTSCAEATTYWKGVAATHMCVVDTCDPV
CVGENTVYRICVTNRGSAEDTNVSLMLKFSKELQPVSFSGPTKGT
ITGNTVVFDSLPRLGSKETVEFSVTLKAVSAGDARGEAILSSDTLT VPVSDTENTHIYHHHHHH
Ct443_E_nIgK_mod METPAQLLFLLLLWLPDTTGSGVLETSMAESLSTNVISLADTKAK 130
DNTSHKSKKARKNHSKETLVDRKEVAPVHESKATGPKQDSCFGR
MYTVKVNDDRNVEITQAVPEYATVGSPYPIEITATGKRDCVDVII
TQQLPCEAEFVRSDPATTPTADGKLVWKIDRLGQGEKSKITVWV
KPLKEGCCFTAATVCACPEIRSVTKCGQPAICVKQEGPENACLRC
PVVYKINVVNQGTAIARNVVVENPVPDGYAHSSGQRVLTFTLGD
MQPGEHRTITVEFCPLKRGRATNIATVSYCGGHKNTASVTTVINE
PCVQVSIAGADWSYVCKPVEYVISVSNPGDLVLRDVVVEDTLSP
GVTVLEAAGAQISCNKVVWTVKELNPGESLQYKVLVRAQTPGQ
FTNNVVVKSCSDCGTCTSCAEATTYWKGVAATHMCVVDTCDPV
CVGENTVYRICVTNRGSAEDTNVSLMLKFSKELQPVSFSGPTKGT
ITGNTVVFDSLPRLGSKETVEFSVTLKAVSAGDARGEAILSSDTLT VPVSDTENTHIY
Ct875_E_nIgK_CO004 METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR
131 SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
AAESGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQ
TSPMAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAA
AREIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGE
YTVGNSMFYDGPQVANLQNVDTGFWLDMSNLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPI
YEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSP
YPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQE
RIPNSQQVEGILRDMLTNGSQTFRDLMKRWNREVDRE Ct875_E_nIgK_CO003
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 132
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
AAESGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQ
TSPMAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAA
AREIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGE
YTVGNSMFYDGPQVANLQNVDTGFWLDMSNLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPI
YEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSP
YPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQE
RIPNSQQVEGILRDMLTNGSQTFRDLMKRWNREVDRE Ct875_E_nIgK_CO002
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 133
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
AAESGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQ
TSPMAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAA
AREIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGE
YTVGNSMFYDGPQVANLQNVDTGFWLDMSNLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPI
YEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSP
YPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQE
RIPNSQQVEGILRDMLTNGSQTFRDLMKRWNREVDRE Ct875_E_nIgK_CO001
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 134
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
AAESGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQ
TSPMAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAA
AREIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGE
YTVGNSMFYDGPQVANLQNVDTGFWLDMSNLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPI
YEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSP
YPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQE
RIPNSQQVEGILRDMLTNGSQTFRDLMKRWNREVDRE Ct875_E_nIgK_cHis_CO005
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 135
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
AAESGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQ
TSPMAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAA
AREIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGE
YTVGNSMFYDGPQVANLQNVDTGFWLDMSNLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPI
YEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSP
YPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQE
RIPNSQQVEGILRDMLTNGSQTFRDLMKRWNREVDREHHHHHH Ct875_E_nIgK_cHis_CO004
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 136
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
AAESGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQ
TSPMAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAA
AREIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGE
YTVGNSMFYDGPQVANLQNVDTGFWLDMSNLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPI
YEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSP
YPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQE
RIPNSQQVEGILRDMLTNGSQTFRDLMKRWNREVDREHHHHHH Ct875_E_nIgK_cHis_CO003
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 137
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
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TSPMAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAA
AREIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGE
YTVGNSMFYDGPQVANLQNVDTGFWLDMSNLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPI
YEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSP
YPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQE
RIPNSQQVEGILRDMLTNGSQTFRDLMKRWNREVDREHHHHHH Ct875_E_nIgK_cHis_CO002
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 138
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
AAESGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQ
TSPMAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAA
AREIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGE
YTVGNSMFYDGPQVANLQNVDTGFWLDMSNLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPI
YEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSP
YPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQE
RIPNSQQVEGILRDMLTNGSQTFRDLMKRWNREVDREHHHHHH Ct875_E_nIgK_cHis_CO001
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 139
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
AAESGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQ
TSPMAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAA
AREIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGE
YTVGNSMFYDGPQVANLQNVDTGFWLDMSNLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPI
YEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSP
YPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQE
RIPNSQQVEGILRDMLTNGSQTFRDLMKRWNREVDREHHHHHH Ct875_E_nIgK_nFLAG
METPAQLLFLLLLWLPDTTGDYKDHDGDYKDHDIDYKDDDDKM 140
SIRGVGGNGNSRIPSHNGDGSNRRSQNTKGNNKVEDRVCSLYSSR
SNENRESPYAVVDVSSMIESTPTSGETTRASRGVLSRFQRGLVRIA
DKVRRAVQCAWSSVSTSRSSATRAAESGSSSRTARGASSGYREY
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AYTSECADHLEAKELAGPDGVAAAREIAKRWEKRVRDLQDKGA
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DTGFWLDMSNLSDVVLSREIQTGLRARATLEESMPMLENLEERF
RRLQETCDAARTEIEESGWTRESASRMEGDEAQGPSRVQQAFQS
FVNECNSIEFSFGSFGEHVRVLCARVSRGLAAAGEAIRRCFSCCK
GSTHRYAPRDDLSPEGASLAETLARFADDMGIERGADGTYDIPLV
DDWRRGVPSIEGEGSDSIYEIMMPIYEVMNMDLETRRSFAVQQG
HYQDPRASDYDLPRASDYDLPRSPYPTPPLPPRYQLQNMDVEAG
FREAVYASFVAGMYNYVVTQPQERIPNSQQVEGILRDMLTNGSQ TFRDLMKRWNREVDRE
Ct875_E_nIgK_cFLAG METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR
141 SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
AAESGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQ
TSPMAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAA
AREIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGE
YTVGNSMFYDGPQVANLQNVDTGFWLDMSNLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPI
YEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSP
YPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQE
RIPNSQQVEGILRDMLTNGSQTFRDLMKRWNREVDREDYKDHD GDYKDHDIDYKDDDDK
Ct875_E_nIgK_nHis METPAQLLFLLLLWLPDTTGHHHHHHMSIRGVGGNGNSRIPSHN 142
GDGSNRRSQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSS
MIESTPTSGETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVS
TSRSSATRAAESGSSSRTARGASSGYREYSPSAARGLRLMFTDFW
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GPDGVAAAREIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNY
QSKNPGEYTVGNSMFYDGPQVANLQNVDTGFWLDMSNLSDVVL
SREIQTGLRARATLEESMPMLENLEERFRRLQETCDAARTEIEESG
WTRESASRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHV
RVLCARVSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASL
AETLARFADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIY
EIMMPIYEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDY
DLPRSPYPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVV
TQPQERIPNSQQVEGILRDMLTNGSQTFRDLMKRWNREVDRE MOMP_E_nTMEM149
MGPGRCLLTALLLLALAPPPEALPVGNPAEPSLMIDGILWEGFGG 143
DPCDPCTTWCDAISMRMGYYGDFVFDRVLKTDVNKEFQMGDKP
TSTTGNATAPTTLTARENPAYGRHMQDAEMFTNAACMALNIWD
RFDVFCTLGASSGYLKGNSASFNLVGLFGDNENQSTVKTNSVPN
MSLDQSVVELYTDTAFSWSVGARAALWECGCATLGASFQYAQS
KPKVEELNVLCNAAEFTINKPKGYVGQEFPLALIAGTDAATGTKD
ASIDYHEWQASLALSYRLNMFTPYIGVKWSRASFDADTIRIAQPK
SATAIFDTTTLNPTIAGAGDVKASAEGQLGDTMQIVSLQLNKMKS
RKSCGIAVGTTIVDADKYAVTVETRLIDERAAHVNAQFRF MOMP_E_nTMEM149_cHis
MGPGRCLLTALLLLALAPPPEALPVGNPAEPSLMIDGILWEGFGG 144
DPCDPCTTWCDAISMRMGYYGDFVFDRVLKTDVNKEFQMGDKP
TSTTGNATAPTTLTARENPAYGRHMQDAEMFTNAACMALNIWD
RFDVFCTLGASSGYLKGNSASFNLVGLFGDNENQSTVKTNSVPN
MSLDQSVVELYTDTAFSWSVGARAALWECGCATLGASFQYAQS
KPKVEELNVLCNAAEFTINKPKGYVGQEFPLALIAGTDAATGTKD
ASIDYHEWQASLALSYRLNMFTPYIGVKWSRASFDADTIRIAQPK
SATAIFDTTTLNPTIAGAGDVKASAEGQLGDTMQIVSLQLNKMKS
RKSCGIAVGTTIVDADKYAVTVETRLIDERAAHVNAQFRFHHHH HH MOMP_E_nFLRT2
MGLQTTKWPSHGAFFLKSWLIISLGLYSQVSKLLALPVGNPAEPS 145
LMIDGILWEGFGGDPCDPCTTWCDAISMRMGYYGDFVFDRVLKT
DVNKEFQMGDKPTSTTGNATAPTTLTARENPAYGRHMQDAEMF
TNAACMALNIWDRFDVFCTLGASSGYLKGNSASFNLVGLFGDNE
NQSTVKTNSVPNMSLDQSVVELYTDTAFSWSVGARAALWECGC
ATLGASFQYAQSKPKVEELNVLCNAAEFTINKPKGYVGQEFPLAL
IAGTDAATGTKDASIDYHEWQASLALSYRLNMFTPYIGVKWSRA
SFDADTIRIAQPKSATAIFDTTTLNPTIAGAGDVKASAEGQLGDTM
QIVSLQLNKMKSRKSCGIAVGTTIVDADKYAVTVETRLIDERAAH VNAQFRF
MOMP_E_nFLRT2_cHis MGLQTTKWPSHGAFFLKSWLIISLGLYSQVSKLLALPVGNPAEPS
146 LMIDGILWEGFGGDPCDPCTTWCDAISMRMGYYGDFVFDRVLKT
DVNKEFQMGDKPTSTTGNATAPTTLTARENPAYGRHMQDAEMF
TNAACMALNIWDRFDVFCTLGASSGYLKGNSASFNLVGLFGDNE
NQSTVKTNSVPNMSLDQSVVELYTDTAFSWSVGARAALWECGC
ATLGASFQYAQSKPKVEELNVLCNAAEFTINKPKGYVGQEFPLAL
IAGTDAATGTKDASIDYHEWQASLALSYRLNMFTPYIGVKWSRA
SFDADTIRIAQPKSATAIFDTTTLNPTIAGAGDVKASAEGQLGDTM
QIVSLQLNKMKSRKSCGIAVGTTIVDADKYAVTVETRLIDERAAH VNAQFRFHHHHHH
MOMP_E_nIgK METPAQLLFLLLLWLPDTTGLPVGNPAEPSLMIDGILWEGFGGDP 147
CDPCTTWCDAISMRMGYYGDFVFDRVLKTDVNKEFQMGDKPTS
TTGNATAPTTLTARENPAYGRHMQDAEMFTNAACMALNIWDRF
DVFCTLGASSGYLKGNSASFNLVGLFGDNENQSTVKTNSVPNMS
LDQSVVELYTDTAFSWSVGARAALWECGCATLGASFQYAQSKP
KVEELNVLCNAAEFTINKPKGYVGQEFPLALIAGTDAATGTKDAS
IDYHEWQASLALSYRLNMFTPYIGVKWSRASFDADTIRIAQPKSA
TAIFDTTTLNPTIAGAGDVKASAEGQLGDTMQIVSLQLNKMKSR
KSCGIAVGTTIVDADKYAVTVETRLIDERAAHVNAQFRF MOMP_E_nIgK_cHis
METPAQLLFLLLLWLPDTTGLPVGNPAEPSLMIDGILWEGFGGDP 148
CDPCTTWCDAISMRMGYYGDFVFDRVLKTDVNKEFQMGDKPTS
TTGNATAPTTLTARENPAYGRHMQDAEMFTNAACMALNIWDRF
DVFCTLGASSGYLKGNSASFNLVGLFGDNENQSTVKTNSVPNMS
LDQSVVELYTDTAFSWSVGARAALWECGCATLGASFQYAQSKP
KVEELNVLCNAAEFTINKPKGYVGQEFPLALIAGTDAATGTKDAS
IDYHEWQASLALSYRLNMFTPYIGVKWSRASFDADTIRIAQPKSA
TAIFDTTTLNPTIAGAGDVKASAEGQLGDTMQIVSLQLNKMKSR
KSCGIAVGTTIVDADKYAVTVETRLIDERAAHVNAQFRFHHHHHH MOMP_E_nOsteo
MWWRLWWLLLLLLLLWPMVWALPVGNPAEPSLMIDGILWEGF 149
GGDPCDPCTTWCDAISMRMGYYGDFVFDRVLKTDVNKEFQMG
DKPTSTTGNATAPTTLTARENPAYGRHMQDAEMFTNAACMALN
IWDRFDVFCTLGASSGYLKGNSASFNLVGLFGDNENQSTVKTNS
VPNMSLDQSVVELYTDTAFSWSVGARAALWECGCATLGASFQY
AQSKPKVEELNVLCNAAEFTINKPKGYVGQEFPLALIAGTDAATG
TKDASIDYHEWQASLALSYRLNMFTPYIGVKWSRASFDADTIRIA
QPKSATAIFDTTTLNPTIAGAGDVKASAEGQLGDTMQIVSLQLNK
MKSRKSCGIAVGTTIVDADKYAVTVETRLIDERAAHVNAQFRF MOMP_E_nOsteo_cHis
MWWRLWWLLLLLLLLWPMVWALPVGNPAEPSLMIDGILWEGF 150
GGDPCDPCTTWCDAISMRMGYYGDFVFDRVLKTDVNKEFQMG
DKPTSTTGNATAPTTLTARENPAYGRHMQDAEMFTNAACMALN
IWDRFDVFCTLGASSGYLKGNSASFNLVGLFGDNENQSTVKTNS
VPNMSLDQSVVELYTDTAFSWSVGARAALWECGCATLGASFQY
AQSKPKVEELNVLCNAAEFTINKPKGYVGQEFPLALIAGTDAATG
TKDASIDYHEWQASLALSYRLNMFTPYIGVKWSRASFDADTIRIA
QPKSATAIFDTTTLNPTIAGAGDVKASAEGQLGDTMQIVSLQLNK
MKSRKSCGIAVGTTIVDADKYAVTVETRLIDERAAHVNAQFRFH HHHHH
Ct-858_E_H97A_nIgK METPAQLLFLLLLWLPDTTGVRGESLVCKNALQDLSFLEHLLQV 151
KYAPKTWKEQYLGWDLVQSSVSAQQKLRTQENPSTSFCQQVLA
DFIGGLNDFAAGVTFFAIESAYLPYTVQKSSDGRFYFVDIMTFSSE
IRVGDELLEVDGAPVQDVLATLYGSNHKGTAAEESAALRTLFSR
MASLGHKVPSGRTTLKIRRPFGTTREVRVKWRYVPEGVGDLATI
APSIRAPQLQKSMRSFFPKKDDAFHRSSSLFYSPMVPHFWAELRN
HYATSGLKSGYNIGSTDGFLPVIGPVIWESEGLFRAYISSVTDGDG
KSHKVGFLRIPTYSWQDMEDFDPSGPPPWEEFAKIIQVFSSNTEAL
IIDQTNNPGGSVLYLYALLSMLTDRPLELPKHRMILTQDEVVDAL
DWLTLLENVDTNVESRLALGDNMEGYTVDLQVAEYLKSFGRQV
LNCWSKGDIELSTPIPLFGFEKIHPHPRVQYSKPICVLINEQDFSCA
DFFPVVLKDNDRALIVGTRTAGAGGFVFNVQFPNRTGIKTCSLTG
SLAVREHGAFIENIGVEPHIDLPFTANDIRYKGYSEYLDKVKKLVC QLINNDGTIILAEDGSF
Ct858_E_H97A_nIgK_cHis METPAQLLFLLLLWLPDTTGVRGESLVCKNALQDLSFLEHLLQV
152 KYAPKTWKEQYLGWDLVQSSVSAQQKLRTQENPSTSFCQQVLA
DFIGGLNDFAAGVTFFAIESAYLPYTVQKSSDGRFYFVDIMTFSSE
IRVGDELLEVDGAPVQDVLATLYGSNHKGTAAEESAALRTLFSR
MASLGHKVPSGRTTLKIRRPFGTTREVRVKWRYVPEGVGDLATI
APSIRAPQLQKSMRSFFPKKDDAFHRSSSLFYSPMVPHFWAELRN
HYATSGLKSGYNIGSTDGFLPVIGPVIWESEGLFRAYISSVTDGDG
KSHKVGFLRIPTYSWQDMEDFDPSGPPPWEEFAKIIQVFSSNTEAL
IIDQTNNPGGSVLYLYALLSMLTDRPLELPKHRMILTQDEVVDAL
DWLTLLENVDTNVESRLALGDNMEGYTVDLQVAEYLKSFGRQV
LNCWSKGDIELSTPIPLFGFEKIHPHPRVQYSKPICVLINEQDFSCA
DFFPVVLKDNDRALIVGTRTAGAGGFVFNVQFPNRTGIKTCSLTG
SLAVREHGAFIENIGVEPHIDLPFTANDIRYKGYSEYLDKVKKLVC
QLINNDGTIILAEDGSFHHHHHH Ct858_E_S491A_nIgK
METPAQLLFLLLLWLPDTTGVRGESLVCKNALQDLSFLEHLLQV 153
KYAPKTWKEQYLGWDLVQSSVSAQQKLRTQENPSTSFCQQVLA
DFIGGLNDFHAGVTFFAIESAYLPYTVQKSSDGRFYFVDIMTFSSE
IRVGDELLEVDGAPVQDVLATLYGSNHKGTAAEESAALRTLFSR
MASLGHKVPSGRTTLKIRRPFGTTREVRVKWRYVPEGVGDLATI
APSIRAPQLQKSMRSFFPKKDDAFHRSSSLFYSPMVPHFWAELRN
HYATSGLKSGYNIGSTDGFLPVIGPVIWESEGLFRAYISSVTDGDG
KSHKVGFLRIPTYSWQDMEDFDPSGPPPWEEFAKIIQVFSSNTEAL
IIDQTNNPGGSVLYLYALLSMLTDRPLELPKHRMILTQDEVVDAL
DWLTLLENVDTNVESRLALGDNMEGYTVDLQVAEYLKSFGRQV
LNCWSKGDIELSTPIPLFGFEKIHPHPRVQYSKPICVLINEQDFACA
DFFPVVLKDNDRALIVGTRTAGAGGFVFNVQFPNRTGIKTCSLTG
SLAVREHGAFIENIGVEPHIDLPFTANDIRYKGYSEYLDKVKKLVC QLINNDGTIILAEDGSF
Ct858_E_S491A_nIgK_cHis
METPAQLLFLLLLWLPDTTGVRGESLVCKNALQDLSFLEHLLQV 154
KYAPKTWKEQYLGWDLVQSSVSAQQKLRTQENPSTSFCQQVLA
DFIGGLNDFHAGVTFFAIESAYLPYTVQKSSDGRFYFVDIMTFSSE
IRVGDELLEVDGAPVQDVLATLYGSNHKGTAAEESAALRTLFSR
MASLGHKVPSGRTTLKIRRPFGTTREVRVKWRYVPEGVGDLATI
APSIRAPQLQKSMRSFFPKKDDAFHRSSSLFYSPMVPHFWAELRN
HYATSGLKSGYNIGSTDGFLPVIGPVIWESEGLFRAYISSVTDGDG
KSHKVGFLRIPTYSWQDMEDFDPSGPPPWEEFAKIIQVFSSNTEAL
IIDQTNNPGGSVLYLYALLSMLTDRPLELPKHRMILTQDEVVDAL
DWLTLLENVDTNVESRLALGDNMEGYTVDLQVAEYLKSFGRQV
LNCWSKGDIELSTPIPLFGFEKIHPHPRVQYSKPICVLINEQDFACA
DFFPVVLKDNDRALIVGTRTAGAGGFVFNVQFPNRTGIKTCSLTG
SLAVREHGAFIENIGVEPHIDLPFTANDIRYKGYSEYLDKVKKLVC
QLINNDGTIILAEDGSFHHHHHH Ct089_E_T306A_nIgK
METPAQLLFLLLLWLPDTTGMTASGGAGGLGSTQTVDVARAQA 155
AAATQDAQEVIGSQEASEASMLKGCEDLINPAAATRIKKKEEKFE
SLEARRKPTADKAEKKSESTEEKGDTPLEDRFTEDLSEVSGEDFR
GLKNSFDDDSSPEEILDALTSKFSDPTIKDLALDYLIQTAPSDRKL
KSALIQAKHQLMSQNPQAIVGGRNVLLASETFASRANTSPSSLRS
LYLQVTSSPSNCDNLRQMLASYLPSEKTAVMEFLVNGMVADLKS
EGPSIPPAKLQVYMTELSNLQALHSVDSFFDRNIGNLENSLKHEG
HAPIPSLTTGNLAKTFLQLVEDKFPSSSKAQKALNELVGPDTGPQ
TEVLNLFFRALNGCSPRIFSGAEKKQQLASVITNTLDAINADNEDY
PKPGDFPRSSFSSTPPHAPVPQSEIPTSPTSTQPPSP Ct089_E_T306A_nIgK_cHis
METPAQLLFLLLLWLPDTTGMTASGGAGGLGSTQTVDVARAQA 156
AAATQDAQEVIGSQEASEASMLKGCEDLINPAAATRIKKKEEKFE
SLEARRKPTADKAEKKSESTEEKGDTPLEDRFTEDLSEVSGEDFR
GLKNSFDDDSSPEEILDALTSKFSDPTIKDLALDYLIQTAPSDRKL
KSALIQAKHQLMSQNPQAIVGGRNVLLASETFASRANTSPSSLRS
LYLQVTSSPSNCDNLRQMLASYLPSEKTAVMEFLVNGMVADLKS
EGPSIPPAKLQVYMTELSNLQALHSVDSFFDRNIGNLENSLKHEG
HAPIPSLTTGNLAKTFLQLVEDKFPSSSKAQKALNELVGPDTGPQ
TEVLNLFFRALNGCSPRIFSGAEKKQQLASVITNTLDAINADNEDY
PKPGDFPRSSFSSTPPHAPVPQSEIPTSPTSTQPPSPHHHHHH
Ct089_E_S198A_T306A_nIgK
METPAQLLFLLLLWLPDTTGMTASGGAGGLGSTQTVDVARAQA 157
AAATQDAQEVIGSQEASEASMLKGCEDLINPAAATRIKKKEEKFE
SLEARRKPTADKAEKKSESTEEKGDTPLEDRFTEDLSEVSGEDFR
GLKNSFDDDSSPEEILDALTSKFSDPTIKDLALDYLIQTAPSDRKL
KSALIQAKHQLMSQNPQAIVGGRNVLLASETFASRANTAPSSLRS
LYLQVTSSPSNCDNLRQMLASYLPSEKTAVMEFLVNGMVADLKS
EGPSIPPAKLQVYMTELSNLQALHSVDSFFDRNIGNLENSLKHEG
HAPIPSLTTGNLAKTFLQLVEDKFPSSSKAQKALNELVGPDTGPQ
TEVLNLFFRALNGCSPRIFSGAEKKQQLASVITNTLDAINADNEDY
PKPGDFPRSSFSSTPPHAPVPQSEIPTSPTSTQPPSP Ct089_E_S198A_T306A_nIgK_cHis
METPAQLLFLLLLWLPDTTGMTASGGAGGLGSTQTVDVARAQA 158
AAATQDAQEVIGSQEASEASMLKGCEDLINPAAATRIKKKEEKFE
SLEARRKPTADKAEKKSESTEEKGDTPLEDRFTEDLSEVSGEDFR
GLKNSFDDDSSPEEILDALTSKFSDPTIKDLALDYLIQTAPSDRKL
KSALIQAKHQLMSQNPQAIVGGRNVLLASETFASRANTAPSSLRS
LYLQVTSSPSNCDNLRQMLASYLPSEKTAVMEFLVNGMVADLKS
EGPSIPPAKLQVYMTELSNLQALHSVDSFFDRNIGNLENSLKHEG
HAPIPSLTTGNLAKTFLQLVEDKFPSSSKAQKALNELVGPDTGPQ
TEVLNLFFRALNGCSPRIFSGAEKKQQLASVITNTLDAINADNEDY
PKPGDFPRSSFSSTPPHAPVPQSEIPTSPTSTQPPSPHHHHHH Ct089_E_S198A_nIgK
METPAQLLFLLLLWLPDTTGMTASGGAGGLGSTQTVDVARAQA 159
AAATQDAQEVIGSQEASEASMLKGCEDLINPAAATRIKKKEEKFE
SLEARRKPTADKAEKKSESTEEKGDTPLEDRFTEDLSEVSGEDFR
GLKNSFDDDSSPEEILDALTSKFSDPTIKDLALDYLIQTAPSDRKL
KSALIQAKHQLMSQNPQAIVGGRNVLLASETFASRANTAPSSLRS
LYLQVTSSPSNCDNLRQMLASYLPSEKTAVMEFLVNGMVADLKS
EGPSIPPAKLQVYMTELSNLQALHSVDSFFDRNIGNLENSLKHEG
HAPIPSLTTGNLTKTFLQLVEDKFPSSSKAQKALNELVGPDTGPQT
EVLNLFFRALNGCSPRIFSGAEKKQQLASVITNTLDAINADNEDYP
KPGDFPRSSFSSTPPHAPVPQSEIPTSPTSTQPPSP Ct089_E_S198A_nIgK_cHis
METPAQLLFLLLLWLPDTTGMTASGGAGGLGSTQTVDVARAQA 160
AAATQDAQEVIGSQEASEASMLKGCEDLINPAAATRIKKKEEKFE
SLEARRKPTADKAEKKSESTEEKGDTPLEDRFTEDLSEVSGEDFR
GLKNSFDDDSSPEEILDALTSKFSDPTIKDLALDYLIQTAPSDRKL
KSALIQAKHQLMSQNPQAIVGGRNVLLASETFASRANTAPSSLRS
LYLQVTSSPSNCDNLRQMLASYLPSEKTAVMEFLVNGMVADLKS
EGPSIPPAKLQVYMTELSNLQALHSVDSFFDRNIGNLENSLKHEG
HAPIPSLTTGNLTKTFLQLVEDKFPSSSKAQKALNELVGPDTGPQT
EVLNLFFRALNGCSPRIFSGAEKKQQLASVITNTLDAINADNEDYP
KPGDFPRSSFSSTPPHAPVPQSEIPTSPTSTQPPSPHHHHHH
Chlamydia_Ct875_nIgk_cHis
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 161
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
AAESGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQ
TSPMAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAA
AREIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGE
YTVGNSMFYDGPQVANLQNVDTGFWLDMSNLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPI
YEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSP
YPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQE
RIPNSQQVEGILRDMLTNGSQTFRDLMKRWNREVDREHHHHHH MOMP_serovarD
MKKLLKSVLVFAALSSASSLQALPVGNPAEPSLMIDGILWEGFGG 162
DPCDPCATWCDAISMRVGYYGDFVFDRVLKTDVNKEFQMGAKP
TTDTGNSAAPSTLTARENPAYGRHMQDAEMFTNAACMALNIWD
RFDVFCTLGATSGYLKGNSASFNLVGLFGDNENQKTVKAESVPN
MSFDQSVVELYTDTTFAWSVGARAALWECGCATLGASFQYAQS
KPKVEELNVLCNAAEFTINKPKGYVGKEFPLDLTAGTDAATGTK
DASIDYHEWQASLALSYRLNMFTPYIGVKWSRASFDADTIRIAQP
KSATAIFDTTTLNPTIAGAGDVKTGAEGQLGDTMQIVSLQLNKM
KSRKSCGIAVGTTIVDADKYAVTVETRLIDERAAHVNAQFRF
Chlamydia_Ct871_pd_serovarD_nIgK
METPAQLLFLLLLWLPDTTGAEIMIPQGIYDGETLTVSFPYTVIGD 163
PSGTTVFSAGELTLKNLDNSIAALPLSCFGNLLGSFTVLGRGHSLT
FENIRTSTNGAALSDSANSGLFTIEGFKELSFSNCNSLLAVLPAATT
NNGSQTPTTTSTPSNGTIYSKTDLLLLNNEKFSFYSNLVSGDGGAI
DAKSLTVQGISKLCVFQENTAQADGGACQVVTSFSAMANEAPIA
FIANVAGVRGGGIAAVQDGQQGVSSSTSTEDPVVSFSRNTAVEFD
GNVARVGGGIYSYGNVAFLNNGKTLFLNNVASPVYIAAEQPTNG
QASNTSDNYGDGGAIFCKNGAQAAGSNNSGSVSFDGEGVVFFSS
NVAAGKGGAIYAKKLSVANCGPVQFLGNIANDGGAIYLGESGEL
SLSADYGDIIFDGNLKRTAKENAADVNGVTVSSQAISMGSGGKIT
TLRAKAGHQILFNDPIEMANGNNQPAQSSEPLKINDGEGYTGDIV
FANGNSTLYQNVTIEQGRIVLREKAKLSVNSLSQTGGSLYMEAGS
TLDFVTPQPPQQPPAANQLITLSNLHLSLSSLLANNAVTNPPTNPP
AQDSHPAIIGSTTAGSVTISGPIFFEDLDDTAYDRYDWLGSNQKID
VLKLQLGTQPSANAPSDLTLGNEMPKYGYQGSWKLAWDPNTAN NGPYTLKATWTKTG
Chlamydia_Ct871_pd_serovarD_nIgK_cHis
METPAQLLFLLLLWLPDTTGAEIMIPQGIYDGETLTVSFPYTVIGD 164
PSGTTVFSAGELTLKNLDNSIAALPLSCFGNLLGSFTVLGRGHSLT
FENIRTSTNGAALSDSANSGLFTIEGFKELSFSNCNSLLAVLPAATT
NNGSQTPTTTSTPSNGTIYSKTDLLLLNNEKFSFYSNLVSGDGGAI
DAKSLTVQGISKLCVFQENTAQADGGACQVVTSFSAMANEAPIA
FIANVAGVRGGGIAAVQDGQQGVSSSTSTEDPVVSFSRNTAVEFD
GNVARVGGGIYSYGNVAFLNNGKTLFLNNVASPVYIAAEQPTNG
QASNTSDNYGDGGAIFCKNGAQAAGSNNSGSVSFDGEGVVFFSS
NVAAGKGGAIYAKKLSVANCGPVQFLGNIANDGGAIYLGESGEL
SLSADYGDIIFDGNLKRTAKENAADVNGVTVSSQAISMGSGGKIT
TLRAKAGHQILFNDPIEMANGNNQPAQSSEPLKINDGEGYTGDIV
FANGNSTLYQNVTIEQGRIVLREKAKLSVNSLSQTGGSLYMEAGS
TLDFVTPQPPQQPPAANQLITLSNLHLSLSSLLANNAVTNPPTNPP
AQDSHPAIIGSTTAGSVTISGPIFFEDLDDTAYDRYDWLGSNQKID
VLKLQLGTQPSANAPSDLTLGNEMPKYGYQGSWKLAWDPNTAN NGPYTLKATWTKTGHHHHHH
Chlamydia_Ct871_pd_serovarL2_nIgK
METPAQLLFLLLLWLPDTTGAEIMIPQGIYDGETLTVSFPYTVIGD 165
PSGTTVFSAGELTLKNLDNSIAALPLSCFGNLLGSFTVLGRGHSLT
FENIRTSTNGAALSNSAADGLFTIEGFKELSFSNCNSLLAVLPAAT
TNKGSQTPTTTSTPSNGTIYSKTDLLLLNNEKFSFYSNLVSGDGGA
IDAKSLTVQGISKLCVFQENTAQADGGACQVVTSFSAMANEAPIA
FVANVAGVRGGGIAAVQDGQQGVSSSTSTEDPVVSFSRNTAVEF
DGNVARVGGGIYSYGNVAFLNNGKTLFLNNVASPVYIAAKQPTS
GQASNTSNNYGDGGAIFCKNGAQAGSNNSGSVSFDGEGVVFFSS
NVAAGKGGAIYAKKLSVANCGPVQFLRNIANDGGAIYLGESGEL
SLSADYGDIIFDGNLKRTAKENAADVNGVTVSSQAISMGSGGKIT
TLRAKAGHQILFNDPIEMANGNNQPAQSSKLLKINDGEGYTGDIV
FANGSSTLYQNVTIEQGRIVLREKAKLSVNSLSQTGGSLYMEAGS
TLDFVTPQPPQQPPAANQLITLSNLHLSLSSLLANNAVTNPPTNPP
AQDSHPAVIGSTTAGSVTISGPIFFEDLDDTAYDRYDWLGSNQKI
NVLKLQLGTKPPANAPSDLTLGNEMPKYGYQGSWKLAWDPNTA NNGPYTLKATWTKTG
Chlamydia_Ct871_pd_serovarL2_nIgK_cHis
METPAQLLFLLLLWLPDTTGAEIMIPQGIYDGETLTVSFPYTVIGD 166
PSGTTVFSAGELTLKNLDNSIAALPLSCFGNLLGSFTVLGRGHSLT
FENIRTSTNGAALSNSAADGLFTIEGFKELSFSNCNSLLAVLPAAT
TNKGSQTPTTTSTPSNGTIYSKTDLLLLNNEKFSFYSNLVSGDGGA
IDAKSLTVQGISKLCVFQENTAQADGGACQVVTSFSAMANEAPIA
FVANVAGVRGGGIAAVQDGQQGVSSSTSTEDPVVSFSRNTAVEF
DGNVARVGGGIYSYGNVAFLNNGKTLFLNNVASPVYIAAKQPTS
GQASNTSNNYGDGGAIFCKNGAQAGSNNSGSVSFDGEGVVFFSS
NVAAGKGGAIYAKKLSVANCGPVQFLRNIANDGGAIYLGESGEL
SLSADYGDIIFDGNLKRTAKENAADVNGVTVSSQAISMGSGGKIT
TLRAKAGHQILFNDPIEMANGNNQPAQSSKLLKINDGEGYTGDIV
FANGSSTLYQNVTIEQGRIVLREKAKLSVNSLSQTGGSLYMEAGS
TLDFVTPQPPQQPPAANQLITLSNLHLSLSSLLANNAVTNPPTNPP
AQDSHPAVIGSTTAGSVTISGPIFFEDLDDTAYDRYDWLGSNQKI
NVLKLQLGTKPPANAPSDLTLGNEMPKYGYQGSWKLAWDPNTA NNGPYTLKATWTKTGHHHHHH
Chlamydia_Ct812_pd_serovarD_nIgK
METPAQLLFLLLLWLPDTTGSCVDLHAGGQSVNELVYVGPQAVL 167
LLDQIRDLFVGSKDSQAEGQYRLIVGDPSSFQEKDADTLPGKVEQ
STLFSVTNPVVFQGVDQQDQVSSQGLICSFTSSNLDSPRDGESFLG
IAFVGDSSKAGITLTDVKASLSGAALYSTEDLIFEKIKGGLEFASCS
SLEQGGACAAQSILIHDCQGLQVKHCTTAVNAEGSSANDHLGFG
GGAFFVTGSLSGEKSLYMPAGDMVVANCDGAISFEGNSANFANG
GAIAASGKVLFVANDKKTSFIENRALSGGAIAASSDIAFQNCAEL
VFKGNCAIGTEDKGSLGGGAISSLGTVLLQGNHGITCDKNESASQ
GGAIFGKNCQISDNEGPVVFRDSTACLGGGAIAAQEIVSIQNNQA
GISFEGGKASFGGGIACGSFSSAGGASVLGTIDISKNLGAISFSRTL
CTTSDLGQMEYQGGGALFGENISLSENAGVLTFKDNIVKTFASNG
KILGGGAILATGKVEITNNSEGISFTGNARAPQALPTQEEFPLFSKK
EGRPLSSGYSGGGAILGREVAILHNAAVVFEQNRLQCSEEEATLL
GCCGGGAVHGMDSTSIVGNSSVRFGNNYAMGQGVSGGALLSKT
VQLAGNGSVDFSRNIASLGGGALQASEGNCELVDNGYVLFRDNR
GRVYGGAISCLRGDVVISGNKGRVEFKDNIATRLYVEETVEKVEE
VEPAPEQKDNNELSFLGRAEQSFITAANQALFASEDGDLSPESSIS
SEELAKRRECAGGAIFAKRVRIVDNQEAVVFSNNFSDIYGGAIFT
GSLREEDKLDGQIPEVLISGNAGDVVFSGNSSKRDEHLPHTGGGA
ICTQNLTISQNTGNVLFYNNVACSGGAVRIEDHGNVLLEAFGGDI
VFKGNSSFRAQGSDAIYFAGKESHITALNATEGHAIVFHDALVFE
NLEERKSAEVLLINSRENPGYTGSIRFLEAESKVPQCIHVQQGSLE
LLNGATLCSYGFKQDAGAKLVLAAGAKLKILDSGTPVQQGHAIS
KPEAEIESSSEPEGAHSLWIAKNAQTTVPMVDIHTISVDLASFSSSQ
QEGTVEAPQVIVPGGSYVRSGELNLELVNTTGTGYENHALLKNE
AKVPLMSFVASGDEASAEISNLSVSDLQIHVVTPEIEEDTYGHMG DWSEAKIQDGTLVISWNPTG
Chlamydia_Ct812_pd_serovarD_nIgK_cHis
METPAQLLFLLLLWLPDTTGSCVDLHAGGQSVNELVYVGPQAVL 168
LLDQIRDLFVGSKDSQAEGQYRLIVGDPSSFQEKDADTLPGKVEQ
STLFSVTNPVVFQGVDQQDQVSSQGLICSFTSSNLDSPRDGESFLG
IAFVGDSSKAGITLTDVKASLSGAALYSTEDLIFEKIKGGLEFASCS
SLEQGGACAAQSILIHDCQGLQVKHCTTAVNAEGSSANDHLGFG
GGAFFVTGSLSGEKSLYMPAGDMVVANCDGAISFEGNSANFANG
GAIAASGKVLFVANDKKTSFIENRALSGGAIAASSDIAFQNCAEL
VFKGNCAIGTEDKGSLGGGAISSLGTVLLQGNHGITCDKNESASQ
GGAIFGKNCQISDNEGPVVFRDSTACLGGGAIAAQEIVSIQNNQA
GISFEGGKASFGGGIACGSFSSAGGASVLGTIDISKNLGAISFSRTL
CTTSDLGQMEYQGGGALFGENISLSENAGVLTFKDNIVKTFASNG
KILGGGAILATGKVEITNNSEGISFTGNARAPQALPTQEEFPLFSKK
EGRPLSSGYSGGGAILGREVAILHNAAVVFEQNRLQCSEEEATLL
GCCGGGAVHGMDSTSIVGNSSVRFGNNYAMGQGVSGGALLSKT
VQLAGNGSVDFSRNIASLGGGALQASEGNCELVDNGYVLFRDNR
GRVYGGAISCLRGDVVISGNKGRVEFKDNIATRLYVEETVEKVEE
VEPAPEQKDNNELSFLGRAEQSFITAANQALFASEDGDLSPESSIS
SEELAKRRECAGGAIFAKRVRIVDNQEAVVFSNNFSDIYGGAIFT
GSLREEDKLDGQIPEVLISGNAGDVVFSGNSSKRDEHLPHTGGGA
ICTQNLTISQNTGNVLFYNNVACSGGAVRIEDHGNVLLEAFGGDI
VFKGNSSFRAQGSDAIYFAGKESHITALNATEGHAIVFHDALVFE
NLEERKSAEVLLINSRENPGYTGSIRFLEAESKVPQCIHVQQGSLE
LLNGATLCSYGFKQDAGAKLVLAAGAKLKILDSGTPVQQGHAIS
KPEAEIESSSEPEGAHSLWIAKNAQTTVPMVDIHTISVDLASFSSSQ
QEGTVEAPQVIVPGGSYVRSGELNLELVNTTGTGYENHALLKNE
AKVPLMSFVASGDEASAEISNLSVSDLQIHVVTPEIEEDTYGHMG
DWSEAKIQDGTLVISWNPTGHHHHHH Chlamydia_Ct812_pd_serovarL2_nIgk
METPAQLLFLLLLWLPDTTGSCVDLHAGGQSVNELVYVGPQAVL 169
LLDQIRDLFVGSKDSQAEGQYRLIVGDPSSFQEKDADTLPGKVEQ
STLFSVTNPVVFQGVDQQDQVSSQGLICSFTSSNLDSPRDGESFLG
IAFVGDSSKAGITLTDVKASLSGAALYSTEDLIFEKIKGGLEFASCS
SLEQGGACAAQSILIHDCQGLQVKHCTTAVNAEGSSANDHLGFG
GGAFFVTGSLSGEKSLYMPAGDMVVANCDGAISFEGNSANFANG
GAIAASGKVLFVANDKKTSFIENRALSGGAIAASSDIAFQNCAEL
VFKGNCAIGTEDKGSLGGGAISSLGTVLLQGNHGITCDKNESASQ
GGAIFGKNCQISDNEGPVVFRDSTACLGGGAIAAQEIVSIQNNQA
GISFEGGKASFGGGIACGSFSSAGGASVLGTIDISKNLGAISFSRTL
CTTSDLGQMEYQGGGALFGENISLSENAGVLTFKDNIVKTFASNG
KILGGGAILATGKVEITNNSGGISFTGNARAPQALPTQEEFPLFSK
KEGRPLSSGYSGGGAILGREVAILHNAAVVFEQNRLQCSEEEATL
LGCCGGGAVHGMDSTSIVGNSSVRFGNNYAMGQGVSGGALLSK
TVQLAGNGSVDFSRNIASLGGGALQASEGNCELVDNGYVLFRDN
RGRVYGGAISCLRGDVVISGNKGRVEFKDNIATRLYVEETVEKVE
EVEPAPEQKDNNELSFLGSVEQSFITAANQALFASEDGDLSPESSIS
SEELAKRRECAGGAIFAKRVRIVDNQEAVVFSNNFSDIYGGAIFT
GSLREEDKLDGQIPEVLISGNAGDVVFSGNSSKRDEHLPHTGGGA
ICTQNLTISQNTGNVLFYNNVACSGGAVRIEDHGNVLLEAFGGDI
VFKGNSSFRAQGSDAIYFAGKESHITALNATEGHAIVFHDALVFE
NLKERKSAEVLLINSRENPGYTGSIRFLEAESKVPQCIHVQQGSLE
LLNGATLCSYGFKQDAGAKLVLAAGSKLKILDSGTPVQGHAISKP
EAEIESSSEPEGAHSLWIAKNAQTTVPMVDIHTISVDLASFSSSQQ
EGTVEAPQVIVPGGSYVRSGELNLELVNTTGTGYENHALLKNEA
KVPLMSFVASSDEASAEISNLSVSDLQIHVATPEIEEDTYGHMGD WSEAKIQDGTLVISWNPTG
Chlamydia_Ct812_pd_serovarL2_nIgk_cHis
METPAQLLFLLLLWLPDTTGSCVDLHAGGQSVNELVYVGPQAVL 170
LLDQIRDLFVGSKDSQAEGQYRLIVGDPSSFQEKDADTLPGKVEQ
STLFSVTNPVVFQGVDQQDQVSSQGLICSFTSSNLDSPRDGESFLG
IAFVGDSSKAGITLTDVKASLSGAALYSTEDLIFEKIKGGLEFASCS
SLEQGGACAAQSILIHDCQGLQVKHCTTAVNAEGSSANDHLGFG
GGAFFVTGSLSGEKSLYMPAGDMVVANCDGAISFEGNSANFANG
GAIAASGKVLFVANDKKTSFIENRALSGGAIAASSDIAFQNCAEL
VFKGNCAIGTEDKGSLGGGAISSLGTVLLQGNHGITCDKNESASQ
GGAIFGKNCQISDNEGPVVFRDSTACLGGGAIAAQEIVSIQNNQA
GISFEGGKASFGGGIACGSFSSAGGASVLGTIDISKNLGAISFSRTL
CTTSDLGQMEYQGGGALFGENISLSENAGVLTFKDNIVKTFASNG
KILGGGAILATGKVEITNNSGGISFTGNARAPQALPTQEEFPLFSK
KEGRPLSSGYSGGGAILGREVAILHNAAVVFEQNRLQCSEEEATL
LGCCGGGAVHGMDSTSIVGNSSVRFGNNYAMGQGVSGGALLSK
TVQLAGNGSVDFSRNIASLGGGALQASEGNCELVDNGYVLFRDN
RGRVYGGAISCLRGDVVISGNKGRVEFKDNIATRLYVEETVEKVE
EVEPAPEQKDNNELSFLGSVEQSFITAANQALFASEDGDLSPESSIS
SEELAKRRECAGGAIFAKRVRIVDNQEAVVFSNNFSDIYGGAIFT
GSLREEDKLDGQIPEVLISGNAGDVVFSGNSSKRDEHLPHTGGGA
ICTQNLTISQNTGNVLFYNNVACSGGAVRIEDHGNVLLEAFGGDI
VFKGNSSFRAQGSDAIYFAGKESHITALNATEGHAIVFHDALVFE
NLKERKSAEVLLINSRENPGYTGSIRFLEAESKVPQCIHVQQGSLE
LLNGATLCSYGFKQDAGAKLVLAAGSKLKILDSGTPVQGHAISKP
EAEIESSSEPEGAHSLWIAKNAQTTVPMVDIHTISVDLASFSSSQQ
EGTVEAPQVIVPGGSYVRSGELNLELVNTTGTGYENHALLKNEA
KVPLMSFVASSDEASAEISNLSVSDLQIHVATPEIEEDTYGHMGD
WSEAKIQDGTLVISWNPTGHHHHHH Chlamydia_Ct460_serovarD_nIgk
METPAQLLFLLLLWLPDTTGMSQNKNSAFMQPVNVSADLAAIVG 171
AGPMPRTEIIKKMWDYIKKNGLQDPTNKRNINPDDKLAKVFGTE KPIDMFQMTKMVSQHIIK
Chlamydia_Ct460_serovarD_nIgk_cHis
METPAQLLFLLLLWLPDTTGMSQNKNSAFMQPVNVSADLAAIVG 172
AGPMPRTEIIKKMWDYIKKNGLQDPTNKRNINPDDKLAKVFGTE
KPIDMFQMTKMVSQHIIKHHHHHH Chlamydia_Ct460_serovarL2_nIgk
METPAQLLFLLLLWLPDTTGMSQNKNSAFMQPVNVSADLAAIVG 173
AGPMPRTEIIKKMWDYIKENSLQDPTNKRNINPDDKLAKVFGTEK PIDMFQMTKMVSQHIIK
Chlamydia_Ct460_serovarL2_nIgk_cHis
METPAQLLFLLLLWLPDTTGMSQNKNSAFMQPVNVSADLAAIVG 174
AGPMPRTEIIKKMWDYIKENSLQDPTNKRNINPDDKLAKVFGTEK
PIDMFQMTKMVSQHIIKHHHHHH Chlamydia_Ct622_serovarE_nIgk
METPAQLLFLLLLWLPDTTGMESGPESVSSNQSSMNPIINGQIASN 175
SETKESTKASEASPSASSSVSSWSFLSSAKNALISLRDAILNKNSSP
TDSLSQLEASTSTSTVTRVAAKDYDEAKSNFDTAKSGLENAKTL
AEYETKMADLMAALQDMERLANSDPSNNHTEEVNNIKKALEAQ
KDTIDKLNKLVTLQNQNKSLTEVLKTTDSADQIPAINSQLEINKNS
ADQIIKDLERQNISYEAVLTNAGEVIKASSEAGIKLGQALQSIVDA
GDQSQAAVLQAQQNNSPDNIAATKELIDAAETKVNELKQEHTGL
TDSPLVKKAEEQISQAQKDIQEIKPSGSDIPIVGPSGSAASAGSAAG
ALKSSNNSGRISLLLDDVDNEMAAIALQGFRSMIEQFNVNNPATA
KELQAMEAQLTAMSDQLVGADGELPAEIQAIKDALAQALKQPSA
DGLATAMGQVAFAAAKVGGGSAGTAGTVQMNVKQLYKTAFSS
TSSSSYAAALSDGYSAYKTLNSLYSESRSGVQSAISQTANPALSRS
VSRSGIESQGRSADASQRAAETIVRDSQTLGDVYSRLQVLDSLMS
TIVSNPQANQEEIMQKLTASISKAPQFGYPAVQNSADSLQKFAAQ
LEREFVDGERSLAESQENAFRKQPAFIQQVLVNIASLFSGYLS
Chlamydia_Ct622_serovarE_nIgk_cHis
METPAQLLFLLLLWLPDTTGMESGPESVSSNQSSMNPIINGQIASN 176
SETKESTKASEASPSASSSVSSWSFLSSAKNALISLRDAILNKNSSP
TDSLSQLEASTSTSTVTRVAAKDYDEAKSNFDTAKSGLENAKTL
AEYETKMADLMAALQDMERLANSDPSNNHTEEVNNIKKALEAQ
KDTIDKLNKLVTLQNQNKSLTEVLKTTDSADQIPAINSQLEINKNS
ADQIIKDLERQNISYEAVLTNAGEVIKASSEAGIKLGQALQSIVDA
GDQSQAAVLQAQQNNSPDNIAATKELIDAAETKVNELKQEHTGL
TDSPLVKKAEEQISQAQKDIQEIKPSGSDIPIVGPSGSAASAGSAAG
ALKSSNNSGRISLLLDDVDNEMAAIALQGFRSMIEQFNVNNPATA
KELQAMEAQLTAMSDQLVGADGELPAEIQAIKDALAQALKQPSA
DGLATAMGQVAFAAAKVGGGSAGTAGTVQMNVKQLYKTAFSS
TSSSSYAAALSDGYSAYKTLNSLYSESRSGVQSAISQTANPALSRS
VSRSGIESQGRSADASQRAAETIVRDSQTLGDVYSRLQVLDSLMS
TIVSNPQANQEEIMQKLTASISKAPQFGYPAVQNSADSLQKFAAQ
LEREFVDGERSLAESQENAFRKQPAFIQQVLVNIASLFSGYLSHHH HHH
Chlamydia_Ct858_nIgk METPAQLLFLLLLWLPDTTGVRGESLVCKNALQDLSFLEHLLQV
177 KYAPKTWKEQYLGWDLVQSSVSAQQKLRTQENPSTSFCQQVLA
DFIGGLNDFHAGVTFFAIESAYLPYTVQKSSDGRFYFVDIMTFSSE
IRVGDELLEVDGAPVQDVLATLYGSNHKGTAAEESAALRTLFSR
MASLGHKVPSGRTTLKIRRPFGTTREVRVKWRYVPEGVGDLATI
APSIRAPQLQKSMRSFFPKKDDAFHRSSSLFYSPMVPHFWAELRN
HYATSGLKSGYNIGSTDGFLPVIGPVIWESEGLFRAYISSVTDGDG
KSHKVGFLRIPTYSWQDMEDFDPSGPPPWEEFAKIIQVFSSNTEAL
IIDQTNNPGGSVLYLYALLSMLTDRPLELPKHRMILTQDEVVDAL
DWLTLLENVDTNVESRLALGDNMEGYTVDLQVAEYLKSFGRQV
LNCWSKGDIELSTPIPLFGFEKIHPHPRVQYSKPICVLINEQDFSCA
DFFPVVLKDNDRALIVGTRTAGAGGFVFNVQFPNRTGIKTCSLTG
SLAVREHGAFIENIGVEPHIDLPFTANDIRYKGYSEYLDKVKKLVC QLINNDGTIILAEDGSF
Chlamydia_Ct858_nIgk_cHis
METPAQLLFLLLLWLPDTTGVRGESLVCKNALQDLSFLEHLLQV 178
KYAPKTWKEQYLGWDLVQSSVSAQQKLRTQENPSTSFCQQVLA
DFIGGLNDFHAGVTFFAIESAYLPYTVQKSSDGRFYFVDIMTFSSE
IRVGDELLEVDGAPVQDVLATLYGSNHKGTAAEESAALRTLFSR
MASLGHKVPSGRTTLKIRRPFGTTREVRVKWRYVPEGVGDLATI
APSIRAPQLQKSMRSFFPKKDDAFHRSSSLFYSPMVPHFWAELRN
HYATSGLKSGYNIGSTDGFLPVIGPVIWESEGLFRAYISSVTDGDG
KSHKVGFLRIPTYSWQDMEDFDPSGPPPWEEFAKIIQVFSSNTEAL
IIDQTNNPGGSVLYLYALLSMLTDRPLELPKHRMILTQDEVVDAL
DWLTLLENVDTNVESRLALGDNMEGYTVDLQVAEYLKSFGRQV
LNCWSKGDIELSTPIPLFGFEKIHPHPRVQYSKPICVLINEQDFSCA
DFFPVVLKDNDRALIVGTRTAGAGGFVFNVQFPNRTGIKTCSLTG
SLAVREHGAFIENIGVEPHIDLPFTANDIRYKGYSEYLDKVKKLVC
QLINNDGTIILAEDGSFHHHHHH Chlamydia_Ct875_nIgk
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 179
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
AAESGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQ
TSPMAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAA
AREIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGE
YTVGNSMFYDGPQVANLQNVDTGFWLDMSNLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPI
YEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSP
YPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQE
RIPNSQQVEGILRDMLTNGSQTFRDLMKRWNREVDRE Chlamydia_Ct875_nIgk_cHis
METPAQLLFLLLLWLPDTTGMSIRGVGGNGNSRIPSHNGDGSNRR 180
SQNTKGNNKVEDRVCSLYSSRSNENRESPYAVVDVSSMIESTPTS
GETTRASRGVLSRFQRGLVRIADKVRRAVQCAWSSVSTSRSSATR
AAESGSSSRTARGASSGYREYSPSAARGLRLMFTDFWRTRVLRQ
TSPMAGVFGNLDVNEARLMAAYTSECADHLEAKELAGPDGVAA
AREIAKRWEKRVRDLQDKGAARKLLNDPLGRRTPNYQSKNPGE
YTVGNSMFYDGPQVANLQNVDTGFWLDMSNLSDVVLSREIQTG
LRARATLEESMPMLENLEERFRRLQETCDAARTEIEESGWTRESA
SRMEGDEAQGPSRVQQAFQSFVNECNSIEFSFGSFGEHVRVLCAR
VSRGLAAAGEAIRRCFSCCKGSTHRYAPRDDLSPEGASLAETLAR
FADDMGIERGADGTYDIPLVDDWRRGVPSIEGEGSDSIYEIMMPI
YEVMNMDLETRRSFAVQQGHYQDPRASDYDLPRASDYDLPRSP
YPTPPLPPRYQLQNMDVEAGFREAVYASFVAGMYNYVVTQPQE
RIPNSQQVEGILRDMLTNGSQTFRDLMKRWNREVDREHHHHHH Chlamydia_Ct089_nIgk
METPAQLLFLLLLWLPDTTGMTASGGAGGLGSTQTVDVARAQA 181
AAATQDAQEVIGSQEASEASMLKGCEDLINPAAATRIKKKEEKFE
SLEARRKPTADKAEKKSESTEEKGDTPLEDRFTEDLSEVSGEDFR
GLKNSFDDDSSPEEILDALTSKFSDPTIKDLALDYLIQTAPSDRKL
KSALIQAKHQLMSQNPQAIVGGRNVLLASETFASRANTSPSSLRS
LYLQVTSSPSNCDNLRQMLASYLPSEKTAVMEFLVNGMVADLKS
EGPSIPPAKLQVYMTELSNLQALHSVDSFFDRNIGNLENSLKHEG
HAPIPSLTTGNLTKTFLQLVEDKFPSSSKAQKALNELVGPDTGPQT
EVLNLFFRALNGCSPRIFSGAEKKQQLASVITNTLDAINADNEDYP
KPGDFPRSSFSSTPPHAPVPQSEIPTSPTSTQPPSP Chlamydia_Ct089_nIgk_cHis
METPAQLLFLLLLWLPDTTGMTASGGAGGLGSTQTVDVARAQA 182
AAATQDAQEVIGSQEASEASMLKGCEDLINPAAATRIKKKEEKFE
SLEARRKPTADKAEKKSESTEEKGDTPLEDRFTEDLSEVSGEDFR
GLKNSFDDDSSPEEILDALTSKFSDPTIKDLALDYLIQTAPSDRKL
KSALIQAKHQLMSQNPQAIVGGRNVLLASETFASRANTSPSSLRS
LYLQVTSSPSNCDNLRQMLASYLPSEKTAVMEFLVNGMVADLKS
EGPSIPPAKLQVYMTELSNLQALHSVDSFFDRNIGNLENSLKHEG
HAPIPSLTTGNLTKTFLQLVEDKFPSSSKAQKALNELVGPDTGPQT
EVLNLFFRALNGCSPRIFSGAEKKQQLASVITNTLDAINADNEDYP
KPGDFPRSSFSSTPPHAPVPQSEIPTSPTSTQPPSPHHHHHH Chlamydia_MOMP
MKKLLKSAFLSAAFFAGHASLHALPVGNPAEPSLLIDGTIWEGMS 183
GDPCDPCATWCDAISLRVGFYGDYVFDRVLKTDVPQKFSMGPIP
TSSTSPEDSAILTERNNAAYGKHMHDAELFTNAGYIALNIWDRFD
IFCTLGATSGYFKGNSSSFNLIGLIGISGADLNSKLPNANISNGVVE
LYTDTTFSWSVGARGALWECGCATLGAEFQYAQSKPRVQELNV
LSNVAQFTVHKPRGYVGQPLPLPLTAGTATDSNDKLKNATINYH
EWQVGAALSYRLNMLVPYIGVQWSRATFDADTIQIAEPKLASPIF
NLTTWNPTLLGQATSVDSGNKFADSLQIVSLQINKLKSRKACGVS
MGATLLDADKWAINGELRLINERAAHLSAQCRF * All Chlamydia mRNA vaccines
contain standard 5'UTR and 3'UTR sequences and G5 Cap 5'UTR:
TCAAGCTTTTGGACCCTCGTACAGAAGCTAATACGACTCACTATAGGGAAATAAGAGAGAAAAGAAG-
AGTAAGAAGAAATATAAGAGCCACC (SEQ ID NO: 295) 5'UTR without promoter
sequence: (SEQ ID NO: 296)
GGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACC 3'UTR:
TGATAATAGGCTGGAGCCTCGGTGGCCATGCTTCTTGCCCCTTGGGCCTCCCCCCAGCCCCTCCTCC-
CCTTCCTGCACCCGTACCCCCGTGGTCTTTGAATAAAGTCTGAGTGGGCGGC (SEQ ID NO:
297)
TABLE-US-00009 TABLE 8 Chlamydia mRNA Constructs (Nucleic Acids)
SEQ mRNA ID Name ORF Sequence (Nucleotide) NO: Cta1_E_EXT_noTM_nIgK
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 184
TGCCTGATACCACCGGCCCTCCCCTGCCCAGCAGCACACAGGA
CAACAGATCCATGGACCAGCAGGACAGCGAAGAGTTCCTGCT
GCAGAACACCCTGGAAGATAGCGAGATCATCAGCATCCCCGA
CACCATGAACCAGATCGCCATCGACACCGAGAAGTGGTTCTAC
CTGAACAAGGACTGCACCAACGTGGGCCCCATCTCCATCGTGC
AGCTGACAGCCTTCCTGAAAGAGTGCAAGCACAGCCCCGAGA
AGGGCATCGACCCCCAGGAACTGTGGGTGTGGAAGAAAGGCA
TGCCCAACTGGGAGAAAGTGAAGAACATCCCCGAGCTGAGCG GCACCGTGAAGGACGAG
Cta1_E_EXT_noTM_nIgK_cHis
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 185
TGCCTGATACCACCGGCCCTCCCCTGCCCAGCAGCACACAGGA
CAACAGATCCATGGACCAGCAGGACAGCGAAGAGTTCCTGCT
GCAGAACACCCTGGAAGATAGCGAGATCATCAGCATCCCCGA
CACCATGAACCAGATCGCCATCGACACCGAGAAGTGGTTCTAC
CTGAACAAGGACTGCACCAACGTGGGCCCCATCTCCATCGTGC
AGCTGACAGCCTTCCTGAAAGAGTGCAAGCACAGCCCCGAGA
AGGGCATCGACCCCCAGGAACTGTGGGTGTGGAAGAAAGGCA
TGCCCAACTGGGAGAAAGTGAAGAACATCCCCGAGCTGAGCG
GCACCGTGAAGGACGAGCACCACCACCATCACCAC Ct875_E_NGM_nFC_cHis
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 186
TGCCTGATACAACCGGCGAGCCTAAGAGCTGCGACAAGACCC
ACACCTGTCCTCCATGTCCTGCTCCAGAACTGCTCGGCGGACC
TTCCGTGTTCCTGTTTCCTCCAAAGCCTAAGGACACCCTGATG
ATCAGCAGAACCCCTGAAGTGACCTGCGTGGTGGTGGATGTGT
CCCACGAGGATCCCGAAGTGAAGTTCAATTGGTACGTGGACG
GCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGAGAGGAAC
AGTACAACAGCACCTACAGAGTGGTGTCCGTGCTGACCGTGCT
GCACCAGGATTGGCTGAACGGCAAAGAGTACAAGTGCAAGGT
GTCCAACAAGGCCCTGCCTGCTCCTATCGAGAAGACCATCAGC
AAGGCCAAGGGCCAGCCAAGAGAACCCCAGGTGTACACACTG
CCTCCAAGCAGAGATGAGCTGACCAAGAACCAGGTGTCCCTG
ACCTGTCTGGTCAAGGGCTTCTACCCCTCCGATATCGCCGTGG
AATGGGAGAGCAATGGCCAGCCTGAGAACAACTACAAGACAA
CCCCTCCTGTGCTGGACAGCGACGGCTCATTCTTCCTGTACAG
CAAGCTGACAGTGGACAAGAGCAGATGGCAGCAGGGCAACGT
GTTCAGCTGCAGCGTGATGCACGAGGCCCTGCACAATCACTAC
ACCCAGAAGTCCCTGTCTCTGAGCCCCGGCAAGATGAGCATCA
GAGGCGTGGGCGGCAACGGCAACAGCAGAATCCCTAGCCACA
ACGGCGACGGCAGCAACAGGCGGAGCCAGAACACCAAGGGC
AACAACAAGGTGGAAGATAGAGTGTGCAGCCTGTACAGCAGC
CGGTCCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTGGAC
GTGTCCAGCATGATCGAGAGCACCCCCACCAGCGGCGAGACA
ACCAGAGCTAGTAGAGGCGTGCTGAGCCGGTTCCAGAGGGGC
CTCGTGCGGATTGCTGACAAAGTGCGGAGAGCCGTGCAGTGC
GCTTGGAGCAGCGTGTCCACAAGCAGAAGCAGCGCCACAAGA
GCCGCCGAGAGCGGCAGCTCTAGCAGAACAGCTAGAGGCGCC
AGCAGCGGCTACAGAGAGTACAGCCCTTCTGCCGCTCGGGGC
CTGCGGCTGATGTTCACCGACTTTTGGCGGACCCGGGTGCTGA
GACAGACCTCTCCTATGGCCGGCGTGTTCGGCAACCTGGACGT
GAACGAGGCCAGACTGATGGCCGCCTACACCAGCGAGTGTGC
CGATCACCTGGAAGCCAAAGAGCTGGCCGGACCTGACGGCGT
GGCAGCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAGT
GCGGGACCTGCAGGACAAGGGCGCTGCCAGAAAGCTGCTGAA
CGACCCCCTGGGCAGACGGACCCCCAACTACCAGAGCAAGAA
CCCCGGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGGC
CCCCAGGTGGCCAACCTGCAGAATGTGGATACCGGCTTCTGGC
TGGACATGCAGCACCTGAGCGACGTGGTGCTGTCCAGAGAGA
TCCAGACCGGCCTGAGAGCCAGAGCCACCCTGGAAGAGTCCA
TGCCCATGCTGGAAAATCTGGAAGAGAGATTCCGGCGGCTGC
AGGAAACCTGCGACGCCGCCAGAACCGAGATCGAGGAAAGCG
GCTGGACCCGGGAAAGCGCCTCCAGAATGGAAGGCGACGAAG
CCCAGGGCCCCAGCAGAGTGCAGCAGGCCTTTCAGAGCTTCGT
GAATGAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCGGC
GAGCACGTGCGGGTGCTGTGTGCCAGAGTGTCAAGAGGACTG
GCCGCTGCCGGCGAGGCCATCAGAAGATGCTTCAGCTGCTGCA
AGGGCAGCACCCACAGATACGCCCCCAGAGATGACCTGTCTC
CTGAGGGCGCCTCTCTGGCCGAAACCCTGGCCAGATTCGCCGA
CGACATGGGCATCGAAAGAGGCGCCGACGGCACCTACGACAT
CCCCCTGGTGGACGATTGGAGAAGGGGCGTGCCATCCATCGA
GGGCGAGGGCAGCGATAGCATCTACGAGATCATGATGCCCAT
CTACGAAGTGATGAACATGGACCTGGAAACCCGGCGGAGCTT
CGCCGTGCAGCAGGGCCATTACCAGGACCCCAGAGCCAGCGA
CTACGACCTGCCTAGAGCCTCCGATTACGATCTGCCCAGAAGC
CCCTACCCCACCCCTCCACTGCCTCCCAGATACCAGCTGCAGA
ACATGGATGTGGAAGCCGGCTTTCGCGAGGCCGTGTACGCCTC
TTTTGTGGCCGGCATGTACAACTACGTCGTGACCCAGCCCCAG
GAACGGATCCCCAATAGCCAGCAGGTGGAAGGCATCCTGCGG
GACATGCTGACCAACGGCGACCAGACCTTCCGGGACCTGATG
AAGCGGTGGAACAGAGAGGTGGACCGCGAGATGAGCCCTATC
CTCGGCTACTGGAAGATCAAAGGCCTGGTGCAGCCCACCAGA
CTGCTGCTGGAATACCTGGAAGAGAAGTACGAGGAACACCTG
TACGAGCGCGACGAGGGCGATAAGTGGCGGAACAAGAAGTTC
GAGCTGGGCCTCGAGTTCCCCAACCTGCCTTACTACATCGACG
GCGACGTGAAGCTGACCCAGAGCATGGCCATCATCCGGTATAT
CGCCGACAAGCACAACATGCTCGGCGGCTGCCCTAAAGAGCG
GGCCGAGATTTCTATGCTGGAAGGCGCCGTGCTGGACATCAGA
TACGGCGTGTCCAGAATCGCCTACAGCAAGGACTTCGAAACCC
TGAAGGTGGACTTCCTGAGCAAGCTGCCCGAGATGCTGAAGA
TGTTCGAGGACCGGCTGTGCCACAAGACCTACCTGAATGGCGA
CCACGTGACACACCCCGACTTCATGCTGTACGACGCCCTGGAT
GTGGTGCTGTACATGGACCCCATGTGCCTGGACGCCTTTCCAA
AGCTCGTGTGCTTCAAGAAGCGGATCGAGGCCATTCCTCAGAT
CGACAAGTACCTGAAGTCCAGCAAGTATATCGCTTGGCCCCTG
CAAGGCTGGCAGGCCACATTTGGAGGCGGAGATCACCCTCCT AAG Ct875_E_nFC_cHis
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 187
TGCCTGATACAACCGGCGAGCCTAAGAGCTGCGACAAGACCC
ACACCTGTCCTCCATGTCCTGCTCCAGAACTGCTCGGCGGACC
TTCCGTGTTCCTGTTTCCTCCAAAGCCTAAGGACACCCTGATG
ATCAGCAGAACCCCTGAAGTGACCTGCGTGGTGGTGGATGTGT
CCCACGAGGATCCCGAAGTGAAGTTCAATTGGTACGTGGACG
GCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGAGAGGAAC
AGTACAACAGCACCTACAGAGTGGTGTCCGTGCTGACCGTGCT
GCACCAGGATTGGCTGAACGGCAAAGAGTACAAGTGCAAGGT
GTCCAACAAGGCCCTGCCTGCTCCTATCGAGAAGACCATCAGC
AAGGCCAAGGGCCAGCCAAGAGAACCCCAGGTGTACACACTG
CCTCCAAGCAGAGATGAGCTGACCAAGAACCAGGTGTCCCTG
ACCTGTCTGGTCAAGGGCTTCTACCCCTCCGATATCGCCGTGG
AATGGGAGAGCAATGGCCAGCCTGAGAACAACTACAAGACAA
CCCCTCCTGTGCTGGACAGCGACGGCTCATTCTTCCTGTACAG
CAAGCTGACAGTGGACAAGAGCAGATGGCAGCAGGGCAACGT
GTTCAGCTGCAGCGTGATGCACGAGGCCCTGCACAATCACTAC
ACCCAGAAGTCCCTGTCTCTGAGCCCCGGCAAGATGAGCATCA
GAGGCGTGGGCGGCAACGGCAACAGCAGAATCCCTAGCCACA
ACGGCGACGGCAGCAACAGGCGGAGCCAGAACACCAAGGGC
AACAACAAGGTGGAAGATAGAGTGTGCAGCCTGTACAGCAGC
CGGTCCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTGGAC
GTGTCCAGCATGATCGAGAGCACCCCCACCAGCGGCGAGACA
ACCAGAGCTAGTAGAGGCGTGCTGAGCCGGTTCCAGAGGGGC
CTCGTGCGGATTGCTGACAAAGTGCGGAGAGCCGTGCAGTGC
GCTTGGAGCAGCGTGTCCACAAGCAGAAGCAGCGCCACAAGA
GCCGCCGAGAGCGGCAGCTCTAGCAGAACAGCTAGAGGCGCC
AGCAGCGGCTACAGAGAGTACAGCCCTTCTGCCGCTCGGGGC
CTGCGGCTGATGTTCACCGACTTTTGGCGGACCCGGGTGCTGA
GACAGACCTCTCCTATGGCCGGCGTGTTCGGCAACCTGGACGT
GAACGAGGCCAGACTGATGGCCGCCTACACCAGCGAGTGTGC
CGATCACCTGGAAGCCAAAGAGCTGGCCGGACCTGACGGCGT
GGCAGCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAGT
GCGGGACCTGCAGGACAAGGGCGCTGCCAGAAAGCTGCTGAA
CGACCCCCTGGGCAGACGGACCCCCAACTACCAGAGCAAGAA
CCCCGGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGGC
CCCCAGGTGGCCAACCTGCAGAATGTGGATACCGGCTTCTGGC
TGGACATGAGCAACCTGAGCGACGTGGTGCTGTCCAGAGAGA
TCCAGACCGGCCTGAGAGCCAGAGCCACCCTGGAAGAGTCCA
TGCCCATGCTGGAAAATCTGGAAGAGAGATTCCGGCGGCTGC
AGGAAACCTGCGACGCCGCCAGAACCGAGATCGAGGAAAGCG
GCTGGACCCGGGAAAGCGCCTCCAGAATGGAAGGCGACGAAG
CCCAGGGCCCCAGCAGAGTGCAGCAGGCCTTTCAGAGCTTCGT
GAATGAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCGGC
GAGCACGTGCGGGTGCTGTGTGCCAGAGTGTCAAGAGGACTG
GCCGCTGCCGGCGAGGCCATCAGAAGATGCTTCAGCTGCTGCA
AGGGCAGCACCCACAGATACGCCCCCAGAGATGACCTGTCTC
CTGAGGGCGCCTCTCTGGCCGAAACCCTGGCCAGATTCGCCGA
CGACATGGGCATCGAAAGAGGCGCCGACGGCACCTACGACAT
CCCCCTGGTGGACGATTGGAGAAGGGGCGTGCCATCCATCGA
GGGCGAGGGCAGCGATAGCATCTACGAGATCATGATGCCCAT
CTACGAAGTGATGAACATGGACCTGGAAACCCGGCGGAGCTT
CGCCGTGCAGCAGGGCCATTACCAGGACCCCAGAGCCAGCGA
CTACGACCTGCCTAGAGCCTCCGATTACGATCTGCCCAGAAGC
CCCTACCCCACCCCTCCACTGCCTCCCAGATACCAGCTGCAGA
ACATGGATGTGGAAGCCGGCTTTCGCGAGGCCGTGTACGCCTC
TTTTGTGGCCGGCATGTACAACTACGTCGTGACCCAGCCCCAG
GAACGGATCCCCAATAGCCAGCAGGTGGAAGGCATCCTGCGG
GACATGCTGACCAACGGCAGCCAGACCTTCCGGGACCTGATG
AAGCGGTGGAACAGAGAGGTGGACCGCGAGCACCACCATCAC CACCAC Ct875_E_NGM_nFC
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 188
TGCCTGATACAACCGGCGAGCCTAAGAGCTGCGACAAGACCC
ACACCTGTCCTCCATGTCCTGCTCCAGAACTGCTCGGCGGACC
TTCCGTGTTCCTGTTTCCTCCAAAGCCTAAGGACACCCTGATG
ATCAGCAGAACCCCTGAAGTGACCTGCGTGGTGGTGGATGTGT
CCCACGAGGATCCCGAAGTGAAGTTCAATTGGTACGTGGACG
GCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGAGAGGAAC
AGTACAACAGCACCTACAGAGTGGTGTCCGTGCTGACCGTGCT
GCACCAGGATTGGCTGAACGGCAAAGAGTACAAGTGCAAGGT
GTCCAACAAGGCCCTGCCTGCTCCTATCGAGAAGACCATCAGC
AAGGCCAAGGGCCAGCCAAGAGAACCCCAGGTGTACACACTG
CCTCCAAGCAGAGATGAGCTGACCAAGAACCAGGTGTCCCTG
ACCTGTCTGGTCAAGGGCTTCTACCCCTCCGATATCGCCGTGG
AATGGGAGAGCAATGGCCAGCCTGAGAACAACTACAAGACAA
CCCCTCCTGTGCTGGACAGCGACGGCTCATTCTTCCTGTACAG
CAAGCTGACAGTGGACAAGAGCAGATGGCAGCAGGGCAACGT
GTTCAGCTGCAGCGTGATGCACGAGGCCCTGCACAATCACTAC
ACCCAGAAGTCCCTGTCTCTGAGCCCCGGCAAGATGAGCATCA
GAGGCGTGGGCGGCAACGGCAACAGCAGAATCCCTAGCCACA
ACGGCGACGGCAGCAACAGGCGGAGCCAGAACACCAAGGGC
AACAACAAGGTGGAAGATAGAGTGTGCAGCCTGTACAGCAGC
CGGTCCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTGGAC
GTGTCCAGCATGATCGAGAGCACCCCCACCAGCGGCGAGACA
ACCAGAGCTAGTAGAGGCGTGCTGAGCCGGTTCCAGAGGGGC
CTCGTGCGGATTGCTGACAAAGTGCGGAGAGCCGTGCAGTGC
GCTTGGAGCAGCGTGTCCACAAGCAGAAGCAGCGCCACAAGA
GCCGCCGAGAGCGGCAGCTCTAGCAGAACAGCTAGAGGCGCC
AGCAGCGGCTACAGAGAGTACAGCCCTTCTGCCGCTCGGGGC
CTGCGGCTGATGTTCACCGACTTTTGGCGGACCCGGGTGCTGA
GACAGACCTCTCCTATGGCCGGCGTGTTCGGCAACCTGGACGT
GAACGAGGCCAGACTGATGGCCGCCTACACCAGCGAGTGTGC
CGATCACCTGGAAGCCAAAGAGCTGGCCGGACCTGACGGCGT
GGCAGCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAGT
GCGGGACCTGCAGGACAAGGGCGCTGCCAGAAAGCTGCTGAA
CGACCCCCTGGGCAGACGGACCCCCAACTACCAGAGCAAGAA
CCCCGGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGGC
CCCCAGGTGGCCAACCTGCAGAATGTGGATACCGGCTTCTGGC
TGGACATGCAGCACCTGAGCGACGTGGTGCTGTCCAGAGAGA
TCCAGACCGGCCTGAGAGCCAGAGCCACCCTGGAAGAGTCCA
TGCCCATGCTGGAAAATCTGGAAGAGAGATTCCGGCGGCTGC
AGGAAACCTGCGACGCCGCCAGAACCGAGATCGAGGAAAGCG
GCTGGACCCGGGAAAGCGCCTCCAGAATGGAAGGCGACGAAG
CCCAGGGCCCCAGCAGAGTGCAGCAGGCCTTTCAGAGCTTCGT
GAATGAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCGGC
GAGCACGTGCGGGTGCTGTGTGCCAGAGTGTCAAGAGGACTG
GCCGCTGCCGGCGAGGCCATCAGAAGATGCTTCAGCTGCTGCA
AGGGCAGCACCCACAGATACGCCCCCAGAGATGACCTGTCTC
CTGAGGGCGCCTCTCTGGCCGAAACCCTGGCCAGATTCGCCGA
CGACATGGGCATCGAAAGAGGCGCCGACGGCACCTACGACAT
CCCCCTGGTGGACGATTGGAGAAGGGGCGTGCCATCCATCGA
GGGCGAGGGCAGCGATAGCATCTACGAGATCATGATGCCCAT
CTACGAAGTGATGAACATGGACCTGGAAACCCGGCGGAGCTT
CGCCGTGCAGCAGGGCCATTACCAGGACCCCAGAGCCAGCGA
CTACGACCTGCCTAGAGCCTCCGATTACGATCTGCCCAGAAGC
CCCTACCCCACCCCTCCACTGCCTCCCAGATACCAGCTGCAGA
ACATGGATGTGGAAGCCGGCTTTCGCGAGGCCGTGTACGCCTC
TTTTGTGGCCGGCATGTACAACTACGTCGTGACCCAGCCCCAG
GAACGGATCCCCAATAGCCAGCAGGTGGAAGGCATCCTGCGG
GACATGCTGACCAACGGCGACCAGACCTTCCGGGACCTGATG
AAGCGGTGGAACAGAGAGGTGGACCGCGAG Ct875_E_nFC
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 189
TGCCTGATACAACCGGCGAGCCTAAGAGCTGCGACAAGACCC
ACACCTGTCCTCCATGTCCTGCTCCAGAACTGCTCGGCGGACC
TTCCGTGTTCCTGTTTCCTCCAAAGCCTAAGGACACCCTGATG
ATCAGCAGAACCCCTGAAGTGACCTGCGTGGTGGTGGATGTGT
CCCACGAGGATCCCGAAGTGAAGTTCAATTGGTACGTGGACG
GCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGAGAGGAAC
AGTACAACAGCACCTACAGAGTGGTGTCCGTGCTGACCGTGCT
GCACCAGGATTGGCTGAACGGCAAAGAGTACAAGTGCAAGGT
GTCCAACAAGGCCCTGCCTGCTCCTATCGAGAAGACCATCAGC
AAGGCCAAGGGCCAGCCAAGAGAACCCCAGGTGTACACACTG
CCTCCAAGCAGAGATGAGCTGACCAAGAACCAGGTGTCCCTG
ACCTGTCTGGTCAAGGGCTTCTACCCCTCCGATATCGCCGTGG
AATGGGAGAGCAATGGCCAGCCTGAGAACAACTACAAGACAA
CCCCTCCTGTGCTGGACAGCGACGGCTCATTCTTCCTGTACAG
CAAGCTGACAGTGGACAAGAGCAGATGGCAGCAGGGCAACGT
GTTCAGCTGCAGCGTGATGCACGAGGCCCTGCACAATCACTAC
ACCCAGAAGTCCCTGTCTCTGAGCCCCGGCAAGATGAGCATCA
GAGGCGTGGGCGGCAACGGCAACAGCAGAATCCCTAGCCACA
ACGGCGACGGCAGCAACAGGCGGAGCCAGAACACCAAGGGC
AACAACAAGGTGGAAGATAGAGTGTGCAGCCTGTACAGCAGC
CGGTCCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTGGAC
GTGTCCAGCATGATCGAGAGCACCCCCACCAGCGGCGAGACA
ACCAGAGCTAGTAGAGGCGTGCTGAGCCGGTTCCAGAGGGGC
CTCGTGCGGATTGCTGACAAAGTGCGGAGAGCCGTGCAGTGC
GCTTGGAGCAGCGTGTCCACAAGCAGAAGCAGCGCCACAAGA
GCCGCCGAGAGCGGCAGCTCTAGCAGAACAGCTAGAGGCGCC
AGCAGCGGCTACAGAGAGTACAGCCCTTCTGCCGCTCGGGGC
CTGCGGCTGATGTTCACCGACTTTTGGCGGACCCGGGTGCTGA
GACAGACCTCTCCTATGGCCGGCGTGTTCGGCAACCTGGACGT
GAACGAGGCCAGACTGATGGCCGCCTACACCAGCGAGTGTGC
CGATCACCTGGAAGCCAAAGAGCTGGCCGGACCTGACGGCGT
GGCAGCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAGT
GCGGGACCTGCAGGACAAGGGCGCTGCCAGAAAGCTGCTGAA
CGACCCCCTGGGCAGACGGACCCCCAACTACCAGAGCAAGAA
CCCCGGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGGC
CCCCAGGTGGCCAACCTGCAGAATGTGGATACCGGCTTCTGGC
TGGACATGAGCAACCTGAGCGACGTGGTGCTGTCCAGAGAGA
TCCAGACCGGCCTGAGAGCCAGAGCCACCCTGGAAGAGTCCA
TGCCCATGCTGGAAAATCTGGAAGAGAGATTCCGGCGGCTGC
AGGAAACCTGCGACGCCGCCAGAACCGAGATCGAGGAAAGCG
GCTGGACCCGGGAAAGCGCCTCCAGAATGGAAGGCGACGAAG
CCCAGGGCCCCAGCAGAGTGCAGCAGGCCTTTCAGAGCTTCGT
GAATGAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCGGC
GAGCACGTGCGGGTGCTGTGTGCCAGAGTGTCAAGAGGACTG
GCCGCTGCCGGCGAGGCCATCAGAAGATGCTTCAGCTGCTGCA
AGGGCAGCACCCACAGATACGCCCCCAGAGATGACCTGTCTC
CTGAGGGCGCCTCTCTGGCCGAAACCCTGGCCAGATTCGCCGA
CGACATGGGCATCGAAAGAGGCGCCGACGGCACCTACGACAT
CCCCCTGGTGGACGATTGGAGAAGGGGCGTGCCATCCATCGA
GGGCGAGGGCAGCGATAGCATCTACGAGATCATGATGCCCAT
CTACGAAGTGATGAACATGGACCTGGAAACCCGGCGGAGCTT
CGCCGTGCAGCAGGGCCATTACCAGGACCCCAGAGCCAGCGA
CTACGACCTGCCTAGAGCCTCCGATTACGATCTGCCCAGAAGC
CCCTACCCCACCCCTCCACTGCCTCCCAGATACCAGCTGCAGA
ACATGGATGTGGAAGCCGGCTTTCGCGAGGCCGTGTACGCCTC
TTTTGTGGCCGGCATGTACAACTACGTCGTGACCCAGCCCCAG
GAACGGATCCCCAATAGCCAGCAGGTGGAAGGCATCCTGCGG
GACATGCTGACCAACGGCAGCCAGACCTTCCGGGACCTGATG
AAGCGGTGGAACAGAGAGGTGGACCGCGAG Ct875_E_NGM_nIgK_nGst_cHis
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 190
TGCCTGACACCACCGGCATGAGCCCTATCCTCGGCTACTGGAA
GATCAAAGGCCTGGTGCAGCCCACCAGACTGCTGCTGGAATA
CCTGGAAGAGAAGTACGAGGAACACCTGTACGAGCGCGACGA
GGGCGATAAGTGGCGGAACAAGAAGTTCGAGCTGGGCCTCGA
GTTCCCCAACCTGCCTTACTACATCGACGGCGACGTGAAGCTG
ACCCAGAGCATGGCCATCATCCGGTATATCGCCGACAAGCAC
AACATGCTCGGCGGCTGCCCTAAAGAGCGGGCCGAGATTTCTA
TGCTGGAAGGCGCCGTGCTGGACATCAGATACGGCGTGTCCA
GAATCGCCTACAGCAAGGACTTCGAAACCCTGAAGGTGGACT
TCCTGAGCAAGCTGCCCGAGATGCTGAAGATGTTCGAGGACC
GGCTGTGCCACAAGACCTACCTGAATGGCGACCACGTGACAC
ACCCCGACTTCATGCTGTACGACGCCCTGGATGTGGTGCTGTA
CATGGACCCCATGTGCCTGGACGCCTTTCCAAAGCTCGTGTGC
TTCAAGAAGCGGATCGAGGCCATTCCTCAGATCGACAAGTACC
TGAAGTCCAGCAAGTATATCGCTTGGCCCCTGCAAGGCTGGCA
GGCCACATTTGGAGGCGGAGATCACCCTCCTAAGATGAGCATC
AGAGGCGTGGGCGGCAACGGCAACAGCAGAATCCCTAGCCAC
AACGGCGACGGCAGCAACAGGCGGAGCCAGAACACCAAGGG
CAACAACAAGGTGGAAGATAGAGTGTGCAGCCTGTACAGCAG
CCGGTCCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTGGA
CGTGTCCAGCATGATCGAGAGCACCCCCACCAGCGGCGAGAC
AACCAGAGCTAGTAGAGGCGTGCTGAGCCGGTTCCAGAGGGG
CCTCGTGCGGATTGCTGACAAAGTGCGGAGAGCCGTGCAGTG
CGCTTGGAGCAGCGTGTCCACAAGCAGAAGCAGCGCCACAAG
AGCCGCCGAGAGCGGCAGCTCTAGCAGAACAGCTAGAGGCGC
CAGCAGCGGCTACAGAGAGTACAGCCCTTCTGCCGCTCGGGG
CCTGCGGCTGATGTTCACCGACTTTTGGCGGACCCGGGTGCTG
AGACAGACCTCTCCTATGGCCGGCGTGTTCGGCAACCTGGACG
TGAACGAGGCCAGACTGATGGCCGCCTACACCAGCGAGTGTG
CCGATCACCTGGAAGCCAAAGAGCTGGCCGGACCTGACGGCG
TGGCAGCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAG
TGCGGGACCTGCAGGACAAGGGCGCTGCCAGAAAGCTGCTGA
ACGACCCCCTGGGCAGACGGACCCCCAACTACCAGAGCAAGA
ACCCCGGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGG
CCCCCAGGTGGCCAACCTGCAGAATGTGGATACCGGCTTCTGG
CTGGACATGCAGCACCTGAGCGACGTGGTGCTGTCCAGAGAG
ATCCAGACCGGCCTGAGAGCCAGAGCCACCCTGGAAGAGTCC
ATGCCCATGCTGGAAAATCTGGAAGAGAGATTCCGGCGGCTG
CAGGAAACCTGCGACGCCGCCAGAACCGAGATCGAGGAAAGC
GGCTGGACCCGGGAAAGCGCCTCCAGAATGGAAGGCGACGAA
GCCCAGGGCCCCAGCAGAGTGCAGCAGGCCTTTCAGAGCTTC
GTGAATGAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCG
GCGAGCACGTGCGGGTGCTGTGTGCCAGAGTGTCAAGAGGAC
TGGCCGCTGCCGGCGAGGCCATCAGAAGATGCTTCAGCTGCTG
CAAGGGCAGCACCCACAGATACGCCCCCAGAGATGACCTGTC
TCCTGAGGGCGCCTCTCTGGCCGAAACCCTGGCCAGATTCGCC
GACGACATGGGCATCGAAAGAGGCGCCGACGGCACCTACGAC
ATCCCCCTGGTGGACGATTGGAGAAGGGGCGTGCCATCCATCG
AGGGCGAGGGCAGCGATAGCATCTACGAGATCATGATGCCCA
TCTACGAAGTGATGAACATGGACCTGGAAACCCGGCGGAGCT
TCGCCGTGCAGCAGGGCCATTACCAGGACCCCAGAGCCAGCG
ACTACGACCTGCCTAGAGCCTCCGATTACGATCTGCCCAGAAG
CCCCTACCCCACCCCTCCACTGCCTCCCAGATACCAGCTGCAG
AACATGGATGTGGAAGCCGGCTTTCGCGAGGCCGTGTACGCCT
CTTTTGTGGCCGGCATGTACAACTACGTCGTGACCCAGCCCCA
GGAACGGATCCCCAATAGCCAGCAGGTGGAAGGCATCCTGCG
GGACATGCTGACCAACGGCGACCAGACCTTCCGGGACCTGAT
GAAGCGGTGGAACAGAGAGGTGGACCGCGAGCACCACCATCA CCACCAC
Ct875_E_nIgK_nGst_cHis ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC
191 TGCCTGACACCACCGGCATGAGCCCTATCCTCGGCTACTGGAA
GATCAAAGGCCTGGTGCAGCCCACCAGACTGCTGCTGGAATA
CCTGGAAGAGAAGTACGAGGAACACCTGTACGAGCGCGACGA
GGGCGATAAGTGGCGGAACAAGAAGTTCGAGCTGGGCCTCGA
GTTCCCCAACCTGCCTTACTACATCGACGGCGACGTGAAGCTG
ACCCAGAGCATGGCCATCATCCGGTATATCGCCGACAAGCAC
AACATGCTCGGCGGCTGCCCTAAAGAGCGGGCCGAGATTTCTA
TGCTGGAAGGCGCCGTGCTGGACATCAGATACGGCGTGTCCA
GAATCGCCTACAGCAAGGACTTCGAAACCCTGAAGGTGGACT
TCCTGAGCAAGCTGCCCGAGATGCTGAAGATGTTCGAGGACC
GGCTGTGCCACAAGACCTACCTGAATGGCGACCACGTGACAC
ACCCCGACTTCATGCTGTACGACGCCCTGGATGTGGTGCTGTA
CATGGACCCCATGTGCCTGGACGCCTTTCCAAAGCTCGTGTGC
TTCAAGAAGCGGATCGAGGCCATTCCTCAGATCGACAAGTACC
TGAAGTCCAGCAAGTATATCGCTTGGCCCCTGCAAGGCTGGCA
GGCCACATTTGGAGGCGGAGATCACCCTCCTAAGATGAGCATC
AGAGGCGTGGGCGGCAACGGCAACAGCAGAATCCCTAGCCAC
AACGGCGACGGCAGCAACAGGCGGAGCCAGAACACCAAGGG
CAACAACAAGGTGGAAGATAGAGTGTGCAGCCTGTACAGCAG
CCGGTCCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTGGA
CGTGTCCAGCATGATCGAGAGCACCCCCACCAGCGGCGAGAC
AACCAGAGCTAGTAGAGGCGTGCTGAGCCGGTTCCAGAGGGG
CCTCGTGCGGATTGCTGACAAAGTGCGGAGAGCCGTGCAGTG
CGCTTGGAGCAGCGTGTCCACAAGCAGAAGCAGCGCCACAAG
AGCCGCCGAGAGCGGCAGCTCTAGCAGAACAGCTAGAGGCGC
CAGCAGCGGCTACAGAGAGTACAGCCCTTCTGCCGCTCGGGG
CCTGCGGCTGATGTTCACCGACTTTTGGCGGACCCGGGTGCTG
AGACAGACCTCTCCTATGGCCGGCGTGTTCGGCAACCTGGACG
TGAACGAGGCCAGACTGATGGCCGCCTACACCAGCGAGTGTG
CCGATCACCTGGAAGCCAAAGAGCTGGCCGGACCTGACGGCG
TGGCAGCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAG
TGCGGGACCTGCAGGACAAGGGCGCTGCCAGAAAGCTGCTGA
ACGACCCCCTGGGCAGACGGACCCCCAACTACCAGAGCAAGA
ACCCCGGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGG
CCCCCAGGTGGCCAACCTGCAGAATGTGGATACCGGCTTCTGG
CTGGACATGAGCAACCTGAGCGACGTGGTGCTGTCCAGAGAG
ATCCAGACCGGCCTGAGAGCCAGAGCCACCCTGGAAGAGTCC
ATGCCCATGCTGGAAAATCTGGAAGAGAGATTCCGGCGGCTG
CAGGAAACCTGCGACGCCGCCAGAACCGAGATCGAGGAAAGC
GGCTGGACCCGGGAAAGCGCCTCCAGAATGGAAGGCGACGAA
GCCCAGGGCCCCAGCAGAGTGCAGCAGGCCTTTCAGAGCTTC
GTGAATGAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCG
GCGAGCACGTGCGGGTGCTGTGTGCCAGAGTGTCAAGAGGAC
TGGCCGCTGCCGGCGAGGCCATCAGAAGATGCTTCAGCTGCTG
CAAGGGCAGCACCCACAGATACGCCCCCAGAGATGACCTGTC
TCCTGAGGGCGCCTCTCTGGCCGAAACCCTGGCCAGATTCGCC
GACGACATGGGCATCGAAAGAGGCGCCGACGGCACCTACGAC
ATCCCCCTGGTGGACGATTGGAGAAGGGGCGTGCCATCCATCG
AGGGCGAGGGCAGCGATAGCATCTACGAGATCATGATGCCCA
TCTACGAAGTGATGAACATGGACCTGGAAACCCGGCGGAGCT
TCGCCGTGCAGCAGGGCCATTACCAGGACCCCAGAGCCAGCG
ACTACGACCTGCCTAGAGCCTCCGATTACGATCTGCCCAGAAG
CCCCTACCCCACCCCTCCACTGCCTCCCAGATACCAGCTGCAG
AACATGGATGTGGAAGCCGGCTTTCGCGAGGCCGTGTACGCCT
CTTTTGTGGCCGGCATGTACAACTACGTCGTGACCCAGCCCCA
GGAACGGATCCCCAATAGCCAGCAGGTGGAAGGCATCCTGCG
GGACATGCTGACCAACGGCAGCCAGACCTTCCGGGACCTGAT
GAAGCGGTGGAACAGAGAGGTGGACCGCGAGCACCACCATCA CCACCAC
Ct875_E_NGM_nIgK_nGst ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC
192 TGCCTGACACCACCGGCATGAGCCCTATCCTCGGCTACTGGAA
GATCAAAGGCCTGGTGCAGCCCACCAGACTGCTGCTGGAATA
CCTGGAAGAGAAGTACGAGGAACACCTGTACGAGCGCGACGA
GGGCGATAAGTGGCGGAACAAGAAGTTCGAGCTGGGCCTCGA
GTTCCCCAACCTGCCTTACTACATCGACGGCGACGTGAAGCTG
ACCCAGAGCATGGCCATCATCCGGTATATCGCCGACAAGCAC
AACATGCTCGGCGGCTGCCCTAAAGAGCGGGCCGAGATTTCTA
TGCTGGAAGGCGCCGTGCTGGACATCAGATACGGCGTGTCCA
GAATCGCCTACAGCAAGGACTTCGAAACCCTGAAGGTGGACT
TCCTGAGCAAGCTGCCCGAGATGCTGAAGATGTTCGAGGACC
GGCTGTGCCACAAGACCTACCTGAATGGCGACCACGTGACAC
ACCCCGACTTCATGCTGTACGACGCCCTGGATGTGGTGCTGTA
CATGGACCCCATGTGCCTGGACGCCTTTCCAAAGCTCGTGTGC
TTCAAGAAGCGGATCGAGGCCATTCCTCAGATCGACAAGTACC
TGAAGTCCAGCAAGTATATCGCTTGGCCCCTGCAAGGCTGGCA
GGCCACATTTGGAGGCGGAGATCACCCTCCTAAGATGAGCATC
AGAGGCGTGGGCGGCAACGGCAACAGCAGAATCCCTAGCCAC
AACGGCGACGGCAGCAACAGGCGGAGCCAGAACACCAAGGG
CAACAACAAGGTGGAAGATAGAGTGTGCAGCCTGTACAGCAG
CCGGTCCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTGGA
CGTGTCCAGCATGATCGAGAGCACCCCCACCAGCGGCGAGAC
AACCAGAGCTAGTAGAGGCGTGCTGAGCCGGTTCCAGAGGGG
CCTCGTGCGGATTGCTGACAAAGTGCGGAGAGCCGTGCAGTG
CGCTTGGAGCAGCGTGTCCACAAGCAGAAGCAGCGCCACAAG
AGCCGCCGAGAGCGGCAGCTCTAGCAGAACAGCTAGAGGCGC
CAGCAGCGGCTACAGAGAGTACAGCCCTTCTGCCGCTCGGGG
CCTGCGGCTGATGTTCACCGACTTTTGGCGGACCCGGGTGCTG
AGACAGACCTCTCCTATGGCCGGCGTGTTCGGCAACCTGGACG
TGAACGAGGCCAGACTGATGGCCGCCTACACCAGCGAGTGTG
CCGATCACCTGGAAGCCAAAGAGCTGGCCGGACCTGACGGCG
TGGCAGCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAG
TGCGGGACCTGCAGGACAAGGGCGCTGCCAGAAAGCTGCTGA
ACGACCCCCTGGGCAGACGGACCCCCAACTACCAGAGCAAGA
ACCCCGGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGG
CCCCCAGGTGGCCAACCTGCAGAATGTGGATACCGGCTTCTGG
CTGGACATGCAGCACCTGAGCGACGTGGTGCTGTCCAGAGAG
ATCCAGACCGGCCTGAGAGCCAGAGCCACCCTGGAAGAGTCC
ATGCCCATGCTGGAAAATCTGGAAGAGAGATTCCGGCGGCTG
CAGGAAACCTGCGACGCCGCCAGAACCGAGATCGAGGAAAGC
GGCTGGACCCGGGAAAGCGCCTCCAGAATGGAAGGCGACGAA
GCCCAGGGCCCCAGCAGAGTGCAGCAGGCCTTTCAGAGCTTC
GTGAATGAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCG
GCGAGCACGTGCGGGTGCTGTGTGCCAGAGTGTCAAGAGGAC
TGGCCGCTGCCGGCGAGGCCATCAGAAGATGCTTCAGCTGCTG
CAAGGGCAGCACCCACAGATACGCCCCCAGAGATGACCTGTC
TCCTGAGGGCGCCTCTCTGGCCGAAACCCTGGCCAGATTCGCC
GACGACATGGGCATCGAAAGAGGCGCCGACGGCACCTACGAC
ATCCCCCTGGTGGACGATTGGAGAAGGGGCGTGCCATCCATCG
AGGGCGAGGGCAGCGATAGCATCTACGAGATCATGATGCCCA
TCTACGAAGTGATGAACATGGACCTGGAAACCCGGCGGAGCT
TCGCCGTGCAGCAGGGCCATTACCAGGACCCCAGAGCCAGCG
ACTACGACCTGCCTAGAGCCTCCGATTACGATCTGCCCAGAAG
CCCCTACCCCACCCCTCCACTGCCTCCCAGATACCAGCTGCAG
AACATGGATGTGGAAGCCGGCTTTCGCGAGGCCGTGTACGCCT
CTTTTGTGGCCGGCATGTACAACTACGTCGTGACCCAGCCCCA
GGAACGGATCCCCAATAGCCAGCAGGTGGAAGGCATCCTGCG
GGACATGCTGACCAACGGCGACCAGACCTTCCGGGACCTGAT
GAAGCGGTGGAACAGAGAGGTGGACCGCGAG Ct875_E_nIgK_nGst
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 193
TGCCTGACACCACCGGCATGAGCCCTATCCTCGGCTACTGGAA
GATCAAAGGCCTGGTGCAGCCCACCAGACTGCTGCTGGAATA
CCTGGAAGAGAAGTACGAGGAACACCTGTACGAGCGCGACGA
GGGCGATAAGTGGCGGAACAAGAAGTTCGAGCTGGGCCTCGA
GTTCCCCAACCTGCCTTACTACATCGACGGCGACGTGAAGCTG
ACCCAGAGCATGGCCATCATCCGGTATATCGCCGACAAGCAC
AACATGCTCGGCGGCTGCCCTAAAGAGCGGGCCGAGATTTCTA
TGCTGGAAGGCGCCGTGCTGGACATCAGATACGGCGTGTCCA
GAATCGCCTACAGCAAGGACTTCGAAACCCTGAAGGTGGACT
TCCTGAGCAAGCTGCCCGAGATGCTGAAGATGTTCGAGGACC
GGCTGTGCCACAAGACCTACCTGAATGGCGACCACGTGACAC
ACCCCGACTTCATGCTGTACGACGCCCTGGATGTGGTGCTGTA
CATGGACCCCATGTGCCTGGACGCCTTTCCAAAGCTCGTGTGC
TTCAAGAAGCGGATCGAGGCCATTCCTCAGATCGACAAGTACC
TGAAGTCCAGCAAGTATATCGCTTGGCCCCTGCAAGGCTGGCA
GGCCACATTTGGAGGCGGAGATCACCCTCCTAAGATGAGCATC
AGAGGCGTGGGCGGCAACGGCAACAGCAGAATCCCTAGCCAC
AACGGCGACGGCAGCAACAGGCGGAGCCAGAACACCAAGGG
CAACAACAAGGTGGAAGATAGAGTGTGCAGCCTGTACAGCAG
CCGGTCCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTGGA
CGTGTCCAGCATGATCGAGAGCACCCCCACCAGCGGCGAGAC
AACCAGAGCTAGTAGAGGCGTGCTGAGCCGGTTCCAGAGGGG
CCTCGTGCGGATTGCTGACAAAGTGCGGAGAGCCGTGCAGTG
CGCTTGGAGCAGCGTGTCCACAAGCAGAAGCAGCGCCACAAG
AGCCGCCGAGAGCGGCAGCTCTAGCAGAACAGCTAGAGGCGC
CAGCAGCGGCTACAGAGAGTACAGCCCTTCTGCCGCTCGGGG
CCTGCGGCTGATGTTCACCGACTTTTGGCGGACCCGGGTGCTG
AGACAGACCTCTCCTATGGCCGGCGTGTTCGGCAACCTGGACG
TGAACGAGGCCAGACTGATGGCCGCCTACACCAGCGAGTGTG
CCGATCACCTGGAAGCCAAAGAGCTGGCCGGACCTGACGGCG
TGGCAGCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAG
TGCGGGACCTGCAGGACAAGGGCGCTGCCAGAAAGCTGCTGA
ACGACCCCCTGGGCAGACGGACCCCCAACTACCAGAGCAAGA
ACCCCGGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGG
CCCCCAGGTGGCCAACCTGCAGAATGTGGATACCGGCTTCTGG
CTGGACATGAGCAACCTGAGCGACGTGGTGCTGTCCAGAGAG
ATCCAGACCGGCCTGAGAGCCAGAGCCACCCTGGAAGAGTCC
ATGCCCATGCTGGAAAATCTGGAAGAGAGATTCCGGCGGCTG
CAGGAAACCTGCGACGCCGCCAGAACCGAGATCGAGGAAAGC
GGCTGGACCCGGGAAAGCGCCTCCAGAATGGAAGGCGACGAA
GCCCAGGGCCCCAGCAGAGTGCAGCAGGCCTTTCAGAGCTTC
GTGAATGAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCG
GCGAGCACGTGCGGGTGCTGTGTGCCAGAGTGTCAAGAGGAC
TGGCCGCTGCCGGCGAGGCCATCAGAAGATGCTTCAGCTGCTG
CAAGGGCAGCACCCACAGATACGCCCCCAGAGATGACCTGTC
TCCTGAGGGCGCCTCTCTGGCCGAAACCCTGGCCAGATTCGCC
GACGACATGGGCATCGAAAGAGGCGCCGACGGCACCTACGAC
ATCCCCCTGGTGGACGATTGGAGAAGGGGCGTGCCATCCATCG
AGGGCGAGGGCAGCGATAGCATCTACGAGATCATGATGCCCA
TCTACGAAGTGATGAACATGGACCTGGAAACCCGGCGGAGCT
TCGCCGTGCAGCAGGGCCATTACCAGGACCCCAGAGCCAGCG
ACTACGACCTGCCTAGAGCCTCCGATTACGATCTGCCCAGAAG
CCCCTACCCCACCCCTCCACTGCCTCCCAGATACCAGCTGCAG
AACATGGATGTGGAAGCCGGCTTTCGCGAGGCCGTGTACGCCT
CTTTTGTGGCCGGCATGTACAACTACGTCGTGACCCAGCCCCA
GGAACGGATCCCCAATAGCCAGCAGGTGGAAGGCATCCTGCG
GGACATGCTGACCAACGGCAGCCAGACCTTCCGGGACCTGAT
GAAGCGGTGGAACAGAGAGGTGGACCGCGAG Ct875_E_574_NGM_nIgK_cHis
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 194
TGCCTGACACCACCGGCATGAGCATCAGAGGCGTGGGCGGCA
ACGGCAACAGCAGAATCCCTAGCCACAACGGCGACGGCAGCA
ACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGTGGAA
GATAGAGTGTGCAGCCTGTACAGCAGCCGGTCCAACGAGAAC
CGCGAGAGCCCTTATGCCGTGGTGGACGTGTCCAGCATGATCG
AGAGCACCCCCACCAGCGGCGAGACAACCAGAGCTAGTAGAG
GCGTGCTGAGCCGGTTCCAGAGGGGCCTCGTGCGGATTGCTGA
CAAAGTGCGGAGAGCCGTGCAGTGCGCTTGGAGCAGCGTGTC
CACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAGCGGCA
GCTCTAGCAGAACAGCTAGAGGCGCCAGCAGCGGCTACAGAG
AGTACAGCCCTTCTGCCGCTCGGGGCCTGCGGCTGATGTTCAC
CGACTTTTGGCGGACCCGGGTGCTGAGACAGACCTCTCCTATG
GCCGGCGTGTTCGGCAACCTGGACGTGAACGAGGCCAGACTG
ATGGCCGCCTACACCAGCGAGTGTGCCGATCACCTGGAAGCC
AAAGAGCTGGCCGGACCTGACGGCGTGGCAGCCGCTAGAGAA
ATCGCCAAGAGATGGGAGAAGAGAGTGCGGGACCTGCAGGAC
AAGGGCGCTGCCAGAAAGCTGCTGAACGACCCCCTGGGCAGA
CGGACCCCCAACTACCAGAGCAAGAACCCCGGCGAGTACACC
GTGGGCAACTCCATGTTCTACGACGGCCCCCAGGTGGCCAACC
TGCAGAATGTGGATACCGGCTTCTGGCTGGACATGCAGCACCT
GAGCGACGTGGTGCTGTCCAGAGAGATCCAGACCGGCCTGAG
AGCCAGAGCCACCCTGGAAGAGTCCATGCCCATGCTGGAAAA
TCTGGAAGAGAGATTCCGGCGGCTGCAGGAAACCTGCGACGC
CGCCAGAACCGAGATCGAGGAAAGCGGCTGGACCCGGGAAAG
CGCCTCCAGAATGGAAGGCGACGAAGCCCAGGGCCCCAGCAG
AGTGCAGCAGGCCTTTCAGAGCTTCGTGAATGAGTGCAACAGC
ATCGAGTTCAGCTTCGGCTCCTTCGGCGAGCACGTGCGGGTGC
TGTGTGCCAGAGTGTCAAGAGGACTGGCCGCTGCCGGCGAGG
CCATCAGAAGATGCTTCAGCTGCTGCAAGGGCAGCACCCACA
GATACGCCCCCAGAGATGACCTGTCTCCTGAGGGCGCCTCTCT
GGCCGAAACCCTGGCCAGATTCGCCGACGACATGGGCATCGA
AAGAGGCGCCGACGGCACCTACGACATCCCCCTGGTGGACGA
TTGGAGAAGGGGCGTGCCATCCATCGAGGGCGAGGGCAGCGA
TAGCATCTACGAGATCATGATGCCCATCTACGAAGTGATGAAC
ATGGACCTGGAAACCCGGCGGAGCTTCGCCGTGCAGCAGGGC
CATTACCAGGACCCCAGAGCCAGCGACTACGACCTGCCTAGA
GCCTCCGATTACGATCTGCCCAGAAGCCCCTACCCCACCCCTC
CACTGCCTCCCAGATACCAGCTGCAGAACATGGATGTGGAAG
CCGGCTTTCGCGAGGCCGTGTACGCCTCTTTTGTGGCCGGCAT
GTACAACTACGTCGTGACCCAGCCCCAGGAACGGATCCCCAAT
AGCCAGCAGGTGGAAGGCATCCTGCGGGACATGCTGACCAAC GGCGACCACCACCATCACCACCAC
Ct875_E_458_NGM_nIgK_cHis
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 195
TGCCTGACACCACCGGCATGAGCATCAGAGGCGTGGGCGGCA
ACGGCAACAGCAGAATCCCTAGCCACAACGGCGACGGCAGCA
ACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGTGGAA
GATAGAGTGTGCAGCCTGTACAGCAGCCGGTCCAACGAGAAC
CGCGAGAGCCCTTATGCCGTGGTGGACGTGTCCAGCATGATCG
AGAGCACCCCCACCAGCGGCGAGACAACCAGAGCTAGTAGAG
GCGTGCTGAGCCGGTTCCAGAGGGGCCTCGTGCGGATTGCTGA
CAAAGTGCGGAGAGCCGTGCAGTGCGCTTGGAGCAGCGTGTC
CACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAGCGGCA
GCTCTAGCAGAACAGCTAGAGGCGCCAGCAGCGGCTACAGAG
AGTACAGCCCTTCTGCCGCTCGGGGCCTGCGGCTGATGTTCAC
CGACTTTTGGCGGACCCGGGTGCTGAGACAGACCTCTCCTATG
GCCGGCGTGTTCGGCAACCTGGACGTGAACGAGGCCAGACTG
ATGGCCGCCTACACCAGCGAGTGTGCCGATCACCTGGAAGCC
AAAGAGCTGGCCGGACCTGACGGCGTGGCAGCCGCTAGAGAA
ATCGCCAAGAGATGGGAGAAGAGAGTGCGGGACCTGCAGGAC
AAGGGCGCTGCCAGAAAGCTGCTGAACGACCCCCTGGGCAGA
CGGACCCCCAACTACCAGAGCAAGAACCCCGGCGAGTACACC
GTGGGCAACTCCATGTTCTACGACGGCCCCCAGGTGGCCAACC
TGCAGAATGTGGATACCGGCTTCTGGCTGGACATGCAGCACCT
GAGCGACGTGGTGCTGTCCAGAGAGATCCAGACCGGCCTGAG
AGCCAGAGCCACCCTGGAAGAGTCCATGCCCATGCTGGAAAA
TCTGGAAGAGAGATTCCGGCGGCTGCAGGAAACCTGCGACGC
CGCCAGAACCGAGATCGAGGAAAGCGGCTGGACCCGGGAAAG
CGCCTCCAGAATGGAAGGCGACGAAGCCCAGGGCCCCAGCAG
AGTGCAGCAGGCCTTTCAGAGCTTCGTGAATGAGTGCAACAGC
ATCGAGTTCAGCTTCGGCTCCTTCGGCGAGCACGTGCGGGTGC
TGTGTGCCAGAGTGTCAAGAGGACTGGCCGCTGCCGGCGAGG
CCATCAGAAGATGCTTCAGCTGCTGCAAGGGCAGCACCCACA
GATACGCCCCCAGAGATGACCTGTCTCCTGAGGGCGCCTCTCT
GGCCGAAACCCTGGCCAGATTCGCCGACGACATGGGCATCGA
AAGAGGCGCCGACGGCACCTACGACATCCCCCTGGTGGACGA
TTGGAGAAGGGGCGTGCCATCCATCGAGGGCGAGGGCAGCCA CCACCATCACCACCAC
Ct875_E_574_nIgK_cHis ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC
196 TGCCTGACACCACCGGCATGAGCATCAGAGGCGTGGGCGGCA
ACGGCAACAGCAGAATCCCTAGCCACAACGGCGACGGCAGCA
ACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGTGGAA
GATAGAGTGTGCAGCCTGTACAGCAGCCGGTCCAACGAGAAC
CGCGAGAGCCCTTATGCCGTGGTGGACGTGTCCAGCATGATCG
AGAGCACCCCCACCAGCGGCGAGACAACCAGAGCTAGTAGAG
GCGTGCTGAGCCGGTTCCAGAGGGGCCTCGTGCGGATTGCTGA
CAAAGTGCGGAGAGCCGTGCAGTGCGCTTGGAGCAGCGTGTC
CACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAGCGGCA
GCTCTAGCAGAACAGCTAGAGGCGCCAGCAGCGGCTACAGAG
AGTACAGCCCTTCTGCCGCTCGGGGCCTGCGGCTGATGTTCAC
CGACTTTTGGCGGACCCGGGTGCTGAGACAGACCTCTCCTATG
GCCGGCGTGTTCGGCAACCTGGACGTGAACGAGGCCAGACTG
ATGGCCGCCTACACCAGCGAGTGTGCCGATCACCTGGAAGCC
AAAGAGCTGGCCGGACCTGACGGCGTGGCAGCCGCTAGAGAA
ATCGCCAAGAGATGGGAGAAGAGAGTGCGGGACCTGCAGGAC
AAGGGCGCTGCCAGAAAGCTGCTGAACGACCCCCTGGGCAGA
CGGACCCCCAACTACCAGAGCAAGAACCCCGGCGAGTACACC
GTGGGCAACTCCATGTTCTACGACGGCCCCCAGGTGGCCAACC
TGCAGAATGTGGATACCGGCTTCTGGCTGGACATGAGCAACCT
GAGCGACGTGGTGCTGTCCAGAGAGATCCAGACCGGCCTGAG
AGCCAGAGCCACCCTGGAAGAGTCCATGCCCATGCTGGAAAA
TCTGGAAGAGAGATTCCGGCGGCTGCAGGAAACCTGCGACGC
CGCCAGAACCGAGATCGAGGAAAGCGGCTGGACCCGGGAAAG
CGCCTCCAGAATGGAAGGCGACGAAGCCCAGGGCCCCAGCAG
AGTGCAGCAGGCCTTTCAGAGCTTCGTGAATGAGTGCAACAGC
ATCGAGTTCAGCTTCGGCTCCTTCGGCGAGCACGTGCGGGTGC
TGTGTGCCAGAGTGTCAAGAGGACTGGCCGCTGCCGGCGAGG
CCATCAGAAGATGCTTCAGCTGCTGCAAGGGCAGCACCCACA
GATACGCCCCCAGAGATGACCTGTCTCCTGAGGGCGCCTCTCT
GGCCGAAACCCTGGCCAGATTCGCCGACGACATGGGCATCGA
AAGAGGCGCCGACGGCACCTACGACATCCCCCTGGTGGACGA
TTGGAGAAGGGGCGTGCCATCCATCGAGGGCGAGGGCAGCGA
TAGCATCTACGAGATCATGATGCCCATCTACGAAGTGATGAAC
ATGGACCTGGAAACCCGGCGGAGCTTCGCCGTGCAGCAGGGC
CATTACCAGGACCCCAGAGCCAGCGACTACGACCTGCCTAGA
GCCTCCGATTACGATCTGCCCAGAAGCCCCTACCCCACCCCTC
CACTGCCTCCCAGATACCAGCTGCAGAACATGGATGTGGAAG
CCGGCTTTCGCGAGGCCGTGTACGCCTCTTTTGTGGCCGGCAT
GTACAACTACGTCGTGACCCAGCCCCAGGAACGGATCCCCAAT
AGCCAGCAGGTGGAAGGCATCCTGCGGGACATGCTGACCAAC GGCAGCCACCACCATCACCACCAC
Ct875_E_458_nIgK_cHis ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC
197 TGCCTGACACCACCGGCATGAGCATCAGAGGCGTGGGCGGCA
ACGGCAACAGCAGAATCCCTAGCCACAACGGCGACGGCAGCA
ACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGTGGAA
GATAGAGTGTGCAGCCTGTACAGCAGCCGGTCCAACGAGAAC
CGCGAGAGCCCTTATGCCGTGGTGGACGTGTCCAGCATGATCG
AGAGCACCCCCACCAGCGGCGAGACAACCAGAGCTAGTAGAG
GCGTGCTGAGCCGGTTCCAGAGGGGCCTCGTGCGGATTGCTGA
CAAAGTGCGGAGAGCCGTGCAGTGCGCTTGGAGCAGCGTGTC
CACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAGCGGCA
GCTCTAGCAGAACAGCTAGAGGCGCCAGCAGCGGCTACAGAG
AGTACAGCCCTTCTGCCGCTCGGGGCCTGCGGCTGATGTTCAC
CGACTTTTGGCGGACCCGGGTGCTGAGACAGACCTCTCCTATG
GCCGGCGTGTTCGGCAACCTGGACGTGAACGAGGCCAGACTG
ATGGCCGCCTACACCAGCGAGTGTGCCGATCACCTGGAAGCC
AAAGAGCTGGCCGGACCTGACGGCGTGGCAGCCGCTAGAGAA
ATCGCCAAGAGATGGGAGAAGAGAGTGCGGGACCTGCAGGAC
AAGGGCGCTGCCAGAAAGCTGCTGAACGACCCCCTGGGCAGA
CGGACCCCCAACTACCAGAGCAAGAACCCCGGCGAGTACACC
GTGGGCAACTCCATGTTCTACGACGGCCCCCAGGTGGCCAACC
TGCAGAATGTGGATACCGGCTTCTGGCTGGACATGAGCAACCT
GAGCGACGTGGTGCTGTCCAGAGAGATCCAGACCGGCCTGAG
AGCCAGAGCCACCCTGGAAGAGTCCATGCCCATGCTGGAAAA
TCTGGAAGAGAGATTCCGGCGGCTGCAGGAAACCTGCGACGC
CGCCAGAACCGAGATCGAGGAAAGCGGCTGGACCCGGGAAAG
CGCCTCCAGAATGGAAGGCGACGAAGCCCAGGGCCCCAGCAG
AGTGCAGCAGGCCTTTCAGAGCTTCGTGAATGAGTGCAACAGC
ATCGAGTTCAGCTTCGGCTCCTTCGGCGAGCACGTGCGGGTGC
TGTGTGCCAGAGTGTCAAGAGGACTGGCCGCTGCCGGCGAGG
CCATCAGAAGATGCTTCAGCTGCTGCAAGGGCAGCACCCACA
GATACGCCCCCAGAGATGACCTGTCTCCTGAGGGCGCCTCTCT
GGCCGAAACCCTGGCCAGATTCGCCGACGACATGGGCATCGA
AAGAGGCGCCGACGGCACCTACGACATCCCCCTGGTGGACGA
TTGGAGAAGGGGCGTGCCATCCATCGAGGGCGAGGGCAGCCA CCACCATCACCACCAC
Ct875_E_574_NGM_nIgK ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC
198 TGCCTGACACCACCGGCATGAGCATCAGAGGCGTGGGCGGCA
ACGGCAACAGCAGAATCCCTAGCCACAACGGCGACGGCAGCA
ACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGTGGAA
GATAGAGTGTGCAGCCTGTACAGCAGCCGGTCCAACGAGAAC
CGCGAGAGCCCTTATGCCGTGGTGGACGTGTCCAGCATGATCG
AGAGCACCCCCACCAGCGGCGAGACAACCAGAGCTAGTAGAG
GCGTGCTGAGCCGGTTCCAGAGGGGCCTCGTGCGGATTGCTGA
CAAAGTGCGGAGAGCCGTGCAGTGCGCTTGGAGCAGCGTGTC
CACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAGCGGCA
GCTCTAGCAGAACAGCTAGAGGCGCCAGCAGCGGCTACAGAG
AGTACAGCCCTTCTGCCGCTCGGGGCCTGCGGCTGATGTTCAC
CGACTTTTGGCGGACCCGGGTGCTGAGACAGACCTCTCCTATG
GCCGGCGTGTTCGGCAACCTGGACGTGAACGAGGCCAGACTG
ATGGCCGCCTACACCAGCGAGTGTGCCGATCACCTGGAAGCC
AAAGAGCTGGCCGGACCTGACGGCGTGGCAGCCGCTAGAGAA
ATCGCCAAGAGATGGGAGAAGAGAGTGCGGGACCTGCAGGAC
AAGGGCGCTGCCAGAAAGCTGCTGAACGACCCCCTGGGCAGA
CGGACCCCCAACTACCAGAGCAAGAACCCCGGCGAGTACACC
GTGGGCAACTCCATGTTCTACGACGGCCCCCAGGTGGCCAACC
TGCAGAATGTGGATACCGGCTTCTGGCTGGACATGCAGCACCT
GAGCGACGTGGTGCTGTCCAGAGAGATCCAGACCGGCCTGAG
AGCCAGAGCCACCCTGGAAGAGTCCATGCCCATGCTGGAAAA
TCTGGAAGAGAGATTCCGGCGGCTGCAGGAAACCTGCGACGC
CGCCAGAACCGAGATCGAGGAAAGCGGCTGGACCCGGGAAAG
CGCCTCCAGAATGGAAGGCGACGAAGCCCAGGGCCCCAGCAG
AGTGCAGCAGGCCTTTCAGAGCTTCGTGAATGAGTGCAACAGC
ATCGAGTTCAGCTTCGGCTCCTTCGGCGAGCACGTGCGGGTGC
TGTGTGCCAGAGTGTCAAGAGGACTGGCCGCTGCCGGCGAGG
CCATCAGAAGATGCTTCAGCTGCTGCAAGGGCAGCACCCACA
GATACGCCCCCAGAGATGACCTGTCTCCTGAGGGCGCCTCTCT
GGCCGAAACCCTGGCCAGATTCGCCGACGACATGGGCATCGA
AAGAGGCGCCGACGGCACCTACGACATCCCCCTGGTGGACGA
TTGGAGAAGGGGCGTGCCATCCATCGAGGGCGAGGGCAGCGA
TAGCATCTACGAGATCATGATGCCCATCTACGAAGTGATGAAC
ATGGACCTGGAAACCCGGCGGAGCTTCGCCGTGCAGCAGGGC
CATTACCAGGACCCCAGAGCCAGCGACTACGACCTGCCTAGA
GCCTCCGATTACGATCTGCCCAGAAGCCCCTACCCCACCCCTC
CACTGCCTCCCAGATACCAGCTGCAGAACATGGATGTGGAAG
CCGGCTTTCGCGAGGCCGTGTACGCCTCTTTTGTGGCCGGCAT
GTACAACTACGTCGTGACCCAGCCCCAGGAACGGATCCCCAAT
AGCCAGCAGGTGGAAGGCATCCTGCGGGACATGCTGACCAAC GGCGAC
Ct875_E_458_NGM_nIgK ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC
199 TGCCTGACACCACCGGCATGAGCATCAGAGGCGTGGGCGGCA
ACGGCAACAGCAGAATCCCTAGCCACAACGGCGACGGCAGCA
ACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGTGGAA
GATAGAGTGTGCAGCCTGTACAGCAGCCGGTCCAACGAGAAC
CGCGAGAGCCCTTATGCCGTGGTGGACGTGTCCAGCATGATCG
AGAGCACCCCCACCAGCGGCGAGACAACCAGAGCTAGTAGAG
GCGTGCTGAGCCGGTTCCAGAGGGGCCTCGTGCGGATTGCTGA
CAAAGTGCGGAGAGCCGTGCAGTGCGCTTGGAGCAGCGTGTC
CACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAGCGGCA
GCTCTAGCAGAACAGCTAGAGGCGCCAGCAGCGGCTACAGAG
AGTACAGCCCTTCTGCCGCTCGGGGCCTGCGGCTGATGTTCAC
CGACTTTTGGCGGACCCGGGTGCTGAGACAGACCTCTCCTATG
GCCGGCGTGTTCGGCAACCTGGACGTGAACGAGGCCAGACTG
ATGGCCGCCTACACCAGCGAGTGTGCCGATCACCTGGAAGCC
AAAGAGCTGGCCGGACCTGACGGCGTGGCAGCCGCTAGAGAA
ATCGCCAAGAGATGGGAGAAGAGAGTGCGGGACCTGCAGGAC
AAGGGCGCTGCCAGAAAGCTGCTGAACGACCCCCTGGGCAGA
CGGACCCCCAACTACCAGAGCAAGAACCCCGGCGAGTACACC
GTGGGCAACTCCATGTTCTACGACGGCCCCCAGGTGGCCAACC
TGCAGAATGTGGATACCGGCTTCTGGCTGGACATGCAGCACCT
GAGCGACGTGGTGCTGTCCAGAGAGATCCAGACCGGCCTGAG
AGCCAGAGCCACCCTGGAAGAGTCCATGCCCATGCTGGAAAA
TCTGGAAGAGAGATTCCGGCGGCTGCAGGAAACCTGCGACGC
CGCCAGAACCGAGATCGAGGAAAGCGGCTGGACCCGGGAAAG
CGCCTCCAGAATGGAAGGCGACGAAGCCCAGGGCCCCAGCAG
AGTGCAGCAGGCCTTTCAGAGCTTCGTGAATGAGTGCAACAGC
ATCGAGTTCAGCTTCGGCTCCTTCGGCGAGCACGTGCGGGTGC
TGTGTGCCAGAGTGTCAAGAGGACTGGCCGCTGCCGGCGAGG
CCATCAGAAGATGCTTCAGCTGCTGCAAGGGCAGCACCCACA
GATACGCCCCCAGAGATGACCTGTCTCCTGAGGGCGCCTCTCT
GGCCGAAACCCTGGCCAGATTCGCCGACGACATGGGCATCGA
AAGAGGCGCCGACGGCACCTACGACATCCCCCTGGTGGACGA
TTGGAGAAGGGGCGTGCCATCCATCGAGGGCGAGGGCAGC Ct875_E_574_nIgK
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 200
TGCCTGACACCACCGGCATGAGCATCAGAGGCGTGGGCGGCA
ACGGCAACAGCAGAATCCCTAGCCACAACGGCGACGGCAGCA
ACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGTGGAA
GATAGAGTGTGCAGCCTGTACAGCAGCCGGTCCAACGAGAAC
CGCGAGAGCCCTTATGCCGTGGTGGACGTGTCCAGCATGATCG
AGAGCACCCCCACCAGCGGCGAGACAACCAGAGCTAGTAGAG
GCGTGCTGAGCCGGTTCCAGAGGGGCCTCGTGCGGATTGCTGA
CAAAGTGCGGAGAGCCGTGCAGTGCGCTTGGAGCAGCGTGTC
CACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAGCGGCA
GCTCTAGCAGAACAGCTAGAGGCGCCAGCAGCGGCTACAGAG
AGTACAGCCCTTCTGCCGCTCGGGGCCTGCGGCTGATGTTCAC
CGACTTTTGGCGGACCCGGGTGCTGAGACAGACCTCTCCTATG
GCCGGCGTGTTCGGCAACCTGGACGTGAACGAGGCCAGACTG
ATGGCCGCCTACACCAGCGAGTGTGCCGATCACCTGGAAGCC
AAAGAGCTGGCCGGACCTGACGGCGTGGCAGCCGCTAGAGAA
ATCGCCAAGAGATGGGAGAAGAGAGTGCGGGACCTGCAGGAC
AAGGGCGCTGCCAGAAAGCTGCTGAACGACCCCCTGGGCAGA
CGGACCCCCAACTACCAGAGCAAGAACCCCGGCGAGTACACC
GTGGGCAACTCCATGTTCTACGACGGCCCCCAGGTGGCCAACC
TGCAGAATGTGGATACCGGCTTCTGGCTGGACATGAGCAACCT
GAGCGACGTGGTGCTGTCCAGAGAGATCCAGACCGGCCTGAG
AGCCAGAGCCACCCTGGAAGAGTCCATGCCCATGCTGGAAAA
TCTGGAAGAGAGATTCCGGCGGCTGCAGGAAACCTGCGACGC
CGCCAGAACCGAGATCGAGGAAAGCGGCTGGACCCGGGAAAG
CGCCTCCAGAATGGAAGGCGACGAAGCCCAGGGCCCCAGCAG
AGTGCAGCAGGCCTTTCAGAGCTTCGTGAATGAGTGCAACAGC
ATCGAGTTCAGCTTCGGCTCCTTCGGCGAGCACGTGCGGGTGC
TGTGTGCCAGAGTGTCAAGAGGACTGGCCGCTGCCGGCGAGG
CCATCAGAAGATGCTTCAGCTGCTGCAAGGGCAGCACCCACA
GATACGCCCCCAGAGATGACCTGTCTCCTGAGGGCGCCTCTCT
GGCCGAAACCCTGGCCAGATTCGCCGACGACATGGGCATCGA
AAGAGGCGCCGACGGCACCTACGACATCCCCCTGGTGGACGA
TTGGAGAAGGGGCGTGCCATCCATCGAGGGCGAGGGCAGCGA
TAGCATCTACGAGATCATGATGCCCATCTACGAAGTGATGAAC
ATGGACCTGGAAACCCGGCGGAGCTTCGCCGTGCAGCAGGGC
CATTACCAGGACCCCAGAGCCAGCGACTACGACCTGCCTAGA
GCCTCCGATTACGATCTGCCCAGAAGCCCCTACCCCACCCCTC
CACTGCCTCCCAGATACCAGCTGCAGAACATGGATGTGGAAG
CCGGCTTTCGCGAGGCCGTGTACGCCTCTTTTGTGGCCGGCAT
GTACAACTACGTCGTGACCCAGCCCCAGGAACGGATCCCCAAT
AGCCAGCAGGTGGAAGGCATCCTGCGGGACATGCTGACCAAC GGCAGC Ct875_E_458_nIgK
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 201
TGCCTGACACCACCGGCATGAGCATCAGAGGCGTGGGCGGCA
ACGGCAACAGCAGAATCCCTAGCCACAACGGCGACGGCAGCA
ACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGTGGAA
GATAGAGTGTGCAGCCTGTACAGCAGCCGGTCCAACGAGAAC
CGCGAGAGCCCTTATGCCGTGGTGGACGTGTCCAGCATGATCG
AGAGCACCCCCACCAGCGGCGAGACAACCAGAGCTAGTAGAG
GCGTGCTGAGCCGGTTCCAGAGGGGCCTCGTGCGGATTGCTGA
CAAAGTGCGGAGAGCCGTGCAGTGCGCTTGGAGCAGCGTGTC
CACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAGCGGCA
GCTCTAGCAGAACAGCTAGAGGCGCCAGCAGCGGCTACAGAG
AGTACAGCCCTTCTGCCGCTCGGGGCCTGCGGCTGATGTTCAC
CGACTTTTGGCGGACCCGGGTGCTGAGACAGACCTCTCCTATG
GCCGGCGTGTTCGGCAACCTGGACGTGAACGAGGCCAGACTG
ATGGCCGCCTACACCAGCGAGTGTGCCGATCACCTGGAAGCC
AAAGAGCTGGCCGGACCTGACGGCGTGGCAGCCGCTAGAGAA
ATCGCCAAGAGATGGGAGAAGAGAGTGCGGGACCTGCAGGAC
AAGGGCGCTGCCAGAAAGCTGCTGAACGACCCCCTGGGCAGA
CGGACCCCCAACTACCAGAGCAAGAACCCCGGCGAGTACACC
GTGGGCAACTCCATGTTCTACGACGGCCCCCAGGTGGCCAACC
TGCAGAATGTGGATACCGGCTTCTGGCTGGACATGAGCAACCT
GAGCGACGTGGTGCTGTCCAGAGAGATCCAGACCGGCCTGAG
AGCCAGAGCCACCCTGGAAGAGTCCATGCCCATGCTGGAAAA
TCTGGAAGAGAGATTCCGGCGGCTGCAGGAAACCTGCGACGC
CGCCAGAACCGAGATCGAGGAAAGCGGCTGGACCCGGGAAAG
CGCCTCCAGAATGGAAGGCGACGAAGCCCAGGGCCCCAGCAG
AGTGCAGCAGGCCTTTCAGAGCTTCGTGAATGAGTGCAACAGC
ATCGAGTTCAGCTTCGGCTCCTTCGGCGAGCACGTGCGGGTGC
TGTGTGCCAGAGTGTCAAGAGGACTGGCCGCTGCCGGCGAGG
CCATCAGAAGATGCTTCAGCTGCTGCAAGGGCAGCACCCACA
GATACGCCCCCAGAGATGACCTGTCTCCTGAGGGCGCCTCTCT
GGCCGAAACCCTGGCCAGATTCGCCGACGACATGGGCATCGA
AAGAGGCGCCGACGGCACCTACGACATCCCCCTGGTGGACGA
TTGGAGAAGGGGCGTGCCATCCATCGAGGGCGAGGGCAGC
Ct875_E_1_574_NGM_nIgK_cHis
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 202
TGCCTGATACCACCGGCATGTCTATCAGAGGCGTTGGCGGCAA
CGGCAACAGCAGAATCCCTAGCCATAATGGCGACGGCAGCAA
CAGGCGGAGCCAGAATACCAAGGGCAACAACAAGGTGGAAG
ATCGCGTGTGCAGCCTGTACAGCTCCAGAAGCAACGAGAACC
GCGAGAGCCCTTATGCCGTGGTGGATGTGTCCAGCATGATCGA
GAGCACCCCTACCAGCGGCGAGACAACAAGAGCTAGTAGAGG
CGTGCTGAGCCGGTTTCAGAGAGGCCTCGTTCGGATCGCTGAC
AAAGTGCGGAGAGCCGTGCAGTGTGCCTGGTCTAGTGTGTCCA
CAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAGCGGATCTT
CTAGCAGAACAGCTAGAGGCGCCAGCAGCGGCTACAGAGAGT
ATTCTCCATCTGCCGCCAGAGGCCTGCGGCTGATGTTTACAGA
TTTCTGGCGGACCCGGGTGCTGAGACAGACATCTCCTATGGCT
GGCGTGTTCGGCAACCTGGATGTGAATGAGGCCAGACTGATG
GCCGCCTACACAAGCGAATGTGCCGATCACCTGGAAGCCAAA
GAGCTGGCTGGACCTGACGGTGTTGCCGCCGCTAGAGAAATC
GCCAAGAGATGGGAGAAGAGAGTGCGGGACCTGCAGGATAA
GGGCGCTGCTAGAAAGCTGCTGAACGACCCTCTGGGCAGAAG
AACCCCTAACTACCAGAGCAAGAACCCCGGCGAGTACACCGT
GGGCAACTCCATGTTCTACGACGGACCCCAGGTGGCCAACCTG
CAGAATGTGGATACAGGCTTCTGGCTGGATATGCAGCACCTGA
GCGACGTGGTGCTGTCCAGAGAGATCCAGACAGGCCTGAGAG
CCAGAGCCACACTGGAAGAGTCCATGCCTATGCTCGAGAACCT
GGAAGAGAGATTCCGGCGGCTGCAAGAGACATGTGACGCCGC
CAGAACCGAGATCGAGGAAAGCGGCTGGACAAGAGAAAGCG
CCTCCAGAATGGAAGGCGACGAAGCCCAAGGACCTAGCAGAG
TGCAGCAGGCCTTCCAGAGCTTCGTGAACGAGTGCAACAGCAT
CGAGTTCAGCTTCGGCTCCTTCGGCGAACATGTGCGGGTGCTG
TGTGCCAGAGTTAGCAGAGGACTTGCTGCCGCTGGCGAGGCC
ATCAGAAGATGCTTCTCTTGCTGCAAGGGCAGCACCCACAGAT
ACGCCCCTAGAGATGATCTGAGCCCTGAGGGCGCTTCTCTGGC
CGAAACACTGGCCAGATTCGCCGACGATATGGGCATTGAAAG
AGGCGCCGACGGAACCTACGACATCCCTCTGGTGGACGATTG
GAGAAGGGGCGTGCCATCTATCGAAGGCGAGGGCAGCGATAG
CATCTACGAGATCATGATGCCCATCTACGAAGTGATGAACATG
GACCTGGAAACCCGGCGGAGCTTTGCCGTGCAGCAAGGCCAT
TACCAGGATCCTAGAGCCAGCGACTACGACCTGCCTAGAGCCT
CCGATTATGATCTGCCTCGGAGCCCCTATCCTACACCTCCTCTG
CCTCCAAGATACCAGCTTCAGAATATGGACGTGGAAGCCGGA
TTCCGCGAGGCCGTGTATGCTAGCTTTGTGGCCGGCATGTACA
ACTACGTGGTCACCCAGCCTCAAGAGAGAATCCCCAACAGCC
AGCAGGTCGAGGGCATCCTGAGAGATATGCTGACCAACGGCG ACCACCACCATCACCATCAT
Ct875_E_NGM_nFc ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 203
TGCCTGATACAACCGGCGAGCCTAAGAGCTGCGACAAGACCC
ACACCTGTCCTCCATGTCCTGCTCCAGAACTGCTCGGCGGACC
TTCCGTGTTCCTGTTTCCTCCAAAGCCTAAGGACACCCTGATG
ATCAGCAGAACCCCTGAAGTGACCTGCGTGGTGGTGGATGTGT
CCCACGAGGATCCCGAAGTGAAGTTCAATTGGTACGTGGACG
GCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGAGAGGAAC
AGTACAACAGCACCTACAGAGTGGTGTCCGTGCTGACCGTGCT
GCACCAGGATTGGCTGAACGGCAAAGAGTACAAGTGCAAGGT
GTCCAACAAGGCCCTGCCTGCTCCTATCGAGAAGACCATCAGC
AAGGCCAAGGGCCAGCCAAGAGAACCCCAGGTGTACACACTG
CCTCCAAGCAGAGATGAGCTGACCAAGAACCAGGTGTCCCTG
ACCTGTCTGGTCAAGGGCTTCTACCCCTCCGATATCGCCGTGG
AATGGGAGAGCAATGGCCAGCCTGAGAACAACTACAAGACAA
CCCCTCCTGTGCTGGACAGCGACGGCTCATTCTTCCTGTACAG
CAAGCTGACAGTGGACAAGAGCAGATGGCAGCAGGGCAACGT
GTTCAGCTGCAGCGTGATGCACGAGGCCCTGCACAATCACTAC
ACCCAGAAGTCCCTGTCTCTGAGCCCCGGCAAGATGAGCATCA
GAGGCGTTGGCGGCAACGGCAACAGCAGAATCCCTAGCCATA
ATGGCGACGGCAGCAACAGGCGGAGCCAGAATACCAAGGGCA
ACAACAAGGTGGAAGATCGCGTGTGCAGCCTGTACTCCAGCA
GAAGCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTCGACG
TGTCCAGCATGATCGAGAGCACACCTACCAGCGGCGAGACAA
CCAGAGCTAGTAGAGGCGTGCTGAGCCGGTTTCAGAGAGGCC
TCGTTCGGATCGCTGACAAAGTGCGGAGAGCCGTGCAGTGTGC
CTGGTCTAGTGTGTCCACCAGCAGATCCTCTGCCACAAGAGCC
GCCGAGTCTGGCAGCTCTAGCAGAACAGCTAGAGGCGCCAGC
AGCGGCTACAGAGAGTATTCTCCATCTGCCGCCAGAGGCCTGC
GGCTGATGTTTACAGATTTCTGGCGGACCCGGGTGCTGAGACA
GACATCTCCTATGGCTGGCGTGTTCGGCAACCTGGATGTGAAT
GAGGCCAGACTGATGGCCGCCTACACAAGCGAATGTGCCGAT
CACCTGGAAGCCAAAGAGCTGGCTGGACCTGACGGTGTTGCC
GCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAGTGCGG
GACCTGCAGGATAAGGGCGCTGCTAGAAAGCTGCTGAACGAC
CCTCTGGGCAGAAGAACCCCTAACTACCAGAGCAAGAACCCC
GGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGGACCTC
AGGTGGCCAACCTGCAGAATGTGGATACCGGCTTCTGGCTGGA
TATGCAGCACCTGTCCGATGTGGTGCTGTCCAGAGAGATCCAG
ACCGGCCTGAGAGCCAGAGCCACACTGGAAGAGTCCATGCCT
ATGCTCGAGAACCTGGAAGAGAGATTCCGGCGGCTGCAAGAG
ACATGTGACGCCGCCAGAACCGAGATCGAGGAAAGCGGCTGG
ACCAGAGAAAGCGCCTCCAGAATGGAAGGCGACGAAGCCCAA
GGACCTAGCAGAGTGCAGCAGGCCTTCCAGAGCTTCGTGAAC
GAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCGGCGAAC
ATGTGCGGGTGCTGTGTGCCAGAGTTAGCAGAGGACTTGCTGC
CGCTGGCGAGGCCATCAGAAGATGCTTCTCTTGCTGCAAGGGC
AGCACCCACAGATACGCCCCTAGAGATGATCTGAGCCCTGAG
GGCGCATCTCTGGCCGAAACACTGGCCAGATTCGCCGACGATA
TGGGCATTGAAAGAGGCGCCGACGGAACCTACGACATCCCTC
TGGTGGACGATTGGAGAAGGGGCGTGCCATCTATCGAAGGCG
AGGGCAGCGATAGCATCTACGAGATCATGATGCCCATCTACG
AAGTGATGAACATGGACCTGGAAACCCGGCGGAGCTTCGCTG
TTCAGCAGGGCCATTACCAGGATCCTAGAGCCAGCGACTACG
ACCTGCCTAGAGCCTCCGATTATGATCTGCCTCGGAGCCCCTA
TCCTACACCTCCACTGCCACCTAGATACCAGCTCCAGAATATG
GACGTGGAAGCCGGATTCCGCGAGGCCGTGTATGCTAGCTTTG
TGGCCGGCATGTACAACTACGTGGTCACCCAGCCTCAAGAGCG
GATCCCCAATTCTCAGCAGGTCGAGGGCATCCTGAGGGACATG
CTGACCAATGGCGACCAGACCTTCCGGGACCTGATGAAGAGA TGGAACAGAGAGGTGGACAGAGAG
Ct875_E_NGM_nFc_cHis ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC
204 TGCCTGATACAACCGGCGAGCCTAAGAGCTGCGACAAGACCC
ACACCTGTCCTCCATGTCCTGCTCCAGAACTGCTCGGCGGACC
TTCCGTGTTCCTGTTTCCTCCAAAGCCTAAGGACACCCTGATG
ATCAGCAGAACCCCTGAAGTGACCTGCGTGGTGGTGGATGTGT
CCCACGAGGATCCCGAAGTGAAGTTCAATTGGTACGTGGACG
GCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGAGAGGAAC
AGTACAACAGCACCTACAGAGTGGTGTCCGTGCTGACCGTGCT
GCACCAGGATTGGCTGAACGGCAAAGAGTACAAGTGCAAGGT
GTCCAACAAGGCCCTGCCTGCTCCTATCGAGAAGACCATCAGC
AAGGCCAAGGGCCAGCCAAGAGAACCCCAGGTGTACACACTG
CCTCCAAGCAGAGATGAGCTGACCAAGAACCAGGTGTCCCTG
ACCTGTCTGGTCAAGGGCTTCTACCCCTCCGATATCGCCGTGG
AATGGGAGAGCAATGGCCAGCCTGAGAACAACTACAAGACAA
CCCCTCCTGTGCTGGACAGCGACGGCTCATTCTTCCTGTACAG
CAAGCTGACAGTGGACAAGAGCAGATGGCAGCAGGGCAACGT
GTTCAGCTGCAGCGTGATGCACGAGGCCCTGCACAATCACTAC
ACCCAGAAGTCCCTGTCTCTGAGCCCCGGCAAGATGAGCATCA
GAGGCGTTGGCGGCAACGGCAACAGCAGAATCCCTAGCCATA
ATGGCGACGGCAGCAACAGGCGGAGCCAGAATACCAAGGGCA
ACAACAAGGTGGAAGATCGCGTGTGCAGCCTGTACTCCAGCA
GAAGCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTCGACG
TGTCCAGCATGATCGAGAGCACACCTACCAGCGGCGAGACAA
CCAGAGCTAGTAGAGGCGTGCTGAGCCGGTTTCAGAGAGGCC
TCGTTCGGATCGCTGACAAAGTGCGGAGAGCCGTGCAGTGTGC
CTGGTCTAGTGTGTCCACCAGCAGATCCTCTGCCACAAGAGCC
GCCGAGTCTGGCAGCTCTAGCAGAACAGCTAGAGGCGCCAGC
AGCGGCTACAGAGAGTATTCTCCATCTGCCGCCAGAGGCCTGC
GGCTGATGTTTACAGATTTCTGGCGGACCCGGGTGCTGAGACA
GACATCTCCTATGGCTGGCGTGTTCGGCAACCTGGATGTGAAT
GAGGCCAGACTGATGGCCGCCTACACAAGCGAATGTGCCGAT
CACCTGGAAGCCAAAGAGCTGGCTGGACCTGACGGTGTTGCC
GCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAGTGCGG
GACCTGCAGGATAAGGGCGCTGCTAGAAAGCTGCTGAACGAC
CCTCTGGGCAGAAGAACCCCTAACTACCAGAGCAAGAACCCC
GGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGGACCTC
AGGTGGCCAACCTGCAGAATGTGGATACCGGCTTCTGGCTGGA
TATGCAGCACCTGTCCGATGTGGTGCTGTCCAGAGAGATCCAG
ACCGGCCTGAGAGCCAGAGCCACACTGGAAGAGTCCATGCCT
ATGCTCGAGAACCTGGAAGAGAGATTCCGGCGGCTGCAAGAG
ACATGTGACGCCGCCAGAACCGAGATCGAGGAAAGCGGCTGG
ACCAGAGAAAGCGCCTCCAGAATGGAAGGCGACGAAGCCCAA
GGACCTAGCAGAGTGCAGCAGGCCTTCCAGAGCTTCGTGAAC
GAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCGGCGAAC
ATGTGCGGGTGCTGTGTGCCAGAGTTAGCAGAGGACTTGCTGC
CGCTGGCGAGGCCATCAGAAGATGCTTCTCTTGCTGCAAGGGC
AGCACCCACAGATACGCCCCTAGAGATGATCTGAGCCCTGAG
GGCGCATCTCTGGCCGAAACACTGGCCAGATTCGCCGACGATA
TGGGCATTGAAAGAGGCGCCGACGGAACCTACGACATCCCTC
TGGTGGACGATTGGAGAAGGGGCGTGCCATCTATCGAAGGCG
AGGGCAGCGATAGCATCTACGAGATCATGATGCCCATCTACG
AAGTGATGAACATGGACCTGGAAACCCGGCGGAGCTTCGCTG
TTCAGCAGGGCCATTACCAGGATCCTAGAGCCAGCGACTACG
ACCTGCCTAGAGCCTCCGATTATGATCTGCCTCGGAGCCCCTA
TCCTACACCTCCACTGCCACCTAGATACCAGCTCCAGAATATG
GACGTGGAAGCCGGATTCCGCGAGGCCGTGTATGCTAGCTTTG
TGGCCGGCATGTACAACTACGTGGTCACCCAGCCTCAAGAGCG
GATCCCCAATTCTCAGCAGGTCGAGGGCATCCTGAGGGACATG
CTGACCAATGGCGACCAGACCTTCCGGGACCTGATGAAGAGA
TGGAACAGAGAGGTGGACCGCGAGCACCACCACCATCACCAT
Ct875_E_1_574_NGM_nIgK_nGST
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 205
TGCCTGATACCACAGGCATGAGCCCTATCCTCGGCTACTGGAA
GATCAAAGGCCTGGTGCAGCCCACCAGACTGCTGCTGGAATA
CCTGGAAGAGAAGTACGAGGAACACCTGTACGAGCGCGACGA
GGGCGATAAGTGGCGGAACAAGAAGTTCGAGCTGGGCCTCGA
GTTCCCCAACCTGCCTTACTACATCGACGGCGACGTGAAGCTG
ACCCAGAGCATGGCCATCATCCGGTATATCGCCGACAAGCAC
AACATGCTCGGCGGCTGCCCTAAAGAGCGGGCCGAGATTTCTA
TGCTGGAAGGCGCCGTGCTGGACATCAGATACGGCGTGTCCA
GAATCGCCTACAGCAAGGACTTCGAAACCCTGAAGGTGGACT
TCCTGAGCAAGCTGCCCGAGATGCTGAAGATGTTCGAGGACC
GGCTGTGCCACAAGACCTACCTGAATGGCGACCACGTGACAC
ACCCCGACTTCATGCTGTACGACGCCCTGGATGTGGTGCTGTA
CATGGACCCCATGTGCCTGGACGCCTTTCCAAAGCTCGTGTGC
TTCAAGAAGCGGATCGAGGCCATTCCTCAGATCGACAAGTACC
TGAAGTCCAGCAAGTATATCGCTTGGCCCCTGCAAGGCTGGCA
GGCCACATTTGGAGGCGGAGATCACCCTCCTAAGATGAGCATC
AGAGGCGTCGGCGGCAACGGCAACAGCAGAATCCCTTCTCAC
AATGGCGACGGCAGCAACAGGCGGAGCCAGAATACCAAGGGC
AACAACAAGGTGGAAGATCGCGTGTGCAGCCTGTACAGCTCC
AGAAGCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTGGAT
GTGTCCAGCATGATCGAGAGCACCCCTACCAGCGGCGAGACA
ACAAGAGCTAGTAGAGGCGTGCTGAGCCGGTTTCAGAGAGGC
CTCGTTCGGATTGCCGACAAAGTGCGGAGAGCCGTGCAGTGTG
CTTGGAGCAGTGTGTCCACAAGCAGAAGCAGCGCCACAAGAG
CCGCCGAATCTGGCAGCTCTAGCAGAACAGCTAGAGGCGCCA
GCAGCGGCTACAGAGAGTATTCTCCATCTGCCGCCAGAGGCCT
GCGGCTGATGTTTACAGATTTCTGGCGGACCCGGGTGCTGAGA
CAGACATCTCCTATGGCTGGCGTGTTCGGCAACCTGGACGTGA
ACGAAGCCAGACTGATGGCCGCCTACACAAGCGAGTGTGCCG
ATCACCTGGAAGCCAAAGAACTGGCCGGACCTGATGGCGTGG
CAGCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAGTGC
GGGACCTGCAGGATAAGGGCGCTGCTAGAAAGCTGCTGAACG
ACCCTCTGGGCAGAAGAACCCCTAACTACCAGAGCAAGAACC
CCGGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGGACC
CCAGGTGGCCAACCTGCAGAATGTGGATACAGGCTTCTGGCTG
GACATGCAGCACCTGTCTGATGTGGTCCTGAGCAGAGAGATCC
AGACCGGCCTGAGAGCCAGAGCCACACTGGAAGAGTCCATGC
CTATGCTCGAGAATCTGGAAGAACGGTTCAGACGGCTGCAAG
AGACATGCGACGCCGCCAGAACAGAGATCGAGGAAAGCGGCT
GGACCAGAGAAAGCGCCTCCAGAATGGAAGGCGACGAAGCCC
AAGGACCTAGCAGAGTGCAGCAGGCCTTCCAGAGCTTCGTGA
ACGAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCGGCGA
ACATGTGCGGGTGCTGTGTGCCAGAGTTAGCAGAGGACTTGCT
GCCGCTGGCGAGGCCATCAGAAGATGCTTCTCTTGCTGCAAGG
GCAGCACCCACAGATACGCCCCTAGAGATGATCTGAGCCCTG
AGGGCGCATCTCTGGCCGAAACACTGGCCAGATTTGCCGACG
ACATGGGCATTGAAAGAGGCGCCGACGGAACCTACGACATCC
CTCTGGTGGACGATTGGAGAAGGGGCGTGCCATCTATCGAAG
GCGAGGGCAGCGATAGCATCTACGAGATCATGATGCCCATCT
ACGAAGTGATGAACATGGACCTGGAAACCCGGCGGAGCTTTG
CCGTGCAACAGGGCCATTACCAGGATCCTAGAGCCAGCGACT
ACGACCTGCCTAGAGCCTCCGATTATGATCTGCCTCGGAGCCC
CTATCCTACACCTCCTCTGCCTCCAAGATACCAGCTTCAGAAT
ATGGACGTGGAAGCCGGATTCCGCGAGGCCGTGTATGCTAGCT
TTGTGGCCGGCATGTACAACTACGTGGTCACCCAGCCTCAAGA
GAGAATCCCCAACAGCCAGCAGGTCGAGGGCATCCTGAGAGA TATGCTGACCAACGGCGAC
Ct875_E_1_574_NGM_nIgK_nGST_cHis
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 206
TGCCTGATACCACAGGCATGAGCCCTATCCTCGGCTACTGGAA
GATCAAAGGCCTGGTGCAGCCCACCAGACTGCTGCTGGAATA
CCTGGAAGAGAAGTACGAGGAACACCTGTACGAGCGCGACGA
GGGCGATAAGTGGCGGAACAAGAAGTTCGAGCTGGGCCTCGA
GTTCCCCAACCTGCCTTACTACATCGACGGCGACGTGAAGCTG
ACCCAGAGCATGGCCATCATCCGGTATATCGCCGACAAGCAC
AACATGCTCGGCGGCTGCCCTAAAGAGCGGGCCGAGATTTCTA
TGCTGGAAGGCGCCGTGCTGGACATCAGATACGGCGTGTCCA
GAATCGCCTACAGCAAGGACTTCGAAACCCTGAAGGTGGACT
TCCTGAGCAAGCTGCCCGAGATGCTGAAGATGTTCGAGGACC
GGCTGTGCCACAAGACCTACCTGAATGGCGACCACGTGACAC
ACCCCGACTTCATGCTGTACGACGCCCTGGATGTGGTGCTGTA
CATGGACCCCATGTGCCTGGACGCCTTTCCAAAGCTCGTGTGC
TTCAAGAAGCGGATCGAGGCCATTCCTCAGATCGACAAGTACC
TGAAGTCCAGCAAGTATATCGCTTGGCCCCTGCAAGGCTGGCA
GGCCACATTTGGAGGCGGAGATCACCCTCCTAAGATGAGCATC
AGAGGCGTCGGCGGCAACGGCAACAGCAGAATCCCTTCTCAC
AATGGCGACGGCAGCAACAGGCGGAGCCAGAATACCAAGGGC
AACAACAAGGTGGAAGATCGCGTGTGCAGCCTGTACAGCTCC
AGAAGCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTGGAT
GTGTCCAGCATGATCGAGAGCACCCCTACCAGCGGCGAGACA
ACAAGAGCTAGTAGAGGCGTGCTGAGCCGGTTTCAGAGAGGC
CTCGTTCGGATTGCCGACAAAGTGCGGAGAGCCGTGCAGTGTG
CTTGGAGCAGTGTGTCCACAAGCAGAAGCAGCGCCACAAGAG
CCGCCGAATCTGGCAGCTCTAGCAGAACAGCTAGAGGCGCCA
GCAGCGGCTACAGAGAGTATTCTCCATCTGCCGCCAGAGGCCT
GCGGCTGATGTTTACAGATTTCTGGCGGACCCGGGTGCTGAGA
CAGACATCTCCTATGGCTGGCGTGTTCGGCAACCTGGACGTGA
ACGAAGCCAGACTGATGGCCGCCTACACAAGCGAGTGTGCCG
ATCACCTGGAAGCCAAAGAACTGGCCGGACCTGATGGCGTGG
CAGCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAGTGC
GGGACCTGCAGGATAAGGGCGCTGCTAGAAAGCTGCTGAACG
ACCCTCTGGGCAGAAGAACCCCTAACTACCAGAGCAAGAACC
CCGGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGGACC
CCAGGTGGCCAACCTGCAGAATGTGGATACAGGCTTCTGGCTG
GACATGCAGCACCTGTCTGATGTGGTCCTGAGCAGAGAGATCC
AGACCGGCCTGAGAGCCAGAGCCACACTGGAAGAGTCCATGC
CTATGCTCGAGAATCTGGAAGAACGGTTCAGACGGCTGCAAG
AGACATGCGACGCCGCCAGAACAGAGATCGAGGAAAGCGGCT
GGACCAGAGAAAGCGCCTCCAGAATGGAAGGCGACGAAGCCC
AAGGACCTAGCAGAGTGCAGCAGGCCTTCCAGAGCTTCGTGA
ACGAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCGGCGA
ACATGTGCGGGTGCTGTGTGCCAGAGTTAGCAGAGGACTTGCT
GCCGCTGGCGAGGCCATCAGAAGATGCTTCTCTTGCTGCAAGG
GCAGCACCCACAGATACGCCCCTAGAGATGATCTGAGCCCTG
AGGGCGCATCTCTGGCCGAAACACTGGCCAGATTTGCCGACG
ACATGGGCATTGAAAGAGGCGCCGACGGAACCTACGACATCC
CTCTGGTGGACGATTGGAGAAGGGGCGTGCCATCTATCGAAG
GCGAGGGCAGCGATAGCATCTACGAGATCATGATGCCCATCT
ACGAAGTGATGAACATGGACCTGGAAACCCGGCGGAGCTTTG
CCGTGCAACAGGGCCATTACCAGGATCCTAGAGCCAGCGACT
ACGACCTGCCTAGAGCCTCCGATTATGATCTGCCTCGGAGCCC
CTATCCTACACCTCCTCTGCCTCCAAGATACCAGCTTCAGAAT
ATGGACGTGGAAGCCGGATTCCGCGAGGCCGTGTATGCTAGCT
TTGTGGCCGGCATGTACAACTACGTGGTCACCCAGCCTCAAGA
GAGAATCCCCAACAGCCAGCAGGTCGAGGGCATCCTGAGAGA
TATGCTGACCAACGGCGACCACCACCATCACCATCAT Ct875_E_NGM_nIgK_nGST
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 207
TGCCTGATACCACAGGCATGAGCCCTATCCTCGGCTACTGGAA
GATCAAAGGCCTGGTGCAGCCCACCAGACTGCTGCTGGAATA
CCTGGAAGAGAAGTACGAGGAACACCTGTACGAGCGCGACGA
GGGCGATAAGTGGCGGAACAAGAAGTTCGAGCTGGGCCTCGA
GTTCCCCAACCTGCCTTACTACATCGACGGCGACGTGAAGCTG
ACCCAGAGCATGGCCATCATCCGGTATATCGCCGACAAGCAC
AACATGCTCGGCGGCTGCCCTAAAGAGCGGGCCGAGATTTCTA
TGCTGGAAGGCGCCGTGCTGGACATCAGATACGGCGTGTCCA
GAATCGCCTACAGCAAGGACTTCGAAACCCTGAAGGTGGACT
TCCTGAGCAAGCTGCCCGAGATGCTGAAGATGTTCGAGGACC
GGCTGTGCCACAAGACCTACCTGAATGGCGACCACGTGACAC
ACCCCGACTTCATGCTGTACGACGCCCTGGATGTGGTGCTGTA
CATGGACCCCATGTGCCTGGACGCCTTTCCAAAGCTCGTGTGC
TTCAAGAAGCGGATCGAGGCCATTCCTCAGATCGACAAGTACC
TGAAGTCCAGCAAGTATATCGCTTGGCCCCTGCAAGGCTGGCA
GGCCACATTTGGAGGCGGAGATCACCCTCCTAAGATGAGCATC
AGAGGCGTCGGCGGCAACGGCAACAGCAGAATCCCTTCTCAC
AATGGCGACGGCAGCAACAGGCGGAGCCAGAATACCAAGGGC
AACAACAAGGTGGAAGATCGCGTGTGCAGCCTGTACAGCTCC
AGAAGCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTGGAT
GTGTCCAGCATGATCGAGAGCACCCCTACCAGCGGCGAGACA
ACAAGAGCTAGTAGAGGCGTGCTGAGCCGGTTTCAGAGAGGC
CTCGTTCGGATTGCCGACAAAGTGCGGAGAGCCGTGCAGTGTG
CTTGGAGCAGTGTGTCCACAAGCAGAAGCAGCGCCACAAGAG
CCGCCGAATCTGGCAGCTCTAGCAGAACAGCTAGAGGCGCCA
GCAGCGGCTACAGAGAGTATTCTCCATCTGCCGCCAGAGGCCT
GCGGCTGATGTTTACAGATTTCTGGCGGACCCGGGTGCTGAGA
CAGACATCTCCTATGGCTGGCGTGTTCGGCAACCTGGACGTGA
ACGAAGCCAGACTGATGGCCGCCTACACAAGCGAGTGTGCCG
ATCACCTGGAAGCCAAAGAACTGGCCGGACCTGATGGCGTGG
CAGCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAGTGC
GGGACCTGCAGGATAAGGGCGCTGCTAGAAAGCTGCTGAACG
ACCCTCTGGGCAGAAGAACCCCTAACTACCAGAGCAAGAACC
CCGGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGGACC
CCAGGTGGCCAACCTGCAGAATGTGGATACAGGCTTCTGGCTG
GACATGCAGCACCTGTCTGATGTGGTCCTGAGCAGAGAGATCC
AGACCGGCCTGAGAGCCAGAGCCACACTGGAAGAGTCCATGC
CTATGCTCGAGAATCTGGAAGAACGGTTCAGACGGCTGCAAG
AGACATGCGACGCCGCCAGAACAGAGATCGAGGAAAGCGGCT
GGACCAGAGAAAGCGCCTCCAGAATGGAAGGCGACGAAGCCC
AAGGACCTAGCAGAGTGCAGCAGGCCTTCCAGAGCTTCGTGA
ACGAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCGGCGA
ACATGTGCGGGTGCTGTGTGCCAGAGTTAGCAGAGGACTTGCT
GCCGCTGGCGAGGCCATCAGAAGATGCTTCTCTTGCTGCAAGG
GCAGCACCCACAGATACGCCCCTAGAGATGATCTGAGCCCTG
AGGGCGCATCTCTGGCCGAAACACTGGCCAGATTTGCCGACG
ACATGGGCATTGAAAGAGGCGCCGACGGAACCTACGACATCC
CTCTGGTGGACGATTGGAGAAGGGGCGTGCCATCTATCGAAG
GCGAGGGCAGCGATAGCATCTACGAGATCATGATGCCCATCT
ACGAAGTGATGAACATGGACCTGGAAACCCGGCGGAGCTTTG
CCGTGCAACAGGGCCATTACCAGGATCCTAGAGCCAGCGACT
ACGACCTGCCTAGAGCCTCCGATTATGATCTGCCTCGGAGCCC
CTATCCTACACCTCCTCTGCCTCCAAGATACCAGCTTCAGAAT
ATGGACGTGGAAGCCGGATTCCGCGAGGCCGTGTATGCTAGCT
TTGTGGCCGGCATGTACAACTACGTGGTCACCCAGCCTCAAGA
GAGAATCCCCAACAGCCAGCAGGTCGAGGGCATCCTGAGAGA
TATGCTGACCAACGGCGACCAGACCTTCCGCGACCTGATGAAG
AGATGGAACAGAGAGGTGGACAGAGAG Ct875_E_NGM_nIgK_nGST_cHis
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 208
TGCCTGATACCACAGGCATGAGCCCTATCCTCGGCTACTGGAA
GATCAAAGGCCTGGTGCAGCCCACCAGACTGCTGCTGGAATA
CCTGGAAGAGAAGTACGAGGAACACCTGTACGAGCGCGACGA
GGGCGATAAGTGGCGGAACAAGAAGTTCGAGCTGGGCCTCGA
GTTCCCCAACCTGCCTTACTACATCGACGGCGACGTGAAGCTG
ACCCAGAGCATGGCCATCATCCGGTATATCGCCGACAAGCAC
AACATGCTCGGCGGCTGCCCTAAAGAGCGGGCCGAGATTTCTA
TGCTGGAAGGCGCCGTGCTGGACATCAGATACGGCGTGTCCA
GAATCGCCTACAGCAAGGACTTCGAAACCCTGAAGGTGGACT
TCCTGAGCAAGCTGCCCGAGATGCTGAAGATGTTCGAGGACC
GGCTGTGCCACAAGACCTACCTGAATGGCGACCACGTGACAC
ACCCCGACTTCATGCTGTACGACGCCCTGGATGTGGTGCTGTA
CATGGACCCCATGTGCCTGGACGCCTTTCCAAAGCTCGTGTGC
TTCAAGAAGCGGATCGAGGCCATTCCTCAGATCGACAAGTACC
TGAAGTCCAGCAAGTATATCGCTTGGCCCCTGCAAGGCTGGCA
GGCCACATTTGGAGGCGGAGATCACCCTCCTAAGATGAGCATC
AGAGGCGTCGGCGGCAACGGCAACAGCAGAATCCCTTCTCAC
AATGGCGACGGCAGCAACAGGCGGAGCCAGAATACCAAGGGC
AACAACAAGGTGGAAGATCGCGTGTGCAGCCTGTACAGCTCC
AGAAGCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTGGAT
GTGTCCAGCATGATCGAGAGCACCCCTACCAGCGGCGAGACA
ACAAGAGCTAGTAGAGGCGTGCTGAGCCGGTTTCAGAGAGGC
CTCGTTCGGATTGCCGACAAAGTGCGGAGAGCCGTGCAGTGTG
CTTGGAGCAGTGTGTCCACAAGCAGAAGCAGCGCCACAAGAG
CCGCCGAATCTGGCAGCTCTAGCAGAACAGCTAGAGGCGCCA
GCAGCGGCTACAGAGAGTATTCTCCATCTGCCGCCAGAGGCCT
GCGGCTGATGTTTACAGATTTCTGGCGGACCCGGGTGCTGAGA
CAGACATCTCCTATGGCTGGCGTGTTCGGCAACCTGGACGTGA
ACGAAGCCAGACTGATGGCCGCCTACACAAGCGAGTGTGCCG
ATCACCTGGAAGCCAAAGAACTGGCCGGACCTGATGGCGTGG
CAGCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAGTGC
GGGACCTGCAGGATAAGGGCGCTGCTAGAAAGCTGCTGAACG
ACCCTCTGGGCAGAAGAACCCCTAACTACCAGAGCAAGAACC
CCGGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGGACC
CCAGGTGGCCAACCTGCAGAATGTGGATACAGGCTTCTGGCTG
GACATGCAGCACCTGTCTGATGTGGTCCTGAGCAGAGAGATCC
AGACCGGCCTGAGAGCCAGAGCCACACTGGAAGAGTCCATGC
CTATGCTCGAGAATCTGGAAGAACGGTTCAGACGGCTGCAAG
AGACATGCGACGCCGCCAGAACAGAGATCGAGGAAAGCGGCT
GGACCAGAGAAAGCGCCTCCAGAATGGAAGGCGACGAAGCCC
AAGGACCTAGCAGAGTGCAGCAGGCCTTCCAGAGCTTCGTGA
ACGAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCGGCGA
ACATGTGCGGGTGCTGTGTGCCAGAGTTAGCAGAGGACTTGCT
GCCGCTGGCGAGGCCATCAGAAGATGCTTCTCTTGCTGCAAGG
GCAGCACCCACAGATACGCCCCTAGAGATGATCTGAGCCCTG
AGGGCGCATCTCTGGCCGAAACACTGGCCAGATTTGCCGACG
ACATGGGCATTGAAAGAGGCGCCGACGGAACCTACGACATCC
CTCTGGTGGACGATTGGAGAAGGGGCGTGCCATCTATCGAAG
GCGAGGGCAGCGATAGCATCTACGAGATCATGATGCCCATCT
ACGAAGTGATGAACATGGACCTGGAAACCCGGCGGAGCTTTG
CCGTGCAACAGGGCCATTACCAGGATCCTAGAGCCAGCGACT
ACGACCTGCCTAGAGCCTCCGATTATGATCTGCCTCGGAGCCC
CTATCCTACACCTCCTCTGCCTCCAAGATACCAGCTTCAGAAT
ATGGACGTGGAAGCCGGATTCCGCGAGGCCGTGTATGCTAGCT
TTGTGGCCGGCATGTACAACTACGTGGTCACCCAGCCTCAAGA
GAGAATCCCCAACAGCCAGCAGGTCGAGGGCATCCTGAGAGA
TATGCTGACCAACGGCGACCAGACCTTCCGCGACCTGATGAAG
AGATGGAACAGAGAGGTGGACAGAGAGCACCACCACCATCAC CAT
Ct875_E_1_458_NGM_nIgK_nGST
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 209
TGCCTGATACCACAGGCATGAGCCCTATCCTCGGCTACTGGAA
GATCAAAGGCCTGGTGCAGCCCACCAGACTGCTGCTGGAATA
CCTGGAAGAGAAGTACGAGGAACACCTGTACGAGCGCGACGA
GGGCGATAAGTGGCGGAACAAGAAGTTCGAGCTGGGCCTCGA
GTTCCCCAACCTGCCTTACTACATCGACGGCGACGTGAAGCTG
ACCCAGAGCATGGCCATCATCCGGTATATCGCCGACAAGCAC
AACATGCTCGGCGGCTGCCCTAAAGAGCGGGCCGAGATTTCTA
TGCTGGAAGGCGCCGTGCTGGACATCAGATACGGCGTGTCCA
GAATCGCCTACAGCAAGGACTTCGAAACCCTGAAGGTGGACT
TCCTGAGCAAGCTGCCCGAGATGCTGAAGATGTTCGAGGACC
GGCTGTGCCACAAGACCTACCTGAATGGCGACCACGTGACAC
ACCCCGACTTCATGCTGTACGACGCCCTGGATGTGGTGCTGTA
CATGGACCCCATGTGCCTGGACGCCTTTCCAAAGCTCGTGTGC
TTCAAGAAGCGGATCGAGGCCATTCCTCAGATCGACAAGTACC
TGAAGTCCAGCAAGTATATCGCTTGGCCCCTGCAAGGCTGGCA
GGCCACATTTGGAGGCGGAGATCACCCTCCTAAGATGAGCATC
AGAGGCGTCGGCGGCAACGGCAACAGCAGAATCCCTTCTCAC
AATGGCGACGGCAGCAACAGGCGGAGCCAGAATACCAAGGGC
AACAACAAGGTGGAAGATCGCGTGTGCAGCCTGTACAGCTCC
AGAAGCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTGGAT
GTGTCCAGCATGATCGAGAGCACCCCTACCAGCGGCGAGACA
ACAAGAGCTAGTAGAGGCGTGCTGAGCCGGTTTCAGAGAGGC
CTCGTTCGGATTGCCGACAAAGTGCGGAGAGCCGTGCAGTGTG
CTTGGAGCAGTGTGTCCACAAGCAGAAGCAGCGCCACAAGAG
CCGCCGAATCTGGCAGCTCTAGCAGAACAGCTAGAGGCGCCA
GCAGCGGCTACAGAGAGTATTCTCCATCTGCCGCCAGAGGCCT
GCGGCTGATGTTTACAGATTTCTGGCGGACCCGGGTGCTGAGA
CAGACATCTCCTATGGCTGGCGTGTTCGGCAACCTGGACGTGA
ACGAAGCCAGACTGATGGCCGCCTACACAAGCGAGTGTGCCG
ATCACCTGGAAGCCAAAGAACTGGCCGGACCTGATGGCGTGG
CAGCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAGTGC
GGGACCTGCAGGATAAGGGCGCTGCTAGAAAGCTGCTGAACG
ACCCTCTGGGCAGAAGAACCCCTAACTACCAGAGCAAGAACC
CCGGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGGACC
CCAGGTGGCCAACCTGCAGAATGTGGATACAGGCTTCTGGCTG
GACATGCAGCACCTGTCTGATGTGGTCCTGAGCAGAGAGATCC
AGACCGGCCTGAGAGCCAGAGCCACACTGGAAGAGTCCATGC
CTATGCTCGAGAATCTGGAAGAACGGTTCAGACGGCTGCAAG
AGACATGCGACGCCGCCAGAACAGAGATCGAGGAAAGCGGCT
GGACCAGAGAAAGCGCCTCCAGAATGGAAGGCGACGAAGCCC
AAGGACCTAGCAGAGTGCAGCAGGCCTTCCAGAGCTTCGTGA
ACGAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCGGCGA
ACATGTGCGGGTGCTGTGTGCCAGAGTTAGCAGAGGACTTGCT
GCCGCTGGCGAGGCCATCAGAAGATGCTTCTCTTGCTGCAAGG
GCAGCACCCACAGATACGCCCCTAGAGATGATCTGAGCCCTG
AGGGCGCATCTCTGGCCGAAACACTGGCCAGATTTGCCGACG
ACATGGGCATTGAAAGAGGCGCCGACGGAACCTACGACATCC
CTCTGGTGGACGATTGGAGAAGGGGCGTGCCATCTATCGAAG GCGAGGGATCT
Ct875_E_1_458_NGM_nIgK_nGST_cHis
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 210
TGCCTGATACCACAGGCATGAGCCCTATCCTCGGCTACTGGAA
GATCAAAGGCCTGGTGCAGCCCACCAGACTGCTGCTGGAATA
CCTGGAAGAGAAGTACGAGGAACACCTGTACGAGCGCGACGA
GGGCGATAAGTGGCGGAACAAGAAGTTCGAGCTGGGCCTCGA
GTTCCCCAACCTGCCTTACTACATCGACGGCGACGTGAAGCTG
ACCCAGAGCATGGCCATCATCCGGTATATCGCCGACAAGCAC
AACATGCTCGGCGGCTGCCCTAAAGAGCGGGCCGAGATTTCTA
TGCTGGAAGGCGCCGTGCTGGACATCAGATACGGCGTGTCCA
GAATCGCCTACAGCAAGGACTTCGAAACCCTGAAGGTGGACT
TCCTGAGCAAGCTGCCCGAGATGCTGAAGATGTTCGAGGACC
GGCTGTGCCACAAGACCTACCTGAATGGCGACCACGTGACAC
ACCCCGACTTCATGCTGTACGACGCCCTGGATGTGGTGCTGTA
CATGGACCCCATGTGCCTGGACGCCTTTCCAAAGCTCGTGTGC
TTCAAGAAGCGGATCGAGGCCATTCCTCAGATCGACAAGTACC
TGAAGTCCAGCAAGTATATCGCTTGGCCCCTGCAAGGCTGGCA
GGCCACATTTGGAGGCGGAGATCACCCTCCTAAGATGAGCATC
AGAGGCGTCGGCGGCAACGGCAACAGCAGAATCCCTTCTCAC
AATGGCGACGGCAGCAACAGGCGGAGCCAGAATACCAAGGGC
AACAACAAGGTGGAAGATCGCGTGTGCAGCCTGTACAGCTCC
AGAAGCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTGGAT
GTGTCCAGCATGATCGAGAGCACCCCTACCAGCGGCGAGACA
ACAAGAGCTAGTAGAGGCGTGCTGAGCCGGTTTCAGAGAGGC
CTCGTTCGGATTGCCGACAAAGTGCGGAGAGCCGTGCAGTGTG
CTTGGAGCAGTGTGTCCACAAGCAGAAGCAGCGCCACAAGAG
CCGCCGAATCTGGCAGCTCTAGCAGAACAGCTAGAGGCGCCA
GCAGCGGCTACAGAGAGTATTCTCCATCTGCCGCCAGAGGCCT
GCGGCTGATGTTTACAGATTTCTGGCGGACCCGGGTGCTGAGA
CAGACATCTCCTATGGCTGGCGTGTTCGGCAACCTGGACGTGA
ACGAAGCCAGACTGATGGCCGCCTACACAAGCGAGTGTGCCG
ATCACCTGGAAGCCAAAGAACTGGCCGGACCTGATGGCGTGG
CAGCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAGTGC
GGGACCTGCAGGATAAGGGCGCTGCTAGAAAGCTGCTGAACG
ACCCTCTGGGCAGAAGAACCCCTAACTACCAGAGCAAGAACC
CCGGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGGACC
CCAGGTGGCCAACCTGCAGAATGTGGATACAGGCTTCTGGCTG
GACATGCAGCACCTGTCTGATGTGGTCCTGAGCAGAGAGATCC
AGACCGGCCTGAGAGCCAGAGCCACACTGGAAGAGTCCATGC
CTATGCTCGAGAATCTGGAAGAACGGTTCAGACGGCTGCAAG
AGACATGCGACGCCGCCAGAACAGAGATCGAGGAAAGCGGCT
GGACCAGAGAAAGCGCCTCCAGAATGGAAGGCGACGAAGCCC
AAGGACCTAGCAGAGTGCAGCAGGCCTTCCAGAGCTTCGTGA
ACGAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCGGCGA
ACATGTGCGGGTGCTGTGTGCCAGAGTTAGCAGAGGACTTGCT
GCCGCTGGCGAGGCCATCAGAAGATGCTTCTCTTGCTGCAAGG
GCAGCACCCACAGATACGCCCCTAGAGATGATCTGAGCCCTG
AGGGCGCATCTCTGGCCGAAACACTGGCCAGATTTGCCGACG
ACATGGGCATTGAAAGAGGCGCCGACGGAACCTACGACATCC
CTCTGGTGGACGATTGGAGAAGGGGCGTGCCATCTATCGAAG
GCGAGGGCTCTCACCACCACCATCACCAT Ct875_E_1_458_NGM_nIgK
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 211
TGCCTGATACCACCGGCATGTCTATCAGAGGCGTTGGCGGCAA
CGGCAACAGCAGAATCCCTAGCCATAATGGCGACGGCAGCAA
CAGGCGGAGCCAGAATACCAAGGGCAACAACAAGGTGGAAG
ATCGCGTGTGCAGCCTGTACAGCTCCAGAAGCAACGAGAACC
GCGAGAGCCCTTATGCCGTGGTGGATGTGTCCAGCATGATCGA
GAGCACCCCTACCAGCGGCGAGACAACAAGAGCTAGTAGAGG
CGTGCTGAGCCGGTTTCAGAGAGGCCTCGTTCGGATCGCTGAC
AAAGTGCGGAGAGCCGTGCAGTGTGCCTGGTCTAGTGTGTCCA
CAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAGCGGATCTT
CTAGCAGAACAGCTAGAGGCGCCAGCAGCGGCTACAGAGAGT
ATTCTCCATCTGCCGCCAGAGGCCTGCGGCTGATGTTTACAGA
TTTCTGGCGGACCCGGGTGCTGAGACAGACATCTCCTATGGCT
GGCGTGTTCGGCAACCTGGATGTGAATGAGGCCAGACTGATG
GCCGCCTACACAAGCGAATGTGCCGATCACCTGGAAGCCAAA
GAGCTGGCTGGACCTGACGGTGTTGCCGCCGCTAGAGAAATC
GCCAAGAGATGGGAGAAGAGAGTGCGGGACCTGCAGGATAA
GGGCGCTGCTAGAAAGCTGCTGAACGACCCTCTGGGCAGAAG
AACCCCTAACTACCAGAGCAAGAACCCCGGCGAGTACACCGT
GGGCAACTCCATGTTCTACGACGGACCCCAGGTGGCCAACCTG
CAGAATGTGGATACAGGCTTCTGGCTGGATATGCAGCACCTGA
GCGACGTGGTGCTGTCCAGAGAGATCCAGACAGGCCTGAGAG
CCAGAGCCACACTGGAAGAGTCCATGCCTATGCTCGAGAACCT
GGAAGAGAGATTCCGGCGGCTGCAAGAGACATGTGACGCCGC
CAGAACCGAGATCGAGGAAAGCGGCTGGACAAGAGAAAGCG
CCTCCAGAATGGAAGGCGACGAAGCCCAAGGACCTAGCAGAG
TGCAGCAGGCCTTCCAGAGCTTCGTGAACGAGTGCAACAGCAT
CGAGTTCAGCTTCGGCTCCTTCGGCGAACATGTGCGGGTGCTG
TGTGCCAGAGTTAGCAGAGGACTTGCTGCCGCTGGCGAGGCC
ATCAGAAGATGCTTCTCTTGCTGCAAGGGCAGCACCCACAGAT
ACGCCCCTAGAGATGATCTGAGCCCTGAGGGCGCTTCTCTGGC
CGAAACACTGGCCAGATTCGCCGACGATATGGGCATTGAAAG
AGGCGCCGACGGAACCTACGACATCCCTCTGGTGGACGATTG
GAGAAGGGGCGTGCCATCTATCGAAGGCGAGGGATCT Ct875_E_1_458_NGM_nIgK_cHis
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 212
TGCCTGATACCACCGGCATGTCTATCAGAGGCGTTGGCGGCAA
CGGCAACAGCAGAATCCCTAGCCATAATGGCGACGGCAGCAA
CAGGCGGAGCCAGAATACCAAGGGCAACAACAAGGTGGAAG
ATCGCGTGTGCAGCCTGTACAGCTCCAGAAGCAACGAGAACC
GCGAGAGCCCTTATGCCGTGGTGGATGTGTCCAGCATGATCGA
GAGCACCCCTACCAGCGGCGAGACAACAAGAGCTAGTAGAGG
CGTGCTGAGCCGGTTTCAGAGAGGCCTCGTTCGGATCGCTGAC
AAAGTGCGGAGAGCCGTGCAGTGTGCCTGGTCTAGTGTGTCCA
CAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAGCGGATCTT
CTAGCAGAACAGCTAGAGGCGCCAGCAGCGGCTACAGAGAGT
ATTCTCCATCTGCCGCCAGAGGCCTGCGGCTGATGTTTACAGA
TTTCTGGCGGACCCGGGTGCTGAGACAGACATCTCCTATGGCT
GGCGTGTTCGGCAACCTGGATGTGAATGAGGCCAGACTGATG
GCCGCCTACACAAGCGAATGTGCCGATCACCTGGAAGCCAAA
GAGCTGGCTGGACCTGACGGTGTTGCCGCCGCTAGAGAAATC
GCCAAGAGATGGGAGAAGAGAGTGCGGGACCTGCAGGATAA
GGGCGCTGCTAGAAAGCTGCTGAACGACCCTCTGGGCAGAAG
AACCCCTAACTACCAGAGCAAGAACCCCGGCGAGTACACCGT
GGGCAACTCCATGTTCTACGACGGACCCCAGGTGGCCAACCTG
CAGAATGTGGATACAGGCTTCTGGCTGGATATGCAGCACCTGA
GCGACGTGGTGCTGTCCAGAGAGATCCAGACAGGCCTGAGAG
CCAGAGCCACACTGGAAGAGTCCATGCCTATGCTCGAGAACCT
GGAAGAGAGATTCCGGCGGCTGCAAGAGACATGTGACGCCGC
CAGAACCGAGATCGAGGAAAGCGGCTGGACAAGAGAAAGCG
CCTCCAGAATGGAAGGCGACGAAGCCCAAGGACCTAGCAGAG
TGCAGCAGGCCTTCCAGAGCTTCGTGAACGAGTGCAACAGCAT
CGAGTTCAGCTTCGGCTCCTTCGGCGAACATGTGCGGGTGCTG
TGTGCCAGAGTTAGCAGAGGACTTGCTGCCGCTGGCGAGGCC
ATCAGAAGATGCTTCTCTTGCTGCAAGGGCAGCACCCACAGAT
ACGCCCCTAGAGATGATCTGAGCCCTGAGGGCGCTTCTCTGGC
CGAAACACTGGCCAGATTCGCCGACGATATGGGCATTGAAAG
AGGCGCCGACGGAACCTACGACATCCCTCTGGTGGACGATTG
GAGAAGGGGCGTGCCATCTATCGAAGGCGAGGGCTCTCACCA CCACCATCACCAT
Ct875_E_1_574_NGM_nIgK ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC
213 TGCCTGATACCACCGGCATGTCTATCAGAGGCGTTGGCGGCAA
CGGCAACAGCAGAATCCCTAGCCATAATGGCGACGGCAGCAA
CAGGCGGAGCCAGAATACCAAGGGCAACAACAAGGTGGAAG
ATCGCGTGTGCAGCCTGTACAGCTCCAGAAGCAACGAGAACC
GCGAGAGCCCTTATGCCGTGGTGGATGTGTCCAGCATGATCGA
GAGCACCCCTACCAGCGGCGAGACAACAAGAGCTAGTAGAGG
CGTGCTGAGCCGGTTTCAGAGAGGCCTCGTTCGGATCGCTGAC
AAAGTGCGGAGAGCCGTGCAGTGTGCCTGGTCTAGTGTGTCCA
CAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAGCGGATCTT
CTAGCAGAACAGCTAGAGGCGCCAGCAGCGGCTACAGAGAGT
ATTCTCCATCTGCCGCCAGAGGCCTGCGGCTGATGTTTACAGA
TTTCTGGCGGACCCGGGTGCTGAGACAGACATCTCCTATGGCT
GGCGTGTTCGGCAACCTGGATGTGAATGAGGCCAGACTGATG
GCCGCCTACACAAGCGAATGTGCCGATCACCTGGAAGCCAAA
GAGCTGGCTGGACCTGACGGTGTTGCCGCCGCTAGAGAAATC
GCCAAGAGATGGGAGAAGAGAGTGCGGGACCTGCAGGATAA
GGGCGCTGCTAGAAAGCTGCTGAACGACCCTCTGGGCAGAAG
AACCCCTAACTACCAGAGCAAGAACCCCGGCGAGTACACCGT
GGGCAACTCCATGTTCTACGACGGACCCCAGGTGGCCAACCTG
CAGAATGTGGATACAGGCTTCTGGCTGGATATGCAGCACCTGA
GCGACGTGGTGCTGTCCAGAGAGATCCAGACAGGCCTGAGAG
CCAGAGCCACACTGGAAGAGTCCATGCCTATGCTCGAGAACCT
GGAAGAGAGATTCCGGCGGCTGCAAGAGACATGTGACGCCGC
CAGAACCGAGATCGAGGAAAGCGGCTGGACAAGAGAAAGCG
CCTCCAGAATGGAAGGCGACGAAGCCCAAGGACCTAGCAGAG
TGCAGCAGGCCTTCCAGAGCTTCGTGAACGAGTGCAACAGCAT
CGAGTTCAGCTTCGGCTCCTTCGGCGAACATGTGCGGGTGCTG
TGTGCCAGAGTTAGCAGAGGACTTGCTGCCGCTGGCGAGGCC
ATCAGAAGATGCTTCTCTTGCTGCAAGGGCAGCACCCACAGAT
ACGCCCCTAGAGATGATCTGAGCCCTGAGGGCGCTTCTCTGGC
CGAAACACTGGCCAGATTCGCCGACGATATGGGCATTGAAAG
AGGCGCCGACGGAACCTACGACATCCCTCTGGTGGACGATTG
GAGAAGGGGCGTGCCATCTATCGAAGGCGAGGGCAGCGATAG
CATCTACGAGATCATGATGCCCATCTACGAAGTGATGAACATG
GACCTGGAAACCCGGCGGAGCTTTGCCGTGCAGCAAGGCCAT
TACCAGGATCCTAGAGCCAGCGACTACGACCTGCCTAGAGCCT
CCGATTATGATCTGCCTCGGAGCCCCTATCCTACACCTCCTCTG
CCTCCAAGATACCAGCTTCAGAATATGGACGTGGAAGCCGGA
TTCCGCGAGGCCGTGTATGCTAGCTTTGTGGCCGGCATGTACA
ACTACGTGGTCACCCAGCCTCAAGAGAGAATCCCCAACAGCC
AGCAGGTCGAGGGCATCCTGAGAGATATGCTGACCAACGGCG AC
Ct875_E_1_574_nIgK_nGST ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC
214 TGCCTGATACCACAGGCATGAGCCCTATCCTCGGCTACTGGAA
GATCAAAGGCCTGGTGCAGCCCACCAGACTGCTGCTGGAATA
CCTGGAAGAGAAGTACGAGGAACACCTGTACGAGCGCGACGA
GGGCGATAAGTGGCGGAACAAGAAGTTCGAGCTGGGCCTCGA
GTTCCCCAACCTGCCTTACTACATCGACGGCGACGTGAAGCTG
ACCCAGAGCATGGCCATCATCCGGTATATCGCCGACAAGCAC
AACATGCTCGGCGGCTGCCCTAAAGAGCGGGCCGAGATTTCTA
TGCTGGAAGGCGCCGTGCTGGACATCAGATACGGCGTGTCCA
GAATCGCCTACAGCAAGGACTTCGAAACCCTGAAGGTGGACT
TCCTGAGCAAGCTGCCCGAGATGCTGAAGATGTTCGAGGACC
GGCTGTGCCACAAGACCTACCTGAATGGCGACCACGTGACAC
ACCCCGACTTCATGCTGTACGACGCCCTGGATGTGGTGCTGTA
CATGGACCCCATGTGCCTGGACGCCTTTCCAAAGCTCGTGTGC
TTCAAGAAGCGGATCGAGGCCATTCCTCAGATCGACAAGTACC
TGAAGTCCAGCAAGTATATCGCTTGGCCCCTGCAAGGCTGGCA
GGCCACATTTGGAGGCGGAGATCACCCTCCTAAGATGAGCATC
AGAGGCGTCGGCGGCAACGGCAACAGCAGAATCCCTTCTCAC
AATGGCGACGGCAGCAACAGGCGGAGCCAGAATACCAAGGGC
AACAACAAGGTGGAAGATCGCGTGTGCAGCCTGTACAGCTCC
AGAAGCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTGGAT
GTGTCCAGCATGATCGAGAGCACCCCTACCAGCGGCGAGACA
ACAAGAGCTAGTAGAGGCGTGCTGAGCCGGTTTCAGAGAGGC
CTCGTTCGGATTGCCGACAAAGTGCGGAGAGCCGTGCAGTGTG
CTTGGAGCAGTGTGTCCACAAGCAGAAGCAGCGCCACAAGAG
CCGCCGAATCTGGCAGCTCTAGCAGAACAGCTAGAGGCGCCA
GCAGCGGCTACAGAGAGTATTCTCCATCTGCCGCCAGAGGCCT
GCGGCTGATGTTTACAGATTTCTGGCGGACCCGGGTGCTGAGA
CAGACATCTCCTATGGCTGGCGTGTTCGGCAACCTGGACGTGA
ACGAAGCCAGACTGATGGCCGCCTACACAAGCGAGTGTGCCG
ATCACCTGGAAGCCAAAGAACTGGCCGGACCTGATGGCGTGG
CAGCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAGTGC
GGGACCTGCAGGATAAGGGCGCTGCTAGAAAGCTGCTGAACG
ACCCTCTGGGCAGAAGAACCCCTAACTACCAGAGCAAGAACC
CCGGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGGACC
CCAGGTGGCCAACCTGCAGAATGTGGATACAGGCTTCTGGCTG
GACATGAGCAACCTGAGCGACGTGGTCCTGAGCAGAGAGATC
CAGACAGGCCTGAGAGCCAGAGCCACACTGGAAGAGTCCATG
CCTATGCTCGAGAATCTGGAAGAACGGTTCAGACGGCTGCAA
GAGACATGCGACGCCGCCAGAACAGAGATCGAGGAAAGCGGC
TGGACCAGAGAAAGCGCCTCCAGAATGGAAGGCGACGAAGCC
CAAGGACCTAGCAGAGTGCAGCAGGCCTTCCAGAGCTTCGTG
AACGAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCGGCG
AACATGTGCGGGTGCTGTGTGCCAGAGTTAGCAGAGGACTTGC
TGCCGCTGGCGAGGCCATCAGAAGATGCTTCTCTTGCTGCAAG
GGCAGCACCCACAGATACGCCCCTAGAGATGATCTGAGCCCT
GAGGGCGCATCTCTGGCCGAAACACTGGCCAGATTTGCCGAC
GACATGGGCATTGAAAGAGGCGCCGACGGAACCTACGACATC
CCTCTGGTGGACGATTGGAGAAGGGGCGTGCCATCTATCGAA
GGCGAGGGCAGCGATAGCATCTACGAGATCATGATGCCCATC
TACGAAGTGATGAACATGGACCTGGAAACCCGGCGGAGCTTT
GCCGTGCAACAGGGCCATTACCAGGATCCTAGAGCCAGCGAC
TACGACCTGCCTAGAGCCTCCGATTATGATCTGCCTCGGAGCC
CCTATCCTACACCTCCTCTGCCTCCAAGATACCAGCTTCAGAA
TATGGACGTGGAAGCCGGATTCCGCGAGGCCGTGTATGCTAGC
TTTGTGGCCGGCATGTACAACTACGTGGTCACCCAGCCTCAAG
AGAGAATCCCCAACAGCCAGCAGGTCGAGGGCATCCTGAGAG ATATGCTGACCAACGGCAGC
Ct875_E_1_574_nIgK_nGST_cHis
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 215
TGCCTGATACCACAGGCATGAGCCCTATCCTCGGCTACTGGAA
GATCAAAGGCCTGGTGCAGCCCACCAGACTGCTGCTGGAATA
CCTGGAAGAGAAGTACGAGGAACACCTGTACGAGCGCGACGA
GGGCGATAAGTGGCGGAACAAGAAGTTCGAGCTGGGCCTCGA
GTTCCCCAACCTGCCTTACTACATCGACGGCGACGTGAAGCTG
ACCCAGAGCATGGCCATCATCCGGTATATCGCCGACAAGCAC
AACATGCTCGGCGGCTGCCCTAAAGAGCGGGCCGAGATTTCTA
TGCTGGAAGGCGCCGTGCTGGACATCAGATACGGCGTGTCCA
GAATCGCCTACAGCAAGGACTTCGAAACCCTGAAGGTGGACT
TCCTGAGCAAGCTGCCCGAGATGCTGAAGATGTTCGAGGACC
GGCTGTGCCACAAGACCTACCTGAATGGCGACCACGTGACAC
ACCCCGACTTCATGCTGTACGACGCCCTGGATGTGGTGCTGTA
CATGGACCCCATGTGCCTGGACGCCTTTCCAAAGCTCGTGTGC
TTCAAGAAGCGGATCGAGGCCATTCCTCAGATCGACAAGTACC
TGAAGTCCAGCAAGTATATCGCTTGGCCCCTGCAAGGCTGGCA
GGCCACATTTGGAGGCGGAGATCACCCTCCTAAGATGAGCATC
AGAGGCGTCGGCGGCAACGGCAACAGCAGAATCCCTTCTCAC
AATGGCGACGGCAGCAACAGGCGGAGCCAGAATACCAAGGGC
AACAACAAGGTGGAAGATCGCGTGTGCAGCCTGTACAGCTCC
AGAAGCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTGGAT
GTGTCCAGCATGATCGAGAGCACCCCTACCAGCGGCGAGACA
ACAAGAGCTAGTAGAGGCGTGCTGAGCCGGTTTCAGAGAGGC
CTCGTTCGGATTGCCGACAAAGTGCGGAGAGCCGTGCAGTGTG
CTTGGAGCAGTGTGTCCACAAGCAGAAGCAGCGCCACAAGAG
CCGCCGAATCTGGCAGCTCTAGCAGAACAGCTAGAGGCGCCA
GCAGCGGCTACAGAGAGTATTCTCCATCTGCCGCCAGAGGCCT
GCGGCTGATGTTTACAGATTTCTGGCGGACCCGGGTGCTGAGA
CAGACATCTCCTATGGCTGGCGTGTTCGGCAACCTGGACGTGA
ACGAAGCCAGACTGATGGCCGCCTACACAAGCGAGTGTGCCG
ATCACCTGGAAGCCAAAGAACTGGCCGGACCTGATGGCGTGG
CAGCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAGTGC
GGGACCTGCAGGATAAGGGCGCTGCTAGAAAGCTGCTGAACG
ACCCTCTGGGCAGAAGAACCCCTAACTACCAGAGCAAGAACC
CCGGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGGACC
CCAGGTGGCCAACCTGCAGAATGTGGATACAGGCTTCTGGCTG
GACATGAGCAACCTGAGCGACGTGGTCCTGAGCAGAGAGATC
CAGACAGGCCTGAGAGCCAGAGCCACACTGGAAGAGTCCATG
CCTATGCTCGAGAATCTGGAAGAACGGTTCAGACGGCTGCAA
GAGACATGCGACGCCGCCAGAACAGAGATCGAGGAAAGCGGC
TGGACCAGAGAAAGCGCCTCCAGAATGGAAGGCGACGAAGCC
CAAGGACCTAGCAGAGTGCAGCAGGCCTTCCAGAGCTTCGTG
AACGAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCGGCG
AACATGTGCGGGTGCTGTGTGCCAGAGTTAGCAGAGGACTTGC
TGCCGCTGGCGAGGCCATCAGAAGATGCTTCTCTTGCTGCAAG
GGCAGCACCCACAGATACGCCCCTAGAGATGATCTGAGCCCT
GAGGGCGCATCTCTGGCCGAAACACTGGCCAGATTTGCCGAC
GACATGGGCATTGAAAGAGGCGCCGACGGAACCTACGACATC
CCTCTGGTGGACGATTGGAGAAGGGGCGTGCCATCTATCGAA
GGCGAGGGCAGCGATAGCATCTACGAGATCATGATGCCCATC
TACGAAGTGATGAACATGGACCTGGAAACCCGGCGGAGCTTT
GCCGTGCAACAGGGCCATTACCAGGATCCTAGAGCCAGCGAC
TACGACCTGCCTAGAGCCTCCGATTATGATCTGCCTCGGAGCC
CCTATCCTACACCTCCTCTGCCTCCAAGATACCAGCTTCAGAA
TATGGACGTGGAAGCCGGATTCCGCGAGGCCGTGTATGCTAGC
TTTGTGGCCGGCATGTACAACTACGTGGTCACCCAGCCTCAAG
AGAGAATCCCCAACAGCCAGCAGGTCGAGGGCATCCTGAGAG
ATATGCTGACCAACGGCAGCCACCACCACCATCACCAT Ct875_E_nIgK_nGST
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 216
TGCCTGATACCACAGGCATGAGCCCTATCCTCGGCTACTGGAA
GATCAAAGGCCTGGTGCAGCCCACCAGACTGCTGCTGGAATA
CCTGGAAGAGAAGTACGAGGAACACCTGTACGAGCGCGACGA
GGGCGATAAGTGGCGGAACAAGAAGTTCGAGCTGGGCCTCGA
GTTCCCCAACCTGCCTTACTACATCGACGGCGACGTGAAGCTG
ACCCAGAGCATGGCCATCATCCGGTATATCGCCGACAAGCAC
AACATGCTCGGCGGCTGCCCTAAAGAGCGGGCCGAGATTTCTA
TGCTGGAAGGCGCCGTGCTGGACATCAGATACGGCGTGTCCA
GAATCGCCTACAGCAAGGACTTCGAAACCCTGAAGGTGGACT
TCCTGAGCAAGCTGCCCGAGATGCTGAAGATGTTCGAGGACC
GGCTGTGCCACAAGACCTACCTGAATGGCGACCACGTGACAC
ACCCCGACTTCATGCTGTACGACGCCCTGGATGTGGTGCTGTA
CATGGACCCCATGTGCCTGGACGCCTTTCCAAAGCTCGTGTGC
TTCAAGAAGCGGATCGAGGCCATTCCTCAGATCGACAAGTACC
TGAAGTCCAGCAAGTATATCGCTTGGCCCCTGCAAGGCTGGCA
GGCCACATTTGGAGGCGGAGATCACCCTCCTAAGATGAGCATC
AGAGGCGTCGGCGGCAACGGCAACAGCAGAATCCCTTCTCAC
AATGGCGACGGCAGCAACAGGCGGAGCCAGAATACCAAGGGC
AACAACAAGGTGGAAGATCGCGTGTGCAGCCTGTACAGCTCC
AGAAGCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTGGAT
GTGTCCAGCATGATCGAGAGCACCCCTACCAGCGGCGAGACA
ACAAGAGCTAGTAGAGGCGTGCTGAGCCGGTTTCAGAGAGGC
CTCGTTCGGATTGCCGACAAAGTGCGGAGAGCCGTGCAGTGTG
CTTGGAGCAGTGTGTCCACAAGCAGAAGCAGCGCCACAAGAG
CCGCCGAATCTGGCAGCTCTAGCAGAACAGCTAGAGGCGCCA
GCAGCGGCTACAGAGAGTATTCTCCATCTGCCGCCAGAGGCCT
GCGGCTGATGTTTACAGATTTCTGGCGGACCCGGGTGCTGAGA
CAGACATCTCCTATGGCTGGCGTGTTCGGCAACCTGGACGTGA
ACGAAGCCAGACTGATGGCCGCCTACACAAGCGAGTGTGCCG
ATCACCTGGAAGCCAAAGAACTGGCCGGACCTGATGGCGTGG
CAGCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAGTGC
GGGACCTGCAGGATAAGGGCGCTGCTAGAAAGCTGCTGAACG
ACCCTCTGGGCAGAAGAACCCCTAACTACCAGAGCAAGAACC
CCGGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGGACC
CCAGGTGGCCAACCTGCAGAATGTGGATACAGGCTTCTGGCTG
GACATGAGCAACCTGAGCGACGTGGTCCTGAGCAGAGAGATC
CAGACAGGCCTGAGAGCCAGAGCCACACTGGAAGAGTCCATG
CCTATGCTCGAGAATCTGGAAGAACGGTTCAGACGGCTGCAA
GAGACATGCGACGCCGCCAGAACAGAGATCGAGGAAAGCGGC
TGGACCAGAGAAAGCGCCTCCAGAATGGAAGGCGACGAAGCC
CAAGGACCTAGCAGAGTGCAGCAGGCCTTCCAGAGCTTCGTG
AACGAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCGGCG
AACATGTGCGGGTGCTGTGTGCCAGAGTTAGCAGAGGACTTGC
TGCCGCTGGCGAGGCCATCAGAAGATGCTTCTCTTGCTGCAAG
GGCAGCACCCACAGATACGCCCCTAGAGATGATCTGAGCCCT
GAGGGCGCATCTCTGGCCGAAACACTGGCCAGATTTGCCGAC
GACATGGGCATTGAAAGAGGCGCCGACGGAACCTACGACATC
CCTCTGGTGGACGATTGGAGAAGGGGCGTGCCATCTATCGAA
GGCGAGGGCAGCGATAGCATCTACGAGATCATGATGCCCATC
TACGAAGTGATGAACATGGACCTGGAAACCCGGCGGAGCTTT
GCCGTGCAACAGGGCCATTACCAGGATCCTAGAGCCAGCGAC
TACGACCTGCCTAGAGCCTCCGATTATGATCTGCCTCGGAGCC
CCTATCCTACACCTCCTCTGCCTCCAAGATACCAGCTTCAGAA
TATGGACGTGGAAGCCGGATTCCGCGAGGCCGTGTATGCTAGC
TTTGTGGCCGGCATGTACAACTACGTGGTCACCCAGCCTCAAG
AGAGAATCCCCAACAGCCAGCAGGTCGAGGGCATCCTGAGAG
ATATGCTGACCAACGGCAGCCAGACCTTCCGCGACCTGATGAA
GAGATGGAACAGAGAGGTGGACAGAGAG Ct875_E_nIgK_nGST_cHis
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 217
TGCCTGATACCACAGGCATGAGCCCTATCCTCGGCTACTGGAA
GATCAAAGGCCTGGTGCAGCCCACCAGACTGCTGCTGGAATA
CCTGGAAGAGAAGTACGAGGAACACCTGTACGAGCGCGACGA
GGGCGATAAGTGGCGGAACAAGAAGTTCGAGCTGGGCCTCGA
GTTCCCCAACCTGCCTTACTACATCGACGGCGACGTGAAGCTG
ACCCAGAGCATGGCCATCATCCGGTATATCGCCGACAAGCAC
AACATGCTCGGCGGCTGCCCTAAAGAGCGGGCCGAGATTTCTA
TGCTGGAAGGCGCCGTGCTGGACATCAGATACGGCGTGTCCA
GAATCGCCTACAGCAAGGACTTCGAAACCCTGAAGGTGGACT
TCCTGAGCAAGCTGCCCGAGATGCTGAAGATGTTCGAGGACC
GGCTGTGCCACAAGACCTACCTGAATGGCGACCACGTGACAC
ACCCCGACTTCATGCTGTACGACGCCCTGGATGTGGTGCTGTA
CATGGACCCCATGTGCCTGGACGCCTTTCCAAAGCTCGTGTGC
TTCAAGAAGCGGATCGAGGCCATTCCTCAGATCGACAAGTACC
TGAAGTCCAGCAAGTATATCGCTTGGCCCCTGCAAGGCTGGCA
GGCCACATTTGGAGGCGGAGATCACCCTCCTAAGATGAGCATC
AGAGGCGTCGGCGGCAACGGCAACAGCAGAATCCCTTCTCAC
AATGGCGACGGCAGCAACAGGCGGAGCCAGAATACCAAGGGC
AACAACAAGGTGGAAGATCGCGTGTGCAGCCTGTACAGCTCC
AGAAGCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTGGAT
GTGTCCAGCATGATCGAGAGCACCCCTACCAGCGGCGAGACA
ACAAGAGCTAGTAGAGGCGTGCTGAGCCGGTTTCAGAGAGGC
CTCGTTCGGATTGCCGACAAAGTGCGGAGAGCCGTGCAGTGTG
CTTGGAGCAGTGTGTCCACAAGCAGAAGCAGCGCCACAAGAG
CCGCCGAATCTGGCAGCTCTAGCAGAACAGCTAGAGGCGCCA
GCAGCGGCTACAGAGAGTATTCTCCATCTGCCGCCAGAGGCCT
GCGGCTGATGTTTACAGATTTCTGGCGGACCCGGGTGCTGAGA
CAGACATCTCCTATGGCTGGCGTGTTCGGCAACCTGGACGTGA
ACGAAGCCAGACTGATGGCCGCCTACACAAGCGAGTGTGCCG
ATCACCTGGAAGCCAAAGAACTGGCCGGACCTGATGGCGTGG
CAGCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAGTGC
GGGACCTGCAGGATAAGGGCGCTGCTAGAAAGCTGCTGAACG
ACCCTCTGGGCAGAAGAACCCCTAACTACCAGAGCAAGAACC
CCGGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGGACC
CCAGGTGGCCAACCTGCAGAATGTGGATACAGGCTTCTGGCTG
GACATGAGCAACCTGAGCGACGTGGTCCTGAGCAGAGAGATC
CAGACAGGCCTGAGAGCCAGAGCCACACTGGAAGAGTCCATG
CCTATGCTCGAGAATCTGGAAGAACGGTTCAGACGGCTGCAA
GAGACATGCGACGCCGCCAGAACAGAGATCGAGGAAAGCGGC
TGGACCAGAGAAAGCGCCTCCAGAATGGAAGGCGACGAAGCC
CAAGGACCTAGCAGAGTGCAGCAGGCCTTCCAGAGCTTCGTG
AACGAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCGGCG
AACATGTGCGGGTGCTGTGTGCCAGAGTTAGCAGAGGACTTGC
TGCCGCTGGCGAGGCCATCAGAAGATGCTTCTCTTGCTGCAAG
GGCAGCACCCACAGATACGCCCCTAGAGATGATCTGAGCCCT
GAGGGCGCATCTCTGGCCGAAACACTGGCCAGATTTGCCGAC
GACATGGGCATTGAAAGAGGCGCCGACGGAACCTACGACATC
CCTCTGGTGGACGATTGGAGAAGGGGCGTGCCATCTATCGAA
GGCGAGGGCAGCGATAGCATCTACGAGATCATGATGCCCATC
TACGAAGTGATGAACATGGACCTGGAAACCCGGCGGAGCTTT
GCCGTGCAACAGGGCCATTACCAGGATCCTAGAGCCAGCGAC
TACGACCTGCCTAGAGCCTCCGATTATGATCTGCCTCGGAGCC
CCTATCCTACACCTCCTCTGCCTCCAAGATACCAGCTTCAGAA
TATGGACGTGGAAGCCGGATTCCGCGAGGCCGTGTATGCTAGC
TTTGTGGCCGGCATGTACAACTACGTGGTCACCCAGCCTCAAG
AGAGAATCCCCAACAGCCAGCAGGTCGAGGGCATCCTGAGAG
ATATGCTGACCAACGGCAGCCAGACCTTCCGCGACCTGATGAA
GAGATGGAACAGAGAGGTGGACAGAGAGCACCACCACCATCA CCAT Ct875_E_nFc
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 218
TGCCTGATACAACCGGCGAGCCTAAGAGCTGCGACAAGACCC
ACACCTGTCCTCCATGTCCTGCTCCAGAACTGCTCGGCGGACC
TTCCGTGTTCCTGTTTCCTCCAAAGCCTAAGGACACCCTGATG
ATCAGCAGAACCCCTGAAGTGACCTGCGTGGTGGTGGATGTGT
CCCACGAGGATCCCGAAGTGAAGTTCAATTGGTACGTGGACG
GCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGAGAGGAAC
AGTACAACAGCACCTACAGAGTGGTGTCCGTGCTGACCGTGCT
GCACCAGGATTGGCTGAACGGCAAAGAGTACAAGTGCAAGGT
GTCCAACAAGGCCCTGCCTGCTCCTATCGAGAAGACCATCAGC
AAGGCCAAGGGCCAGCCAAGAGAACCCCAGGTGTACACACTG
CCTCCAAGCAGAGATGAGCTGACCAAGAACCAGGTGTCCCTG
ACCTGTCTGGTCAAGGGCTTCTACCCCTCCGATATCGCCGTGG
AATGGGAGAGCAATGGCCAGCCTGAGAACAACTACAAGACAA
CCCCTCCTGTGCTGGACAGCGACGGCTCATTCTTCCTGTACAG
CAAGCTGACAGTGGACAAGAGCAGATGGCAGCAGGGCAACGT
GTTCAGCTGCAGCGTGATGCACGAGGCCCTGCACAATCACTAC
ACCCAGAAGTCCCTGTCTCTGAGCCCCGGCAAGATGAGCATCA
GAGGCGTTGGCGGCAACGGCAACAGCAGAATCCCTAGCCATA
ATGGCGACGGCAGCAACAGGCGGAGCCAGAATACCAAGGGCA
ACAACAAGGTGGAAGATCGCGTGTGCAGCCTGTACTCCAGCA
GAAGCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTCGACG
TGTCCAGCATGATCGAGAGCACACCTACCAGCGGCGAGACAA
CCAGAGCTAGTAGAGGCGTGCTGAGCCGGTTTCAGAGAGGCC
TCGTTCGGATCGCTGACAAAGTGCGGAGAGCCGTGCAGTGTGC
CTGGTCTAGTGTGTCCACCAGCAGATCCTCTGCCACAAGAGCC
GCCGAGTCTGGCAGCTCTAGCAGAACAGCTAGAGGCGCCAGC
AGCGGCTACAGAGAGTATTCTCCATCTGCCGCCAGAGGCCTGC
GGCTGATGTTTACAGATTTCTGGCGGACCCGGGTGCTGAGACA
GACATCTCCTATGGCTGGCGTGTTCGGCAACCTGGATGTGAAT
GAGGCCAGACTGATGGCCGCCTACACAAGCGAATGTGCCGAT
CACCTGGAAGCCAAAGAGCTGGCTGGACCTGACGGTGTTGCC
GCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAGTGCGG
GACCTGCAGGATAAGGGCGCTGCTAGAAAGCTGCTGAACGAC
CCTCTGGGCAGAAGAACCCCTAACTACCAGAGCAAGAACCCC
GGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGGACCTC
AGGTGGCCAACCTGCAGAATGTGGATACCGGCTTCTGGCTGGA
TATGAGCAACCTGAGCGACGTGGTGCTGTCCAGAGAGATCCA
GACAGGCCTGAGAGCCAGAGCCACACTGGAAGAGTCCATGCC
TATGCTCGAGAACCTGGAAGAGAGATTCCGGCGGCTGCAAGA
GACATGTGACGCCGCCAGAACCGAGATCGAGGAAAGCGGCTG
GACCAGAGAAAGCGCCTCCAGAATGGAAGGCGACGAAGCCCA
AGGACCTAGCAGAGTGCAGCAGGCCTTCCAGAGCTTCGTGAA
CGAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCGGCGAA
CATGTGCGGGTGCTGTGTGCCAGAGTTAGCAGAGGACTTGCTG
CCGCTGGCGAGGCCATCAGAAGATGCTTCTCTTGCTGCAAGGG
CAGCACCCACAGATACGCCCCTAGAGATGATCTGAGCCCTGA
GGGCGCATCTCTGGCCGAAACACTGGCCAGATTCGCCGACGAT
ATGGGCATTGAAAGAGGCGCCGACGGAACCTACGACATCCCT
CTGGTGGACGATTGGAGAAGGGGCGTGCCATCTATCGAAGGC
GAGGGCAGCGATAGCATCTACGAGATCATGATGCCCATCTAC
GAAGTGATGAACATGGACCTGGAAACCCGGCGGAGCTTCGCT
GTTCAGCAGGGCCATTACCAGGATCCTAGAGCCAGCGACTAC
GACCTGCCTAGAGCCTCCGATTATGATCTGCCTCGGAGCCCCT
ATCCTACACCTCCACTGCCACCTAGATACCAGCTCCAGAATAT
GGACGTGGAAGCCGGATTCCGCGAGGCCGTGTATGCTAGCTTT
GTGGCCGGCATGTACAACTACGTGGTCACCCAGCCTCAAGAGC
GGATCCCCAATTCTCAGCAGGTCGAGGGCATCCTGAGGGACAT
GCTGACAAATGGCAGCCAGACCTTCCGGGACCTGATGAAGAG
ATGGAACAGAGAGGTGGACAGAGAG Ct875_E_nFc_cHis
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 219
TGCCTGATACAACCGGCGAGCCTAAGAGCTGCGACAAGACCC
ACACCTGTCCTCCATGTCCTGCTCCAGAACTGCTCGGCGGACC
TTCCGTGTTCCTGTTTCCTCCAAAGCCTAAGGACACCCTGATG
ATCAGCAGAACCCCTGAAGTGACCTGCGTGGTGGTGGATGTGT
CCCACGAGGATCCCGAAGTGAAGTTCAATTGGTACGTGGACG
GCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGAGAGGAAC
AGTACAACAGCACCTACAGAGTGGTGTCCGTGCTGACCGTGCT
GCACCAGGATTGGCTGAACGGCAAAGAGTACAAGTGCAAGGT
GTCCAACAAGGCCCTGCCTGCTCCTATCGAGAAGACCATCAGC
AAGGCCAAGGGCCAGCCAAGAGAACCCCAGGTGTACACACTG
CCTCCAAGCAGAGATGAGCTGACCAAGAACCAGGTGTCCCTG
ACCTGTCTGGTCAAGGGCTTCTACCCCTCCGATATCGCCGTGG
AATGGGAGAGCAATGGCCAGCCTGAGAACAACTACAAGACAA
CCCCTCCTGTGCTGGACAGCGACGGCTCATTCTTCCTGTACAG
CAAGCTGACAGTGGACAAGAGCAGATGGCAGCAGGGCAACGT
GTTCAGCTGCAGCGTGATGCACGAGGCCCTGCACAATCACTAC
ACCCAGAAGTCCCTGTCTCTGAGCCCCGGCAAGATGAGCATCA
GAGGCGTTGGCGGCAACGGCAACAGCAGAATCCCTAGCCATA
ATGGCGACGGCAGCAACAGGCGGAGCCAGAATACCAAGGGCA
ACAACAAGGTGGAAGATCGCGTGTGCAGCCTGTACTCCAGCA
GAAGCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTCGACG
TGTCCAGCATGATCGAGAGCACACCTACCAGCGGCGAGACAA
CCAGAGCTAGTAGAGGCGTGCTGAGCCGGTTTCAGAGAGGCC
TCGTTCGGATCGCTGACAAAGTGCGGAGAGCCGTGCAGTGTGC
CTGGTCTAGTGTGTCCACCAGCAGATCCTCTGCCACAAGAGCC
GCCGAGTCTGGCAGCTCTAGCAGAACAGCTAGAGGCGCCAGC
AGCGGCTACAGAGAGTATTCTCCATCTGCCGCCAGAGGCCTGC
GGCTGATGTTTACAGATTTCTGGCGGACCCGGGTGCTGAGACA
GACATCTCCTATGGCTGGCGTGTTCGGCAACCTGGATGTGAAT
GAGGCCAGACTGATGGCCGCCTACACAAGCGAATGTGCCGAT
CACCTGGAAGCCAAAGAGCTGGCTGGACCTGACGGTGTTGCC
GCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGAGTGCGG
GACCTGCAGGATAAGGGCGCTGCTAGAAAGCTGCTGAACGAC
CCTCTGGGCAGAAGAACCCCTAACTACCAGAGCAAGAACCCC
GGCGAGTACACCGTGGGCAACTCCATGTTCTACGACGGACCTC
AGGTGGCCAACCTGCAGAATGTGGATACCGGCTTCTGGCTGGA
TATGAGCAACCTGAGCGACGTGGTGCTGTCCAGAGAGATCCA
GACAGGCCTGAGAGCCAGAGCCACACTGGAAGAGTCCATGCC
TATGCTCGAGAACCTGGAAGAGAGATTCCGGCGGCTGCAAGA
GACATGTGACGCCGCCAGAACCGAGATCGAGGAAAGCGGCTG
GACCAGAGAAAGCGCCTCCAGAATGGAAGGCGACGAAGCCCA
AGGACCTAGCAGAGTGCAGCAGGCCTTCCAGAGCTTCGTGAA
CGAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTCGGCGAA
CATGTGCGGGTGCTGTGTGCCAGAGTTAGCAGAGGACTTGCTG
CCGCTGGCGAGGCCATCAGAAGATGCTTCTCTTGCTGCAAGGG
CAGCACCCACAGATACGCCCCTAGAGATGATCTGAGCCCTGA
GGGCGCATCTCTGGCCGAAACACTGGCCAGATTCGCCGACGAT
ATGGGCATTGAAAGAGGCGCCGACGGAACCTACGACATCCCT
CTGGTGGACGATTGGAGAAGGGGCGTGCCATCTATCGAAGGC
GAGGGCAGCGATAGCATCTACGAGATCATGATGCCCATCTAC
GAAGTGATGAACATGGACCTGGAAACCCGGCGGAGCTTCGCT
GTTCAGCAGGGCCATTACCAGGATCCTAGAGCCAGCGACTAC
GACCTGCCTAGAGCCTCCGATTATGATCTGCCTCGGAGCCCCT
ATCCTACACCTCCACTGCCACCTAGATACCAGCTCCAGAATAT
GGACGTGGAAGCCGGATTCCGCGAGGCCGTGTATGCTAGCTTT
GTGGCCGGCATGTACAACTACGTGGTCACCCAGCCTCAAGAGC
GGATCCCCAATTCTCAGCAGGTCGAGGGCATCCTGAGGGACAT
GCTGACAAATGGCAGCCAGACCTTCCGGGACCTGATGAAGAG
ATGGAACAGAGAGGTGGACCGCGAGCACCACCACCATCACCAT Ct043_E_NGM_nIgK_no4A
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 220
TGCCTGATACCACCGGAATGAGCAGACAGAACGCCGAGGAGA
ACCTGAAGAACTTCGCCAAAGAGCTGAAGCTGCCCGACGTGG
CCTTCGACCAGAACAATGCCTGCATCCTGTTCGTGGACGGCGA
GTTCTCTCTGCACCTGACCTACGAGGAACACAGCGACCGGCTG
TATGTGTACGCCCCTCTGCTGGATGGCCTGCCTGACAACCCTC
AGAGAAAGCTGGCCCTGTACGAGAAGCTGCTGGAAGGCTCTA
TGCTCGGCGGACAAATGGCTGGTGGCGGAGTGGGAGTTGCCA
CCAAAGAACAGCTGATCCTGATGCACTGCGTGCTGGACATGA
AGTACGCCGAGACTAACCTGCTGAAGGCTTTCGCCCAGCTGTT
CATCGAGACAGTGGTCAAGTGGCGGACCGTGTGCAGCGATAT
TAGCGCCGGCAGAGAACCCACCGTGGACACCATGCCTCAAAT
GCCACAAGGCGGCGGAGGCGGAATTCAACCTCCTCCAGCCGG AATTAGAGCC
Ct043_E_NGM_nIgK_cHis_no4A
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 221
TGCCTGATACCACCGGAATGAGCAGACAGAACGCCGAGGAGA
ACCTGAAGAACTTCGCCAAAGAGCTGAAGCTGCCCGACGTGG
CCTTCGACCAGAACAATGCCTGCATCCTGTTCGTGGACGGCGA
GTTCTCTCTGCACCTGACCTACGAGGAACACAGCGACCGGCTG
TATGTGTACGCCCCTCTGCTGGATGGCCTGCCTGACAACCCTC
AGAGAAAGCTGGCCCTGTACGAGAAGCTGCTGGAAGGCTCTA
TGCTCGGCGGACAAATGGCTGGTGGCGGAGTGGGAGTTGCCA
CCAAAGAACAGCTGATCCTGATGCACTGCGTGCTGGACATGA
AGTACGCCGAGACTAACCTGCTGAAGGCTTTCGCCCAGCTGTT
CATCGAGACAGTGGTCAAGTGGCGGACCGTGTGCAGCGATAT
TAGCGCCGGCAGAGAACCCACCGTGGACACCATGCCTCAAAT
GCCACAAGGCGGCGGAGGCGGAATTCAACCTCCTCCAGCCGG
AATCAGAGCCCACCACCATCACCATCAT Ct043_E_nIgK_no4A
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 222
TGCCTGATACCACCGGAATGAGCAGACAGAACGCCGAGGAGA
ACCTGAAGAACTTCGCCAAAGAGCTGAAGCTGCCCGACGTGG
CCTTCGACCAGAACAATACCTGCATCCTGTTCGTGGACGGCGA
GTTCAGCCTGCACCTGACCTACGAGGAACACAGCGACCGGCT
GTATGTGTACGCCCCTCTGCTGGATGGCCTGCCTGACAACCCT
CAGAGAAAGCTGGCCCTGTACGAGAAGCTGCTGGAAGGCTCT
ATGCTCGGCGGACAAATGGCTGGTGGCGGAGTGGGAGTTGCC
ACCAAAGAACAGCTGATCCTGATGCACTGCGTGCTGGACATG
AAGTACGCCGAGACTAACCTGCTGAAGGCTTTCGCCCAGCTGT
TCATCGAGACAGTGGTCAAGTGGCGGACCGTGTGCAGCGATA
TTAGCGCCGGCAGAGAACCCACCGTGGACACCATGCCTCAAA
TGCCACAAGGCGGCGGAGGCGGAATTCAACCTCCTCCAGCCG GAATTAGAGCC
Ct043_E_nIgK_cHis_no4A ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC
223 TGCCTGATACCACCGGAATGAGCAGACAGAACGCCGAGGAGA
ACCTGAAGAACTTCGCCAAAGAGCTGAAGCTGCCCGACGTGG
CCTTCGACCAGAACAATACCTGCATCCTGTTCGTGGACGGCGA
GTTCAGCCTGCACCTGACCTACGAGGAACACAGCGACCGGCT
GTATGTGTACGCCCCTCTGCTGGATGGCCTGCCTGACAACCCT
CAGAGAAAGCTGGCCCTGTACGAGAAGCTGCTGGAAGGCTCT
ATGCTCGGCGGACAAATGGCTGGTGGCGGAGTGGGAGTTGCC
ACCAAAGAACAGCTGATCCTGATGCACTGCGTGCTGGACATG
AAGTACGCCGAGACTAACCTGCTGAAGGCTTTCGCCCAGCTGT
TCATCGAGACAGTGGTCAAGTGGCGGACCGTGTGCAGCGATA
TTAGCGCCGGCAGAGAACCCACCGTGGACACCATGCCTCAAA
TGCCACAAGGCGGCGGAGGCGGAATTCAACCTCCTCCAGCCG
GAATCAGAGCCCACCACCATCACCATCAT
Chlamydia_Ct812_pd_serovarD_nIgK_cHis_nopolyN
ATGGAAACTCCTGCCCAACTGTTGTTCCTTCTGCTGCTCTGGTT 224
GCCCGACACCACCGGATCGTGCGTGGATCTCCACGCTGGCGGC
CAGTCCGTGAACGAGCTTGTGTACGTGGGCCCACAGGCCGTGC
TTCTGCTGGACCAGATCAGAGATCTCTTCGTGGGTTCCAAGGA
CTCCCAGGCCGAGGGACAGTACCGGCTCATCGTCGGCGACCCT
TCAAGCTTCCAAGAGAAGGATGCCGACACTCTTCCGGGGAAG
GTGGAACAGTCCACTCTGTTTTCCGTGACCAACCCAGTCGTGT
TTCAAGGGGTGGACCAGCAGGACCAGGTGTCCAGCCAAGGAC
TGATCTGTTCATTCACCTCGAGCAATTTGGACAGCCCCCGGGA
CGGCGAATCGTTCCTTGGCATCGCATTCGTGGGAGACTCATCC
AAAGCAGGAATCACCCTTACCGATGTGAAGGCGTCCCTGAGC
GGCGCTGCTCTGTACTCCACCGAAGATCTCATCTTCGAGAAGA
TCAAGGGTGGACTGGAGTTCGCCAGCTGCTCCTCACTGGAACA
GGGAGGAGCCTGTGCCGCCCAAAGCATCCTCATCCACGATTGC
CAGGGGCTCCAAGTGAAGCATTGTACCACTGCCGTGAACGCC
GAGGGATCATCCGCTAACGATCACCTCGGTTTCGGAGGGGGTG
CCTTCTTCGTGACCGGTTCGCTGTCGGGAGAGAAGTCACTGTA
TATGCCCGCGGGCGACATGGTGGTCGCCAACTGCGATGGAGC
CATCTCATTCGAGGGAAACTCCGCCAACTTCGCAAACGGCGGC
GCTATCGCCGCTAGCGGGAAGGTGCTGTTCGTGGCTAACGACA
AGAAGACGTCCTTCATCGAGAACCGCGCCCTGTCGGGAGGTG
CCATTGCCGCCAGCTCCGACATTGCCTTCCAGAACTGTGCGGA
ACTGGTGTTCAAAGGAAACTGCGCCATCGGCACCGAAGATAA
GGGAAGCCTGGGAGGCGGCGCCATTTCCTCCCTCGGCACCGTG
CTGCTTCAGGGAAACCACGGCATCACTTGTGACAAGAACGAA
AGCGCGTCCCAGGGGGGAGCGATCTTCGGGAAGAACTGCCAG
ATTTCCGACAACGAGGGACCGGTGGTGTTCAGAGACTCCACTG
CCTGCCTGGGCGGCGGAGCGATCGCAGCACAGGAAATTGTCA
GCATCCAGAACAACCAGGCCGGCATCAGCTTCGAGGGGGGAA
AGGCTTCGTTCGGCGGAGGTATTGCCTGCGGATCGTTCTCGTC
CGCGGGCGGAGCCTCCGTGCTCGGAACCATCGACATTTCCAAG
AACCTGGGCGCTATCTCGTTTTCTCGCACCCTGTGCACTACTTC
CGACCTGGGTCAGATGGAGTACCAGGGAGGCGGAGCGCTGTT
TGGAGAGAACATCTCTCTGAGCGAGAACGCGGGAGTGCTGAC
CTTCAAGGACAACATTGTGAAGACCTTCGCCTCAAACGGAAA
GATCCTGGGGGGAGGCGCCATCCTGGCAACCGGGAAGGTCGA
AATCACCAACAATTCAGAGGGTATCTCCTTCACTGGCAACGCC
CGGGCCCCCCAAGCCCTGCCGACTCAGGAAGAGTTCCCCCTGT
TCTCCAAGAAGGAAGGACGCCCTTTGTCATCCGGCTACTCCGG
TGGTGGAGCGATTCTGGGTCGGGAAGTGGCCATCCTGCATAAT
GCGGCCGTGGTGTTTGAGCAGAACAGACTCCAATGCTCCGAA
GAAGAGGCCACCCTCCTGGGGTGCTGCGGGGGCGGAGCAGTG
CATGGCATGGATTCCACTTCCATCGTGGGAAACTCCAGCGTCC
GCTTCGGAAACAACTACGCTATGGGACAGGGAGTGTCAGGCG
GGGCCCTGCTGTCCAAGACCGTCCAGTTGGCCGGAAACGGTTC
GGTGGATTTCTCACGCAATATCGCCTCGCTGGGAGGCGGCGCG
CTGCAGGCCTCCGAAGGAAATTGCGAACTGGTCGACAACGGC
TACGTGCTGTTCCGGGACAACCGCGGCAGGGTGTACGGCGGA
GCAATCTCGTGCCTTCGGGGCGACGTCGTGATCTCGGGAAATA
AGGGACGGGTCGAGTTTAAGGACAACATCGCTACCAGGCTCT
ACGTGGAGGAAACTGTGGAGAAGGTGGAGGAAGTGGAGCCTG
CCCCGGAACAGAAGGACAACAACGAGCTGTCGTTCCTCGGTC
GGGCAGAACAGTCCTTCATTACTGCCGCCAACCAGGCCCTGTT
CGCGTCCGAAGATGGTGACCTCAGCCCGGAATCCAGCATCTCC
TCCGAGGAACTGGCCAAGCGGAGAGAATGCGCGGGAGGCGCA
ATCTTTGCGAAGCGGGTCCGGATCGTGGACAACCAGGAAGCT
GTGGTGTTCAGCAACAACTTTTCCGACATCTACGGTGGTGCAA
TTTTCACCGGCTCACTCCGGGAGGAGGACAAGCTGGACGGCC
AGATTCCCGAGGTGCTCATTTCCGGCAATGCCGGCGACGTGGT
GTTCTCCGGAAACTCCTCCAAGAGGGACGAACACCTCCCGCAT
ACCGGAGGAGGAGCCATCTGCACTCAGAACCTGACGATCTCG
CAGAACACCGGCAATGTGCTGTTCTACAACAACGTCGCATGTT
CCGGTGGCGCCGTCAGAATCGAGGACCACGGAAACGTGCTGC
TGGAAGCATTCGGGGGTGATATTGTGTTCAAGGGAAACAGCA
GCTTCCGGGCCCAGGGATCAGATGCAATCTACTTCGCCGGGAA
GGAGAGCCACATTACCGCCCTGAACGCCACCGAGGGTCACGC
CATCGTGTTCCACGATGCCCTGGTGTTCGAGAACCTGGAGGAG
CGCAAGAGCGCCGAAGTGCTGCTTATCAATTCCCGCGAGAACC
CGGGCTACACCGGATCCATCCGGTTCCTCGAAGCGGAGTCGAA
GGTCCCGCAGTGTATTCATGTGCAACAGGGGTCCCTGGAACTG
CTTAACGGAGCCACCCTGTGCTCCTACGGCTTTAAGCAGGACG
CGGGCGCTAAACTGGTGCTGGCGGCCGGCGCCAAGCTTAAGA
TCCTCGACTCCGGAACCCCGGTGCAGCAGGGGCACGCTATTAG
CAAGCCTGAAGCCGAGATTGAGTCGTCATCCGAACCCGAAGG
GGCGCACTCCCTGTGGATAGCCAAGAACGCGCAGACCACCGT
GCCAATGGTCGATATCCACACAATCTCCGTGGACCTCGCCAGC
TTCTCGTCGAGCCAGCAGGAGGGAACTGTCGAAGCGCCTCAG
GTCATCGTGCCGGGAGGTTCCTACGTGCGCTCGGGGGAGCTCA
ACCTGGAACTCGTGAATACCACTGGAACGGGATATGAGAACC
ACGCCCTGCTGAAGAACGAAGCCAAAGTGCCACTGATGTCCTT
CGTCGCCTCCGGCGACGAGGCCTCCGCCGAGATTAGCAACCTG
TCGGTGTCAGATCTGCAAATTCACGTGGTGACCCCTGAGATTG
AGGAGGACACCTACGGGCACATGGGCGATTGGTCCGAGGCGA
AGATCCAGGACGGCACACTGGTCATTTCATGGAACCCTACCGG ACATCACCACCACCATCAC
Chlamydia_Ct812_pd_serovarD_nIgK_nopolyN
ATGGAAACTCCTGCCCAACTGTTGTTCCTTCTGCTGCTCTGGTT 225
GCCCGACACCACCGGATCGTGCGTGGATCTCCACGCTGGCGGC
CAGTCCGTGAACGAGCTTGTGTACGTGGGCCCACAGGCCGTGC
TTCTGCTGGACCAGATCAGAGATCTCTTCGTGGGTTCCAAGGA
CTCCCAGGCCGAGGGACAGTACCGGCTCATCGTCGGCGACCCT
TCAAGCTTCCAAGAGAAGGATGCCGACACTCTTCCGGGGAAG
GTGGAACAGTCCACTCTGTTTTCCGTGACCAACCCAGTCGTGT
TTCAAGGGGTGGACCAGCAGGACCAGGTGTCCAGCCAAGGAC
TGATCTGTTCATTCACCTCGAGCAATTTGGACAGCCCCCGGGA
CGGCGAATCGTTCCTTGGCATCGCATTCGTGGGAGACTCATCC
AAAGCAGGAATCACCCTTACCGATGTGAAGGCGTCCCTGAGC
GGCGCTGCTCTGTACTCCACCGAAGATCTCATCTTCGAGAAGA
TCAAGGGTGGACTGGAGTTCGCCAGCTGCTCCTCACTGGAACA
GGGAGGAGCCTGTGCCGCCCAAAGCATCCTCATCCACGATTGC
CAGGGGCTCCAAGTGAAGCATTGTACCACTGCCGTGAACGCC
GAGGGATCATCCGCTAACGATCACCTCGGTTTCGGAGGGGGTG
CCTTCTTCGTGACCGGTTCGCTGTCGGGAGAGAAGTCACTGTA
TATGCCCGCGGGCGACATGGTGGTCGCCAACTGCGATGGAGC
CATCTCATTCGAGGGAAACTCCGCCAACTTCGCAAACGGCGGC
GCTATCGCCGCTAGCGGGAAGGTGCTGTTCGTGGCTAACGACA
AGAAGACGTCCTTCATCGAGAACCGCGCCCTGTCGGGAGGTG
CCATTGCCGCCAGCTCCGACATTGCCTTCCAGAACTGTGCGGA
ACTGGTGTTCAAAGGAAACTGCGCCATCGGCACCGAAGATAA
GGGAAGCCTGGGAGGCGGCGCCATTTCCTCCCTCGGCACCGTG
CTGCTTCAGGGAAACCACGGCATCACTTGTGACAAGAACGAA
AGCGCGTCCCAGGGGGGAGCGATCTTCGGGAAGAACTGCCAG
ATTTCCGACAACGAGGGACCGGTGGTGTTCAGAGACTCCACTG
CCTGCCTGGGCGGCGGAGCGATCGCAGCACAGGAAATTGTCA
GCATCCAGAACAACCAGGCCGGCATCAGCTTCGAGGGGGGAA
AGGCTTCGTTCGGCGGAGGTATTGCCTGCGGATCGTTCTCGTC
CGCGGGCGGAGCCTCCGTGCTCGGAACCATCGACATTTCCAAG
AACCTGGGCGCTATCTCGTTTTCTCGCACCCTGTGCACTACTTC
CGACCTGGGTCAGATGGAGTACCAGGGAGGCGGAGCGCTGTT
TGGAGAGAACATCTCTCTGAGCGAGAACGCGGGAGTGCTGAC
CTTCAAGGACAACATTGTGAAGACCTTCGCCTCAAACGGAAA
GATCCTGGGGGGAGGCGCCATCCTGGCAACCGGGAAGGTCGA
AATCACCAACAATTCAGAGGGTATCTCCTTCACTGGCAACGCC
CGGGCCCCCCAAGCCCTGCCGACTCAGGAAGAGTTCCCCCTGT
TCTCCAAGAAGGAAGGACGCCCTTTGTCATCCGGCTACTCCGG
TGGTGGAGCGATTCTGGGTCGGGAAGTGGCCATCCTGCATAAT
GCGGCCGTGGTGTTTGAGCAGAACAGACTCCAATGCTCCGAA
GAAGAGGCCACCCTCCTGGGGTGCTGCGGGGGCGGAGCAGTG
CATGGCATGGATTCCACTTCCATCGTGGGAAACTCCAGCGTCC
GCTTCGGAAACAACTACGCTATGGGACAGGGAGTGTCAGGCG
GGGCCCTGCTGTCCAAGACCGTCCAGTTGGCCGGAAACGGTTC
GGTGGATTTCTCACGCAATATCGCCTCGCTGGGAGGCGGCGCG
CTGCAGGCCTCCGAAGGAAATTGCGAACTGGTCGACAACGGC
TACGTGCTGTTCCGGGACAACCGCGGCAGGGTGTACGGCGGA
GCAATCTCGTGCCTTCGGGGCGACGTCGTGATCTCGGGAAATA
AGGGACGGGTCGAGTTTAAGGACAACATCGCTACCAGGCTCT
ACGTGGAGGAAACTGTGGAGAAGGTGGAGGAAGTGGAGCCTG
CCCCGGAACAGAAGGACAACAACGAGCTGTCGTTCCTCGGTC
GGGCAGAACAGTCCTTCATTACTGCCGCCAACCAGGCCCTGTT
CGCGTCCGAAGATGGTGACCTCAGCCCGGAATCCAGCATCTCC
TCCGAGGAACTGGCCAAGCGGAGAGAATGCGCGGGAGGCGCA
ATCTTTGCGAAGCGGGTCCGGATCGTGGACAACCAGGAAGCT
GTGGTGTTCAGCAACAACTTTTCCGACATCTACGGTGGTGCAA
TTTTCACCGGCTCACTCCGGGAGGAGGACAAGCTGGACGGCC
AGATTCCCGAGGTGCTCATTTCCGGCAATGCCGGCGACGTGGT
GTTCTCCGGAAACTCCTCCAAGAGGGACGAACACCTCCCGCAT
ACCGGAGGAGGAGCCATCTGCACTCAGAACCTGACGATCTCG
CAGAACACCGGCAATGTGCTGTTCTACAACAACGTCGCATGTT
CCGGTGGCGCCGTCAGAATCGAGGACCACGGAAACGTGCTGC
TGGAAGCATTCGGGGGTGATATTGTGTTCAAGGGAAACAGCA
GCTTCCGGGCCCAGGGATCAGATGCAATCTACTTCGCCGGGAA
GGAGAGCCACATTACCGCCCTGAACGCCACCGAGGGTCACGC
CATCGTGTTCCACGATGCCCTGGTGTTCGAGAACCTGGAGGAG
CGCAAGAGCGCCGAAGTGCTGCTTATCAATTCCCGCGAGAACC
CGGGCTACACCGGATCCATCCGGTTCCTCGAAGCGGAGTCGAA
GGTCCCGCAGTGTATTCATGTGCAACAGGGGTCCCTGGAACTG
CTTAACGGAGCCACCCTGTGCTCCTACGGCTTTAAGCAGGACG
CGGGCGCTAAACTGGTGCTGGCGGCCGGCGCCAAGCTTAAGA
TCCTCGACTCCGGAACCCCGGTGCAGCAGGGGCACGCTATTAG
CAAGCCTGAAGCCGAGATTGAGTCGTCATCCGAACCCGAAGG
GGCGCACTCCCTGTGGATAGCCAAGAACGCGCAGACCACCGT
GCCAATGGTCGATATCCACACAATCTCCGTGGACCTCGCCAGC
TTCTCGTCGAGCCAGCAGGAGGGAACTGTCGAAGCGCCTCAG
GTCATCGTGCCGGGAGGTTCCTACGTGCGCTCGGGGGAGCTCA
ACCTGGAACTCGTGAATACCACTGGAACGGGATATGAGAACC
ACGCCCTGCTGAAGAACGAAGCCAAAGTGCCACTGATGTCCTT
CGTCGCCTCCGGCGACGAGGCCTCCGCCGAGATTAGCAACCTG
TCGGTGTCAGATCTGCAAATTCACGTGGTGACCCCTGAGATTG
AGGAGGACACCTACGGGCACATGGGCGATTGGTCCGAGGCGA
AGATCCAGGACGGCACACTGGTCATTTCATGGAACCCTACCGGA
Ct812pd_PmpD_D_NGM_nIgK_nopolyN
ATGGAAACTCCTGCCCAACTGTTGTTCCTTCTGCTGCTCTGGTT 226
GCCCGACACCACCGGATCGTGCGTGGATCTCCACGCTGGCGGC
CAGTCCGTGAACGAGCTTGTGTACGTGGGCCCACAGGCCGTGC
TTCTGCTGGACCAGATCAGAGATCTCTTCGTGGGTTCCAAGGA
CTCCCAGGCCGAGGGACAGTACCGGCTCATCGTCGGCGACCCT
TCAAGCTTCCAAGAGAAGGATGCCGACACTCTTCCGGGGAAG
GTGGAACAGTCCACTCTGTTTTCCGTGACCAACCCAGTCGTGT
TTCAAGGGGTGGACCAGCAGGACCAGGTGTCCAGCCAAGGAC
TGATCTGTTCATTCACCTCGAGCAATTTGGACAGCCCCCGGGA
CGGCGAATCGTTCCTTGGCATCGCATTCGTGGGAGACTCATCC
AAAGCAGGAATCACCCTTACCGATGTGAAGGCGTCCCTGAGC
GGCGCTGCTCTGTACTCCACCGAAGATCTCATCTTCGAGAAGA
TCAAGGGTGGACTGGAGTTCGCCAGCTGCTCCTCACTGGAACA
GGGAGGAGCCTGTGCCGCCCAAAGCATCCTCATCCACGATTGC
CAGGGGCTCCAAGTGAAGCATTGTACCACTGCCGTGAACGCC
GAGGGATCATCCGCTAACGATCACCTCGGTTTCGGAGGGGGTG
CCTTCTTCGTGACCGGTTCGCTGTCGGGAGAGAAGTCACTGTA
TATGCCCGCGGGCGACATGGTGGTCGCCAACTGCGATGGAGC
CATCTCATTCGAGGGAAACTCCGCCAACTTCGCAAACGGCGGC
GCTATCGCCGCTAGCGGGAAGGTGCTGTTCGTGGCTAACGACA
AGAAGACGTCCTTCATCGAGAACCGCGCCCTGTCGGGAGGTG
CCATTGCCGCCAGCTCCGACATTGCCTTCCAGAACTGTGCGGA
ACTGGTGTTCAAAGGAAACTGCGCCATCGGCACCGAAGATAA
GGGAAGCCTGGGAGGCGGCGCCATTTCCTCCCTCGGCACCGTG
CTGCTTCAGGGAAACCACGGCATCACTTGTGACAAGAACGAA
GCAGCGTCCCAGGGGGGAGCGATCTTCGGGAAGAACTGCCAG
ATTTCCGACAACGAGGGACCGGTGGTGTTCAGAGACTCCACTG
CCTGCCTGGGCGGCGGAGCGATCGCAGCACAGGAAATTGTCA
GCATCCAGAACAACCAGGCCGGCATCAGCTTCGAGGGGGGAA
AGGCTTCGTTCGGCGGAGGTATTGCCTGCGGATCGTTCTCGTC
CGCGGGCGGAGCCTCCGTGCTCGGAACCATCGACATTTCCAAG
AACCTGGGCGCTATCTCGTTTTCTCGCACCCTGTGCACTACTTC
CGACCTGGGTCAGATGGAGTACCAGGGAGGCGGAGCGCTGTT
TGGAGAGAACATCGCTCTGAGCGAGAACGCGGGAGTGCTGAC
CTTCAAGGACAACATTGTGAAGACCTTCGCCTCAAACGGAAA
GATCCTGGGGGGAGGCGCCATCCTGGCAACCGGGAAGGTCGA
AATCACCAACAATGCAGAGGGTATCTCCTTCACTGGCAACGCC
CGGGCCCCCCAAGCCCTGCCGACTCAGGAAGAGTTCCCCCTGT
TCTCCAAGAAGGAAGGACGCCCTTTGTCATCCGGCTACTCCGG
TGGTGGAGCGATTCTGGGTCGGGAAGTGGCCATCCTGCATAAT
GCGGCCGTGGTGTTTGAGCAGAACAGACTCCAATGCTCCGAA
GAAGAGGCCACCCTCCTGGGGTGCTGCGGGGGCGGAGCAGTG
CATGGCATGGATTCCACTTCCATCGTGGGAAACTCCGCAGTCC
GCTTCGGAAACAACTACGCTATGGGACAGGGAGTGTCAGGCG
GGGCCCTGCTGTCCAAGACCGTCCAGTTGGCCGGAAACGGTGC
GGTGGATTTCTCACGCAATATCGCCTCGCTGGGAGGCGGCGCG
CTGCAGGCCTCCGAAGGAAATTGCGAACTGGTCGACAACGGC
TACGTGCTGTTCCGGGACAACCGCGGCAGGGTGTACGGCGGA
GCAATCTCGTGCCTTCGGGGCGACGTCGTGATCTCGGGAAATA
AGGGACGGGTCGAGTTTAAGGACAACATCGCTACCAGGCTCT
ACGTGGAGGAAACTGTGGAGAAGGTGGAGGAAGTGGAGCCTG
CCCCGGAACAGAAGGACAACAACGAGCTGTCGTTCCTCGGTC
GGGCAGAACAGTCCTTCATTACTGCCGCCAACCAGGCCCTGTT
CGCGTCCGAAGATGGTGACCTCAGCCCGGAATCCAGCATCTCC
TCCGAGGAACTGGCCAAGCGGAGAGAATGCGCGGGAGGCGCA
ATCTTTGCGAAGCGGGTCCGGATCGTGGACAACCAGGAAGCT
GTGGTGTTCAGCAACAACTTTGCCGACATCTACGGTGGTGCAA
TTTTCACCGGCTCACTCCGGGAGGAGGACAAGCTGGACGGCC
AGATTCCCGAGGTGCTCATTTCCGGCAATGCCGGCGACGTGGT
GTTCTCCGGAAACTCCGCCAAGAGGGACGAACACCTCCCGCAT
ACCGGAGGAGGAGCCATCTGCACTCAGAACCTGGCAATCTCG
CAGAACACCGGCAATGTGCTGTTCTACAACAACGTCGCATGTT
CCGGTGGCGCCGTCAGAATCGAGGACCACGGAAACGTGCTGC
TGGAAGCATTCGGGGGTGATATTGTGTTCAAGGGAAACAGCG
CATTCCGGGCCCAGGGATCAGATGCAATCTACTTCGCCGGGAA
GGAGAGCCACATTACCGCCCTGAACGCCGCCGAGGGTCACGC
CATCGTGTTCCACGATGCCCTGGTGTTCGAGAACCTGGAGGAG
CGCAAGAGCGCCGAAGTGCTGCTTATCAATTCCCGCGAGAACC
CGGGCTACACCGGATCCATCCGGTTCCTCGAAGCGGAGTCGAA
GGTCCCGCAGTGTATTCATGTGCAACAGGGGTCCCTGGAACTG
CTTAACGGAGCCACCCTGTGCTCCTACGGCTTTAAGCAGGACG
CGGGCGCTAAACTGGTGCTGGCGGCCGGCGCCAAGCTTAAGA
TCCTCGACTCCGGAACCCCGGTGCAGCAGGGGCACGCTATTAG
CAAGCCTGAAGCCGAGATTGAGTCGTCATCCGAACCCGAAGG
GGCGCACTCCCTGTGGATAGCCAAGAACGCGCAGACCACCGT
GCCAATGGTCGATATCCACACAATCTCCGTGGACCTCGCCAGC
TTCTCGTCGAGCCAGCAGGAGGGAACTGTCGAAGCGCCTCAG
GTCATCGTGCCGGGAGGTTCCTACGTGCGCTCGGGGGAGCTCA
ACCTGGAACTCGTGAATACCGCTGGAACGGGATATGAGAACC
ACGCCCTGCTGAAGAACGAAGCCAAAGTGCCACTGATGTCCTT
CGTCGCCTCCGGCGACGAGGCCTCCGCCGAGATTAGCAACCTG
GCGGTGTCAGATCTGCAAATTCACGTGGTGACCCCTGAGATTG
AGGAGGACACCTACGGGCACATGGGCGATTGGTCCGAGGCGA
AGATCCAGGACGGCACACTGGTCATTTCATGGAACCCTGCCGGA
Ct812pd_PmpD_D_NGM_nIgK_cHis_nopolyN
ATGGAAACTCCTGCCCAACTGTTGTTCCTTCTGCTGCTCTGGTT 227
GCCCGACACCACCGGATCGTGCGTGGATCTCCACGCTGGCGGC
CAGTCCGTGAACGAGCTTGTGTACGTGGGCCCACAGGCCGTGC
TTCTGCTGGACCAGATCAGAGATCTCTTCGTGGGTTCCAAGGA
CTCCCAGGCCGAGGGACAGTACCGGCTCATCGTCGGCGACCCT
TCAAGCTTCCAAGAGAAGGATGCCGACACTCTTCCGGGGAAG
GTGGAACAGTCCACTCTGTTTTCCGTGACCAACCCAGTCGTGT
TTCAAGGGGTGGACCAGCAGGACCAGGTGTCCAGCCAAGGAC
TGATCTGTTCATTCACCTCGAGCAATTTGGACAGCCCCCGGGA
CGGCGAATCGTTCCTTGGCATCGCATTCGTGGGAGACTCATCC
AAAGCAGGAATCACCCTTACCGATGTGAAGGCGTCCCTGAGC
GGCGCTGCTCTGTACTCCACCGAAGATCTCATCTTCGAGAAGA
TCAAGGGTGGACTGGAGTTCGCCAGCTGCTCCTCACTGGAACA
GGGAGGAGCCTGTGCCGCCCAAAGCATCCTCATCCACGATTGC
CAGGGGCTCCAAGTGAAGCATTGTACCACTGCCGTGAACGCC
GAGGGATCATCCGCTAACGATCACCTCGGTTTCGGAGGGGGTG
CCTTCTTCGTGACCGGTTCGCTGTCGGGAGAGAAGTCACTGTA
TATGCCCGCGGGCGACATGGTGGTCGCCAACTGCGATGGAGC
CATCTCATTCGAGGGAAACTCCGCCAACTTCGCAAACGGCGGC
GCTATCGCCGCTAGCGGGAAGGTGCTGTTCGTGGCTAACGACA
AGAAGACGTCCTTCATCGAGAACCGCGCCCTGTCGGGAGGTG
CCATTGCCGCCAGCTCCGACATTGCCTTCCAGAACTGTGCGGA
ACTGGTGTTCAAAGGAAACTGCGCCATCGGCACCGAAGATAA
GGGAAGCCTGGGAGGCGGCGCCATTTCCTCCCTCGGCACCGTG
CTGCTTCAGGGAAACCACGGCATCACTTGTGACAAGAACGAA
GCAGCGTCCCAGGGGGGAGCGATCTTCGGGAAGAACTGCCAG
ATTTCCGACAACGAGGGACCGGTGGTGTTCAGAGACTCCACTG
CCTGCCTGGGCGGCGGAGCGATCGCAGCACAGGAAATTGTCA
GCATCCAGAACAACCAGGCCGGCATCAGCTTCGAGGGGGGAA
AGGCTTCGTTCGGCGGAGGTATTGCCTGCGGATCGTTCTCGTC
CGCGGGCGGAGCCTCCGTGCTCGGAACCATCGACATTTCCAAG
AACCTGGGCGCTATCTCGTTTTCTCGCACCCTGTGCACTACTTC
CGACCTGGGTCAGATGGAGTACCAGGGAGGCGGAGCGCTGTT
TGGAGAGAACATCGCTCTGAGCGAGAACGCGGGAGTGCTGAC
CTTCAAGGACAACATTGTGAAGACCTTCGCCTCAAACGGAAA
GATCCTGGGGGGAGGCGCCATCCTGGCAACCGGGAAGGTCGA
AATCACCAACAATGCAGAGGGTATCTCCTTCACTGGCAACGCC
CGGGCCCCCCAAGCCCTGCCGACTCAGGAAGAGTTCCCCCTGT
TCTCCAAGAAGGAAGGACGCCCTTTGTCATCCGGCTACTCCGG
TGGTGGAGCGATTCTGGGTCGGGAAGTGGCCATCCTGCATAAT
GCGGCCGTGGTGTTTGAGCAGAACAGACTCCAATGCTCCGAA
GAAGAGGCCACCCTCCTGGGGTGCTGCGGGGGCGGAGCAGTG
CATGGCATGGATTCCACTTCCATCGTGGGAAACTCCGCAGTCC
GCTTCGGAAACAACTACGCTATGGGACAGGGAGTGTCAGGCG
GGGCCCTGCTGTCCAAGACCGTCCAGTTGGCCGGAAACGGTGC
GGTGGATTTCTCACGCAATATCGCCTCGCTGGGAGGCGGCGCG
CTGCAGGCCTCCGAAGGAAATTGCGAACTGGTCGACAACGGC
TACGTGCTGTTCCGGGACAACCGCGGCAGGGTGTACGGCGGA
GCAATCTCGTGCCTTCGGGGCGACGTCGTGATCTCGGGAAATA
AGGGACGGGTCGAGTTTAAGGACAACATCGCTACCAGGCTCT
ACGTGGAGGAAACTGTGGAGAAGGTGGAGGAAGTGGAGCCTG
CCCCGGAACAGAAGGACAACAACGAGCTGTCGTTCCTCGGTC
GGGCAGAACAGTCCTTCATTACTGCCGCCAACCAGGCCCTGTT
CGCGTCCGAAGATGGTGACCTCAGCCCGGAATCCAGCATCTCC
TCCGAGGAACTGGCCAAGCGGAGAGAATGCGCGGGAGGCGCA
ATCTTTGCGAAGCGGGTCCGGATCGTGGACAACCAGGAAGCT
GTGGTGTTCAGCAACAACTTTGCCGACATCTACGGTGGTGCAA
TTTTCACCGGCTCACTCCGGGAGGAGGACAAGCTGGACGGCC
AGATTCCCGAGGTGCTCATTTCCGGCAATGCCGGCGACGTGGT
GTTCTCCGGAAACTCCGCCAAGAGGGACGAACACCTCCCGCAT
ACCGGAGGAGGAGCCATCTGCACTCAGAACCTGGCAATCTCG
CAGAACACCGGCAATGTGCTGTTCTACAACAACGTCGCATGTT
CCGGTGGCGCCGTCAGAATCGAGGACCACGGAAACGTGCTGC
TGGAAGCATTCGGGGGTGATATTGTGTTCAAGGGAAACAGCG
CATTCCGGGCCCAGGGATCAGATGCAATCTACTTCGCCGGGAA
GGAGAGCCACATTACCGCCCTGAACGCCGCCGAGGGTCACGC
CATCGTGTTCCACGATGCCCTGGTGTTCGAGAACCTGGAGGAG
CGCAAGAGCGCCGAAGTGCTGCTTATCAATTCCCGCGAGAACC
CGGGCTACACCGGATCCATCCGGTTCCTCGAAGCGGAGTCGAA
GGTCCCGCAGTGTATTCATGTGCAACAGGGGTCCCTGGAACTG
CTTAACGGAGCCACCCTGTGCTCCTACGGCTTTAAGCAGGACG
CGGGCGCTAAACTGGTGCTGGCGGCCGGCGCCAAGCTTAAGA
TCCTCGACTCCGGAACCCCGGTGCAGCAGGGGCACGCTATTAG
CAAGCCTGAAGCCGAGATTGAGTCGTCATCCGAACCCGAAGG
GGCGCACTCCCTGTGGATAGCCAAGAACGCGCAGACCACCGT
GCCAATGGTCGATATCCACACAATCTCCGTGGACCTCGCCAGC
TTCTCGTCGAGCCAGCAGGAGGGAACTGTCGAAGCGCCTCAG
GTCATCGTGCCGGGAGGTTCCTACGTGCGCTCGGGGGAGCTCA
ACCTGGAACTCGTGAATACCGCTGGAACGGGATATGAGAACC
ACGCCCTGCTGAAGAACGAAGCCAAAGTGCCACTGATGTCCTT
CGTCGCCTCCGGCGACGAGGCCTCCGCCGAGATTAGCAACCTG
GCGGTGTCAGATCTGCAAATTCACGTGGTGACCCCTGAGATTG
AGGAGGACACCTACGGGCACATGGGCGATTGGTCCGAGGCGA
AGATCCAGGACGGCACACTGGTCATTTCATGGAACCCTGCCGG ACATCACCACCACCATCAC
Ct871pd_PmpG_D_NGM_nIgK ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC
228 TGCCTGATACAACAGGCGCCGAGATCATGATTCCCCAGGGCAT
CTACGACGGCGAAACCCTGACCGTGTCTTTCCCCTATACCGTG
ATCGGCGATCCTAGCGGCACCACCGTGTTTTCTGCTGGCGAGC
TGACCCTGAAGAACCTGGACAACTCTATCGCCGCTCTGCCCCT
GAGCTGCTTCGGAAATCTGCTGGGCAGCTTCACCGTGCTCGGC
AGAGGACACAGCCTGACCTTCGAGAACATCCGGACCAGCACA
AATGGCGCTGCCCTGAGCGATAGCGCCAATAGCGGCCTGTTTA
CCATCGAGGGCTTCAAAGAGCTGAGCTTCAGCAACTGCAACA
GCCTGCTGGCAGTGCTGCCTGCCGCCACAACAAATAGCGGCA
GCCAGACACCTACCACCACCAGCACACCTTCTAACGGCGCCAT
CTACAGCAAGACCGACCTGCTGCTCCTGAACAACGAGAAGTTC
AGCTTCTACTCCAACCTGGTGTCCGGCGACGGCGGAGCCATTG
ATGCCAAATCTCTGACCGTGCAGGGCATCAGCAAGCTGTGCGT
GTTCCAAGAGAACACAGCCCAGGCTGATGGCGGAGCCTGTCA
GGTGGTCACAAGCTTTAGCGCCATGGCCAACGAGGCCCCTATC
GCCTTTATTGCCAATGTGGCCGGCGTTAGAGGCGGAGGAATTG
CCGCTGTTCAGGATGGACAGCAGGGCGTGTCCAGCAGCACAA
GCACTGAGGATCCTGTGGTGTCCTTCAGCAGAAACACCGCCGT
GGAATTCGATGGCAACGTGGCCAGAGTTGGCGGCGGAATCTA
CAGCTACGGAAACGTGGCCTTTCTGAACAATGGCAAGACCCTG
TTCCTCAACAACGTGGCAAGCCCCGTGTATATCGCCGCCGAGC
AGCCTACAAATGGCCAGGCCTCTAATACCGCCGACAACTATGG
CGACGGTGGCGCAATCTTCTGCAAGAATGGTGCTCAGGCCGCT
GGCAGCAACAATGCCGGCTCTGTGTCCTTTGATGGCGAAGGCG
TGGTGTTCTTCTCCTCTAACGTGGCCGCTGGAAAAGGCGGCGC
TATCTACGCCAAGAAACTGAGCGTGGCCAACTGCGGCCCTGTG
CAGTTTCTGGGCAATATCGCCAATGATGGCGGTGCCATCTACC
TGGGAGAGTCCGGCGAACTGTCTCTGAGCGCCGATTACGGCG
ACATCATCTTCGACGGCAACCTGAAGCGGACCGCCAAAGAAA
ATGCCGCCGATGTGAATGGCGTGACAGTGTCCAGCCAGGCCAT
CTCTATGGGCTCTGGCGGCAAGATCACCACACTGAGAGCCAA
GGCCGGCCACCAGATCCTGTTCAACGACCCTATCGAGATGGCC
AATGGCAACAACCAGCCTGCTCAGAGCAGCGAGCCCCTGAAG
ATTAACGATGGCGAGGGCTACACCGGCGATATCGTGTTCGCCA
ACGGCAACAGCGCCCTGTACCAGAATGTGGCCATCGAGCAGG
GCAGAATCGTGCTGAGAGAGAAGGCCAAGCTGAGCGTGAACA
GCCTGAGTCAGACAGGCGGCAGCCTGTATATGGAAGCCGGCA
GCACCCTGGACTTCGTGACACCTCAACCTCCACAGCAACCTCC
AGCCGCCAACCAGCTGATCACCCTGTCTAATCTGCACCTGAGC
CTGAGTTCCCTGCTGGCCAACAACGCCGTGACCAATCCTCCTA
CCAATCCACCAGCTCAGGACTCTCACCCTGCCATCATCGGCTC
TACAACAGCCGGAAGCGTGACAATCAGCGGCCCCATCTTCTTC
GAGGACCTGGACGATACCGCCTACGACAGATACGATTGGCTG
GGCTCCAACCAGAAAATCGACGTGCTGAAACTGCAGCTGGGC
ACCCAGCCATCTGCCAACGCTCCATCTGATCTGACCCTGGGCA
ACGAGATGCCTAAGTACGGCTACCAAGGCAGCTGGAAGCTGG
CCTGGGATCCTAACACAGCCAACAATGGCCCCTACACACTGAA GGCCACCTGGACCAAGACAGGC
Ct871pd_PmpG_D_NGM_nIgK_cHis
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 229
TGCCTGATACAACAGGCGCCGAGATCATGATTCCCCAGGGCAT
CTACGACGGCGAAACCCTGACCGTGTCTTTCCCCTATACCGTG
ATCGGCGATCCTAGCGGCACCACCGTGTTTTCTGCTGGCGAGC
TGACCCTGAAGAACCTGGACAACTCTATCGCCGCTCTGCCCCT
GAGCTGCTTCGGAAATCTGCTGGGCAGCTTCACCGTGCTCGGC
AGAGGACACAGCCTGACCTTCGAGAACATCCGGACCAGCACA
AATGGCGCTGCCCTGAGCGATAGCGCCAATAGCGGCCTGTTTA
CCATCGAGGGCTTCAAAGAGCTGAGCTTCAGCAACTGCAACA
GCCTGCTGGCAGTGCTGCCTGCCGCCACAACAAATAGCGGCA
GCCAGACACCTACCACCACCAGCACACCTTCTAACGGCGCCAT
CTACAGCAAGACCGACCTGCTGCTCCTGAACAACGAGAAGTTC
AGCTTCTACTCCAACCTGGTGTCCGGCGACGGCGGAGCCATTG
ATGCCAAATCTCTGACCGTGCAGGGCATCAGCAAGCTGTGCGT
GTTCCAAGAGAACACAGCCCAGGCTGATGGCGGAGCCTGTCA
GGTGGTCACAAGCTTTAGCGCCATGGCCAACGAGGCCCCTATC
GCCTTTATTGCCAATGTGGCCGGCGTTAGAGGCGGAGGAATTG
CCGCTGTTCAGGATGGACAGCAGGGCGTGTCCAGCAGCACAA
GCACTGAGGATCCTGTGGTGTCCTTCAGCAGAAACACCGCCGT
GGAATTCGATGGCAACGTGGCCAGAGTTGGCGGCGGAATCTA
CAGCTACGGAAACGTGGCCTTTCTGAACAATGGCAAGACCCTG
TTCCTCAACAACGTGGCAAGCCCCGTGTATATCGCCGCCGAGC
AGCCTACAAATGGCCAGGCCTCTAATACCGCCGACAACTATGG
CGACGGTGGCGCAATCTTCTGCAAGAATGGTGCTCAGGCCGCT
GGCAGCAACAATGCCGGCTCTGTGTCCTTTGATGGCGAAGGCG
TGGTGTTCTTCTCCTCTAACGTGGCCGCTGGAAAAGGCGGCGC
TATCTACGCCAAGAAACTGAGCGTGGCCAACTGCGGCCCTGTG
CAGTTTCTGGGCAATATCGCCAATGATGGCGGTGCCATCTACC
TGGGAGAGTCCGGCGAACTGTCTCTGAGCGCCGATTACGGCG
ACATCATCTTCGACGGCAACCTGAAGCGGACCGCCAAAGAAA
ATGCCGCCGATGTGAATGGCGTGACAGTGTCCAGCCAGGCCAT
CTCTATGGGCTCTGGCGGCAAGATCACCACACTGAGAGCCAA
GGCCGGCCACCAGATCCTGTTCAACGACCCTATCGAGATGGCC
AATGGCAACAACCAGCCTGCTCAGAGCAGCGAGCCCCTGAAG
ATTAACGATGGCGAGGGCTACACCGGCGATATCGTGTTCGCCA
ACGGCAACAGCGCCCTGTACCAGAATGTGGCCATCGAGCAGG
GCAGAATCGTGCTGAGAGAGAAGGCCAAGCTGAGCGTGAACA
GCCTGAGTCAGACAGGCGGCAGCCTGTATATGGAAGCCGGCA
GCACCCTGGACTTCGTGACACCTCAACCTCCACAGCAACCTCC
AGCCGCCAACCAGCTGATCACCCTGTCTAATCTGCACCTGAGC
CTGAGTTCCCTGCTGGCCAACAACGCCGTGACCAATCCTCCTA
CCAATCCACCAGCTCAGGACTCTCACCCTGCCATCATCGGCTC
TACAACAGCCGGAAGCGTGACAATCAGCGGCCCCATCTTCTTC
GAGGACCTGGACGATACCGCCTACGACAGATACGATTGGCTG
GGCTCCAACCAGAAAATCGACGTGCTGAAACTGCAGCTGGGC
ACCCAGCCATCTGCCAACGCTCCATCTGATCTGACCCTGGGCA
ACGAGATGCCTAAGTACGGCTACCAAGGCAGCTGGAAGCTGG
CCTGGGATCCTAACACAGCCAACAATGGCCCCTACACACTGAA
GGCCACCTGGACCAAGACAGGCCACCACCATCACCATCAC Ct460_D_S16A_nIgK
ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC 230
TGCCTGATACCACAGGCATGAGCCAGAACAAGAACAGCGCCT
TCATGCAGCCCGTGAACGTGGCAGCTGATCTGGCCGCTATAGT
TGGCGCTGGCCCTATGCCTAGAACCGAGATCATCAAGAAGAT
GTGGGACTACATTAAGAAGAACGGCCTGCAGGACCCCACCAA
CAAGCGGAACATCAACCCCGACGACAAGCTGGCCAAGGTGTT
CGGCACAGAGAAGCCCATCGACATGTTCCAGATGACCAAGAT GGTGTCCCAGCACATCATCAAG
Ct460_D_S16A_nIgK_cHis ATGGAAACCCCTGCTCAGCTGCTGTTCCTGCTGCTGCTGTGGC
231 TGCCTGATACCACAGGCATGAGCCAGAACAAGAACAGCGCCT
TCATGCAGCCCGTGAACGTGGCAGCTGATCTGGCCGCTATAGT
TGGCGCTGGCCCTATGCCTAGAACCGAGATCATCAAGAAGAT
GTGGGACTACATTAAGAAGAACGGCCTGCAGGACCCCACCAA
CAAGCGGAACATCAACCCCGACGACAAGCTGGCCAAGGTGTT
CGGCACAGAGAAGCCCATCGACATGTTCCAGATGACCAAGAT
GGTGTCCCAGCACATCATCAAGCACCACCACCATCACCAC
Ct875_E_S274Q_N275H_S574D_nIgK
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 232
TGCCTGACACCACCGGCATGAGCATCAGAGGCGTGGGCGGCA
ACGGCAACAGCAGAATCCCTAGCCACAACGGCGACGGCAGCA
ACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGTGGAA
GATAGAGTGTGCAGCCTGTACAGCAGCCGGTCCAACGAGAAC
CGCGAGAGCCCTTATGCCGTGGTGGACGTGTCCAGCATGATCG
AGAGCACCCCCACCAGCGGCGAGACAACCAGAGCTAGTAGAG
GCGTGCTGAGCCGGTTCCAGAGGGGCCTCGTGCGGATTGCTGA
CAAAGTGCGGAGAGCCGTGCAGTGCGCTTGGAGCAGCGTGTC
CACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAGCGGCA
GCTCTAGCAGAACAGCTAGAGGCGCCAGCAGCGGCTACAGAG
AGTACAGCCCTTCTGCCGCTCGGGGCCTGCGGCTGATGTTCAC
CGACTTTTGGCGGACCCGGGTGCTGAGACAGACCTCTCCTATG
GCCGGCGTGTTCGGCAACCTGGACGTGAACGAGGCCAGACTG
ATGGCCGCCTACACCAGCGAGTGTGCCGATCACCTGGAAGCC
AAAGAGCTGGCCGGACCTGACGGCGTGGCAGCCGCTAGAGAA
ATCGCCAAGAGATGGGAGAAGAGAGTGCGGGACCTGCAGGAC
AAGGGCGCTGCCAGAAAGCTGCTGAACGACCCCCTGGGCAGA
CGGACCCCCAACTACCAGAGCAAGAACCCCGGCGAGTACACC
GTGGGCAACTCCATGTTCTACGACGGCCCCCAGGTGGCCAACC
TGCAGAATGTGGATACCGGCTTCTGGCTGGACATGCAGCACCT
GAGCGACGTGGTGCTGTCCAGAGAGATCCAGACCGGCCTGAG
AGCCAGAGCCACCCTGGAAGAGTCCATGCCCATGCTGGAAAA
TCTGGAAGAGAGATTCCGGCGGCTGCAGGAAACCTGCGACGC
CGCCAGAACCGAGATCGAGGAAAGCGGCTGGACCCGGGAAAG
CGCCTCCAGAATGGAAGGCGACGAAGCCCAGGGCCCCAGCAG
AGTGCAGCAGGCCTTTCAGAGCTTCGTGAATGAGTGCAACAGC
ATCGAGTTCAGCTTCGGCTCCTTCGGCGAGCACGTGCGGGTGC
TGTGTGCCAGAGTGTCAAGAGGACTGGCCGCTGCCGGCGAGG
CCATCAGAAGATGCTTCAGCTGCTGCAAGGGCAGCACCCACA
GATACGCCCCCAGAGATGACCTGTCTCCTGAGGGCGCCTCTCT
GGCCGAAACCCTGGCCAGATTCGCCGACGACATGGGCATCGA
AAGAGGCGCCGACGGCACCTACGACATCCCCCTGGTGGACGA
TTGGAGAAGGGGCGTGCCATCCATCGAGGGCGAGGGCAGCGA
TAGCATCTACGAGATCATGATGCCCATCTACGAAGTGATGAAC
ATGGACCTGGAAACCCGGCGGAGCTTCGCCGTGCAGCAGGGC
CATTACCAGGACCCCAGAGCCAGCGACTACGACCTGCCTAGA
GCCTCCGATTACGATCTGCCCAGAAGCCCCTACCCCACCCCTC
CACTGCCTCCCAGATACCAGCTGCAGAACATGGATGTGGAAG
CCGGCTTTCGCGAGGCCGTGTACGCCTCTTTTGTGGCCGGCAT
GTACAACTACGTCGTGACCCAGCCCCAGGAACGGATCCCCAAT
AGCCAGCAGGTGGAAGGCATCCTGCGGGACATGCTGACCAAC
GGCGATCAGACCTTCCGGGACCTGATGAAGCGGTGGAACAGA GAGGTGGACCGCGAG
Ct875_E_S274Q_N275H_S574D_nIgK_cHis
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 233
TGCCTGACACCACCGGCATGAGCATCAGAGGCGTGGGCGGCA
ACGGCAACAGCAGAATCCCTAGCCACAACGGCGACGGCAGCA
ACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGTGGAA
GATAGAGTGTGCAGCCTGTACAGCAGCCGGTCCAACGAGAAC
CGCGAGAGCCCTTATGCCGTGGTGGACGTGTCCAGCATGATCG
AGAGCACCCCCACCAGCGGCGAGACAACCAGAGCTAGTAGAG
GCGTGCTGAGCCGGTTCCAGAGGGGCCTCGTGCGGATTGCTGA
CAAAGTGCGGAGAGCCGTGCAGTGCGCTTGGAGCAGCGTGTC
CACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAGCGGCA
GCTCTAGCAGAACAGCTAGAGGCGCCAGCAGCGGCTACAGAG
AGTACAGCCCTTCTGCCGCTCGGGGCCTGCGGCTGATGTTCAC
CGACTTTTGGCGGACCCGGGTGCTGAGACAGACCTCTCCTATG
GCCGGCGTGTTCGGCAACCTGGACGTGAACGAGGCCAGACTG
ATGGCCGCCTACACCAGCGAGTGTGCCGATCACCTGGAAGCC
AAAGAGCTGGCCGGACCTGACGGCGTGGCAGCCGCTAGAGAA
ATCGCCAAGAGATGGGAGAAGAGAGTGCGGGACCTGCAGGAC
AAGGGCGCTGCCAGAAAGCTGCTGAACGACCCCCTGGGCAGA
CGGACCCCCAACTACCAGAGCAAGAACCCCGGCGAGTACACC
GTGGGCAACTCCATGTTCTACGACGGCCCCCAGGTGGCCAACC
TGCAGAATGTGGATACCGGCTTCTGGCTGGACATGCAGCACCT
GAGCGACGTGGTGCTGTCCAGAGAGATCCAGACCGGCCTGAG
AGCCAGAGCCACCCTGGAAGAGTCCATGCCCATGCTGGAAAA
TCTGGAAGAGAGATTCCGGCGGCTGCAGGAAACCTGCGACGC
CGCCAGAACCGAGATCGAGGAAAGCGGCTGGACCCGGGAAAG
CGCCTCCAGAATGGAAGGCGACGAAGCCCAGGGCCCCAGCAG
AGTGCAGCAGGCCTTTCAGAGCTTCGTGAATGAGTGCAACAGC
ATCGAGTTCAGCTTCGGCTCCTTCGGCGAGCACGTGCGGGTGC
TGTGTGCCAGAGTGTCAAGAGGACTGGCCGCTGCCGGCGAGG
CCATCAGAAGATGCTTCAGCTGCTGCAAGGGCAGCACCCACA
GATACGCCCCCAGAGATGACCTGTCTCCTGAGGGCGCCTCTCT
GGCCGAAACCCTGGCCAGATTCGCCGACGACATGGGCATCGA
AAGAGGCGCCGACGGCACCTACGACATCCCCCTGGTGGACGA
TTGGAGAAGGGGCGTGCCATCCATCGAGGGCGAGGGCAGCGA
TAGCATCTACGAGATCATGATGCCCATCTACGAAGTGATGAAC
ATGGACCTGGAAACCCGGCGGAGCTTCGCCGTGCAGCAGGGC
CATTACCAGGACCCCAGAGCCAGCGACTACGACCTGCCTAGA
GCCTCCGATTACGATCTGCCCAGAAGCCCCTACCCCACCCCTC
CACTGCCTCCCAGATACCAGCTGCAGAACATGGATGTGGAAG
CCGGCTTTCGCGAGGCCGTGTACGCCTCTTTTGTGGCCGGCAT
GTACAACTACGTCGTGACCCAGCCCCAGGAACGGATCCCCAAT
AGCCAGCAGGTGGAAGGCATCCTGCGGGACATGCTGACCAAC
GGCGATCAGACCTTCCGGGACCTGATGAAGCGGTGGAACAGA
GAGGTGGACCGCGAGCACCACCATCACCACCAC Ct622_E_S13N_S179A_S220N_nIgK
ATGGAAACCCCTGCCCAACTGCTTTTCTTGCTGCTGCTCTGGCT 234
CCCTGACACCACCGGAATGGAATCTGGACCCGAGTCCGTGTCA
AGCAACCAGAACTCCATGAACCCCATCATTAATGGACAGATC
GCATCCAATTCCGAAACCAAGGAAAGCACCAAGGCATCGGAG
GCCTCCCCATCCGCCTCAAGCTCCGTGTCGTCCTGGTCGTTTCT
GTCGAGCGCGAAGAATGCCCTGATCTCACTGCGGGACGCGATT
CTGAACAAGAACAGCTCCCCAACCGACTCCCTGAGCCAACTCG
AGGCCTCAACTTCCACTTCGACTGTGACTAGGGTCGCTGCCAA
GGATTATGACGAGGCCAAGAGCAACTTCGACACCGCCAAGAG
CGGACTGGAAAACGCCAAAACCCTGGCCGAATACGAAACTAA
GATGGCCGATCTCATGGCGGCCCTGCAAGACATGGAACGGCT
GGCGAACTCCGATCCGTCCAACAACCACACTGAGGAAGTGAA
CAACATCAAGAAGGCTCTCGAGGCCCAGAAGGATACCATCGA
CAAGTTGAACAAGCTTGTGACGCTGCAGAACCAAAACAAGGC
CCTGACGGAAGTGCTCAAAACCACCGACTCGGCCGACCAGAT
TCCGGCCATCAACAGCCAGCTGGAGATTAACAAGAACTCGGC
CGATCAGATTATCAAGGACCTGGAGCGCCAGAACATTAACTA
CGAGGCCGTCTTGACTAACGCCGGCGAAGTGATCAAGGCGTC
ATCCGAAGCCGGCATTAAGCTGGGACAGGCGCTGCAATCCAT
CGTCGACGCCGGCGACCAGTCCCAGGCGGCGGTGCTGCAGGC
CCAGCAGAACAACTCCCCCGATAACATCGCTGCAACCAAGGA
ACTGATTGACGCGGCCGAAACCAAAGTCAACGAACTGAAGCA
GGAGCACACTGGTCTGACCGACTCGCCGCTCGTGAAGAAGGC
CGAAGAACAGATCAGCCAGGCTCAGAAGGATATCCAGGAAAT
CAAGCCTTCGGGGAGCGACATCCCGATCGTGGGACCGTCCGGT
TCCGCCGCTTCCGCCGGGTCCGCAGCCGGGGCCCTTAAGTCGT
CGAACAATAGCGGCAGAATATCCCTGCTGCTCGACGATGTGG
ATAACGAGATGGCCGCCATTGCGCTGCAAGGATTCCGGTCCAT
GATCGAGCAGTTCAACGTGAACAACCCCGCCACCGCCAAGGA
GCTGCAGGCTATGGAGGCCCAACTCACTGCCATGTCCGACCAG
CTCGTGGGAGCGGACGGAGAACTGCCAGCCGAGATCCAGGCC
ATCAAGGACGCTCTGGCCCAGGCACTGAAGCAGCCGTCCGCG
GATGGCCTGGCCACCGCCATGGGCCAGGTCGCGTTCGCCGCCG
CTAAAGTCGGCGGAGGTTCGGCCGGCACTGCCGGGACCGTGC
AGATGAATGTCAAGCAGCTGTACAAGACTGCGTTCTCGTCGAC
CAGCTCCAGCTCCTACGCCGCGGCCCTGTCCGACGGTTACAGC
GCGTACAAGACCCTGAACTCCCTTTACTCCGAATCGAGATCCG
GGGTCCAGTCCGCAATTTCACAAACCGCCAATCCTGCCCTGTC
GCGCTCAGTGTCACGCAGCGGCATCGAGTCACAGGGCAGAAG
CGCCGACGCTAGCCAAAGGGCCGCAGAAACCATTGTGCGGGA
CTCCCAGACACTTGGAGATGTCTACAGCCGCCTCCAAGTGCTG
GACTCCCTCATGTCCACCATCGTGTCAAACCCTCAGGCTAACC
AGGAGGAAATCATGCAGAAGCTGACCGCAAGCATTTCCAAGG
CTCCGCAGTTTGGATACCCCGCTGTGCAAAACTCCGCGGACAG
CTTGCAGAAATTCGCAGCCCAGTTGGAGAGGGAGTTCGTGGA
CGGGGAGCGGTCCCTCGCGGAGTCCCAGGAGAACGCATTCCG
GAAGCAGCCCGCCTTCATTCAACAAGTGCTTGTGAACATCGCC
TCCCTGTTCTCCGGTTACCTGTCT
Ct622_E_S13N_S179A_S220N_nIgK_cHis
ATGGAAACCCCTGCCCAACTGCTTTTCTTGCTGCTGCTCTGGCT 235
CCCTGACACCACCGGAATGGAATCTGGACCCGAGTCCGTGTCA
AGCAACCAGAACTCCATGAACCCCATCATTAATGGACAGATC
GCATCCAATTCCGAAACCAAGGAAAGCACCAAGGCATCGGAG
GCCTCCCCATCCGCCTCAAGCTCCGTGTCGTCCTGGTCGTTTCT
GTCGAGCGCGAAGAATGCCCTGATCTCACTGCGGGACGCGATT
CTGAACAAGAACAGCTCCCCAACCGACTCCCTGAGCCAACTCG
AGGCCTCAACTTCCACTTCGACTGTGACTAGGGTCGCTGCCAA
GGATTATGACGAGGCCAAGAGCAACTTCGACACCGCCAAGAG
CGGACTGGAAAACGCCAAAACCCTGGCCGAATACGAAACTAA
GATGGCCGATCTCATGGCGGCCCTGCAAGACATGGAACGGCT
GGCGAACTCCGATCCGTCCAACAACCACACTGAGGAAGTGAA
CAACATCAAGAAGGCTCTCGAGGCCCAGAAGGATACCATCGA
CAAGTTGAACAAGCTTGTGACGCTGCAGAACCAAAACAAGGC
CCTGACGGAAGTGCTCAAAACCACCGACTCGGCCGACCAGAT
TCCGGCCATCAACAGCCAGCTGGAGATTAACAAGAACTCGGC
CGATCAGATTATCAAGGACCTGGAGCGCCAGAACATTAACTA
CGAGGCCGTCTTGACTAACGCCGGCGAAGTGATCAAGGCGTC
ATCCGAAGCCGGCATTAAGCTGGGACAGGCGCTGCAATCCAT
CGTCGACGCCGGCGACCAGTCCCAGGCGGCGGTGCTGCAGGC
CCAGCAGAACAACTCCCCCGATAACATCGCTGCAACCAAGGA
ACTGATTGACGCGGCCGAAACCAAAGTCAACGAACTGAAGCA
GGAGCACACTGGTCTGACCGACTCGCCGCTCGTGAAGAAGGC
CGAAGAACAGATCAGCCAGGCTCAGAAGGATATCCAGGAAAT
CAAGCCTTCGGGGAGCGACATCCCGATCGTGGGACCGTCCGGT
TCCGCCGCTTCCGCCGGGTCCGCAGCCGGGGCCCTTAAGTCGT
CGAACAATAGCGGCAGAATATCCCTGCTGCTCGACGATGTGG
ATAACGAGATGGCCGCCATTGCGCTGCAAGGATTCCGGTCCAT
GATCGAGCAGTTCAACGTGAACAACCCCGCCACCGCCAAGGA
GCTGCAGGCTATGGAGGCCCAACTCACTGCCATGTCCGACCAG
CTCGTGGGAGCGGACGGAGAACTGCCAGCCGAGATCCAGGCC
ATCAAGGACGCTCTGGCCCAGGCACTGAAGCAGCCGTCCGCG
GATGGCCTGGCCACCGCCATGGGCCAGGTCGCGTTCGCCGCCG
CTAAAGTCGGCGGAGGTTCGGCCGGCACTGCCGGGACCGTGC
AGATGAATGTCAAGCAGCTGTACAAGACTGCGTTCTCGTCGAC
CAGCTCCAGCTCCTACGCCGCGGCCCTGTCCGACGGTTACAGC
GCGTACAAGACCCTGAACTCCCTTTACTCCGAATCGAGATCCG
GGGTCCAGTCCGCAATTTCACAAACCGCCAATCCTGCCCTGTC
GCGCTCAGTGTCACGCAGCGGCATCGAGTCACAGGGCAGAAG
CGCCGACGCTAGCCAAAGGGCCGCAGAAACCATTGTGCGGGA
CTCCCAGACACTTGGAGATGTCTACAGCCGCCTCCAAGTGCTG
GACTCCCTCATGTCCACCATCGTGTCAAACCCTCAGGCTAACC
AGGAGGAAATCATGCAGAAGCTGACCGCAAGCATTTCCAAGG
CTCCGCAGTTTGGATACCCCGCTGTGCAAAACTCCGCGGACAG
CTTGCAGAAATTCGCAGCCCAGTTGGAGAGGGAGTTCGTGGA
CGGGGAGCGGTCCCTCGCGGAGTCCCAGGAGAACGCATTCCG
GAAGCAGCCCGCCTTCATTCAACAAGTGCTTGTGAACATCGCC
TCCCTGTTCTCCGGTTACCTGTCTCATCACCACCACCATCAC Cta1_E_noTM_nIgK_cHis
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 236
TGCCTGATACCACCGGCCCTAGCAGCACCCAGGACAACAGAT
CCATGGACCAGCAGGACAGCGAGGAATTTCTGCTGCAGAACA
CCCTGGAAGATAGCGAGATCATCAGCATCCCCGACACCATGA
ACCAGATCGCCATCGACACCGAGAAGTGGTTCTACCTGAACA
AGGACTGCACCAACGTGGGCCCCATCTCCATCGTGCAGCTGAC
CGCCTTCCTGAAAGAGTGCAAGCACAGCCCCGAGAAGGGCAT
CGACCCCCAGGAACTGTGGGTGTGGAAGAAAGGCATGCCCAA
CTGGGAGAAAGTGAAGAACATCCCCGAGCTGAGCGGCACCGT
GAAGGACGAGCACCACCACCATCACCAC Cta1_E_noTM_nIgK
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 237
TGCCTGATACCACCGGCCCTAGCAGCACCCAGGACAACAGAT
CCATGGACCAGCAGGACAGCGAGGAATTTCTGCTGCAGAACA
CCCTGGAAGATAGCGAGATCATCAGCATCCCCGACACCATGA
ACCAGATCGCCATCGACACCGAGAAGTGGTTCTACCTGAACA
AGGACTGCACCAACGTGGGCCCCATCTCCATCGTGCAGCTGAC
CGCCTTCCTGAAAGAGTGCAAGCACAGCCCCGAGAAGGGCAT
CGACCCCCAGGAACTGTGGGTGTGGAAGAAAGGCATGCCCAA
CTGGGAGAAAGTGAAGAACATCCCCGAGCTGAGCGGCACCGT GAAGGACGAA Cta1_E_cHis
ATGAACAGCGGGATGTTCCCCTTCACCTTCTTTCTGCTGTACAT 238
CTGCCTGGGCATGCTGACCGCCTACCTGGCCAACAAGAAGAA
CCGGAACCTGATCGGCTGGTTCCTGGCCGGCATGTTCTTCGGA
ATCTTCGCCATCATTTTTCTGCTGATCCTGCCCCCCCTGCCCAG
CAGCACACAGGACAACAGATCCATGGACCAGCAGGACAGCGA
AGAGTTCCTGCTGCAGAACACCCTGGAAGATAGCGAGATCAT
CAGCATCCCCGACACCATGAACCAGATCGCCATCGACACCGA
GAAGTGGTTCTACCTGAACAAGGACTGCACCAACGTGGGCCC
CATCTCCATCGTGCAGCTGACAGCCTTCCTGAAAGAGTGCAAG
CACAGCCCCGAGAAGGGCATCGACCCCCAGGAACTGTGGGTG
TGGAAGAAAGGCATGCCCAACTGGGAGAAAGTGAAGAACATC
CCCGAGCTGAGCGGCACCGTGAAGGACGAGCACCACCACCAT CACCAC Cta1_E
ATGAACAGCGGGATGTTCCCCTTCACCTTCTTTCTGCTGTACAT 239
CTGCCTGGGCATGCTGACCGCCTACCTGGCCAACAAGAAGAA
CCGGAACCTGATCGGCTGGTTCCTGGCCGGCATGTTCTTCGGA
ATCTTCGCCATCATTTTTCTGCTGATCCTGCCCCCCCTGCCCAG
CAGCACACAGGACAACAGATCCATGGACCAGCAGGACAGCGA
AGAGTTCCTGCTGCAGAACACCCTGGAAGATAGCGAGATCAT
CAGCATCCCCGACACCATGAACCAGATCGCCATCGACACCGA
GAAGTGGTTCTACCTGAACAAGGACTGCACCAACGTGGGCCC
CATCTCCATCGTGCAGCTGACAGCCTTCCTGAAAGAGTGCAAG
CACAGCCCCGAGAAGGGCATCGACCCCCAGGAACTGTGGGTG
TGGAAGAAAGGCATGCCCAACTGGGAGAAAGTGAAGAACATC
CCCGAGCTGAGCGGCACCGTGAAGGACGAA Ct443_E_nIgK_cHis_mod
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTCCTGCTGTGGC 240
TGCCTGATACCACAGGCAGCGGCGTGCTGGAAACCAGCATGG
CCGAGAGCCTGAGCACCAACGTGATCAGCCTGGCCGACACCA
AGGCCAAGGACAACACCAGCCACAAGAGCAAGAAGGCCCGG
AAGAACCACAGCAAAGAAACCCTGGTGGACCGGAAAGAGGTG
GCCCCTGTGCACGAGTCTAAGGCCACAGGCCCCAAGCAGGAC
AGCTGCTTCGGCCGGATGTACACCGTGAAAGTGAACGACGAC
CGGAACGTGGAAATCACCCAGGCCGTGCCTGAGTACGCCACA
GTGGGCAGCCCTTACCCCATCGAGATCACCGCCACCGGCAAG
AGGGATTGCGTGGATGTGATCATTACCCAACAGCTGCCTTGCG
AGGCCGAGTTCGTGCGCTCTGATCCTGCCACCACCCCTACCGC
CGATGGCAAGCTCGTGTGGAAGATCGACAGACTGGGCCAGGG
CGAGAAGTCCAAAATCACTGTGTGGGTCAAGCCCCTGAAAGA
GGGGTGCTGCTTTACCGCAGCCACCGTGTGTGCCTGCCCCGAG
ATTAGAAGCGTGACCAAGTGTGGCCAGCCCGCCATCTGCGTGA
AGCAGGAAGGACCTGAGAACGCCTGCCTGAGATGCCCCGTGG
TGTACAAGATCAACGTCGTGAACCAGGGCACCGCCATTGCCA
GAAACGTGGTGGTGGAAAACCCCGTGCCCGACGGCTACGCCC
ACAGCTCTGGACAGAGAGTGCTGACCTTCACCCTGGGCGACAT
GCAGCCCGGCGAGCACAGAACCATCACCGTGGAATTCTGCCC
CCTGAAGCGGGGCAGAGCCACCAACATTGCGACAGTGTCCTA
CTGTGGCGGGCACAAGAACACCGCCTCCGTGACCACCGTGATC
AACGAGCCTTGCGTGCAGGTGTCCATTGCCGGCGCTGACTGGT
CCTACGTGTGCAAGCCAGTGGAGTACGTGATCTCCGTGTCCAA
CCCCGGCGACCTGGTGCTGAGAGATGTGGTGGTTGAGGATACC
CTGAGCCCTGGCGTGACAGTCCTGGAAGCTGCTGGCGCCCAGA
TCAGCTGCAACAAGGTGGTGTGGACAGTGAAAGAGCTGAACC
CCGGGGAGTCCCTGCAGTACAAGGTGCTCGTGCGGGCCCAGA
CCCCTGGCCAGTTCACCAACAATGTGGTCGTGAAGTCCTGCAG
CGACTGCGGCACCTGTACCTCTTGTGCCGAGGCCACCACGTAC
TGGAAAGGCGTGGCCGCTACCCATATGTGCGTGGTGGATACCT
GCGACCCCGTCTGCGTGGGCGAAAACACCGTGTACCGGATCTG
TGTGACCAACCGGGGCAGCGCCGAGGACACCAATGTGTCCCT
GATGCTGAAGTTCTCCAAAGAACTGCAACCCGTGAGCTTCAGC
GGCCCCACCAAGGGAACAATCACTGGCAACACCGTCGTTTTCG
ACAGCCTGCCTCGGCTGGGCTCTAAGGAAACTGTGGAGTTCAG
CGTGACACTGAAGGCCGTGTCTGCCGGGGATGCTAGAGGCGA
GGCCATCCTGAGCAGCGACACACTGACGGTCCCTGTGTCCGAC
ACCGAGAATACCCACATCTACCACCACCATCATCACCAT Ct443_E_nIgK_mod
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTCCTGCTGTGGC 241
TGCCTGATACCACAGGCAGCGGCGTGCTGGAAACCAGCATGG
CCGAGAGCCTGAGCACCAACGTGATCAGCCTGGCCGACACCA
AGGCCAAGGACAACACCAGCCACAAGAGCAAGAAGGCCCGG
AAGAACCACAGCAAAGAAACCCTGGTGGACCGGAAAGAGGTG
GCCCCTGTGCACGAGTCTAAGGCCACAGGCCCCAAGCAGGAC
AGCTGCTTCGGCCGGATGTACACCGTGAAAGTGAACGACGAC
CGGAACGTGGAAATCACCCAGGCCGTGCCTGAGTACGCCACA
GTGGGCAGCCCTTACCCCATCGAGATCACCGCCACCGGCAAG
AGGGATTGCGTGGATGTGATCATTACCCAACAGCTGCCTTGCG
AGGCCGAGTTCGTGCGCTCTGATCCTGCCACCACCCCTACCGC
CGATGGCAAGCTCGTGTGGAAGATCGACAGACTGGGCCAGGG
CGAGAAGTCCAAAATCACTGTGTGGGTCAAGCCCCTGAAAGA
GGGGTGCTGCTTTACCGCAGCCACCGTGTGTGCCTGCCCCGAG
ATTAGAAGCGTGACCAAGTGTGGCCAGCCCGCCATCTGCGTGA
AGCAGGAAGGACCTGAGAACGCCTGCCTGAGATGCCCCGTGG
TGTACAAGATCAACGTCGTGAACCAGGGCACCGCCATTGCCA
GAAACGTGGTGGTGGAAAACCCCGTGCCCGACGGCTACGCCC
ACAGCTCTGGACAGAGAGTGCTGACCTTCACCCTGGGCGACAT
GCAGCCCGGCGAGCACAGAACCATCACCGTGGAATTCTGCCC
CCTGAAGCGGGGCAGAGCCACCAACATTGCGACAGTGTCCTA
CTGTGGCGGGCACAAGAACACCGCCTCCGTGACCACCGTGATC
AACGAGCCTTGCGTGCAGGTGTCCATTGCCGGCGCTGACTGGT
CCTACGTGTGCAAGCCAGTGGAGTACGTGATCTCCGTGTCCAA
CCCCGGCGACCTGGTGCTGAGAGATGTGGTGGTTGAGGATACC
CTGAGCCCTGGCGTGACAGTCCTGGAAGCTGCTGGCGCCCAGA
TCAGCTGCAACAAGGTGGTGTGGACAGTGAAAGAGCTGAACC
CCGGGGAGTCCCTGCAGTACAAGGTGCTCGTGCGGGCCCAGA
CCCCTGGCCAGTTCACCAACAATGTGGTCGTGAAGTCCTGCAG
CGACTGCGGCACCTGTACCTCTTGTGCCGAGGCCACCACGTAC
TGGAAAGGCGTGGCCGCTACCCATATGTGCGTGGTGGATACCT
GCGACCCCGTCTGCGTGGGCGAAAACACCGTGTACCGGATCTG
TGTGACCAACCGGGGCAGCGCCGAGGACACCAATGTGTCCCT
GATGCTGAAGTTCTCCAAAGAACTGCAACCCGTGAGCTTCAGC
GGCCCCACCAAGGGAACAATCACTGGCAACACCGTCGTTTTCG
ACAGCCTGCCTCGGCTGGGCTCTAAGGAAACTGTGGAGTTCAG
CGTGACACTGAAGGCCGTGTCTGCCGGGGATGCTAGAGGCGA
GGCCATCCTGAGCAGCGACACACTGACGGTCCCTGTGTCCGAC ACCGAGAATACCCACATCTAC
Ct875_E_nIgK_CO004 ATGGAAACTCCCGCACAGTTACTTTTCTTGTTGCTTCTATGGCT 242
CCCCGATACCACCGGGATGAGCATCAGAGGCGTCGGCGGGAA
CGGCAACAGCAGAATTCCCTCCCACAACGGCGACGGCAGCAA
CAGAAGATCCCAGAACACAAAGGGCAATAATAAGGTCGAGGA
CAGAGTGTGCAGCCTCTACTCCAGCAGGTCTAACGAGAATAG
GGAGTCCCCGTACGCCGTTGTCGACGTGAGTTCTATGATAGAG
AGCACGCCCACGTCCGGAGAAACAACTAGAGCAAGCAGGGGC
GTCCTGAGCCGGTTCCAGAGAGGTCTGGTGCGAATTGCCGACA
AGGTGAGACGGGCAGTGCAATGCGCCTGGAGCAGCGTCTCCA
CCAGCAGAAGCAGCGCCACCCGCGCTGCCGAATCAGGCAGCA
GCTCCAGAACGGCACGGGGCGCCTCCTCCGGCTACCGAGAGT
ACTCCCCTAGCGCCGCCAGAGGCCTGAGACTGATGTTCACCGA
TTTTTGGAGGACACGGGTTCTGAGACAGACCTCCCCCATGGCT
GGGGTGTTCGGCAACCTGGACGTCAATGAAGCCAGACTCATG
GCCGCATATACTTCTGAGTGCGCTGACCACCTGGAAGCTAAGG
AACTGGCGGGCCCCGATGGCGTGGCCGCGGCCCGGGAGATCG
CCAAGAGATGGGAGAAGAGAGTGCGGGACCTGCAAGACAAG
GGGGCCGCCCGGAAGCTGCTGAACGATCCCTTGGGCCGCCGG
ACACCGAACTATCAGAGCAAGAACCCGGGCGAGTACACCGTG
GGAAACAGCATGTTCTATGACGGACCTCAGGTGGCAAACCTG
CAGAACGTGGACACTGGATTTTGGCTCGACATGAGTAACCTCT
CCGATGTCGTTCTGTCTCGTGAGATACAGACAGGTCTGCGGGC
TAGAGCCACCCTTGAGGAGAGCATGCCTATGTTGGAGAATCTG
GAGGAGCGGTTCAGAAGACTGCAGGAGACTTGCGATGCCGCC
AGGACCGAGATTGAGGAGAGCGGCTGGACCCGGGAAAGCGCC
TCAAGGATGGAGGGAGACGAGGCCCAGGGACCCTCCAGGGTT
CAGCAGGCCTTCCAGTCGTTCGTGAATGAATGCAACAGCATCG
AGTTCAGCTTCGGAAGCTTCGGAGAGCACGTGCGAGTGCTGTG
CGCCAGAGTATCCAGAGGTCTGGCCGCTGCAGGCGAGGCCAT
CCGGAGATGCTTCTCCTGCTGCAAAGGCAGCACCCACAGGTAT
GCTCCCAGGGATGATCTTTCTCCCGAGGGAGCCAGCCTGGCTG
AGACTCTTGCAAGATTCGCCGATGACATGGGGATCGAGCGGG
GCGCTGACGGCACCTACGACATTCCCCTGGTGGACGACTGGAG
GAGGGGAGTGCCCTCCATCGAGGGCGAGGGCTCCGATTCAAT
CTATGAGATCATGATGCCTATTTACGAGGTGATGAACATGGAC
CTGGAGACAAGAAGAAGTTTCGCCGTCCAGCAGGGTCATTAC
CAGGACCCCCGAGCAAGCGACTACGATCTGCCTCGCGCCAGC
GATTACGACCTGCCTAGAAGCCCCTACCCTACACCTCCACTGC
CCCCAAGATATCAGCTCCAGAACATGGACGTGGAGGCCGGCT
TCAGGGAGGCCGTGTACGCCAGCTTTGTGGCCGGCATGTACAA
CTATGTCGTGACACAGCCTCAGGAACGCATTCCCAATAGCCAA
CAGGTGGAGGGCATCCTGAGAGACATGCTGACCAACGGCTCT
CAGACTTTTAGAGATCTGATGAAAAGATGGAACAGAGAAGTG GACAGGGAG
Ct875_E_nIgK_CO003 ATGGAAACACCAGCTCAGCTCCTTTTCTTACTCCTCTTGTGGTT 243
GCCGGATACCACAGGCATGAGCATCCGGGGCGTCGGCGGCAA
CGGAAACAGCCGGATCCCCAGCCACAACGGAGACGGCTCTAA
TAGAAGATCACAGAATACCAAGGGAAATAACAAGGTCGAAGA
TAGAGTCTGCAGCTTATATTCCAGCAGATCCAACGAGAATAGG
GAAAGCCCCTACGCCGTCGTTGACGTGAGCTCCATGATCGAAA
GCACCCCAACAAGTGGCGAGACTACAAGAGCCTCAAGGGGCG
TCCTGTCAAGATTCCAAAGAGGCCTGGTGAGGATCGCAGACA
AGGTGCGGCGGGCCGTGCAGTGCGCCTGGAGCTCTGTGTCGAC
AAGCAGATCAAGTGCCACCAGGGCCGCCGAGAGCGGATCCTC
CAGTCGGACCGCCCGCGGCGCCTCTAGTGGGTACAGAGAATA
TAGTCCCAGCGCCGCTAGGGGGCTGCGCCTCATGTTCACCGAC
TTCTGGAGAACCCGCGTGCTCAGGCAGACATCCCCTATGGCCG
GGGTGTTCGGCAACCTGGACGTGAACGAGGCCCGGCTTATGG
CCGCATATACAAGCGAGTGTGCCGACCACCTGGAGGCCAAGG
AGCTGGCTGGCCCCGACGGCGTGGCCGCCGCACGCGAGATTG
CCAAGAGGTGGGAAAAGAGGGTGAGAGATCTGCAGGATAAG
GGCGCCGCCAGAAAACTGCTGAATGACCCCCTGGGGAGGAGG
ACACCCAATTACCAGTCAAAGAATCCAGGGGAGTACACTGTT
GGAAATTCTATGTTTTATGACGGCCCTCAGGTGGCCAACCTTC
AGAATGTGGACACAGGCTTCTGGCTTGACATGAGCAACCTCAG
CGACGTGGTGCTGTCTAGGGAGATCCAGACAGGCTTAAGAGC
ACGGGCTACCCTGGAAGAGTCGATGCCCATGCTCGAAAATCTG
GAGGAGAGGTTCAGACGCCTGCAAGAGACATGCGACGCCGCG
AGGACTGAAATCGAGGAGAGCGGCTGGACCAGGGAGTCCGCT
TCTCGCATGGAAGGGGACGAGGCTCAGGGCCCCAGCAGGGTG
CAGCAGGCCTTCCAGAGCTTTGTGAACGAGTGCAACTCCATTG
AGTTCAGCTTTGGAAGCTTCGGAGAGCACGTGCGGGTGCTGTG
CGCCCGCGTGTCCAGGGGCCTGGCCGCAGCTGGCGAGGCTAT
ACGTCGCTGCTTCAGCTGTTGTAAGGGAAGCACCCATAGGTAC
GCCCCTCGTGACGATCTGTCTCCCGAAGGGGCCAGCCTGGCTG
AGACACTGGCCCGCTTCGCCGATGATATGGGGATTGAACGGG
GCGCCGACGGAACCTACGACATCCCTCTTGTGGACGACTGGAG
GAGAGGCGTCCCCTCTATCGAGGGCGAGGGCTCTGACTCCATC
TACGAGATTATGATGCCTATCTACGAGGTCATGAACATGGACC
TGGAAACCAGAAGAAGCTTCGCAGTTCAGCAGGGACACTACC
AAGACCCACGGGCTAGTGATTATGACCTCCCAAGAGCATCCG
ACTATGATCTGCCAAGGTCACCTTACCCTACCCCACCCCTGCC
CCCACGGTACCAGTTACAGAACATGGATGTGGAGGCCGGCTTC
AGGGAAGCCGTCTATGCATCCTTCGTGGCCGGCATGTACAACT
ACGTGGTGACTCAACCTCAGGAACGGATCCCCAACAGTCAGC
AGGTGGAGGGGATCCTTAGGGATATGCTGACTAATGGAAGCC
AGACCTTCAGAGATCTGATGAAGCGGTGGAATAGGGAGGTGG ACAGGGAG
Ct875_E_nIgK_CO002 ATGGAGACACCCGCACAGCTCCTCTTCTTATTGCTCTTGTGGCT 244
ACCGGACACCACAGGCATGTCTATCCGGGGCGTTGGCGGGAA
CGGCAACTCTAGGATCCCCTCTCACAACGGCGACGGGAGCAA
CAGGAGAAGCCAGAACACCAAAGGCAATAACAAAGTCGAGG
ACAGAGTTTGTTCTCTCTATAGCTCTAGGAGCAACGAAAACCG
CGAATCTCCTTACGCCGTCGTCGACGTCAGCAGCATGATAGAG
TCAACCCCTACCTCTGGAGAAACAACACGCGCCTCCAGAGGC
GTTCTGTCCAGGTTCCAGAGGGGCCTGGTGAGAATTGCCGACA
AGGTCAGACGAGCCGTGCAGTGTGCCTGGTCCAGCGTCTCTAC
CAGCAGAAGCTCCGCCACCAGAGCCGCTGAGAGTGGCAGCTC
CAGCAGGACAGCCAGGGGGGCTTCCAGCGGCTATAGAGAGTA
TAGCCCTTCAGCCGCCAGAGGCCTGCGGCTGATGTTCACAGAC
TTTTGGAGAACAAGGGTGCTGCGGCAGACCAGCCCCATGGCC
GGCGTGTTTGGCAATCTGGACGTGAACGAGGCCCGGCTGATG
GCCGCATACACCAGCGAGTGTGCGGACCACCTGGAGGCAAAG
GAGCTGGCTGGACCCGACGGTGTGGCCGCTGCCCGAGAAATT
GCCAAGAGGTGGGAGAAGAGAGTTCGCGACCTGCAGGATAAG
GGCGCCGCACGGAAACTCCTGAACGACCCACTCGGCAGAAGA
ACCCCCAACTACCAGTCAAAGAACCCTGGGGAGTATACCGTG
GGAAATTCAATGTTCTACGATGGCCCTCAGGTTGCTAATCTCC
AGAACGTGGACACTGGGTTCTGGCTGGACATGAGCAACCTGA
GTGACGTGGTGCTGTCTCGGGAAATTCAGACAGGCCTGCGGGC
CAGAGCCACCCTGGAAGAGTCCATGCCTATGCTTGAGAACCTG
GAGGAGCGCTTTAGGCGACTCCAAGAAACCTGCGATGCTGCC
AGGACCGAGATCGAGGAGTCTGGATGGACCAGAGAAAGCGCC
TCCAGGATGGAGGGCGATGAGGCCCAGGGCCCCAGCAGGGTG
CAGCAGGCTTTCCAGAGCTTCGTGAACGAATGTAACAGTATCG
AATTCTCTTTCGGTAGCTTCGGCGAGCACGTGCGGGTGTTATG
CGCCAGGGTCAGCAGGGGCCTGGCGGCCGCCGGCGAGGCCAT
CAGAAGATGCTTCAGCTGTTGCAAAGGCTCAACCCACAGATAT
GCCCCTAGGGACGATCTGTCTCCAGAGGGCGCTAGCTTGGCCG
AGACACTAGCAAGGTTCGCCGACGATATGGGTATCGAGAGGG
GCGCCGACGGTACCTACGACATCCCCCTGGTGGACGACTGGA
GGAGAGGCGTGCCCAGTATTGAGGGCGAGGGATCCGACAGCA
TCTACGAGATCATGATGCCGATCTACGAGGTGATGAATATGGA
TCTGGAGACTCGTAGATCATTCGCTGTCCAGCAGGGCCACTAC
CAGGATCCTAGAGCCTCGGACTACGACTTGCCCAGGGCTAGCG
ATTACGACCTGCCTAGATCCCCCTACCCCACTCCCCCTCTTCCC
CCTCGGTATCAGCTGCAGAACATGGACGTGGAGGCCGGTTTCC
GAGAGGCTGTGTACGCCTCCTTCGTGGCCGGGATGTACAACTA
CGTCGTGACCCAGCCCCAGGAGAGAATCCCTAATTCCCAGCAG
GTGGAGGGCATCTTGAGAGATATGCTCACAAACGGGAGCCAG
ACCTTTCGTGACTTAATGAAGCGATGGAACAGAGAGGTGGAT AGGGAG
Ct875_E_nIgK_CO001 ATGGAAACCCCCGCCCAGCTTCTCTTCCTCCTCTTGCTTTGGCT 245
CCCAGACACAACCGGCATGAGTATCAGAGGCGTAGGAGGCAA
CGGCAATAGCCGTATCCCCTCACACAACGGCGACGGCTCCAAC
AGACGGAGCCAGAACACCAAGGGGAATAATAAGGTGGAGGA
CCGGGTCTGTTCACTTTACAGCTCCAGGTCTAACGAGAATCGG
GAAAGCCCTTACGCCGTAGTCGACGTTAGCAGTATGATCGAAA
GCACCCCCACCAGCGGCGAGACAACAAGGGCCTCTCGAGGAG
TTCTGAGCAGATTTCAGAGAGGCCTGGTGCGGATCGCCGACAA
GGTGCGGAGAGCCGTGCAGTGCGCCTGGAGCAGCGTGAGTAC
ATCTCGGAGCAGCGCCACCAGAGCAGCCGAAAGCGGCTCATC
TAGCAGGACCGCTAGAGGCGCCAGCTCGGGGTACAGGGAATA
TTCACCCTCCGCCGCAAGGGGGCTGAGACTGATGTTTACAGAC
TTCTGGAGAACCAGGGTGCTGCGCCAGACAAGCCCAATGGCA
GGGGTGTTTGGTAACCTGGATGTGAATGAGGCCAGACTGATG
GCCGCCTACACTTCTGAGTGCGCGGATCATCTTGAGGCCAAGG
AACTGGCAGGCCCCGACGGCGTGGCCGCCGCCCGGGAGATTG
CTAAGAGATGGGAGAAGCGGGTCAGAGATCTGCAGGATAAGG
GGGCCGCTAGGAAACTCCTGAATGACCCCCTAGGCAGGAGAA
CCCCTAACTACCAGAGCAAAAATCCTGGGGAATACACCGTGG
GCAATTCCATGTTTTACGATGGCCCCCAAGTCGCAAACCTCCA
GAATGTGGACACCGGCTTCTGGCTGGACATGTCCAACTTGAGC
GACGTGGTTCTAAGCAGAGAAATCCAGACCGGACTCCGCGCG
AGAGCTACACTCGAGGAAAGCATGCCTATGCTGGAGAATCTG
GAGGAGCGATTCCGTCGTCTACAGGAGACTTGTGACGCCGCTA
GGACCGAGATCGAGGAGAGCGGCTGGACAAGAGAAAGCGCCT
CTCGAATGGAGGGCGATGAGGCCCAGGGCCCCTCCCGGGTGC
AGCAGGCCTTTCAGAGCTTCGTGAATGAGTGCAATTCTATTGA
GTTCAGCTTCGGCTCTTTTGGCGAGCACGTGCGGGTGCTTTGC
GCCAGGGTGTCCCGGGGACTGGCAGCCGCCGGCGAGGCCATA
AGAAGATGTTTCTCCTGCTGCAAGGGCAGCACCCACCGGTATG
CTCCCAGAGACGACCTGTCTCCAGAAGGGGCATCGCTGGCCG
AGACACTGGCACGGTTCGCCGACGATATGGGCATTGAGAGGG
GAGCCGACGGCACTTATGATATCCCTCTCGTGGACGACTGGAG
AAGAGGAGTCCCCTCAATTGAGGGCGAAGGATCCGATTCTATC
TATGAGATCATGATGCCTATCTACGAAGTGATGAATATGGACC
TGGAAACCAGGAGATCTTTCGCTGTGCAGCAGGGCCATTACCA
GGATCCCCGCGCCAGCGATTATGACCTGCCCAGAGCCTCAGAC
TACGATTTGCCCAGAAGCCCCTACCCCACCCCTCCGCTGCCCC
CTAGATACCAGCTGCAGAATATGGACGTGGAGGCTGGCTTTAG
GGAGGCTGTGTACGCTAGCTTCGTGGCCGGCATGTACAACTAC
GTGGTGACACAGCCCCAGGAGAGAATTCCCAATTCTCAACAA
GTAGAGGGCATCCTGAGAGACATGTTAACAAACGGATCTCAG
ACCTTCCGCGACCTGATGAAGCGGTGGAACCGGGAAGTGGAC CGCGAG
Ct875_E_nIgK_cHis_CO005
ATGGAAACACCCGCCCAGCTCCTCTTTCTACTTCTCCTTTGGCT 246
TCCCGACACCACCGGTATGAGCATTAGAGGAGTCGGCGGGAA
CGGGAATAGCCGTATCCCCTCCCACAACGGCGACGGCAGCAA
CCGCAGAAGCCAGAATACTAAGGGAAACAATAAGGTTGAGGA
CCGCGTCTGTAGCTTGTACAGCTCAAGAAGTAACGAGAACAG
AGAGAGCCCCTACGCCGTGGTCGACGTTTCCAGCATGATCGAG
TCAACGCCCACAAGCGGCGAAACCACCCGCGCGTCAAGGGGG
GTCCTGTCCCGGTTCCAGAGAGGCCTGGTGAGGATCGCCGACA
AGGTGAGACGGGCCGTGCAGTGCGCCTGGTCCAGCGTCAGCA
CATCACGGTCCTCCGCTACCAGGGCCGCCGAGTCAGGCAGCA
GCTCTCGTACCGCCCGGGGAGCCTCAAGCGGGTACAGAGAGT
ACAGCCCTTCTGCCGCTAGAGGCCTGAGACTCATGTTTACAGA
CTTCTGGCGGACAAGGGTTCTCAGGCAGACTAGCCCTATGGCT
GGCGTGTTTGGCAATCTTGATGTTAACGAAGCCAGGCTGATGG
CTGCATATACAAGCGAATGCGCCGACCATCTGGAAGCTAAGG
AGCTGGCCGGGCCCGACGGCGTGGCCGCTGCCAGGGAGATCG
CCAAGAGGTGGGAGAAAAGGGTGCGAGATCTCCAGGATAAGG
GAGCAGCTAGAAAGCTGCTGAACGACCCCCTGGGCAGGCGGA
CCCCTAACTACCAGAGCAAAAATCCGGGCGAGTACACCGTCG
GCAACAGCATGTTTTACGATGGCCCTCAGGTGGCCAACCTTCA
GAACGTGGACACCGGCTTCTGGCTCGATATGTCTAATCTTTCC
GACGTCGTGCTCAGCCGGGAAATCCAGACTGGTCTGCGCGCCA
GAGCTACCTTGGAAGAGAGCATGCCCATGCTGGAGAACCTGG
AGGAGAGATTTCGGCGCTTACAGGAAACATGTGACGCTGCTA
GGACCGAGATTGAAGAGAGCGGGTGGACAAGGGAGTCGGCG
AGCAGGATGGAGGGGGACGAGGCCCAGGGCCCCAGCAGGGT
GCAACAGGCTTTTCAGTCCTTCGTGAACGAGTGCAACAGCATC
GAGTTCTCCTTCGGCAGCTTCGGGGAGCACGTGAGAGTGTTGT
GCGCCCGCGTGTCTAGGGGATTAGCCGCCGCAGGCGAAGCCA
TCCGGCGCTGCTTCAGCTGCTGCAAGGGCTCCACCCATCGCTA
CGCCCCTAGAGACGACCTGTCTCCCGAAGGCGCCTCCCTGGCC
GAGACTCTGGCCCGATTCGCCGATGACATGGGCATCGAGCGG
GGGGCCGATGGCACCTACGACATCCCTCTGGTCGATGACTGGC
GGAGGGGCGTTCCCTCTATTGAGGGCGAGGGCTCTGACTCTAT
TTACGAGATTATGATGCCCATCTACGAAGTGATGAACATGGAC
TTGGAAACTCGCAGATCGTTTGCAGTGCAACAGGGTCATTACC
AGGACCCTAGAGCCTCCGATTATGACCTGCCAAGAGCTAGCG
ATTATGACCTCCCTAGATCACCCTACCCCACACCTCCTCTCCCT
CCACGGTATCAGCTGCAGAACATGGACGTTGAGGCAGGGTTT
AGGGAGGCCGTGTACGCCAGCTTCGTGGCAGGCATGTATAATT
ATGTGGTAACCCAGCCACAGGAGCGAATTCCCAACTCTCAACA
GGTGGAGGGCATCCTGAGAGACATGCTCACCAACGGCAGCCA
AACCTTCAGGGACCTTATGAAACGGTGGAATAGAGAAGTTGA
TCGCGAGCACCACCACCACCACCAC Ct875_E_nIgK_cHis_CO004
ATGGAAACTCCCGCACAGTTACTTTTCTTGTTGCTTCTATGGCT 247
CCCCGATACCACCGGGATGAGCATCAGAGGCGTCGGCGGGAA
CGGCAACAGCAGAATTCCCTCCCACAACGGCGACGGCAGCAA
CAGAAGATCCCAGAACACAAAGGGCAATAATAAGGTCGAGGA
CAGAGTGTGCAGCCTCTACTCCAGCAGGTCTAACGAGAATAG
GGAGTCCCCGTACGCCGTTGTCGACGTGAGTTCTATGATAGAG
AGCACGCCCACGTCCGGAGAAACAACTAGAGCAAGCAGGGGC
GTCCTGAGCCGGTTCCAGAGAGGTCTGGTGCGAATTGCCGACA
AGGTGAGACGGGCAGTGCAATGCGCCTGGAGCAGCGTCTCCA
CCAGCAGAAGCAGCGCCACCCGCGCTGCCGAATCAGGCAGCA
GCTCCAGAACGGCACGGGGCGCCTCCTCCGGCTACCGAGAGT
ACTCCCCTAGCGCCGCCAGAGGCCTGAGACTGATGTTCACCGA
TTTTTGGAGGACACGGGTTCTGAGACAGACCTCCCCCATGGCT
GGGGTGTTCGGCAACCTGGACGTCAATGAAGCCAGACTCATG
GCCGCATATACTTCTGAGTGCGCTGACCACCTGGAAGCTAAGG
AACTGGCGGGCCCCGATGGCGTGGCCGCGGCCCGGGAGATCG
CCAAGAGATGGGAGAAGAGAGTGCGGGACCTGCAAGACAAG
GGGGCCGCCCGGAAGCTGCTGAACGATCCCTTGGGCCGCCGG
ACACCGAACTATCAGAGCAAGAACCCGGGCGAGTACACCGTG
GGAAACAGCATGTTCTATGACGGACCTCAGGTGGCAAACCTG
CAGAACGTGGACACTGGATTTTGGCTCGACATGAGTAACCTCT
CCGATGTCGTTCTGTCTCGTGAGATACAGACAGGTCTGCGGGC
TAGAGCCACCCTTGAGGAGAGCATGCCTATGTTGGAGAATCTG
GAGGAGCGGTTCAGAAGACTGCAGGAGACTTGCGATGCCGCC
AGGACCGAGATTGAGGAGAGCGGCTGGACCCGGGAAAGCGCC
TCAAGGATGGAGGGAGACGAGGCCCAGGGACCCTCCAGGGTT
CAGCAGGCCTTCCAGTCGTTCGTGAATGAATGCAACAGCATCG
AGTTCAGCTTCGGAAGCTTCGGAGAGCACGTGCGAGTGCTGTG
CGCCAGAGTATCCAGAGGTCTGGCCGCTGCAGGCGAGGCCAT
CCGGAGATGCTTCTCCTGCTGCAAAGGCAGCACCCACAGGTAT
GCTCCCAGGGATGATCTTTCTCCCGAGGGAGCCAGCCTGGCTG
AGACTCTTGCAAGATTCGCCGATGACATGGGGATCGAGCGGG
GCGCTGACGGCACCTACGACATTCCCCTGGTGGACGACTGGAG
GAGGGGAGTGCCCTCCATCGAGGGCGAGGGCTCCGATTCAAT
CTATGAGATCATGATGCCTATTTACGAGGTGATGAACATGGAC
CTGGAGACAAGAAGAAGTTTCGCCGTCCAGCAGGGTCATTAC
CAGGACCCCCGAGCAAGCGACTACGATCTGCCTCGCGCCAGC
GATTACGACCTGCCTAGAAGCCCCTACCCTACACCTCCACTGC
CCCCAAGATATCAGCTCCAGAACATGGACGTGGAGGCCGGCT
TCAGGGAGGCCGTGTACGCCAGCTTTGTGGCCGGCATGTACAA
CTATGTCGTGACACAGCCTCAGGAACGCATTCCCAATAGCCAA
CAGGTGGAGGGCATCCTGAGAGACATGCTGACCAACGGCTCT
CAGACTTTTAGAGATCTGATGAAAAGATGGAACAGAGAAGTG
GACAGGGAGCACCACCACCACCACCAC Ct875_E_nIgK_cHis_CO003
ATGGAAACACCAGCTCAGCTCCTTTTCTTACTCCTCTTGTGGTT 248
GCCGGATACCACAGGCATGAGCATCCGGGGCGTCGGCGGCAA
CGGAAACAGCCGGATCCCCAGCCACAACGGAGACGGCTCTAA
TAGAAGATCACAGAATACCAAGGGAAATAACAAGGTCGAAGA
TAGAGTCTGCAGCTTATATTCCAGCAGATCCAACGAGAATAGG
GAAAGCCCCTACGCCGTCGTTGACGTGAGCTCCATGATCGAAA
GCACCCCAACAAGTGGCGAGACTACAAGAGCCTCAAGGGGCG
TCCTGTCAAGATTCCAAAGAGGCCTGGTGAGGATCGCAGACA
AGGTGCGGCGGGCCGTGCAGTGCGCCTGGAGCTCTGTGTCGAC
AAGCAGATCAAGTGCCACCAGGGCCGCCGAGAGCGGATCCTC
CAGTCGGACCGCCCGCGGCGCCTCTAGTGGGTACAGAGAATA
TAGTCCCAGCGCCGCTAGGGGGCTGCGCCTCATGTTCACCGAC
TTCTGGAGAACCCGCGTGCTCAGGCAGACATCCCCTATGGCCG
GGGTGTTCGGCAACCTGGACGTGAACGAGGCCCGGCTTATGG
CCGCATATACAAGCGAGTGTGCCGACCACCTGGAGGCCAAGG
AGCTGGCTGGCCCCGACGGCGTGGCCGCCGCACGCGAGATTG
CCAAGAGGTGGGAAAAGAGGGTGAGAGATCTGCAGGATAAG
GGCGCCGCCAGAAAACTGCTGAATGACCCCCTGGGGAGGAGG
ACACCCAATTACCAGTCAAAGAATCCAGGGGAGTACACTGTT
GGAAATTCTATGTTTTATGACGGCCCTCAGGTGGCCAACCTTC
AGAATGTGGACACAGGCTTCTGGCTTGACATGAGCAACCTCAG
CGACGTGGTGCTGTCTAGGGAGATCCAGACAGGCTTAAGAGC
ACGGGCTACCCTGGAAGAGTCGATGCCCATGCTCGAAAATCTG
GAGGAGAGGTTCAGACGCCTGCAAGAGACATGCGACGCCGCG
AGGACTGAAATCGAGGAGAGCGGCTGGACCAGGGAGTCCGCT
TCTCGCATGGAAGGGGACGAGGCTCAGGGCCCCAGCAGGGTG
CAGCAGGCCTTCCAGAGCTTTGTGAACGAGTGCAACTCCATTG
AGTTCAGCTTTGGAAGCTTCGGAGAGCACGTGCGGGTGCTGTG
CGCCCGCGTGTCCAGGGGCCTGGCCGCAGCTGGCGAGGCTAT
ACGTCGCTGCTTCAGCTGTTGTAAGGGAAGCACCCATAGGTAC
GCCCCTCGTGACGATCTGTCTCCCGAAGGGGCCAGCCTGGCTG
AGACACTGGCCCGCTTCGCCGATGATATGGGGATTGAACGGG
GCGCCGACGGAACCTACGACATCCCTCTTGTGGACGACTGGAG
GAGAGGCGTCCCCTCTATCGAGGGCGAGGGCTCTGACTCCATC
TACGAGATTATGATGCCTATCTACGAGGTCATGAACATGGACC
TGGAAACCAGAAGAAGCTTCGCAGTTCAGCAGGGACACTACC
AAGACCCACGGGCTAGTGATTATGACCTCCCAAGAGCATCCG
ACTATGATCTGCCAAGGTCACCTTACCCTACCCCACCCCTGCC
CCCACGGTACCAGTTACAGAACATGGATGTGGAGGCCGGCTTC
AGGGAAGCCGTCTATGCATCCTTCGTGGCCGGCATGTACAACT
ACGTGGTGACTCAACCTCAGGAACGGATCCCCAACAGTCAGC
AGGTGGAGGGGATCCTTAGGGATATGCTGACTAATGGAAGCC
AGACCTTCAGAGATCTGATGAAGCGGTGGAATAGGGAGGTGG
ACAGGGAGCACCATCACCATCACCAC Ct875_E_nIgK_cHis_CO002
ATGGAGACACCCGCACAGCTCCTCTTCTTATTGCTCTTGTGGCT 249
ACCGGACACCACAGGCATGTCTATCCGGGGCGTTGGCGGGAA
CGGCAACTCTAGGATCCCCTCTCACAACGGCGACGGGAGCAA
CAGGAGAAGCCAGAACACCAAAGGCAATAACAAAGTCGAGG
ACAGAGTTTGTTCTCTCTATAGCTCTAGGAGCAACGAAAACCG
CGAATCTCCTTACGCCGTCGTCGACGTCAGCAGCATGATAGAG
TCAACCCCTACCTCTGGAGAAACAACACGCGCCTCCAGAGGC
GTTCTGTCCAGGTTCCAGAGGGGCCTGGTGAGAATTGCCGACA
AGGTCAGACGAGCCGTGCAGTGTGCCTGGTCCAGCGTCTCTAC
CAGCAGAAGCTCCGCCACCAGAGCCGCTGAGAGTGGCAGCTC
CAGCAGGACAGCCAGGGGGGCTTCCAGCGGCTATAGAGAGTA
TAGCCCTTCAGCCGCCAGAGGCCTGCGGCTGATGTTCACAGAC
TTTTGGAGAACAAGGGTGCTGCGGCAGACCAGCCCCATGGCC
GGCGTGTTTGGCAATCTGGACGTGAACGAGGCCCGGCTGATG
GCCGCATACACCAGCGAGTGTGCGGACCACCTGGAGGCAAAG
GAGCTGGCTGGACCCGACGGTGTGGCCGCTGCCCGAGAAATT
GCCAAGAGGTGGGAGAAGAGAGTTCGCGACCTGCAGGATAAG
GGCGCCGCACGGAAACTCCTGAACGACCCACTCGGCAGAAGA
ACCCCCAACTACCAGTCAAAGAACCCTGGGGAGTATACCGTG
GGAAATTCAATGTTCTACGATGGCCCTCAGGTTGCTAATCTCC
AGAACGTGGACACTGGGTTCTGGCTGGACATGAGCAACCTGA
GTGACGTGGTGCTGTCTCGGGAAATTCAGACAGGCCTGCGGGC
CAGAGCCACCCTGGAAGAGTCCATGCCTATGCTTGAGAACCTG
GAGGAGCGCTTTAGGCGACTCCAAGAAACCTGCGATGCTGCC
AGGACCGAGATCGAGGAGTCTGGATGGACCAGAGAAAGCGCC
TCCAGGATGGAGGGCGATGAGGCCCAGGGCCCCAGCAGGGTG
CAGCAGGCTTTCCAGAGCTTCGTGAACGAATGTAACAGTATCG
AATTCTCTTTCGGTAGCTTCGGCGAGCACGTGCGGGTGTTATG
CGCCAGGGTCAGCAGGGGCCTGGCGGCCGCCGGCGAGGCCAT
CAGAAGATGCTTCAGCTGTTGCAAAGGCTCAACCCACAGATAT
GCCCCTAGGGACGATCTGTCTCCAGAGGGCGCTAGCTTGGCCG
AGACACTAGCAAGGTTCGCCGACGATATGGGTATCGAGAGGG
GCGCCGACGGTACCTACGACATCCCCCTGGTGGACGACTGGA
GGAGAGGCGTGCCCAGTATTGAGGGCGAGGGATCCGACAGCA
TCTACGAGATCATGATGCCGATCTACGAGGTGATGAATATGGA
TCTGGAGACTCGTAGATCATTCGCTGTCCAGCAGGGCCACTAC
CAGGATCCTAGAGCCTCGGACTACGACTTGCCCAGGGCTAGCG
ATTACGACCTGCCTAGATCCCCCTACCCCACTCCCCCTCTTCCC
CCTCGGTATCAGCTGCAGAACATGGACGTGGAGGCCGGTTTCC
GAGAGGCTGTGTACGCCTCCTTCGTGGCCGGGATGTACAACTA
CGTCGTGACCCAGCCCCAGGAGAGAATCCCTAATTCCCAGCAG
GTGGAGGGCATCTTGAGAGATATGCTCACAAACGGGAGCCAG
ACCTTTCGTGACTTAATGAAGCGATGGAACAGAGAGGTGGAT AGGGAGCACCACCATCACCACCAC
Ct875_E_nIgK_cHis_CO001
ATGGAAACCCCCGCCCAGCTTCTCTTCCTCCTCTTGCTTTGGCT 250
CCCAGACACAACCGGCATGAGTATCAGAGGCGTAGGAGGCAA
CGGCAATAGCCGTATCCCCTCACACAACGGCGACGGCTCCAAC
AGACGGAGCCAGAACACCAAGGGGAATAATAAGGTGGAGGA
CCGGGTCTGTTCACTTTACAGCTCCAGGTCTAACGAGAATCGG
GAAAGCCCTTACGCCGTAGTCGACGTTAGCAGTATGATCGAAA
GCACCCCCACCAGCGGCGAGACAACAAGGGCCTCTCGAGGAG
TTCTGAGCAGATTTCAGAGAGGCCTGGTGCGGATCGCCGACAA
GGTGCGGAGAGCCGTGCAGTGCGCCTGGAGCAGCGTGAGTAC
ATCTCGGAGCAGCGCCACCAGAGCAGCCGAAAGCGGCTCATC
TAGCAGGACCGCTAGAGGCGCCAGCTCGGGGTACAGGGAATA
TTCACCCTCCGCCGCAAGGGGGCTGAGACTGATGTTTACAGAC
TTCTGGAGAACCAGGGTGCTGCGCCAGACAAGCCCAATGGCA
GGGGTGTTTGGTAACCTGGATGTGAATGAGGCCAGACTGATG
GCCGCCTACACTTCTGAGTGCGCGGATCATCTTGAGGCCAAGG
AACTGGCAGGCCCCGACGGCGTGGCCGCCGCCCGGGAGATTG
CTAAGAGATGGGAGAAGCGGGTCAGAGATCTGCAGGATAAGG
GGGCCGCTAGGAAACTCCTGAATGACCCCCTAGGCAGGAGAA
CCCCTAACTACCAGAGCAAAAATCCTGGGGAATACACCGTGG
GCAATTCCATGTTTTACGATGGCCCCCAAGTCGCAAACCTCCA
GAATGTGGACACCGGCTTCTGGCTGGACATGTCCAACTTGAGC
GACGTGGTTCTAAGCAGAGAAATCCAGACCGGACTCCGCGCG
AGAGCTACACTCGAGGAAAGCATGCCTATGCTGGAGAATCTG
GAGGAGCGATTCCGTCGTCTACAGGAGACTTGTGACGCCGCTA
GGACCGAGATCGAGGAGAGCGGCTGGACAAGAGAAAGCGCCT
CTCGAATGGAGGGCGATGAGGCCCAGGGCCCCTCCCGGGTGC
AGCAGGCCTTTCAGAGCTTCGTGAATGAGTGCAATTCTATTGA
GTTCAGCTTCGGCTCTTTTGGCGAGCACGTGCGGGTGCTTTGC
GCCAGGGTGTCCCGGGGACTGGCAGCCGCCGGCGAGGCCATA
AGAAGATGTTTCTCCTGCTGCAAGGGCAGCACCCACCGGTATG
CTCCCAGAGACGACCTGTCTCCAGAAGGGGCATCGCTGGCCG
AGACACTGGCACGGTTCGCCGACGATATGGGCATTGAGAGGG
GAGCCGACGGCACTTATGATATCCCTCTCGTGGACGACTGGAG
AAGAGGAGTCCCCTCAATTGAGGGCGAAGGATCCGATTCTATC
TATGAGATCATGATGCCTATCTACGAAGTGATGAATATGGACC
TGGAAACCAGGAGATCTTTCGCTGTGCAGCAGGGCCATTACCA
GGATCCCCGCGCCAGCGATTATGACCTGCCCAGAGCCTCAGAC
TACGATTTGCCCAGAAGCCCCTACCCCACCCCTCCGCTGCCCC
CTAGATACCAGCTGCAGAATATGGACGTGGAGGCTGGCTTTAG
GGAGGCTGTGTACGCTAGCTTCGTGGCCGGCATGTACAACTAC
GTGGTGACACAGCCCCAGGAGAGAATTCCCAATTCTCAACAA
GTAGAGGGCATCCTGAGAGACATGTTAACAAACGGATCTCAG
ACCTTCCGCGACCTGATGAAGCGGTGGAACCGGGAAGTGGAC CGCGAGCACCACCACCACCATCAT
Ct875_E_nIgK_nFLAG ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 251
TGCCTGACACCACCGGCGACTATAAAGACCACGATGGCGATT
ACAAAGATCACGACATCGATTACAAGGATGACGACGACAAAA
TGAGCATCAGAGGCGTGGGCGGCAACGGCAACAGCAGAATCC
CTAGCCACAACGGCGACGGCAGCAACAGGCGGAGCCAGAACA
CCAAGGGCAACAACAAGGTGGAAGATAGAGTGTGCAGCCTGT
ACAGCAGCCGGTCCAACGAGAACCGCGAGAGCCCTTATGCCG
TGGTGGACGTGTCCAGCATGATCGAGAGCACCCCCACCAGCG
GCGAGACAACCAGAGCTAGTAGAGGCGTGCTGAGCCGGTTCC
AGAGGGGCCTCGTGCGGATTGCTGACAAAGTGCGGAGAGCCG
TGCAGTGCGCTTGGAGCAGCGTGTCCACAAGCAGAAGCAGCG
CCACAAGAGCCGCCGAGAGCGGCAGCTCTAGCAGAACAGCTA
GAGGCGCCAGCAGCGGCTACAGAGAGTACAGCCCTTCTGCCG
CTCGGGGCCTGCGGCTGATGTTCACCGACTTTTGGCGGACCCG
GGTGCTGAGACAGACCTCTCCTATGGCCGGCGTGTTCGGCAAC
CTGGACGTGAACGAGGCCAGACTGATGGCCGCCTACACCAGC
GAGTGTGCCGATCACCTGGAAGCCAAAGAGCTGGCCGGACCT
GACGGCGTGGCAGCCGCTAGAGAAATCGCCAAGAGATGGGAG
AAGAGAGTGCGGGACCTGCAGGACAAGGGCGCTGCCAGAAAG
CTGCTGAACGACCCCCTGGGCAGACGGACCCCCAACTACCAG
AGCAAGAACCCCGGCGAGTACACCGTGGGCAACTCCATGTTCT
ACGACGGCCCCCAGGTGGCCAACCTGCAGAATGTGGATACCG
GCTTCTGGCTGGACATGAGCAACCTGAGCGACGTGGTGCTGTC
CAGAGAGATCCAGACCGGCCTGAGAGCCAGAGCCACCCTGGA
AGAGTCCATGCCCATGCTGGAAAATCTGGAAGAGAGATTCCG
GCGGCTGCAGGAAACCTGCGACGCCGCCAGAACCGAGATCGA
GGAAAGCGGCTGGACCCGGGAAAGCGCCTCCAGAATGGAAGG
CGACGAAGCCCAGGGCCCCAGCAGAGTGCAGCAGGCCTTTCA
GAGCTTCGTGAATGAGTGCAACAGCATCGAGTTCAGCTTCGGC
TCCTTCGGCGAGCACGTGCGGGTGCTGTGTGCCAGAGTGTCAA
GAGGACTGGCCGCTGCCGGCGAGGCCATCAGAAGATGCTTCA
GCTGCTGCAAGGGCAGCACCCACAGATACGCCCCCAGAGATG
ACCTGTCTCCTGAGGGCGCCTCTCTGGCCGAAACCCTGGCCAG
ATTCGCCGACGACATGGGCATCGAAAGAGGCGCCGACGGCAC
CTACGACATCCCCCTGGTGGACGATTGGAGAAGGGGCGTGCC
ATCCATCGAGGGCGAGGGCAGCGATAGCATCTACGAGATCAT
GATGCCCATCTACGAAGTGATGAACATGGACCTGGAAACCCG
GCGGAGCTTCGCCGTGCAGCAGGGCCATTACCAGGACCCCAG
AGCCAGCGACTACGACCTGCCTAGAGCCTCCGATTACGATCTG
CCCAGAAGCCCCTACCCCACCCCTCCACTGCCTCCCAGATACC
AGCTGCAGAACATGGATGTGGAAGCCGGCTTTCGCGAGGCCG
TGTACGCCTCTTTTGTGGCCGGCATGTACAACTACGTCGTGAC
CCAGCCCCAGGAACGGATCCCCAATAGCCAGCAGGTGGAAGG
CATCCTGCGGGACATGCTGACCAACGGCAGCCAGACCTTCCGG
GACCTGATGAAGCGGTGGAACAGAGAGGTGGACCGCGAG Ct875_E_nIgK_cFLAG
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 252
TGCCTGACACCACCGGCATGAGCATCAGAGGCGTGGGCGGCA
ACGGCAACAGCAGAATCCCTAGCCACAACGGCGACGGCAGCA
ACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGTGGAA
GATAGAGTGTGCAGCCTGTACAGCAGCCGGTCCAACGAGAAC
CGCGAGAGCCCTTATGCCGTGGTGGACGTGTCCAGCATGATCG
AGAGCACCCCCACCAGCGGCGAGACAACCAGAGCTAGTAGAG
GCGTGCTGAGCCGGTTCCAGAGGGGCCTCGTGCGGATTGCTGA
CAAAGTGCGGAGAGCCGTGCAGTGCGCTTGGAGCAGCGTGTC
CACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAGCGGCA
GCTCTAGCAGAACAGCTAGAGGCGCCAGCAGCGGCTACAGAG
AGTACAGCCCTTCTGCCGCTCGGGGCCTGCGGCTGATGTTCAC
CGACTTTTGGCGGACCCGGGTGCTGAGACAGACCTCTCCTATG
GCCGGCGTGTTCGGCAACCTGGACGTGAACGAGGCCAGACTG
ATGGCCGCCTACACCAGCGAGTGTGCCGATCACCTGGAAGCC
AAAGAGCTGGCCGGACCTGACGGCGTGGCAGCCGCTAGAGAA
ATCGCCAAGAGATGGGAGAAGAGAGTGCGGGACCTGCAGGAC
AAGGGCGCTGCCAGAAAGCTGCTGAACGACCCCCTGGGCAGA
CGGACCCCCAACTACCAGAGCAAGAACCCCGGCGAGTACACC
GTGGGCAACTCCATGTTCTACGACGGCCCCCAGGTGGCCAACC
TGCAGAATGTGGATACCGGCTTCTGGCTGGACATGAGCAACCT
GAGCGACGTGGTGCTGTCCAGAGAGATCCAGACCGGCCTGAG
AGCCAGAGCCACCCTGGAAGAGTCCATGCCCATGCTGGAAAA
TCTGGAAGAGAGATTCCGGCGGCTGCAGGAAACCTGCGACGC
CGCCAGAACCGAGATCGAGGAAAGCGGCTGGACCCGGGAAAG
CGCCTCCAGAATGGAAGGCGACGAAGCCCAGGGCCCCAGCAG
AGTGCAGCAGGCCTTTCAGAGCTTCGTGAATGAGTGCAACAGC
ATCGAGTTCAGCTTCGGCTCCTTCGGCGAGCACGTGCGGGTGC
TGTGTGCCAGAGTGTCAAGAGGACTGGCCGCTGCCGGCGAGG
CCATCAGAAGATGCTTCAGCTGCTGCAAGGGCAGCACCCACA
GATACGCCCCCAGAGATGACCTGTCTCCTGAGGGCGCCTCTCT
GGCCGAAACCCTGGCCAGATTCGCCGACGACATGGGCATCGA
AAGAGGCGCCGACGGCACCTACGACATCCCCCTGGTGGACGA
TTGGAGAAGGGGCGTGCCATCCATCGAGGGCGAGGGCAGCGA
TAGCATCTACGAGATCATGATGCCCATCTACGAAGTGATGAAC
ATGGACCTGGAAACCCGGCGGAGCTTCGCCGTGCAGCAGGGC
CATTACCAGGACCCCAGAGCCAGCGACTACGACCTGCCTAGA
GCCTCCGATTACGATCTGCCCAGAAGCCCCTACCCCACCCCTC
CACTGCCTCCCAGATACCAGCTGCAGAACATGGATGTGGAAG
CCGGCTTTCGCGAGGCCGTGTACGCCTCTTTTGTGGCCGGCAT
GTACAACTACGTCGTGACCCAGCCCCAGGAACGGATCCCCAAT
AGCCAGCAGGTGGAAGGCATCCTGCGGGACATGCTGACCAAC
GGCAGCCAGACCTTCCGGGACCTGATGAAGCGGTGGAACAGA
GAGGTGGACCGCGAGGACTATAAAGACCACGATGGCGATTAC
AAAGATCACGACATCGATTACAAGGATGACGACGACAAA Ct875_E_nIgK_nHis
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 253
TGCCTGACACCACCGGCCACCACCATCACCACCACATGAGCAT
CAGAGGCGTGGGCGGCAACGGCAACAGCAGAATCCCTAGCCA
CAACGGCGACGGCAGCAACAGGCGGAGCCAGAACACCAAGG
GCAACAACAAGGTGGAAGATAGAGTGTGCAGCCTGTACAGCA
GCCGGTCCAACGAGAACCGCGAGAGCCCTTATGCCGTGGTGG
ACGTGTCCAGCATGATCGAGAGCACCCCCACCAGCGGCGAGA
CAACCAGAGCTAGTAGAGGCGTGCTGAGCCGGTTCCAGAGGG
GCCTCGTGCGGATTGCTGACAAAGTGCGGAGAGCCGTGCAGT
GCGCTTGGAGCAGCGTGTCCACAAGCAGAAGCAGCGCCACAA
GAGCCGCCGAGAGCGGCAGCTCTAGCAGAACAGCTAGAGGCG
CCAGCAGCGGCTACAGAGAGTACAGCCCTTCTGCCGCTCGGG
GCCTGCGGCTGATGTTCACCGACTTTTGGCGGACCCGGGTGCT
GAGACAGACCTCTCCTATGGCCGGCGTGTTCGGCAACCTGGAC
GTGAACGAGGCCAGACTGATGGCCGCCTACACCAGCGAGTGT
GCCGATCACCTGGAAGCCAAAGAGCTGGCCGGACCTGACGGC
GTGGCAGCCGCTAGAGAAATCGCCAAGAGATGGGAGAAGAGA
GTGCGGGACCTGCAGGACAAGGGCGCTGCCAGAAAGCTGCTG
AACGACCCCCTGGGCAGACGGACCCCCAACTACCAGAGCAAG
AACCCCGGCGAGTACACCGTGGGCAACTCCATGTTCTACGACG
GCCCCCAGGTGGCCAACCTGCAGAATGTGGATACCGGCTTCTG
GCTGGACATGAGCAACCTGAGCGACGTGGTGCTGTCCAGAGA
GATCCAGACCGGCCTGAGAGCCAGAGCCACCCTGGAAGAGTC
CATGCCCATGCTGGAAAATCTGGAAGAGAGATTCCGGCGGCT
GCAGGAAACCTGCGACGCCGCCAGAACCGAGATCGAGGAAAG
CGGCTGGACCCGGGAAAGCGCCTCCAGAATGGAAGGCGACGA
AGCCCAGGGCCCCAGCAGAGTGCAGCAGGCCTTTCAGAGCTT
CGTGAATGAGTGCAACAGCATCGAGTTCAGCTTCGGCTCCTTC
GGCGAGCACGTGCGGGTGCTGTGTGCCAGAGTGTCAAGAGGA
CTGGCCGCTGCCGGCGAGGCCATCAGAAGATGCTTCAGCTGCT
GCAAGGGCAGCACCCACAGATACGCCCCCAGAGATGACCTGT
CTCCTGAGGGCGCCTCTCTGGCCGAAACCCTGGCCAGATTCGC
CGACGACATGGGCATCGAAAGAGGCGCCGACGGCACCTACGA
CATCCCCCTGGTGGACGATTGGAGAAGGGGCGTGCCATCCATC
GAGGGCGAGGGCAGCGATAGCATCTACGAGATCATGATGCCC
ATCTACGAAGTGATGAACATGGACCTGGAAACCCGGCGGAGC
TTCGCCGTGCAGCAGGGCCATTACCAGGACCCCAGAGCCAGC
GACTACGACCTGCCTAGAGCCTCCGATTACGATCTGCCCAGAA
GCCCCTACCCCACCCCTCCACTGCCTCCCAGATACCAGCTGCA
GAACATGGATGTGGAAGCCGGCTTTCGCGAGGCCGTGTACGC
CTCTTTTGTGGCCGGCATGTACAACTACGTCGTGACCCAGCCC
CAGGAACGGATCCCCAATAGCCAGCAGGTGGAAGGCATCCTG
CGGGACATGCTGACCAACGGCAGCCAGACCTTCCGGGACCTG
ATGAAGCGGTGGAACAGAGAGGTGGACCGCGAG MOMP_E_nTMEM149
ATGGGCCCTGGCAGATGTCTGCTGACAGCCCTGCTGCTGCTGG 254
CCCTGGCTCCTCCACCTGAAGCTCTGCCCGTGGGAAATCCTGC
CGAGCCCAGCCTGATGATCGACGGCATTCTGTGGGAGGGCTTC
GGCGGCGACCCTTGCGATCCTTGTACCACTTGGTGCGACGCCA
TCAGCATGAGAATGGGCTACTACGGCGACTTCGTGTTCGACCG
GGTGCTGAAAACCGACGTGAACAAAGAATTCCAGATGGGCGA
CAAGCCCACCAGCACCACCGGAAATGCCACCGCCCCTACCAC
CCTGACCGCCAGAGAAAATCCCGCCTACGGCCGGCACATGCA
GGACGCCGAGATGTTCACCAACGCCGCCTGCATGGCCCTGAAC
ATCTGGGACAGATTCGACGTGTTCTGCACCCTGGGCGCCAGCA
GCGGCTACCTGAAGGGCAATAGCGCCAGCTTCAACCTCGTGG
GCCTGTTCGGCGACAACGAGAACCAGAGCACCGTGAAAACAA
ACAGCGTGCCCAACATGAGCCTGGACCAGAGCGTGGTGGAAC
TGTACACCGACACCGCATTCTCTTGGAGCGTGGGAGCCAGAGC
TGCCCTGTGGGAGTGTGGATGTGCCACACTGGGCGCTAGCTTC
CAGTACGCCCAGAGCAAGCCCAAGGTGGAAGAACTGAACGTG
CTGTGCAATGCCGCCGAGTTCACCATCAACAAGCCTAAGGGCT
ACGTGGGCCAGGAATTCCCCCTGGCCCTGATCGCCGGAACAG
ATGCCGCCACCGGAACAAAGGACGCCAGCATCGACTACCACG
AGTGGCAGGCTTCTCTGGCCCTGTCCTACCGGCTGAATATGTT
CACCCCCTACATCGGCGTGAAGTGGTCCCGGGCCAGCTTCGAT
GCCGACACCATCAGAATCGCCCAGCCCAAGAGCGCCACCGCC
ATCTTCGATACCACCACACTGAACCCCACCATTGCCGGCGCTG
GCGACGTGAAAGCCTCTGCCGAAGGACAGCTGGGCGACACAA
TGCAGATCGTGTCCCTGCAGCTGAACAAGATGAAGTCCCGGA
AGTCCTGCGGAATCGCCGTGGGCACCACAATCGTGGACGCCG
ATAAGTACGCCGTGACCGTGGAAACCCGGCTGATCGATGAGA
GGGCCGCTCACGTGAACGCCCAGTTCAGATTC MOMP_E_nTMEM149_cHis
ATGGGCCCTGGCAGATGTCTGCTGACAGCCCTGCTGCTGCTGG 255
CCCTGGCTCCTCCACCTGAAGCTCTGCCCGTGGGAAATCCTGC
CGAGCCCAGCCTGATGATCGACGGCATTCTGTGGGAGGGCTTC
GGCGGCGACCCTTGCGATCCTTGTACCACTTGGTGCGACGCCA
TCAGCATGAGAATGGGCTACTACGGCGACTTCGTGTTCGACCG
GGTGCTGAAAACCGACGTGAACAAAGAATTCCAGATGGGCGA
CAAGCCCACCAGCACCACCGGAAATGCCACCGCCCCTACCAC
CCTGACCGCCAGAGAAAATCCCGCCTACGGCCGGCACATGCA
GGACGCCGAGATGTTCACCAACGCCGCCTGCATGGCCCTGAAC
ATCTGGGACAGATTCGACGTGTTCTGCACCCTGGGCGCCAGCA
GCGGCTACCTGAAGGGCAATAGCGCCAGCTTCAACCTCGTGG
GCCTGTTCGGCGACAACGAGAACCAGAGCACCGTGAAAACAA
ACAGCGTGCCCAACATGAGCCTGGACCAGAGCGTGGTGGAAC
TGTACACCGACACCGCATTCTCTTGGAGCGTGGGAGCCAGAGC
TGCCCTGTGGGAGTGTGGATGTGCCACACTGGGCGCTAGCTTC
CAGTACGCCCAGAGCAAGCCCAAGGTGGAAGAACTGAACGTG
CTGTGCAATGCCGCCGAGTTCACCATCAACAAGCCTAAGGGCT
ACGTGGGCCAGGAATTCCCCCTGGCCCTGATCGCCGGAACAG
ATGCCGCCACCGGAACAAAGGACGCCAGCATCGACTACCACG
AGTGGCAGGCTTCTCTGGCCCTGTCCTACCGGCTGAATATGTT
CACCCCCTACATCGGCGTGAAGTGGTCCCGGGCCAGCTTCGAT
GCCGACACCATCAGAATCGCCCAGCCCAAGAGCGCCACCGCC
ATCTTCGATACCACCACACTGAACCCCACCATTGCCGGCGCTG
GCGACGTGAAAGCCTCTGCCGAAGGACAGCTGGGCGACACAA
TGCAGATCGTGTCCCTGCAGCTGAACAAGATGAAGTCCCGGA
AGTCCTGCGGAATCGCCGTGGGCACCACAATCGTGGACGCCG
ATAAGTACGCCGTGACCGTGGAAACCCGGCTGATCGATGAGA
GGGCCGCTCACGTGAACGCCCAGTTCAGATTCCACCACCACCA TCACCAC MOMP_E_nFLRT2
ATGGGCCTGCAGACCACCAAGTGGCCTAGCCACGGCGCATTCT 256
TTCTGAAGTCCTGGCTGATCATCTCCCTGGGCCTGTACAGCCA
GGTGTCCAAGCTGCTGGCTCTGCCCGTGGGAAATCCTGCCGAG
CCCAGCCTGATGATCGACGGCATTCTGTGGGAGGGCTTCGGCG
GCGACCCTTGCGATCCTTGTACCACTTGGTGCGACGCCATCAG
CATGAGAATGGGCTACTACGGCGACTTCGTGTTCGACCGGGTG
CTGAAAACCGACGTGAACAAAGAATTCCAGATGGGCGACAAG
CCCACCAGCACCACCGGAAATGCCACCGCCCCTACCACCCTGA
CCGCCAGAGAAAATCCCGCCTACGGCCGGCACATGCAGGACG
CCGAGATGTTCACCAACGCCGCCTGCATGGCCCTGAACATCTG
GGACAGATTCGACGTGTTCTGCACCCTGGGCGCCAGCAGCGGC
TACCTGAAGGGCAATAGCGCCAGCTTCAACCTCGTGGGCCTGT
TCGGCGACAACGAGAACCAGAGCACCGTGAAAACAAACAGCG
TGCCCAACATGAGCCTGGACCAGAGCGTGGTGGAACTGTACA
CCGACACCGCATTCTCTTGGAGCGTGGGAGCCAGAGCTGCCCT
GTGGGAGTGTGGATGTGCCACACTGGGCGCTAGCTTCCAGTAC
GCCCAGAGCAAGCCCAAGGTGGAAGAACTGAACGTGCTGTGC
AATGCCGCCGAGTTCACCATCAACAAGCCTAAGGGCTACGTG
GGCCAGGAATTCCCCCTGGCCCTGATCGCCGGAACAGATGCCG
CCACCGGAACAAAGGACGCCAGCATCGACTACCACGAGTGGC
AGGCTTCTCTGGCCCTGTCCTACCGGCTGAATATGTTCACCCCC
TACATCGGCGTGAAGTGGTCCCGGGCCAGCTTCGATGCCGACA
CCATCAGAATCGCCCAGCCCAAGAGCGCCACCGCCATCTTCGA
TACCACCACACTGAACCCCACCATTGCCGGCGCTGGCGACGTG
AAAGCCTCTGCCGAAGGACAGCTGGGCGACACAATGCAGATC
GTGTCCCTGCAGCTGAACAAGATGAAGTCCCGGAAGTCCTGCG
GAATCGCCGTGGGCACCACAATCGTGGACGCCGATAAGTACG
CCGTGACCGTGGAAACCCGGCTGATCGATGAGAGGGCCGCTC ACGTGAACGCCCAGTTCAGATTC
MOMP_E_nFLRT2_cHis ATGGGCCTGCAGACCACCAAGTGGCCTAGCCACGGCGCATTCT 257
TTCTGAAGTCCTGGCTGATCATCTCCCTGGGCCTGTACAGCCA
GGTGTCCAAGCTGCTGGCTCTGCCCGTGGGAAATCCTGCCGAG
CCCAGCCTGATGATCGACGGCATTCTGTGGGAGGGCTTCGGCG
GCGACCCTTGCGATCCTTGTACCACTTGGTGCGACGCCATCAG
CATGAGAATGGGCTACTACGGCGACTTCGTGTTCGACCGGGTG
CTGAAAACCGACGTGAACAAAGAATTCCAGATGGGCGACAAG
CCCACCAGCACCACCGGAAATGCCACCGCCCCTACCACCCTGA
CCGCCAGAGAAAATCCCGCCTACGGCCGGCACATGCAGGACG
CCGAGATGTTCACCAACGCCGCCTGCATGGCCCTGAACATCTG
GGACAGATTCGACGTGTTCTGCACCCTGGGCGCCAGCAGCGGC
TACCTGAAGGGCAATAGCGCCAGCTTCAACCTCGTGGGCCTGT
TCGGCGACAACGAGAACCAGAGCACCGTGAAAACAAACAGCG
TGCCCAACATGAGCCTGGACCAGAGCGTGGTGGAACTGTACA
CCGACACCGCATTCTCTTGGAGCGTGGGAGCCAGAGCTGCCCT
GTGGGAGTGTGGATGTGCCACACTGGGCGCTAGCTTCCAGTAC
GCCCAGAGCAAGCCCAAGGTGGAAGAACTGAACGTGCTGTGC
AATGCCGCCGAGTTCACCATCAACAAGCCTAAGGGCTACGTG
GGCCAGGAATTCCCCCTGGCCCTGATCGCCGGAACAGATGCCG
CCACCGGAACAAAGGACGCCAGCATCGACTACCACGAGTGGC
AGGCTTCTCTGGCCCTGTCCTACCGGCTGAATATGTTCACCCCC
TACATCGGCGTGAAGTGGTCCCGGGCCAGCTTCGATGCCGACA
CCATCAGAATCGCCCAGCCCAAGAGCGCCACCGCCATCTTCGA
TACCACCACACTGAACCCCACCATTGCCGGCGCTGGCGACGTG
AAAGCCTCTGCCGAAGGACAGCTGGGCGACACAATGCAGATC
GTGTCCCTGCAGCTGAACAAGATGAAGTCCCGGAAGTCCTGCG
GAATCGCCGTGGGCACCACAATCGTGGACGCCGATAAGTACG
CCGTGACCGTGGAAACCCGGCTGATCGATGAGAGGGCCGCTC
ACGTGAACGCCCAGTTCAGATTCCACCACCACCATCACCAC MOMP_E_nIgK
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 258
TGCCTGACACCACCGGCCTGCCCGTGGGAAATCCTGCCGAGCC
CAGCCTGATGATCGACGGCATTCTGTGGGAGGGCTTCGGCGGC
GACCCTTGCGATCCTTGTACCACTTGGTGCGACGCCATCAGCA
TGAGAATGGGCTACTACGGCGACTTCGTGTTCGACCGGGTGCT
GAAAACCGACGTGAACAAAGAATTCCAGATGGGCGACAAGCC
CACCAGCACCACCGGAAATGCCACCGCCCCTACCACCCTGACC
GCCAGAGAAAATCCCGCCTACGGCCGGCACATGCAGGACGCC
GAGATGTTCACCAACGCCGCCTGCATGGCCCTGAACATCTGGG
ACAGATTCGACGTGTTCTGCACCCTGGGCGCCAGCAGCGGCTA
CCTGAAGGGCAATAGCGCCAGCTTCAACCTCGTGGGCCTGTTC
GGCGACAACGAGAACCAGAGCACCGTGAAAACAAACAGCGTG
CCCAACATGAGCCTGGACCAGAGCGTGGTGGAACTGTACACC
GACACCGCATTCTCTTGGAGCGTGGGAGCCAGAGCTGCCCTGT
GGGAGTGTGGATGTGCCACACTGGGCGCTAGCTTCCAGTACGC
CCAGAGCAAGCCCAAGGTGGAAGAACTGAACGTGCTGTGCAA
TGCCGCCGAGTTCACCATCAACAAGCCTAAGGGCTACGTGGGC
CAGGAATTCCCCCTGGCCCTGATCGCCGGAACAGATGCCGCCA
CCGGAACAAAGGACGCCAGCATCGACTACCACGAGTGGCAGG
CTTCTCTGGCCCTGTCCTACCGGCTGAATATGTTCACCCCCTAC
ATCGGCGTGAAGTGGTCCCGGGCCAGCTTCGATGCCGACACCA
TCAGAATCGCCCAGCCCAAGAGCGCCACCGCCATCTTCGATAC
CACCACACTGAACCCCACCATTGCCGGCGCTGGCGACGTGAA
AGCCTCTGCCGAAGGACAGCTGGGCGACACAATGCAGATCGT
GTCCCTGCAGCTGAACAAGATGAAGTCCCGGAAGTCCTGCGG
AATCGCCGTGGGCACCACAATCGTGGACGCCGATAAGTACGC
CGTGACCGTGGAAACCCGGCTGATCGATGAGAGGGCCGCTCA CGTGAACGCCCAGTTCAGATTC
MOMP_E_nIgK_cHis ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 259
TGCCTGACACCACCGGCCTGCCCGTGGGAAATCCTGCCGAGCC
CAGCCTGATGATCGACGGCATTCTGTGGGAGGGCTTCGGCGGC
GACCCTTGCGATCCTTGTACCACTTGGTGCGACGCCATCAGCA
TGAGAATGGGCTACTACGGCGACTTCGTGTTCGACCGGGTGCT
GAAAACCGACGTGAACAAAGAATTCCAGATGGGCGACAAGCC
CACCAGCACCACCGGAAATGCCACCGCCCCTACCACCCTGACC
GCCAGAGAAAATCCCGCCTACGGCCGGCACATGCAGGACGCC
GAGATGTTCACCAACGCCGCCTGCATGGCCCTGAACATCTGGG
ACAGATTCGACGTGTTCTGCACCCTGGGCGCCAGCAGCGGCTA
CCTGAAGGGCAATAGCGCCAGCTTCAACCTCGTGGGCCTGTTC
GGCGACAACGAGAACCAGAGCACCGTGAAAACAAACAGCGTG
CCCAACATGAGCCTGGACCAGAGCGTGGTGGAACTGTACACC
GACACCGCATTCTCTTGGAGCGTGGGAGCCAGAGCTGCCCTGT
GGGAGTGTGGATGTGCCACACTGGGCGCTAGCTTCCAGTACGC
CCAGAGCAAGCCCAAGGTGGAAGAACTGAACGTGCTGTGCAA
TGCCGCCGAGTTCACCATCAACAAGCCTAAGGGCTACGTGGGC
CAGGAATTCCCCCTGGCCCTGATCGCCGGAACAGATGCCGCCA
CCGGAACAAAGGACGCCAGCATCGACTACCACGAGTGGCAGG
CTTCTCTGGCCCTGTCCTACCGGCTGAATATGTTCACCCCCTAC
ATCGGCGTGAAGTGGTCCCGGGCCAGCTTCGATGCCGACACCA
TCAGAATCGCCCAGCCCAAGAGCGCCACCGCCATCTTCGATAC
CACCACACTGAACCCCACCATTGCCGGCGCTGGCGACGTGAA
AGCCTCTGCCGAAGGACAGCTGGGCGACACAATGCAGATCGT
GTCCCTGCAGCTGAACAAGATGAAGTCCCGGAAGTCCTGCGG
AATCGCCGTGGGCACCACAATCGTGGACGCCGATAAGTACGC
CGTGACCGTGGAAACCCGGCTGATCGATGAGAGGGCCGCTCA
CGTGAACGCCCAGTTCAGATTCCACCACCACCATCACCAC MOMP_E_nOsteo
ATGTGGTGGCGGCTGTGGTGGCTTCTCCTTCTCCTCCTGCTGCT 260
GTGGCCCATGGTGTGGGCCCTGCCCGTGGGAAATCCTGCCGAG
CCCAGCCTGATGATCGACGGCATTCTGTGGGAGGGCTTCGGCG
GCGACCCTTGCGATCCTTGTACCACTTGGTGCGACGCCATCAG
CATGAGAATGGGCTACTACGGCGACTTCGTGTTCGACCGGGTG
CTGAAAACCGACGTGAACAAAGAATTCCAGATGGGCGACAAG
CCCACCAGCACCACCGGAAATGCCACCGCCCCTACCACCCTGA
CCGCCAGAGAAAATCCCGCCTACGGCCGGCACATGCAGGACG
CCGAGATGTTCACCAACGCCGCCTGCATGGCCCTGAACATCTG
GGACAGATTCGACGTGTTCTGCACCCTGGGCGCCAGCAGCGGC
TACCTGAAGGGCAATAGCGCCAGCTTCAACCTCGTGGGCCTGT
TCGGCGACAACGAGAACCAGAGCACCGTGAAAACAAACAGCG
TGCCCAACATGAGCCTGGACCAGAGCGTGGTGGAACTGTACA
CCGACACCGCATTCTCTTGGAGCGTGGGAGCCAGAGCTGCCCT
GTGGGAGTGTGGATGTGCCACACTGGGCGCTAGCTTCCAGTAC
GCCCAGAGCAAGCCCAAGGTGGAAGAACTGAACGTGCTGTGC
AATGCCGCCGAGTTCACCATCAACAAGCCTAAGGGCTACGTG
GGCCAGGAATTCCCCCTGGCCCTGATCGCCGGAACAGATGCCG
CCACCGGAACAAAGGACGCCAGCATCGACTACCACGAGTGGC
AGGCTTCTCTGGCCCTGTCCTACCGGCTGAATATGTTCACCCCC
TACATCGGCGTGAAGTGGTCCCGGGCCAGCTTCGATGCCGACA
CCATCAGAATCGCCCAGCCCAAGAGCGCCACCGCCATCTTCGA
TACCACCACACTGAACCCCACCATTGCCGGCGCTGGCGACGTG
AAAGCCTCTGCCGAAGGACAGCTGGGCGACACAATGCAGATC
GTGTCCCTGCAGCTGAACAAGATGAAGTCCCGGAAGTCCTGCG
GAATCGCCGTGGGCACCACAATCGTGGACGCCGATAAGTACG
CCGTGACCGTGGAAACCCGGCTGATCGATGAGAGGGCCGCTC ACGTGAACGCCCAGTTCAGATTC
MOMP_E_nOsteo_cHis ATGTGGTGGCGGCTGTGGTGGCTTCTCCTTCTCCTCCTGCTGCT 261
GTGGCCCATGGTGTGGGCCCTGCCCGTGGGAAATCCTGCCGAG
CCCAGCCTGATGATCGACGGCATTCTGTGGGAGGGCTTCGGCG
GCGACCCTTGCGATCCTTGTACCACTTGGTGCGACGCCATCAG
CATGAGAATGGGCTACTACGGCGACTTCGTGTTCGACCGGGTG
CTGAAAACCGACGTGAACAAAGAATTCCAGATGGGCGACAAG
CCCACCAGCACCACCGGAAATGCCACCGCCCCTACCACCCTGA
CCGCCAGAGAAAATCCCGCCTACGGCCGGCACATGCAGGACG
CCGAGATGTTCACCAACGCCGCCTGCATGGCCCTGAACATCTG
GGACAGATTCGACGTGTTCTGCACCCTGGGCGCCAGCAGCGGC
TACCTGAAGGGCAATAGCGCCAGCTTCAACCTCGTGGGCCTGT
TCGGCGACAACGAGAACCAGAGCACCGTGAAAACAAACAGCG
TGCCCAACATGAGCCTGGACCAGAGCGTGGTGGAACTGTACA
CCGACACCGCATTCTCTTGGAGCGTGGGAGCCAGAGCTGCCCT
GTGGGAGTGTGGATGTGCCACACTGGGCGCTAGCTTCCAGTAC
GCCCAGAGCAAGCCCAAGGTGGAAGAACTGAACGTGCTGTGC
AATGCCGCCGAGTTCACCATCAACAAGCCTAAGGGCTACGTG
GGCCAGGAATTCCCCCTGGCCCTGATCGCCGGAACAGATGCCG
CCACCGGAACAAAGGACGCCAGCATCGACTACCACGAGTGGC
AGGCTTCTCTGGCCCTGTCCTACCGGCTGAATATGTTCACCCCC
TACATCGGCGTGAAGTGGTCCCGGGCCAGCTTCGATGCCGACA
CCATCAGAATCGCCCAGCCCAAGAGCGCCACCGCCATCTTCGA
TACCACCACACTGAACCCCACCATTGCCGGCGCTGGCGACGTG
AAAGCCTCTGCCGAAGGACAGCTGGGCGACACAATGCAGATC
GTGTCCCTGCAGCTGAACAAGATGAAGTCCCGGAAGTCCTGCG
GAATCGCCGTGGGCACCACAATCGTGGACGCCGATAAGTACG
CCGTGACCGTGGAAACCCGGCTGATCGATGAGAGGGCCGCTC
ACGTGAACGCCCAGTTCAGATTCCACCACCACCATCACCAC Ct-858_E_H97A_nIgK
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 262
TGCCTGATACCACAGGCGTGCGGGGAGAGTCCCTCGTGTGCAA
GAATGCCCTGCAGGACCTGAGCTTCCTGGAACATCTGCTGCAA
GTGAAGTACGCCCCCAAGACCTGGAAAGAGCAGTACCTGGGC
TGGGACCTGGTGCAGTCCTCTGTGTCTGCCCAGCAGAAGCTGC
GGACCCAGGAAAACCCCTCTACCAGCTTCTGTCAGCAAGTGCT
GGCCGACTTCATCGGCGGCCTGAACGATTTCGCCGCCGGCGTG
ACCTTTTTCGCCATCGAGAGCGCCTACCTGCCCTACACCGTGC
AGAAGTCCAGCGACGGCCGGTTCTACTTCGTGGACATCATGAC
CTTCAGCAGCGAGATCAGAGTGGGCGACGAGCTGCTGGAAGT
GGATGGCGCTCCTGTGCAGGATGTGCTGGCCACACTGTACGGC
AGCAACCACAAGGGCACAGCCGCCGAAGAATCTGCCGCCCTG
AGAACCCTGTTCAGCCGGATGGCCTCTCTGGGCCACAAGGTGC
CAAGCGGCAGAACCACCCTGAAGATCAGACGGCCCTTTGGCA
CCACCCGGGAAGTGCGCGTGAAGTGGCGCTATGTGCCTGAGG
GCGTGGGCGACCTGGCCACAATCGCCCCTTCTATCAGAGCCCC
CCAGCTGCAGAAATCCATGCGGTCATTCTTCCCAAAGAAGGAC
GACGCCTTCCACCGGTCCAGCAGCCTGTTCTACAGCCCTATGG
TGCCCCACTTCTGGGCCGAGCTGAGAAACCACTACGCCACCTC
CGGCCTGAAGTCCGGCTACAACATCGGCAGCACCGACGGCTTT
CTGCCCGTGATCGGACCCGTGATCTGGGAGAGCGAGGGCCTGT
TCAGAGCCTACATCAGCAGCGTGACCGACGGCGACGGCAAGA
GCCACAAAGTGGGCTTTCTGAGAATCCCCACCTACAGCTGGCA
GGACATGGAAGATTTCGACCCCAGCGGCCCACCCCCCTGGGA
GGAATTTGCCAAGATCATCCAGGTGTTCAGCAGCAACACCGA
GGCCCTGATCATCGACCAGACCAACAACCCTGGCGGCAGCGT
GCTGTACCTGTACGCCCTGCTGAGCATGCTGACCGACAGACCC
CTGGAACTGCCCAAGCACCGGATGATCCTGACCCAGGACGAG
GTGGTGGACGCCCTGGATTGGCTGACCCTGCTGGAAAACGTGG
ACACCAACGTGGAAAGCCGGCTGGCCCTGGGCGACAACATGG
AAGGCTACACAGTGGATCTGCAGGTGGCCGAGTACCTGAAAA
GCTTCGGCAGACAGGTGCTGAACTGCTGGTCCAAGGGCGACA
TCGAGCTGAGCACCCCCATCCCCCTGTTCGGCTTCGAGAAGAT
CCACCCCCACCCCAGAGTGCAGTACAGCAAGCCCATCTGCGTG
CTGATCAACGAGCAGGACTTCTCCTGCGCCGACTTCTTCCCAG
TGGTGCTGAAGGACAACGACAGAGCCCTGATCGTGGGCACCA
GAACAGCTGGCGCTGGCGGCTTCGTGTTCAACGTGCAGTTCCC
CAACCGGACCGGCATCAAGACCTGTAGCCTGACAGGCTCTCTG
GCCGTGCGGGAACACGGCGCCTTCATCGAGAACATCGGCGTG
GAACCCCACATCGACCTGCCTTTCACCGCCAACGACATCCGGT
ACAAGGGCTACTCTGAGTACCTGGACAAAGTGAAGAAACTCG
TGTGCCAGCTGATTAACAACGACGGCACCATCATCCTGGCCGA GGACGGCAGCTTC
Ct858_E_H97A_nIgK_cHis ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC
263 TGCCTGATACCACAGGCGTGCGGGGAGAGTCCCTCGTGTGCAA
GAATGCCCTGCAGGACCTGAGCTTCCTGGAACATCTGCTGCAA
GTGAAGTACGCCCCCAAGACCTGGAAAGAGCAGTACCTGGGC
TGGGACCTGGTGCAGTCCTCTGTGTCTGCCCAGCAGAAGCTGC
GGACCCAGGAAAACCCCTCTACCAGCTTCTGTCAGCAAGTGCT
GGCCGACTTCATCGGCGGCCTGAACGATTTCGCCGCCGGCGTG
ACCTTTTTCGCCATCGAGAGCGCCTACCTGCCCTACACCGTGC
AGAAGTCCAGCGACGGCCGGTTCTACTTCGTGGACATCATGAC
CTTCAGCAGCGAGATCAGAGTGGGCGACGAGCTGCTGGAAGT
GGATGGCGCTCCTGTGCAGGATGTGCTGGCCACACTGTACGGC
AGCAACCACAAGGGCACAGCCGCCGAAGAATCTGCCGCCCTG
AGAACCCTGTTCAGCCGGATGGCCTCTCTGGGCCACAAGGTGC
CAAGCGGCAGAACCACCCTGAAGATCAGACGGCCCTTTGGCA
CCACCCGGGAAGTGCGCGTGAAGTGGCGCTATGTGCCTGAGG
GCGTGGGCGACCTGGCCACAATCGCCCCTTCTATCAGAGCCCC
CCAGCTGCAGAAATCCATGCGGTCATTCTTCCCAAAGAAGGAC
GACGCCTTCCACCGGTCCAGCAGCCTGTTCTACAGCCCTATGG
TGCCCCACTTCTGGGCCGAGCTGAGAAACCACTACGCCACCTC
CGGCCTGAAGTCCGGCTACAACATCGGCAGCACCGACGGCTTT
CTGCCCGTGATCGGACCCGTGATCTGGGAGAGCGAGGGCCTGT
TCAGAGCCTACATCAGCAGCGTGACCGACGGCGACGGCAAGA
GCCACAAAGTGGGCTTTCTGAGAATCCCCACCTACAGCTGGCA
GGACATGGAAGATTTCGACCCCAGCGGCCCACCCCCCTGGGA
GGAATTTGCCAAGATCATCCAGGTGTTCAGCAGCAACACCGA
GGCCCTGATCATCGACCAGACCAACAACCCTGGCGGCAGCGT
GCTGTACCTGTACGCCCTGCTGAGCATGCTGACCGACAGACCC
CTGGAACTGCCCAAGCACCGGATGATCCTGACCCAGGACGAG
GTGGTGGACGCCCTGGATTGGCTGACCCTGCTGGAAAACGTGG
ACACCAACGTGGAAAGCCGGCTGGCCCTGGGCGACAACATGG
AAGGCTACACAGTGGATCTGCAGGTGGCCGAGTACCTGAAAA
GCTTCGGCAGACAGGTGCTGAACTGCTGGTCCAAGGGCGACA
TCGAGCTGAGCACCCCCATCCCCCTGTTCGGCTTCGAGAAGAT
CCACCCCCACCCCAGAGTGCAGTACAGCAAGCCCATCTGCGTG
CTGATCAACGAGCAGGACTTCTCCTGCGCCGACTTCTTCCCAG
TGGTGCTGAAGGACAACGACAGAGCCCTGATCGTGGGCACCA
GAACAGCTGGCGCTGGCGGCTTCGTGTTCAACGTGCAGTTCCC
CAACCGGACCGGCATCAAGACCTGTAGCCTGACAGGCTCTCTG
GCCGTGCGGGAACACGGCGCCTTCATCGAGAACATCGGCGTG
GAACCCCACATCGACCTGCCTTTCACCGCCAACGACATCCGGT
ACAAGGGCTACTCTGAGTACCTGGACAAAGTGAAGAAACTCG
TGTGCCAGCTGATTAACAACGACGGCACCATCATCCTGGCCGA
GGACGGCAGCTTCCACCACCACCATCACCAC Ct858_E_S491A_nIgK
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 264
TGCCTGATACCACAGGCGTGCGGGGAGAGTCCCTCGTGTGCAA
GAATGCCCTGCAGGACCTGAGCTTCCTGGAACATCTGCTGCAA
GTGAAGTACGCCCCCAAGACCTGGAAAGAGCAGTACCTGGGC
TGGGACCTGGTGCAGTCCTCTGTGTCTGCCCAGCAGAAGCTGC
GGACCCAGGAAAACCCCTCTACCAGCTTCTGTCAGCAAGTGCT
GGCCGACTTCATCGGCGGCCTGAACGATTTCCATGCCGGCGTG
ACCTTTTTCGCCATCGAGAGCGCCTACCTGCCCTACACCGTGC
AGAAGTCCAGCGACGGCCGGTTCTACTTCGTGGACATCATGAC
CTTCAGCAGCGAGATCAGAGTGGGCGACGAGCTGCTGGAAGT
GGATGGCGCTCCTGTGCAGGATGTGCTGGCCACACTGTACGGC
AGCAACCACAAGGGCACAGCCGCCGAAGAATCTGCCGCCCTG
AGAACCCTGTTCAGCCGGATGGCCTCTCTGGGCCACAAGGTGC
CAAGCGGCAGAACCACCCTGAAGATCAGACGGCCCTTTGGCA
CCACCCGGGAAGTGCGCGTGAAGTGGCGCTATGTGCCTGAGG
GCGTGGGCGACCTGGCCACAATCGCCCCTTCTATCAGAGCCCC
CCAGCTGCAGAAATCCATGCGGTCATTCTTCCCAAAGAAGGAC
GACGCCTTCCACCGGTCCAGCAGCCTGTTCTACAGCCCTATGG
TGCCCCACTTCTGGGCCGAGCTGAGAAACCACTACGCCACCTC
CGGCCTGAAGTCCGGCTACAACATCGGCAGCACCGACGGCTTT
CTGCCCGTGATCGGACCCGTGATCTGGGAGAGCGAGGGCCTGT
TCAGAGCCTACATCAGCAGCGTGACCGACGGCGACGGCAAGA
GCCACAAAGTGGGCTTTCTGAGAATCCCCACCTACAGCTGGCA
GGACATGGAAGATTTCGACCCCAGCGGCCCACCCCCCTGGGA
GGAATTTGCCAAGATCATCCAGGTGTTCAGCAGCAACACCGA
GGCCCTGATCATCGACCAGACCAACAACCCTGGCGGCAGCGT
GCTGTACCTGTACGCCCTGCTGAGCATGCTGACCGACAGACCC
CTGGAACTGCCCAAGCACCGGATGATCCTGACCCAGGACGAG
GTGGTGGACGCCCTGGATTGGCTGACCCTGCTGGAAAACGTGG
ACACCAACGTGGAAAGCCGGCTGGCCCTGGGCGACAACATGG
AAGGCTACACAGTGGATCTGCAGGTGGCCGAGTACCTGAAAA
GCTTCGGCAGACAGGTGCTGAACTGCTGGTCCAAGGGCGACA
TCGAGCTGAGCACCCCCATCCCCCTGTTCGGCTTCGAGAAGAT
CCACCCCCACCCCAGAGTGCAGTACAGCAAGCCCATCTGCGTG
CTGATCAACGAGCAGGACTTCGCCTGCGCCGACTTCTTCCCAG
TGGTGCTGAAGGACAACGACAGAGCCCTGATCGTGGGCACCA
GAACAGCTGGCGCTGGCGGCTTCGTGTTCAACGTGCAGTTCCC
CAACCGGACCGGCATCAAGACCTGTAGCCTGACAGGCTCTCTG
GCCGTGCGGGAACACGGCGCCTTCATCGAGAACATCGGCGTG
GAACCCCACATCGACCTGCCTTTCACCGCCAACGACATCCGGT
ACAAGGGCTACTCTGAGTACCTGGACAAAGTGAAGAAACTCG
TGTGCCAGCTGATTAACAACGACGGCACCATCATCCTGGCCGA GGACGGCAGCTTC
Ct858_E_S491A_nIgK_cHis ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC
265 TGCCTGATACCACAGGCGTGCGGGGAGAGTCCCTCGTGTGCAA
GAATGCCCTGCAGGACCTGAGCTTCCTGGAACATCTGCTGCAA
GTGAAGTACGCCCCCAAGACCTGGAAAGAGCAGTACCTGGGC
TGGGACCTGGTGCAGTCCTCTGTGTCTGCCCAGCAGAAGCTGC
GGACCCAGGAAAACCCCTCTACCAGCTTCTGTCAGCAAGTGCT
GGCCGACTTCATCGGCGGCCTGAACGATTTCCATGCCGGCGTG
ACCTTTTTCGCCATCGAGAGCGCCTACCTGCCCTACACCGTGC
AGAAGTCCAGCGACGGCCGGTTCTACTTCGTGGACATCATGAC
CTTCAGCAGCGAGATCAGAGTGGGCGACGAGCTGCTGGAAGT
GGATGGCGCTCCTGTGCAGGATGTGCTGGCCACACTGTACGGC
AGCAACCACAAGGGCACAGCCGCCGAAGAATCTGCCGCCCTG
AGAACCCTGTTCAGCCGGATGGCCTCTCTGGGCCACAAGGTGC
CAAGCGGCAGAACCACCCTGAAGATCAGACGGCCCTTTGGCA
CCACCCGGGAAGTGCGCGTGAAGTGGCGCTATGTGCCTGAGG
GCGTGGGCGACCTGGCCACAATCGCCCCTTCTATCAGAGCCCC
CCAGCTGCAGAAATCCATGCGGTCATTCTTCCCAAAGAAGGAC
GACGCCTTCCACCGGTCCAGCAGCCTGTTCTACAGCCCTATGG
TGCCCCACTTCTGGGCCGAGCTGAGAAACCACTACGCCACCTC
CGGCCTGAAGTCCGGCTACAACATCGGCAGCACCGACGGCTTT
CTGCCCGTGATCGGACCCGTGATCTGGGAGAGCGAGGGCCTGT
TCAGAGCCTACATCAGCAGCGTGACCGACGGCGACGGCAAGA
GCCACAAAGTGGGCTTTCTGAGAATCCCCACCTACAGCTGGCA
GGACATGGAAGATTTCGACCCCAGCGGCCCACCCCCCTGGGA
GGAATTTGCCAAGATCATCCAGGTGTTCAGCAGCAACACCGA
GGCCCTGATCATCGACCAGACCAACAACCCTGGCGGCAGCGT
GCTGTACCTGTACGCCCTGCTGAGCATGCTGACCGACAGACCC
CTGGAACTGCCCAAGCACCGGATGATCCTGACCCAGGACGAG
GTGGTGGACGCCCTGGATTGGCTGACCCTGCTGGAAAACGTGG
ACACCAACGTGGAAAGCCGGCTGGCCCTGGGCGACAACATGG
AAGGCTACACAGTGGATCTGCAGGTGGCCGAGTACCTGAAAA
GCTTCGGCAGACAGGTGCTGAACTGCTGGTCCAAGGGCGACA
TCGAGCTGAGCACCCCCATCCCCCTGTTCGGCTTCGAGAAGAT
CCACCCCCACCCCAGAGTGCAGTACAGCAAGCCCATCTGCGTG
CTGATCAACGAGCAGGACTTCGCCTGCGCCGACTTCTTCCCAG
TGGTGCTGAAGGACAACGACAGAGCCCTGATCGTGGGCACCA
GAACAGCTGGCGCTGGCGGCTTCGTGTTCAACGTGCAGTTCCC
CAACCGGACCGGCATCAAGACCTGTAGCCTGACAGGCTCTCTG
GCCGTGCGGGAACACGGCGCCTTCATCGAGAACATCGGCGTG
GAACCCCACATCGACCTGCCTTTCACCGCCAACGACATCCGGT
ACAAGGGCTACTCTGAGTACCTGGACAAAGTGAAGAAACTCG
TGTGCCAGCTGATTAACAACGACGGCACCATCATCCTGGCCGA
GGACGGCAGCTTCCACCACCACCATCACCAC Ct089_E_T306A_nIgK
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 266
TGCCTGACACCACCGGCATGACAGCATCTGGCGGAGCTGGCG
GCCTGGGCTCTACACAGACAGTGGATGTGGCCAGGGCCCAGG
CTGCTGCCGCTACACAGGATGCCCAGGAAGTGATCGGCAGCC
AGGAAGCCAGCGAGGCCTCTATGCTGAAGGGCTGCGAGGACC
TGATCAACCCTGCCGCCGCTACCCGCATCAAGAAGAAAGAGG
AAAAGTTCGAGTCCCTGGAAGCCAGACGGAAGCCCACCGCCG
ACAAGGCCGAGAAGAAGTCCGAGAGCACCGAGGAAAAGGGC
GACACCCCCCTGGAAGATCGGTTCACCGAGGATCTGAGCGAG
GTGTCCGGCGAGGACTTCCGGGGCCTGAAGAACAGCTTCGAC
GACGACAGCAGCCCCGAGGAAATCCTGGACGCCCTGACCAGC
AAGTTCAGCGACCCCACCATCAAGGACCTGGCCCTGGACTACC
TGATCCAGACCGCCCCCAGCGACCGGAAGCTGAAGTCTGCCCT
GATTCAGGCCAAGCACCAGCTGATGAGCCAGAACCCCCAGGC
CATCGTGGGCGGCAGAAATGTGCTGCTGGCCTCCGAGACATTC
GCCAGCAGAGCCAACACCAGCCCCAGCTCCCTGCGGAGCCTG
TATCTGCAAGTGACCAGCTCCCCCAGCAACTGCGACAACCTGA
GACAGATGCTGGCTAGCTACCTGCCCTCCGAGAAAACCGCCGT
GATGGAATTCCTCGTGAACGGCATGGTGGCCGACCTGAAAAG
CGAGGGCCCTAGCATCCCTCCCGCCAAGCTGCAGGTGTACATG
ACCGAGCTGAGCAACCTGCAGGCCCTGCACAGCGTGGACAGC
TTTTTCGACCGGAACATCGGCAACCTGGAAAACAGCCTGAAGC
ACGAGGGCCACGCCCCCATCCCTTCTCTGACAACCGGCAATCT
GGCCAAGACCTTCCTGCAGCTGGTGGAAGATAAGTTCCCCAGC
AGCTCCAAGGCCCAGAAGGCCCTGAACGAGCTCGTGGGCCCT
GATACCGGACCTCAGACCGAGGTGCTGAACCTGTTCTTTCGGG
CCCTGAATGGCTGCTCCCCCCGGATCTTTTCTGGCGCTGAGAA
GAAGCAGCAGCTGGCCAGCGTGATCACCAACACCCTGGATGC
CATCAACGCCGACAACGAGGACTACCCCAAGCCCGGCGACTT
CCCCAGAAGCAGCTTTAGCAGCACCCCCCCTCATGCCCCTGTG
CCCCAGTCTGAGATCCCTACCAGCCCAACCAGCACCCAGCCTC CAAGCCCT
Ct089_E_T306A_nIgK_cHis ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC
267 TGCCTGACACCACCGGCATGACAGCATCTGGCGGAGCTGGCG
GCCTGGGCTCTACACAGACAGTGGATGTGGCCAGGGCCCAGG
CTGCTGCCGCTACACAGGATGCCCAGGAAGTGATCGGCAGCC
AGGAAGCCAGCGAGGCCTCTATGCTGAAGGGCTGCGAGGACC
TGATCAACCCTGCCGCCGCTACCCGCATCAAGAAGAAAGAGG
AAAAGTTCGAGTCCCTGGAAGCCAGACGGAAGCCCACCGCCG
ACAAGGCCGAGAAGAAGTCCGAGAGCACCGAGGAAAAGGGC
GACACCCCCCTGGAAGATCGGTTCACCGAGGATCTGAGCGAG
GTGTCCGGCGAGGACTTCCGGGGCCTGAAGAACAGCTTCGAC
GACGACAGCAGCCCCGAGGAAATCCTGGACGCCCTGACCAGC
AAGTTCAGCGACCCCACCATCAAGGACCTGGCCCTGGACTACC
TGATCCAGACCGCCCCCAGCGACCGGAAGCTGAAGTCTGCCCT
GATTCAGGCCAAGCACCAGCTGATGAGCCAGAACCCCCAGGC
CATCGTGGGCGGCAGAAATGTGCTGCTGGCCTCCGAGACATTC
GCCAGCAGAGCCAACACCAGCCCCAGCTCCCTGCGGAGCCTG
TATCTGCAAGTGACCAGCTCCCCCAGCAACTGCGACAACCTGA
GACAGATGCTGGCTAGCTACCTGCCCTCCGAGAAAACCGCCGT
GATGGAATTCCTCGTGAACGGCATGGTGGCCGACCTGAAAAG
CGAGGGCCCTAGCATCCCTCCCGCCAAGCTGCAGGTGTACATG
ACCGAGCTGAGCAACCTGCAGGCCCTGCACAGCGTGGACAGC
TTTTTCGACCGGAACATCGGCAACCTGGAAAACAGCCTGAAGC
ACGAGGGCCACGCCCCCATCCCTTCTCTGACAACCGGCAATCT
GGCCAAGACCTTCCTGCAGCTGGTGGAAGATAAGTTCCCCAGC
AGCTCCAAGGCCCAGAAGGCCCTGAACGAGCTCGTGGGCCCT
GATACCGGACCTCAGACCGAGGTGCTGAACCTGTTCTTTCGGG
CCCTGAATGGCTGCTCCCCCCGGATCTTTTCTGGCGCTGAGAA
GAAGCAGCAGCTGGCCAGCGTGATCACCAACACCCTGGATGC
CATCAACGCCGACAACGAGGACTACCCCAAGCCCGGCGACTT
CCCCAGAAGCAGCTTTAGCAGCACCCCCCCTCATGCCCCTGTG
CCCCAGTCTGAGATCCCTACCAGCCCAACCAGCACCCAGCCTC
CAAGCCCTCACCACCACCATCACCAC Ct089_E_S198A_T306A_nIgK
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 268
TGCCTGACACCACCGGCATGACAGCATCTGGCGGAGCTGGCG
GCCTGGGCTCTACACAGACAGTGGATGTGGCCAGGGCCCAGG
CTGCTGCCGCTACACAGGATGCCCAGGAAGTGATCGGCAGCC
AGGAAGCCAGCGAGGCCTCTATGCTGAAGGGCTGCGAGGACC
TGATCAACCCTGCCGCCGCTACCCGCATCAAGAAGAAAGAGG
AAAAGTTCGAGTCCCTGGAAGCCAGACGGAAGCCCACCGCCG
ACAAGGCCGAGAAGAAGTCCGAGAGCACCGAGGAAAAGGGC
GACACCCCCCTGGAAGATCGGTTCACCGAGGATCTGAGCGAG
GTGTCCGGCGAGGACTTCCGGGGCCTGAAGAACAGCTTCGAC
GACGACAGCAGCCCCGAGGAAATCCTGGACGCCCTGACCAGC
AAGTTCAGCGACCCCACCATCAAGGACCTGGCCCTGGACTACC
TGATCCAGACCGCCCCCAGCGACCGGAAGCTGAAGTCTGCCCT
GATTCAGGCCAAGCACCAGCTGATGAGCCAGAACCCCCAGGC
CATCGTGGGCGGCAGAAATGTGCTGCTGGCCTCCGAGACATTC
GCCAGCAGAGCCAACACCGCCCCCAGCTCCCTGCGGAGCCTGT
ATCTGCAAGTGACCAGCTCCCCCAGCAACTGCGACAACCTGAG
ACAGATGCTGGCTAGCTACCTGCCCTCCGAGAAAACCGCCGTG
ATGGAATTCCTCGTGAACGGCATGGTGGCCGACCTGAAAAGC
GAGGGCCCTAGCATCCCTCCCGCCAAGCTGCAGGTGTACATGA
CCGAGCTGAGCAACCTGCAGGCCCTGCACAGCGTGGACAGCT
TTTTCGACCGGAACATCGGCAACCTGGAAAACAGCCTGAAGC
ACGAGGGCCACGCCCCCATCCCTTCTCTGACAACCGGCAATCT
GGCCAAGACCTTCCTGCAGCTGGTGGAAGATAAGTTCCCCAGC
AGCTCCAAGGCCCAGAAGGCCCTGAACGAGCTCGTGGGCCCT
GATACCGGACCTCAGACCGAGGTGCTGAACCTGTTCTTTCGGG
CCCTGAATGGCTGCTCCCCCCGGATCTTTTCTGGCGCTGAGAA
GAAGCAGCAGCTGGCCAGCGTGATCACCAACACCCTGGATGC
CATCAACGCCGACAACGAGGACTACCCCAAGCCCGGCGACTT
CCCCAGAAGCAGCTTTAGCAGCACCCCCCCTCATGCCCCTGTG
CCCCAGTCTGAGATCCCTACCAGCCCAACCAGCACCCAGCCTC CAAGCCCT
Ct089_E_S198A_T306A_nIgK_cHis
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 269
TGCCTGACACCACCGGCATGACAGCATCTGGCGGAGCTGGCG
GCCTGGGCTCTACACAGACAGTGGATGTGGCCAGGGCCCAGG
CTGCTGCCGCTACACAGGATGCCCAGGAAGTGATCGGCAGCC
AGGAAGCCAGCGAGGCCTCTATGCTGAAGGGCTGCGAGGACC
TGATCAACCCTGCCGCCGCTACCCGCATCAAGAAGAAAGAGG
AAAAGTTCGAGTCCCTGGAAGCCAGACGGAAGCCCACCGCCG
ACAAGGCCGAGAAGAAGTCCGAGAGCACCGAGGAAAAGGGC
GACACCCCCCTGGAAGATCGGTTCACCGAGGATCTGAGCGAG
GTGTCCGGCGAGGACTTCCGGGGCCTGAAGAACAGCTTCGAC
GACGACAGCAGCCCCGAGGAAATCCTGGACGCCCTGACCAGC
AAGTTCAGCGACCCCACCATCAAGGACCTGGCCCTGGACTACC
TGATCCAGACCGCCCCCAGCGACCGGAAGCTGAAGTCTGCCCT
GATTCAGGCCAAGCACCAGCTGATGAGCCAGAACCCCCAGGC
CATCGTGGGCGGCAGAAATGTGCTGCTGGCCTCCGAGACATTC
GCCAGCAGAGCCAACACCGCCCCCAGCTCCCTGCGGAGCCTGT
ATCTGCAAGTGACCAGCTCCCCCAGCAACTGCGACAACCTGAG
ACAGATGCTGGCTAGCTACCTGCCCTCCGAGAAAACCGCCGTG
ATGGAATTCCTCGTGAACGGCATGGTGGCCGACCTGAAAAGC
GAGGGCCCTAGCATCCCTCCCGCCAAGCTGCAGGTGTACATGA
CCGAGCTGAGCAACCTGCAGGCCCTGCACAGCGTGGACAGCT
TTTTCGACCGGAACATCGGCAACCTGGAAAACAGCCTGAAGC
ACGAGGGCCACGCCCCCATCCCTTCTCTGACAACCGGCAATCT
GGCCAAGACCTTCCTGCAGCTGGTGGAAGATAAGTTCCCCAGC
AGCTCCAAGGCCCAGAAGGCCCTGAACGAGCTCGTGGGCCCT
GATACCGGACCTCAGACCGAGGTGCTGAACCTGTTCTTTCGGG
CCCTGAATGGCTGCTCCCCCCGGATCTTTTCTGGCGCTGAGAA
GAAGCAGCAGCTGGCCAGCGTGATCACCAACACCCTGGATGC
CATCAACGCCGACAACGAGGACTACCCCAAGCCCGGCGACTT
CCCCAGAAGCAGCTTTAGCAGCACCCCCCCTCATGCCCCTGTG
CCCCAGTCTGAGATCCCTACCAGCCCAACCAGCACCCAGCCTC
CAAGCCCTCACCACCACCATCACCAC Ct089_E_S198A_nIgK
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 270
TGCCTGACACCACCGGCATGACAGCATCTGGCGGAGCTGGCG
GCCTGGGCTCTACACAGACAGTGGATGTGGCCAGGGCCCAGG
CTGCTGCCGCTACACAGGATGCCCAGGAAGTGATCGGCAGCC
AGGAAGCCAGCGAGGCCTCTATGCTGAAGGGCTGCGAGGACC
TGATCAACCCTGCCGCCGCTACCCGCATCAAGAAGAAAGAGG
AAAAGTTCGAGTCCCTGGAAGCCAGACGGAAGCCCACCGCCG
ACAAGGCCGAGAAGAAGTCCGAGAGCACCGAGGAAAAGGGC
GACACCCCCCTGGAAGATCGGTTCACCGAGGATCTGAGCGAG
GTGTCCGGCGAGGACTTCCGGGGCCTGAAGAACAGCTTCGAC
GACGACAGCAGCCCCGAGGAAATCCTGGACGCCCTGACCAGC
AAGTTCAGCGACCCCACCATCAAGGACCTGGCCCTGGACTACC
TGATCCAGACCGCCCCCAGCGACCGGAAGCTGAAGTCTGCCCT
GATTCAGGCCAAGCACCAGCTGATGAGCCAGAACCCCCAGGC
CATCGTGGGCGGCAGAAATGTGCTGCTGGCCTCCGAGACATTC
GCCAGCAGAGCCAACACCGCCCCCAGCTCCCTGCGGAGCCTGT
ATCTGCAAGTGACCAGCTCCCCCAGCAACTGCGACAACCTGAG
ACAGATGCTGGCTAGCTACCTGCCCTCCGAGAAAACCGCCGTG
ATGGAATTCCTCGTGAACGGCATGGTGGCCGACCTGAAAAGC
GAGGGCCCTAGCATCCCTCCCGCCAAGCTGCAGGTGTACATGA
CCGAGCTGAGCAACCTGCAGGCCCTGCACAGCGTGGACAGCT
TTTTCGACCGGAACATCGGCAACCTGGAAAACAGCCTGAAGC
ACGAGGGCCACGCCCCCATCCCTTCTCTGACAACCGGCAATCT
GACCAAGACCTTCCTGCAGCTGGTGGAAGATAAGTTCCCCAGC
AGCTCCAAGGCCCAGAAGGCCCTGAACGAGCTCGTGGGCCCT
GATACCGGACCTCAGACCGAGGTGCTGAACCTGTTCTTTCGGG
CCCTGAATGGCTGCTCCCCCCGGATCTTTTCTGGCGCTGAGAA
GAAGCAGCAGCTGGCCAGCGTGATCACCAACACCCTGGATGC
CATCAACGCCGACAACGAGGACTACCCCAAGCCCGGCGACTT
CCCCAGAAGCAGCTTTAGCAGCACCCCCCCTCATGCCCCTGTG
CCCCAGTCTGAGATCCCTACCAGCCCAACCAGCACCCAGCCTC CAAGCCCT
Ct089_E_S198A_nIgK_cHis ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC
271 TGCCTGACACCACCGGCATGACAGCATCTGGCGGAGCTGGCG
GCCTGGGCTCTACACAGACAGTGGATGTGGCCAGGGCCCAGG
CTGCTGCCGCTACACAGGATGCCCAGGAAGTGATCGGCAGCC
AGGAAGCCAGCGAGGCCTCTATGCTGAAGGGCTGCGAGGACC
TGATCAACCCTGCCGCCGCTACCCGCATCAAGAAGAAAGAGG
AAAAGTTCGAGTCCCTGGAAGCCAGACGGAAGCCCACCGCCG
ACAAGGCCGAGAAGAAGTCCGAGAGCACCGAGGAAAAGGGC
GACACCCCCCTGGAAGATCGGTTCACCGAGGATCTGAGCGAG
GTGTCCGGCGAGGACTTCCGGGGCCTGAAGAACAGCTTCGAC
GACGACAGCAGCCCCGAGGAAATCCTGGACGCCCTGACCAGC
AAGTTCAGCGACCCCACCATCAAGGACCTGGCCCTGGACTACC
TGATCCAGACCGCCCCCAGCGACCGGAAGCTGAAGTCTGCCCT
GATTCAGGCCAAGCACCAGCTGATGAGCCAGAACCCCCAGGC
CATCGTGGGCGGCAGAAATGTGCTGCTGGCCTCCGAGACATTC
GCCAGCAGAGCCAACACCGCCCCCAGCTCCCTGCGGAGCCTGT
ATCTGCAAGTGACCAGCTCCCCCAGCAACTGCGACAACCTGAG
ACAGATGCTGGCTAGCTACCTGCCCTCCGAGAAAACCGCCGTG
ATGGAATTCCTCGTGAACGGCATGGTGGCCGACCTGAAAAGC
GAGGGCCCTAGCATCCCTCCCGCCAAGCTGCAGGTGTACATGA
CCGAGCTGAGCAACCTGCAGGCCCTGCACAGCGTGGACAGCT
TTTTCGACCGGAACATCGGCAACCTGGAAAACAGCCTGAAGC
ACGAGGGCCACGCCCCCATCCCTTCTCTGACAACCGGCAATCT
GACCAAGACCTTCCTGCAGCTGGTGGAAGATAAGTTCCCCAGC
AGCTCCAAGGCCCAGAAGGCCCTGAACGAGCTCGTGGGCCCT
GATACCGGACCTCAGACCGAGGTGCTGAACCTGTTCTTTCGGG
CCCTGAATGGCTGCTCCCCCCGGATCTTTTCTGGCGCTGAGAA
GAAGCAGCAGCTGGCCAGCGTGATCACCAACACCCTGGATGC
CATCAACGCCGACAACGAGGACTACCCCAAGCCCGGCGACTT
CCCCAGAAGCAGCTTTAGCAGCACCCCCCCTCATGCCCCTGTG
CCCCAGTCTGAGATCCCTACCAGCCCAACCAGCACCCAGCCTC
CAAGCCCTCACCACCACCATCACCAC Chlamydia_Ct875_nIgk_cHis
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 272
TGCCTGACACCACCGGCATGAGCATCAGAGGCGTGGGCGGCA
ACGGCAACAGCAGAATCCCTAGCCACAACGGCGACGGCAGCA
ACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGTGGAA
GATAGAGTGTGCAGCCTGTACAGCAGCCGGTCCAACGAGAAC
CGCGAGAGCCCTTATGCCGTGGTGGACGTGTCCAGCATGATCG
AGAGCACCCCCACCAGCGGCGAGACAACCAGAGCTAGTAGAG
GCGTGCTGAGCCGGTTCCAGAGGGGCCTCGTGCGGATTGCTGA
CAAAGTGCGGAGAGCCGTGCAGTGCGCTTGGAGCAGCGTGTC
CACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAGCGGCA
GCTCTAGCAGAACAGCTAGAGGCGCCAGCAGCGGCTACAGAG
AGTACAGCCCTTCTGCCGCTCGGGGCCTGCGGCTGATGTTCAC
CGACTTTTGGCGGACCCGGGTGCTGAGACAGACCTCTCCTATG
GCCGGCGTGTTCGGCAACCTGGACGTGAACGAGGCCAGACTG
ATGGCCGCCTACACCAGCGAGTGTGCCGATCACCTGGAAGCC
AAAGAGCTGGCCGGACCTGACGGCGTGGCAGCCGCTAGAGAA
ATCGCCAAGAGATGGGAGAAGAGAGTGCGGGACCTGCAGGAC
AAGGGCGCTGCCAGAAAGCTGCTGAACGACCCCCTGGGCAGA
CGGACCCCCAACTACCAGAGCAAGAACCCCGGCGAGTACACC
GTGGGCAACTCCATGTTCTACGACGGCCCCCAGGTGGCCAACC
TGCAGAATGTGGATACCGGCTTCTGGCTGGACATGAGCAACCT
GAGCGACGTGGTGCTGTCCAGAGAGATCCAGACCGGCCTGAG
AGCCAGAGCCACCCTGGAAGAGTCCATGCCCATGCTGGAAAA
TCTGGAAGAGAGATTCCGGCGGCTGCAGGAAACCTGCGACGC
CGCCAGAACCGAGATCGAGGAAAGCGGCTGGACCCGGGAAAG
CGCCTCCAGAATGGAAGGCGACGAAGCCCAGGGCCCCAGCAG
AGTGCAGCAGGCCTTTCAGAGCTTCGTGAATGAGTGCAACAGC
ATCGAGTTCAGCTTCGGCTCCTTCGGCGAGCACGTGCGGGTGC
TGTGTGCCAGAGTGTCAAGAGGACTGGCCGCTGCCGGCGAGG
CCATCAGAAGATGCTTCAGCTGCTGCAAGGGCAGCACCCACA
GATACGCCCCCAGAGATGACCTGTCTCCTGAGGGCGCCTCTCT
GGCCGAAACCCTGGCCAGATTCGCCGACGACATGGGCATCGA
AAGAGGCGCCGACGGCACCTACGACATCCCCCTGGTGGACGA
TTGGAGAAGGGGCGTGCCATCCATCGAGGGCGAGGGCAGCGA
TAGCATCTACGAGATCATGATGCCCATCTACGAAGTGATGAAC
ATGGACCTGGAAACCCGGCGGAGCTTCGCCGTGCAGCAGGGC
CATTACCAGGACCCCAGAGCCAGCGACTACGACCTGCCTAGA
GCCTCCGATTACGATCTGCCCAGAAGCCCCTACCCCACCCCTC
CACTGCCTCCCAGATACCAGCTGCAGAACATGGATGTGGAAG
CCGGCTTTCGCGAGGCCGTGTACGCCTCTTTTGTGGCCGGCAT
GTACAACTACGTCGTGACCCAGCCCCAGGAACGGATCCCCAAT
AGCCAGCAGGTGGAAGGCATCCTGCGGGACATGCTGACCAAC
GGCAGCCAGACCTTCCGGGACCTGATGAAGCGGTGGAACAGA
GAGGTGGACCGCGAGCACCACCATCACCACCAC MOMP_serovarD
ATGAAGAAACTGCTGAAGTCCGTGCTGGTGTTCGCCGCCCTGT 273
CTAGCGCAAGCTCTCTGCAGGCTCTGCCCGTGGGAAATCCTGC
CGAGCCCAGCCTGATGATCGACGGCATTCTGTGGGAGGGCTTC
GGCGGCGACCCTTGCGATCCTTGTGCTACTTGGTGCGACGCCA
TCAGCATGAGAGTGGGCTACTACGGCGACTTCGTGTTCGACCG
GGTGCTGAAAACCGACGTGAACAAAGAATTCCAGATGGGCGC
CAAGCCCACCACCGACACCGGAAATTCTGCCGCCCCTAGCACC
CTGACCGCCAGAGAGAATCCTGCCTACGGCCGGCACATGCAG
GACGCCGAGATGTTCACCAACGCCGCCTGCATGGCCCTGAACA
TCTGGGACAGATTCGACGTGTTCTGCACCCTGGGCGCCACCAG
CGGCTACCTGAAAGGCAATAGCGCCAGCTTCAACCTCGTGGGC
CTGTTCGGCGACAACGAGAACCAGAAAACCGTGAAGGCCGAG
AGCGTGCCCAACATGAGCTTCGACCAGAGCGTGGTGGAACTG
TACACCGATACCACCTTCGCTTGGAGCGTGGGAGCCAGAGCCG
CTCTGTGGGAATGTGGCTGTGCCACACTGGGGGCCAGCTTCCA
GTACGCCCAGAGCAAGCCCAAGGTGGAAGAACTGAACGTGCT
GTGCAATGCCGCCGAGTTCACCATCAACAAGCCTAAGGGCTAC
GTGGGCAAAGAGTTCCCCCTGGATCTGACCGCCGGAACCGAT
GCCGCCACCGGAACAAAGGACGCCAGCATCGACTACCACGAG
TGGCAGGCTTCTCTGGCCCTGAGCTACCGGCTGAATATGTTCA
CCCCCTACATCGGCGTGAAGTGGTCCAGAGCCAGCTTCGACGC
CGACACCATCAGAATCGCCCAGCCCAAGAGCGCCACCGCCAT
CTTTGATACCACCACCCTGAACCCCACCATTGCCGGCGCTGGC
GACGTGAAAACAGGCGCCGAAGGACAGCTGGGCGACACAATG
CAGATCGTGTCCCTGCAGCTGAACAAGATGAAGTCCCGGAAG
TCCTGCGGAATCGCCGTGGGCACCACAATCGTGGACGCCGATA
AGTACGCCGTGACCGTGGAAACCCGGCTGATCGATGAGAGGG
CCGCTCACGTGAACGCCCAGTTCAGATTC Chlamydia_Ct871_pd_serovarD_nIgK
ATGGAAACCCCCGCCCAACTCCTGTTCCTTCTTCTGCTCTGGCT 274
CCCTGACACTACTGGTGCTGAGATTATGATACCTCAGGGAATC
TACGACGGAGAGACTCTGACTGTCTCGTTCCCGTATACCGTGA
TCGGCGACCCCTCTGGCACCACCGTCTTTTCCGCCGGGGAGCT
GACCCTGAAAAACCTGGACAACAGCATCGCGGCCCTGCCCCT
GAGCTGTTTCGGAAACTTGTTGGGTTCCTTCACTGTGCTCGGA
CGGGGTCACTCCCTGACCTTTGAGAATATCCGGACTTCGACTA
ACGGCGCCGCCCTGTCGGATTCAGCCAACTCCGGACTCTTCAC
CATCGAAGGCTTCAAGGAACTCAGCTTTAGCAATTGCAACTCG
CTGCTGGCGGTGCTGCCAGCGGCTACCACTAACAACGGATCCC
AAACTCCCACCACCACTTCGACTCCGTCCAATGGGACCATCTA
CTCCAAGACCGATCTCCTTCTCCTGAACAACGAGAAGTTCTCC
TTCTACTCCAACCTGGTGTCCGGGGATGGGGGTGCCATTGACG
CCAAGTCACTGACAGTGCAGGGCATCTCCAAGCTCTGTGTGTT
CCAAGAAAACACCGCCCAGGCCGATGGGGGAGCGTGCCAGGT
CGTCACCTCCTTCTCTGCAATGGCCAACGAGGCCCCCATCGCC
TTCATTGCAAACGTGGCGGGCGTGCGCGGCGGCGGCATTGCCG
CGGTGCAAGACGGCCAGCAGGGAGTGTCGTCCTCAACCTCGA
CCGAAGATCCGGTCGTGTCCTTCTCCCGGAATACTGCCGTGGA
ATTCGACGGAAACGTGGCTCGCGTGGGAGGCGGAATCTACAG
CTATGGAAACGTCGCCTTTCTGAACAACGGCAAAACGCTTTTC
CTGAACAATGTCGCTAGCCCTGTGTACATCGCTGCCGAACAGC
CGACCAACGGACAGGCATCCAACACCAGCGACAACTATGGCG
ATGGCGGCGCGATCTTCTGCAAGAACGGGGCCCAGGCGGCCG
GGAGCAACAACTCAGGATCCGTGTCCTTCGACGGAGAAGGCG
TCGTGTTCTTCTCCTCAAACGTGGCTGCCGGAAAGGGTGGAGC
CATCTACGCGAAGAAGCTCTCCGTGGCCAATTGCGGACCGGTC
CAGTTCCTGGGAAACATTGCCAACGACGGAGGTGCAATCTACC
TGGGAGAAAGCGGAGAACTGTCGCTCTCCGCCGACTACGGCG
ATATCATCTTCGACGGCAACCTCAAGCGGACCGCAAAGGAGA
ACGCGGCAGACGTCAATGGAGTGACCGTGTCGAGCCAAGCCA
TTTCAATGGGTTCCGGCGGGAAGATCACCACCTTGAGGGCCAA
GGCCGGCCACCAGATTCTGTTCAACGATCCTATTGAGATGGCC
AACGGGAACAACCAGCCTGCGCAGTCCTCGGAACCCCTGAAG
ATCAATGACGGAGAGGGCTACACTGGAGACATCGTGTTCGCC
AACGGAAACTCCACCTTGTACCAGAACGTGACGATTGAGCAG
GGGAGAATTGTGCTGAGAGAAAAAGCGAAGCTGTCCGTGAAT
AGCTTGAGCCAGACCGGGGGCTCACTGTACATGGAGGCCGGA
TCCACCCTGGACTTCGTGACACCGCAGCCACCGCAGCAGCCTC
CCGCCGCGAACCAACTGATTACCCTCTCGAACCTTCACCTGAG
CCTGTCCTCACTGCTGGCAAACAACGCTGTGACTAACCCTCCA
ACCAACCCGCCGGCCCAGGACAGCCATCCGGCCATTATCGGCT
CCACCACCGCCGGTTCTGTGACCATCAGCGGCCCAATCTTTTT
CGAGGATCTGGACGACACCGCTTACGACCGCTACGATTGGCTG
GGATCCAACCAGAAGATCGACGTGCTTAAGCTGCAACTGGGA
ACGCAACCCTCCGCCAACGCCCCGTCGGACCTGACCCTGGGGA
ACGAAATGCCTAAGTACGGATACCAGGGGAGCTGGAAGCTCG
CCTGGGATCCCAACACCGCCAACAACGGTCCGTACACTCTGAA GGCCACCTGGACTAAGACTGGT
Chlamydia_Ct871_pd_serovarD_nIgK_cHis
ATGGAAACCCCCGCCCAACTCCTGTTCCTTCTTCTGCTCTGGCT 275
CCCTGACACTACTGGTGCTGAGATTATGATACCTCAGGGAATC
TACGACGGAGAGACTCTGACTGTCTCGTTCCCGTATACCGTGA
TCGGCGACCCCTCTGGCACCACCGTCTTTTCCGCCGGGGAGCT
GACCCTGAAAAACCTGGACAACAGCATCGCGGCCCTGCCCCT
GAGCTGTTTCGGAAACTTGTTGGGTTCCTTCACTGTGCTCGGA
CGGGGTCACTCCCTGACCTTTGAGAATATCCGGACTTCGACTA
ACGGCGCCGCCCTGTCGGATTCAGCCAACTCCGGACTCTTCAC
CATCGAAGGCTTCAAGGAACTCAGCTTTAGCAATTGCAACTCG
CTGCTGGCGGTGCTGCCAGCGGCTACCACTAACAACGGATCCC
AAACTCCCACCACCACTTCGACTCCGTCCAATGGGACCATCTA
CTCCAAGACCGATCTCCTTCTCCTGAACAACGAGAAGTTCTCC
TTCTACTCCAACCTGGTGTCCGGGGATGGGGGTGCCATTGACG
CCAAGTCACTGACAGTGCAGGGCATCTCCAAGCTCTGTGTGTT
CCAAGAAAACACCGCCCAGGCCGATGGGGGAGCGTGCCAGGT
CGTCACCTCCTTCTCTGCAATGGCCAACGAGGCCCCCATCGCC
TTCATTGCAAACGTGGCGGGCGTGCGCGGCGGCGGCATTGCCG
CGGTGCAAGACGGCCAGCAGGGAGTGTCGTCCTCAACCTCGA
CCGAAGATCCGGTCGTGTCCTTCTCCCGGAATACTGCCGTGGA
ATTCGACGGAAACGTGGCTCGCGTGGGAGGCGGAATCTACAG
CTATGGAAACGTCGCCTTTCTGAACAACGGCAAAACGCTTTTC
CTGAACAATGTCGCTAGCCCTGTGTACATCGCTGCCGAACAGC
CGACCAACGGACAGGCATCCAACACCAGCGACAACTATGGCG
ATGGCGGCGCGATCTTCTGCAAGAACGGGGCCCAGGCGGCCG
GGAGCAACAACTCAGGATCCGTGTCCTTCGACGGAGAAGGCG
TCGTGTTCTTCTCCTCAAACGTGGCTGCCGGAAAGGGTGGAGC
CATCTACGCGAAGAAGCTCTCCGTGGCCAATTGCGGACCGGTC
CAGTTCCTGGGAAACATTGCCAACGACGGAGGTGCAATCTACC
TGGGAGAAAGCGGAGAACTGTCGCTCTCCGCCGACTACGGCG
ATATCATCTTCGACGGCAACCTCAAGCGGACCGCAAAGGAGA
ACGCGGCAGACGTCAATGGAGTGACCGTGTCGAGCCAAGCCA
TTTCAATGGGTTCCGGCGGGAAGATCACCACCTTGAGGGCCAA
GGCCGGCCACCAGATTCTGTTCAACGATCCTATTGAGATGGCC
AACGGGAACAACCAGCCTGCGCAGTCCTCGGAACCCCTGAAG
ATCAATGACGGAGAGGGCTACACTGGAGACATCGTGTTCGCC
AACGGAAACTCCACCTTGTACCAGAACGTGACGATTGAGCAG
GGGAGAATTGTGCTGAGAGAAAAAGCGAAGCTGTCCGTGAAT
AGCTTGAGCCAGACCGGGGGCTCACTGTACATGGAGGCCGGA
TCCACCCTGGACTTCGTGACACCGCAGCCACCGCAGCAGCCTC
CCGCCGCGAACCAACTGATTACCCTCTCGAACCTTCACCTGAG
CCTGTCCTCACTGCTGGCAAACAACGCTGTGACTAACCCTCCA
ACCAACCCGCCGGCCCAGGACAGCCATCCGGCCATTATCGGCT
CCACCACCGCCGGTTCTGTGACCATCAGCGGCCCAATCTTTTT
CGAGGATCTGGACGACACCGCTTACGACCGCTACGATTGGCTG
GGATCCAACCAGAAGATCGACGTGCTTAAGCTGCAACTGGGA
ACGCAACCCTCCGCCAACGCCCCGTCGGACCTGACCCTGGGGA
ACGAAATGCCTAAGTACGGATACCAGGGGAGCTGGAAGCTCG
CCTGGGATCCCAACACCGCCAACAACGGTCCGTACACTCTGAA
GGCCACCTGGACTAAGACTGGTCACCATCATCACCACCAC
Chlamydia_Ct871_pd_serovarL2_nIgK
ATGGAAACCCCTGCCCAACTTCTGTTCCTCCTTCTGCTCTGGCT 276
CCCCGACACTACCGGTGCTGAGATCATGATTCCGCAAGGCATC
TACGACGGGGAAACTCTGACCGTGTCCTTTCCATACACCGTCA
TTGGTGATCCTTCCGGAACTACCGTGTTCTCCGCGGGCGAACT
GACCTTGAAGAATCTTGACAATTCCATCGCGGCCCTGCCCCTG
AGCTGCTTCGGCAACTTGCTGGGATCGTTCACTGTGCTGGGGC
GCGGACATTCGCTGACTTTCGAAAACATTAGAACCAGCACCAA
CGGTGCTGCGCTTTCGAATAGCGCCGCTGATGGCTTGTTCACC
ATCGAGGGTTTCAAGGAACTGAGCTTCTCCAACTGCAACTCGC
TGCTCGCCGTGCTGCCGGCCGCTACTACGAACAAGGGCAGCCA
GACTCCGACGACAACCTCCACTCCCTCAAACGGCACCATCTAC
TCCAAGACCGATCTGCTGCTGCTCAACAACGAGAAGTTCTCAT
TCTACTCCAACCTCGTGTCCGGCGACGGAGGCGCAATTGACGC
CAAGAGCCTGACCGTGCAGGGAATCTCAAAGCTGTGCGTCTTT
CAAGAGAACACTGCGCAGGCAGACGGAGGAGCCTGTCAGGTC
GTGACCTCCTTTTCCGCCATGGCCAACGAGGCCCCTATCGCCT
TCGTGGCCAACGTGGCCGGCGTGCGGGGTGGAGGAATCGCAG
CCGTGCAAGACGGCCAGCAGGGAGTGTCTAGCAGCACTTCCA
CCGAGGACCCCGTGGTGTCGTTCTCCCGGAACACCGCCGTGGA
GTTCGATGGAAACGTGGCGCGCGTGGGGGGAGGCATCTACTC
CTACGGGAACGTCGCCTTTCTTAACAACGGAAAGACCCTGTTC
CTGAACAATGTGGCCTCGCCGGTGTACATCGCCGCCAAGCAGC
CAACTAGCGGCCAGGCCTCCAACACCTCCAACAACTATGGCG
ACGGCGGAGCCATCTTCTGCAAGAACGGCGCTCAAGCTGGAT
CGAACAACAGCGGTTCTGTCTCCTTCGACGGCGAAGGAGTCGT
GTTTTTCTCCTCCAACGTCGCGGCCGGCAAAGGGGGGGCCATA
TACGCGAAGAAACTGTCAGTGGCGAACTGCGGACCCGTGCAG
TTCCTCCGGAACATTGCCAACGACGGGGGTGCAATCTACCTGG
GAGAGTCAGGAGAACTGAGCCTCTCGGCGGATTACGGCGACA
TCATTTTCGACGGAAATCTGAAGCGGACCGCCAAGGAAAACG
CGGCAGATGTGAACGGGGTCACCGTGTCAAGCCAGGCCATTTC
TATGGGGTCCGGAGGGAAGATTACCACCCTGCGCGCCAAGGC
CGGCCATCAGATTCTCTTCAACGACCCTATCGAGATGGCTAAT
GGAAACAATCAGCCCGCCCAGTCCTCCAAGCTGCTGAAAATC
AACGACGGAGAGGGGTACACCGGGGATATCGTGTTCGCCAAC
GGAAGCTCGACTCTCTACCAAAACGTGACCATTGAGCAGGGG
AGGATCGTGCTGAGGGAAAAGGCTAAGCTGTCCGTCAACTCG
CTGAGCCAGACCGGAGGCTCCCTCTACATGGAAGCAGGATCG
ACGCTGGACTTCGTGACTCCGCAACCACCGCAGCAGCCTCCCG
CCGCCAACCAGCTGATCACCTTGTCCAATCTGCACCTGAGCCT
GTCGTCCTTGCTCGCCAACAACGCCGTGACTAACCCTCCTACT
AACCCGCCGGCCCAGGACTCGCACCCGGCCGTCATCGGATCA
ACCACAGCAGGAAGCGTGACTATCTCCGGTCCTATCTTCTTCG
AGGACCTGGATGACACCGCCTACGATAGATACGATTGGTTGG
GTTCCAACCAGAAGATTAACGTGCTGAAGCTGCAGCTGGGAA
CCAAGCCACCGGCGAACGCCCCGTCCGACCTGACCCTCGGCA
ACGAAATGCCCAAATACGGATACCAGGGCTCCTGGAAGCTCG
CGTGGGACCCCAATACCGCGAACAACGGTCCCTATACACTCAA GGCCACTTGGACCAAGACCGGC
Chlamydia_Ct871_pd_serovarL2_nIgK_cHis
ATGGAAACCCCTGCCCAACTTCTGTTCCTCCTTCTGCTCTGGCT 277
CCCCGACACTACCGGTGCTGAGATCATGATTCCGCAAGGCATC
TACGACGGGGAAACTCTGACCGTGTCCTTTCCATACACCGTCA
TTGGTGATCCTTCCGGAACTACCGTGTTCTCCGCGGGCGAACT
GACCTTGAAGAATCTTGACAATTCCATCGCGGCCCTGCCCCTG
AGCTGCTTCGGCAACTTGCTGGGATCGTTCACTGTGCTGGGGC
GCGGACATTCGCTGACTTTCGAAAACATTAGAACCAGCACCAA
CGGTGCTGCGCTTTCGAATAGCGCCGCTGATGGCTTGTTCACC
ATCGAGGGTTTCAAGGAACTGAGCTTCTCCAACTGCAACTCGC
TGCTCGCCGTGCTGCCGGCCGCTACTACGAACAAGGGCAGCCA
GACTCCGACGACAACCTCCACTCCCTCAAACGGCACCATCTAC
TCCAAGACCGATCTGCTGCTGCTCAACAACGAGAAGTTCTCAT
TCTACTCCAACCTCGTGTCCGGCGACGGAGGCGCAATTGACGC
CAAGAGCCTGACCGTGCAGGGAATCTCAAAGCTGTGCGTCTTT
CAAGAGAACACTGCGCAGGCAGACGGAGGAGCCTGTCAGGTC
GTGACCTCCTTTTCCGCCATGGCCAACGAGGCCCCTATCGCCT
TCGTGGCCAACGTGGCCGGCGTGCGGGGTGGAGGAATCGCAG
CCGTGCAAGACGGCCAGCAGGGAGTGTCTAGCAGCACTTCCA
CCGAGGACCCCGTGGTGTCGTTCTCCCGGAACACCGCCGTGGA
GTTCGATGGAAACGTGGCGCGCGTGGGGGGAGGCATCTACTC
CTACGGGAACGTCGCCTTTCTTAACAACGGAAAGACCCTGTTC
CTGAACAATGTGGCCTCGCCGGTGTACATCGCCGCCAAGCAGC
CAACTAGCGGCCAGGCCTCCAACACCTCCAACAACTATGGCG
ACGGCGGAGCCATCTTCTGCAAGAACGGCGCTCAAGCTGGAT
CGAACAACAGCGGTTCTGTCTCCTTCGACGGCGAAGGAGTCGT
GTTTTTCTCCTCCAACGTCGCGGCCGGCAAAGGGGGGGCCATA
TACGCGAAGAAACTGTCAGTGGCGAACTGCGGACCCGTGCAG
TTCCTCCGGAACATTGCCAACGACGGGGGTGCAATCTACCTGG
GAGAGTCAGGAGAACTGAGCCTCTCGGCGGATTACGGCGACA
TCATTTTCGACGGAAATCTGAAGCGGACCGCCAAGGAAAACG
CGGCAGATGTGAACGGGGTCACCGTGTCAAGCCAGGCCATTTC
TATGGGGTCCGGAGGGAAGATTACCACCCTGCGCGCCAAGGC
CGGCCATCAGATTCTCTTCAACGACCCTATCGAGATGGCTAAT
GGAAACAATCAGCCCGCCCAGTCCTCCAAGCTGCTGAAAATC
AACGACGGAGAGGGGTACACCGGGGATATCGTGTTCGCCAAC
GGAAGCTCGACTCTCTACCAAAACGTGACCATTGAGCAGGGG
AGGATCGTGCTGAGGGAAAAGGCTAAGCTGTCCGTCAACTCG
CTGAGCCAGACCGGAGGCTCCCTCTACATGGAAGCAGGATCG
ACGCTGGACTTCGTGACTCCGCAACCACCGCAGCAGCCTCCCG
CCGCCAACCAGCTGATCACCTTGTCCAATCTGCACCTGAGCCT
GTCGTCCTTGCTCGCCAACAACGCCGTGACTAACCCTCCTACT
AACCCGCCGGCCCAGGACTCGCACCCGGCCGTCATCGGATCA
ACCACAGCAGGAAGCGTGACTATCTCCGGTCCTATCTTCTTCG
AGGACCTGGATGACACCGCCTACGATAGATACGATTGGTTGG
GTTCCAACCAGAAGATTAACGTGCTGAAGCTGCAGCTGGGAA
CCAAGCCACCGGCGAACGCCCCGTCCGACCTGACCCTCGGCA
ACGAAATGCCCAAATACGGATACCAGGGCTCCTGGAAGCTCG
CGTGGGACCCCAATACCGCGAACAACGGTCCCTATACACTCAA
GGCCACTTGGACCAAGACCGGCCACCACCATCACCACCAC
Chlamydia_Ct812_pd_serovarD_nIgK
ATGGAAACTCCTGCCCAACTGTTGTTCCTTCTGCTGCTCTGGTT 278
GCCCGACACCACCGGATCGTGCGTGGATCTCCACGCTGGCGGC
CAGTCCGTGAACGAGCTTGTGTACGTGGGCCCACAGGCCGTGC
TTCTGCTGGACCAGATCAGAGATCTCTTCGTGGGTTCCAAGGA
CTCCCAGGCCGAGGGACAGTACCGGCTCATCGTCGGCGACCCT
TCAAGCTTCCAAGAGAAGGATGCCGACACTCTTCCGGGGAAG
GTGGAACAGTCCACTCTGTTTTCCGTGACCAACCCAGTCGTGT
TTCAAGGGGTGGACCAGCAGGACCAGGTGTCCAGCCAAGGAC
TGATCTGTTCATTCACCTCGAGCAATTTGGACAGCCCCCGGGA
CGGCGAATCGTTCCTTGGCATCGCATTCGTGGGAGACTCATCC
AAAGCAGGAATCACCCTTACCGATGTGAAGGCGTCCCTGAGC
GGCGCTGCTCTGTACTCCACCGAAGATCTCATCTTCGAGAAGA
TCAAGGGTGGACTGGAGTTCGCCAGCTGCTCCTCACTGGAACA
GGGAGGAGCCTGTGCCGCCCAAAGCATCCTCATCCACGATTGC
CAGGGGCTCCAAGTGAAGCATTGTACCACTGCCGTGAACGCC
GAGGGATCATCCGCTAACGATCACCTCGGTTTCGGAGGGGGTG
CCTTCTTCGTGACCGGTTCGCTGTCGGGAGAAAAGTCACTGTA
TATGCCCGCGGGCGACATGGTGGTCGCCAACTGCGATGGAGC
CATCTCATTCGAGGGAAACTCCGCCAACTTCGCAAACGGCGGC
GCTATCGCCGCTAGCGGGAAGGTGCTGTTCGTGGCTAACGACA
AGAAAACGTCCTTCATCGAAAACCGCGCCCTGTCGGGAGGTG
CCATTGCCGCCAGCTCCGACATTGCCTTCCAAAACTGTGCGGA
ACTGGTGTTCAAAGGAAACTGCGCCATCGGCACCGAAGATAA
GGGAAGCCTGGGGGGGGGCGCCATTTCCTCCCTCGGCACCGTG
CTGCTTCAGGGAAACCACGGCATCACTTGTGACAAGAACGAA
AGCGCGTCCCAGGGGGGAGCGATCTTCGGGAAAAACTGCCAG
ATTTCCGACAACGAGGGACCGGTGGTGTTCAGAGACTCCACTG
CCTGCCTGGGCGGCGGAGCGATCGCAGCACAGGAAATTGTCA
GCATCCAGAACAACCAGGCCGGCATCAGCTTCGAGGGGGGAA
AGGCTTCGTTCGGCGGAGGTATTGCCTGCGGATCGTTCTCGTC
CGCGGGCGGAGCCTCCGTGCTCGGAACCATCGACATTTCCAAG
AACCTGGGCGCTATCTCGTTTTCTCGCACCCTGTGCACTACTTC
CGACCTGGGTCAGATGGAGTACCAGGGAGGCGGAGCGCTGTT
TGGAGAGAACATCTCTCTGAGCGAGAACGCGGGAGTGCTGAC
CTTCAAGGACAACATTGTGAAAACCTTCGCCTCAAACGGAAA
GATCCTGGGGGGAGGCGCCATCCTGGCAACCGGGAAGGTCGA
AATCACCAACAATTCAGAGGGTATCTCCTTCACTGGCAACGCC
CGGGCCCCCCAAGCCCTGCCGACTCAGGAAGAGTTCCCCCTGT
TCTCCAAGAAGGAAGGACGCCCTTTGTCATCCGGCTACTCCGG
TGGTGGAGCGATTCTGGGTCGGGAAGTGGCCATCCTGCATAAT
GCGGCCGTGGTGTTTGAGCAAAACAGACTCCAATGCTCCGAA
GAAGAGGCCACCCTCCTGGGGTGCTGCGGGGGCGGAGCAGTG
CATGGCATGGATTCCACTTCCATCGTGGGAAACTCCAGCGTCC
GCTTCGGAAACAACTACGCTATGGGACAGGGAGTGTCAGGGG
GGGCCCTGCTGTCCAAGACCGTCCAGTTGGCCGGAAACGGTTC
GGTGGATTTCTCACGCAATATCGCCTCGCTGGGAGGCGGCGCG
CTGCAGGCCTCCGAAGGAAATTGCGAACTGGTCGACAACGGC
TACGTGCTGTTCCGGGACAACCGCGGCAGGGTGTACGGCGGA
GCAATCTCGTGCCTTCGGGGCGACGTCGTGATCTCGGGAAATA
AGGGACGGGTCGAGTTTAAGGACAACATCGCTACCAGGCTCT
ACGTGGAGGAAACTGTGGAGAAGGTGGAGGAAGTGGAGCCTG
CCCCGGAACAGAAGGACAACAACGAGCTGTCGTTCCTCGGTC
GGGCAGAACAGTCCTTCATTACTGCCGCCAACCAGGCCCTGTT
CGCGTCCGAAGATGGTGACCTCAGCCCGGAATCCAGCATCTCC
TCCGAGGAACTGGCCAAGCGGAGAGAATGCGCGGGAGGCGCA
ATCTTTGCGAAGCGGGTCCGGATCGTGGACAACCAGGAAGCT
GTGGTGTTCAGCAACAACTTTTCCGACATCTACGGTGGTGCAA
TTTTCACCGGCTCACTCCGGGAGGAGGACAAGCTGGACGGCC
AGATTCCCGAGGTGCTCATTTCCGGCAATGCCGGCGACGTGGT
GTTCTCCGGAAACTCCTCCAAGAGGGACGAACACCTCCCGCAT
ACCGGAGGAGGAGCCATCTGCACTCAGAACCTGACGATCTCG
CAGAACACCGGCAATGTGCTGTTCTACAACAACGTCGCATGTT
CCGGTGGCGCCGTCAGAATCGAGGACCACGGAAACGTGCTGC
TGGAAGCATTCGGGGGTGATATTGTGTTCAAGGGAAACAGCA
GCTTCCGGGCCCAGGGATCAGATGCAATCTACTTCGCCGGGAA
GGAGAGCCACATTACCGCCCTGAACGCCACCGAGGGTCACGC
CATCGTGTTCCACGATGCCCTGGTGTTCGAAAACCTGGAGGAG
CGCAAGAGCGCCGAAGTGCTGCTTATCAATTCCCGCGAAAACC
CGGGCTACACCGGATCCATCCGGTTCCTCGAAGCGGAGTCGAA
GGTCCCGCAGTGTATTCATGTGCAACAGGGGTCCCTGGAACTG
CTTAACGGAGCCACCCTGTGCTCCTACGGCTTTAAGCAGGACG
CGGGCGCTAAACTGGTGCTGGCGGCCGGCGCCAAGCTTAAGA
TCCTCGACTCCGGAACCCCGGTGCAGCAGGGGCACGCTATTAG
CAAGCCTGAAGCCGAGATTGAGTCGTCATCCGAACCCGAAGG
GGCGCACTCCCTGTGGATAGCCAAGAACGCGCAGACCACCGT
GCCAATGGTCGATATCCACACAATCTCCGTGGACCTCGCCAGC
TTCTCGTCGAGCCAGCAGGAGGGAACTGTCGAAGCGCCTCAG
GTCATCGTGCCGGGAGGTTCCTACGTGCGCTCGGGGGAGCTCA
ACCTGGAACTCGTGAATACCACTGGAACGGGATATGAGAACC
ACGCCCTGCTGAAGAACGAAGCCAAAGTGCCACTGATGTCCTT
CGTCGCCTCCGGCGACGAGGCCTCCGCCGAGATTAGCAACCTG
TCGGTGTCAGATCTGCAAATTCACGTGGTGACCCCTGAGATTG
AGGAGGACACCTACGGGCACATGGGCGATTGGTCCGAGGCGA
AGATCCAGGACGGCACACTGGTCATTTCATGGAACCCTACCGGA
Chlamydia_Ct812_pd_serovarD_nIgK_cHis
ATGGAAACTCCTGCCCAACTGTTGTTCCTTCTGCTGCTCTGGTT 279
GCCCGACACCACCGGATCGTGCGTGGATCTCCACGCTGGCGGC
CAGTCCGTGAACGAGCTTGTGTACGTGGGCCCACAGGCCGTGC
TTCTGCTGGACCAGATCAGAGATCTCTTCGTGGGTTCCAAGGA
CTCCCAGGCCGAGGGACAGTACCGGCTCATCGTCGGCGACCCT
TCAAGCTTCCAAGAGAAGGATGCCGACACTCTTCCGGGGAAG
GTGGAACAGTCCACTCTGTTTTCCGTGACCAACCCAGTCGTGT
TTCAAGGGGTGGACCAGCAGGACCAGGTGTCCAGCCAAGGAC
TGATCTGTTCATTCACCTCGAGCAATTTGGACAGCCCCCGGGA
CGGCGAATCGTTCCTTGGCATCGCATTCGTGGGAGACTCATCC
AAAGCAGGAATCACCCTTACCGATGTGAAGGCGTCCCTGAGC
GGCGCTGCTCTGTACTCCACCGAAGATCTCATCTTCGAGAAGA
TCAAGGGTGGACTGGAGTTCGCCAGCTGCTCCTCACTGGAACA
GGGAGGAGCCTGTGCCGCCCAAAGCATCCTCATCCACGATTGC
CAGGGGCTCCAAGTGAAGCATTGTACCACTGCCGTGAACGCC
GAGGGATCATCCGCTAACGATCACCTCGGTTTCGGAGGGGGTG
CCTTCTTCGTGACCGGTTCGCTGTCGGGAGAAAAGTCACTGTA
TATGCCCGCGGGCGACATGGTGGTCGCCAACTGCGATGGAGC
CATCTCATTCGAGGGAAACTCCGCCAACTTCGCAAACGGCGGC
GCTATCGCCGCTAGCGGGAAGGTGCTGTTCGTGGCTAACGACA
AGAAAACGTCCTTCATCGAAAACCGCGCCCTGTCGGGAGGTG
CCATTGCCGCCAGCTCCGACATTGCCTTCCAAAACTGTGCGGA
ACTGGTGTTCAAAGGAAACTGCGCCATCGGCACCGAAGATAA
GGGAAGCCTGGGGGGGGGCGCCATTTCCTCCCTCGGCACCGTG
CTGCTTCAGGGAAACCACGGCATCACTTGTGACAAGAACGAA
AGCGCGTCCCAGGGGGGAGCGATCTTCGGGAAAAACTGCCAG
ATTTCCGACAACGAGGGACCGGTGGTGTTCAGAGACTCCACTG
CCTGCCTGGGCGGCGGAGCGATCGCAGCACAGGAAATTGTCA
GCATCCAGAACAACCAGGCCGGCATCAGCTTCGAGGGGGGAA
AGGCTTCGTTCGGCGGAGGTATTGCCTGCGGATCGTTCTCGTC
CGCGGGCGGAGCCTCCGTGCTCGGAACCATCGACATTTCCAAG
AACCTGGGCGCTATCTCGTTTTCTCGCACCCTGTGCACTACTTC
CGACCTGGGTCAGATGGAGTACCAGGGAGGCGGAGCGCTGTT
TGGAGAGAACATCTCTCTGAGCGAGAACGCGGGAGTGCTGAC
CTTCAAGGACAACATTGTGAAAACCTTCGCCTCAAACGGAAA
GATCCTGGGGGGAGGCGCCATCCTGGCAACCGGGAAGGTCGA
AATCACCAACAATTCAGAGGGTATCTCCTTCACTGGCAACGCC
CGGGCCCCCCAAGCCCTGCCGACTCAGGAAGAGTTCCCCCTGT
TCTCCAAGAAGGAAGGACGCCCTTTGTCATCCGGCTACTCCGG
TGGTGGAGCGATTCTGGGTCGGGAAGTGGCCATCCTGCATAAT
GCGGCCGTGGTGTTTGAGCAAAACAGACTCCAATGCTCCGAA
GAAGAGGCCACCCTCCTGGGGTGCTGCGGGGGCGGAGCAGTG
CATGGCATGGATTCCACTTCCATCGTGGGAAACTCCAGCGTCC
GCTTCGGAAACAACTACGCTATGGGACAGGGAGTGTCAGGGG
GGGCCCTGCTGTCCAAGACCGTCCAGTTGGCCGGAAACGGTTC
GGTGGATTTCTCACGCAATATCGCCTCGCTGGGAGGCGGCGCG
CTGCAGGCCTCCGAAGGAAATTGCGAACTGGTCGACAACGGC
TACGTGCTGTTCCGGGACAACCGCGGCAGGGTGTACGGCGGA
GCAATCTCGTGCCTTCGGGGCGACGTCGTGATCTCGGGAAATA
AGGGACGGGTCGAGTTTAAGGACAACATCGCTACCAGGCTCT
ACGTGGAGGAAACTGTGGAGAAGGTGGAGGAAGTGGAGCCTG
CCCCGGAACAGAAGGACAACAACGAGCTGTCGTTCCTCGGTA
GAGCCGAACAGTCCTTCATTACTGCCGCCAACCAGGCCCTGTT
CGCGTCCGAAGATGGTGACCTCAGCCCGGAATCCAGCATCTCC
TCCGAGGAACTGGCCAAGCGGAGAGAATGCGCGGGAGGCGCA
ATCTTTGCGAAGCGGGTCCGGATCGTGGACAACCAGGAAGCT
GTGGTGTTCAGCAACAACTTTTCCGACATCTACGGTGGTGCAA
TTTTCACCGGCTCACTCCGGGAGGAGGACAAGCTGGACGGCC
AGATTCCCGAGGTGCTCATTTCCGGCAATGCCGGCGACGTGGT
GTTCTCCGGAAACTCCTCCAAGAGGGACGAACACCTCCCGCAT
ACCGGAGGAGGAGCCATCTGCACTCAGAACCTGACGATCTCG
CAGAACACCGGCAATGTGCTGTTCTACAACAACGTCGCATGTT
CCGGTGGCGCCGTCAGAATCGAGGACCACGGAAACGTGCTGC
TGGAAGCATTCGGGGGTGATATTGTGTTCAAGGGAAACAGCA
GCTTCCGGGCCCAGGGATCAGATGCAATCTACTTCGCCGGGAA
GGAGAGCCACATTACCGCCCTGAACGCCACCGAGGGTCACGC
CATCGTGTTCCACGATGCCCTGGTGTTCGAAAACCTGGAGGAG
CGCAAGAGCGCCGAAGTGCTGCTTATCAATTCCCGCGAAAACC
CGGGCTACACCGGATCCATCCGGTTCCTCGAAGCGGAGTCGAA
GGTCCCGCAGTGTATTCATGTGCAACAGGGGTCCCTGGAACTG
CTTAACGGAGCCACCCTGTGCTCCTACGGCTTTAAGCAGGACG
CGGGCGCTAAACTGGTGCTGGCGGCCGGCGCCAAGCTTAAGA
TCCTCGACTCCGGAACCCCGGTGCAGCAGGGGCACGCTATTAG
CAAGCCTGAAGCCGAGATTGAGTCGTCATCCGAACCCGAAGG
GGCGCACTCCCTGTGGATAGCCAAGAACGCGCAGACCACCGT
GCCAATGGTCGATATCCACACAATCTCCGTGGACCTCGCCAGC
TTCTCGTCGAGCCAGCAGGAGGGAACTGTCGAAGCGCCTCAG
GTCATCGTGCCGGGAGGTTCCTACGTGCGCTCGGGGGAGCTCA
ACCTGGAACTCGTGAATACCACTGGAACGGGATATGAGAACC
ACGCCCTGCTGAAGAACGAAGCCAAAGTGCCACTGATGTCCTT
CGTCGCCTCCGGGGACGAGGCCTCCGCCGAGATTAGCAACCTG
TCGGTGTCAGATCTGCAAATTCACGTGGTCACCCCTGAGATTG
AGGAGGACACCTACGGGCACATGGGCGATTGGTCCGAGGCGA
AGATCCAGGACGGCACACTGGTCATTTCATGGAACCCTACCGG ACATCACCACCACCATCAC
Chlamydia_Ct812_pd_serovarL2_nIgk
ATGGAAACTCCTGCCCAACTGTTGTTCCTTCTGCTGCTCTGGTT 280
GCCCGACACCACCGGATCGTGCGTGGATCTCCACGCTGGCGGC
CAGTCCGTGAACGAGCTTGTGTACGTGGGCCCACAGGCCGTGC
TTCTGCTGGACCAGATCAGAGATCTCTTCGTGGGTTCCAAGGA
CTCCCAGGCCGAGGGACAGTACCGGCTCATCGTCGGCGACCCT
TCAAGCTTCCAAGAGAAGGATGCCGACACTCTTCCGGGGAAG
GTGGAACAGTCCACTCTGTTTTCCGTGACCAACCCAGTCGTGT
TTCAAGGGGTGGACCAGCAGGACCAGGTGTCCAGCCAAGGAC
TGATCTGTTCATTCACCTCGAGCAATTTGGACAGCCCCCGGGA
CGGCGAATCGTTCCTTGGCATCGCATTCGTGGGAGACTCATCC
AAAGCAGGAATCACCCTTACCGATGTGAAGGCGTCCCTGAGC
GGCGCTGCTCTGTACTCCACCGAAGATCTCATCTTCGAGAAGA
TCAAGGGTGGACTGGAGTTCGCCAGCTGCTCCTCACTGGAACA
GGGAGGAGCCTGTGCCGCCCAAAGCATCCTCATCCACGATTGC
CAGGGGCTCCAAGTGAAGCATTGTACCACTGCCGTGAACGCC
GAGGGATCATCCGCTAACGATCACCTCGGTTTCGGAGGGGGTG
CCTTCTTCGTGACCGGTTCGCTGTCGGGAGAAAAGTCACTGTA
TATGCCCGCGGGCGACATGGTGGTCGCCAACTGCGATGGAGC
CATCTCATTCGAGGGAAACTCCGCCAACTTCGCAAACGGCGGC
GCTATCGCCGCTAGCGGGAAGGTGCTGTTCGTGGCTAACGACA
AGAAAACGTCCTTCATCGAAAACCGCGCCCTGTCGGGAGGTG
CCATTGCCGCCAGCTCCGACATTGCCTTCCAAAACTGTGCGGA
ACTGGTGTTCAAAGGAAACTGCGCCATCGGCACCGAAGATAA
GGGAAGCCTGGGGGGGGGCGCCATTTCCTCCCTCGGCACCGTG
CTGCTTCAGGGAAACCACGGCATCACTTGTGACAAGAACGAA
AGCGCGTCCCAGGGGGGAGCGATCTTCGGGAAAAACTGCCAG
ATTTCCGACAACGAGGGACCGGTGGTGTTCAGAGACTCCACTG
CCTGCCTGGGCGGCGGAGCGATCGCAGCACAGGAAATTGTCA
GCATCCAGAACAACCAGGCCGGCATCAGCTTCGAGGGGGGAA
AGGCTTCGTTCGGCGGAGGTATTGCCTGCGGATCGTTCTCGTC
CGCGGGCGGAGCCTCCGTGCTCGGAACCATCGACATTTCCAAG
AACCTGGGCGCTATCTCGTTTTCTCGCACCCTGTGCACTACTTC
CGACCTGGGTCAGATGGAGTACCAGGGAGGCGGAGCGCTGTT
TGGAGAGAACATCTCTCTGAGCGAGAACGCGGGAGTGCTGAC
CTTCAAGGACAACATTGTGAAAACCTTCGCCTCAAACGGAAA
GATCCTGGGGGGAGGCGCCATCCTGGCAACCGGGAAGGTCGA
AATCACCAACAATTCAGGCGGTATCTCCTTCACTGGCAACGCC
CGGGCCCCCCAAGCCCTGCCGACTCAGGAAGAGTTCCCCCTGT
TCTCCAAGAAGGAAGGACGCCCTTTGTCATCCGGCTACTCCGG
TGGTGGAGCGATTCTGGGTCGGGAAGTGGCCATCCTGCATAAT
GCGGCCGTGGTGTTTGAGCAAAACAGACTCCAATGCTCCGAA
GAAGAGGCCACCCTCCTGGGGTGCTGCGGGGGCGGAGCAGTG
CATGGCATGGATTCCACTTCCATCGTGGGAAACTCCAGCGTCC
GCTTCGGAAACAACTACGCTATGGGACAGGGAGTGTCAGGGG
GGGCCCTGCTGTCCAAGACCGTCCAGTTGGCCGGAAACGGTTC
GGTGGATTTCTCACGCAATATCGCCTCGCTGGGAGGCGGCGCG
CTGCAGGCCTCCGAAGGAAATTGCGAACTGGTCGACAACGGC
TACGTGCTGTTCCGGGACAACCGCGGCAGGGTGTACGGCGGA
GCAATCTCGTGCCTTCGGGGCGACGTCGTGATCTCGGGAAATA
AGGGACGGGTCGAGTTTAAGGACAACATCGCTACCAGGCTCT
ACGTGGAGGAAACTGTGGAGAAGGTGGAGGAAGTGGAGCCTG
CCCCGGAACAGAAGGACAACAACGAGCTGTCGTTCCTCGGTTC
CGTCGAACAGTCCTTCATTACTGCCGCCAACCAGGCCCTGTTC
GCGTCCGAAGATGGTGACCTCAGCCCGGAATCCAGCATCTCCT
CCGAGGAACTGGCCAAGCGGAGAGAATGCGCGGGAGGCGCA
ATCTTTGCGAAGCGGGTCCGGATCGTGGACAACCAGGAAGCT
GTGGTGTTCAGCAACAACTTTTCCGACATCTACGGTGGTGCAA
TTTTCACCGGCTCACTCCGGGAGGAGGACAAGCTGGACGGCC
AGATTCCCGAGGTGCTCATTTCCGGCAATGCCGGCGACGTGGT
GTTCTCCGGAAACTCCTCCAAGAGGGACGAACACCTCCCGCAT
ACCGGAGGAGGAGCCATCTGCACTCAGAACCTGACGATCTCG
CAGAACACCGGCAATGTGCTGTTCTACAACAACGTCGCATGTT
CCGGTGGCGCCGTCAGAATCGAGGACCACGGAAACGTGCTGC
TGGAAGCATTCGGGGGTGATATTGTGTTCAAGGGAAACAGCA
GCTTCCGGGCCCAGGGATCAGATGCAATCTACTTCGCCGGGAA
GGAGAGCCACATTACCGCCCTGAACGCCACCGAGGGTCACGC
CATCGTGTTCCACGATGCCCTGGTGTTCGAAAACCTGAAGGAG
CGCAAGAGCGCCGAAGTGCTGCTTATCAATTCCCGCGAAAACC
CGGGCTACACCGGATCCATCCGGTTCCTCGAAGCGGAGTCGAA
GGTCCCGCAGTGTATTCATGTGCAACAGGGGTCCCTGGAACTG
CTTAACGGAGCCACCCTGTGCTCCTACGGCTTTAAGCAGGACG
CGGGCGCTAAACTGGTGCTGGCGGCCGGCTCCAAGCTTAAGAT
CCTCGACTCCGGAACCCCGGTGCAGGGGCACGCTATTAGCAA
GCCTGAAGCCGAGATTGAGTCGTCATCCGAACCCGAAGGGGC
GCACTCCCTGTGGATAGCCAAGAACGCGCAGACCACCGTGCC
AATGGTCGATATCCACACAATCTCCGTGGACCTCGCCAGCTTC
TCGTCGAGCCAGCAGGAGGGAACTGTCGAAGCGCCTCAGGTC
ATCGTGCCGGGAGGTTCCTACGTGCGCTCGGGGGAGCTCAACC
TGGAACTCGTGAATACCACTGGAACGGGATATGAGAACCACG
CCCTGCTGAAGAACGAAGCCAAAGTGCCACTGATGTCCTTCGT
CGCCTCCTCCGACGAGGCCTCCGCCGAGATTAGCAACCTGTCG
GTGTCAGATCTGCAAATTCACGTGGCCACCCCTGAGATTGAGG
AGGACACCTACGGGCACATGGGCGATTGGTCCGAGGCGAAGA
TCCAGGACGGCACACTGGTCATTTCATGGAACCCTACCGGA
Chlamydia_Ct812_pd_serovarL2_nIgk_cHis
ATGGAAACTCCTGCCCAACTGTTGTTCCTTCTGCTGCTCTGGTT 281
GCCCGACACCACCGGATCGTGCGTGGATCTCCACGCTGGCGGC
CAGTCCGTGAACGAGCTTGTGTACGTGGGCCCACAGGCCGTGC
TTCTGCTGGACCAGATCAGAGATCTCTTCGTGGGTTCCAAGGA
CTCCCAGGCCGAGGGACAGTACCGGCTCATCGTCGGCGACCCT
TCAAGCTTCCAAGAGAAGGATGCCGACACTCTTCCGGGGAAG
GTGGAACAGTCCACTCTGTTTTCCGTGACCAACCCAGTCGTGT
TTCAAGGGGTGGACCAGCAGGACCAGGTGTCCAGCCAAGGAC
TGATCTGTTCATTCACCTCGAGCAATTTGGACAGCCCCCGGGA
CGGCGAATCGTTCCTTGGCATCGCATTCGTGGGAGACTCATCC
AAAGCAGGAATCACCCTTACCGATGTGAAGGCGTCCCTGAGC
GGCGCTGCTCTGTACTCCACCGAAGATCTCATCTTCGAGAAGA
TCAAGGGTGGACTGGAGTTCGCCAGCTGCTCCTCACTGGAACA
GGGAGGAGCCTGTGCCGCCCAAAGCATCCTCATCCACGATTGC
CAGGGGCTCCAAGTGAAGCATTGTACCACTGCCGTGAACGCC
GAGGGATCATCCGCTAACGATCACCTCGGTTTCGGAGGGGGTG
CCTTCTTCGTGACCGGTTCGCTGTCGGGAGAAAAGTCACTGTA
TATGCCCGCGGGCGACATGGTGGTCGCCAACTGCGATGGAGC
CATCTCATTCGAGGGAAACTCCGCCAACTTCGCAAACGGCGGC
GCTATCGCCGCTAGCGGGAAGGTGCTGTTCGTGGCTAACGACA
AGAAAACGTCCTTCATCGAAAACCGCGCCCTGTCGGGAGGTG
CCATTGCCGCCAGCTCCGACATTGCCTTCCAAAACTGTGCGGA
ACTGGTGTTCAAAGGAAACTGCGCCATCGGCACCGAAGATAA
GGGAAGCCTGGGGGGGGGCGCCATTTCCTCCCTCGGCACCGTG
CTGCTTCAGGGAAACCACGGCATCACTTGTGACAAGAACGAA
AGCGCGTCCCAGGGGGGAGCGATCTTCGGGAAAAACTGCCAG
ATTTCCGACAACGAGGGACCGGTGGTGTTCAGAGACTCCACTG
CCTGCCTGGGCGGCGGAGCGATCGCAGCACAGGAAATTGTCA
GCATCCAGAACAACCAGGCCGGCATCAGCTTCGAGGGGGGAA
AGGCTTCGTTCGGCGGAGGTATTGCCTGCGGATCGTTCTCGTC
CGCGGGCGGAGCCTCCGTGCTCGGAACCATCGACATTTCCAAG
AACCTGGGCGCTATCTCGTTTTCTCGCACCCTGTGCACTACTTC
CGACCTGGGTCAGATGGAGTACCAGGGAGGCGGAGCGCTGTT
TGGAGAGAACATCTCTCTGAGCGAGAACGCGGGAGTGCTGAC
CTTCAAGGACAACATTGTGAAAACCTTCGCCTCAAACGGAAA
GATCCTGGGGGGAGGCGCCATCCTGGCAACCGGGAAGGTCGA
AATCACCAACAATTCAGGCGGTATCTCCTTCACTGGCAACGCC
CGGGCCCCCCAAGCCCTGCCGACTCAGGAAGAGTTCCCCCTGT
TCTCCAAGAAGGAAGGACGCCCTTTGTCATCCGGCTACTCCGG
TGGTGGAGCGATTCTGGGTCGGGAAGTGGCCATCCTGCATAAT
GCGGCCGTGGTGTTTGAGCAAAACAGACTCCAATGCTCCGAA
GAAGAGGCCACCCTCCTGGGGTGCTGCGGGGGCGGAGCAGTG
CATGGCATGGATTCCACTTCCATCGTGGGAAACTCCAGCGTCC
GCTTCGGAAACAACTACGCTATGGGACAGGGAGTGTCAGGGG
GGGCCCTGCTGTCCAAGACCGTCCAGTTGGCCGGAAACGGTTC
GGTGGATTTCTCACGCAATATCGCCTCGCTGGGAGGCGGCGCG
CTGCAGGCCTCCGAAGGAAATTGCGAACTGGTCGACAACGGC
TACGTGCTGTTCCGGGACAACCGCGGCAGGGTGTACGGCGGA
GCAATCTCGTGCCTTCGGGGCGACGTCGTGATCTCGGGAAATA
AGGGACGGGTCGAGTTTAAGGACAACATCGCTACCAGGCTCT
ACGTGGAGGAAACTGTGGAGAAGGTGGAGGAAGTGGAGCCTG
CCCCGGAACAGAAGGACAACAACGAGCTGTCGTTCCTCGGTTC
CGTCGAACAGTCCTTCATTACTGCCGCCAACCAGGCCCTGTTC
GCGTCCGAAGATGGTGACCTCAGCCCGGAATCCAGCATCTCCT
CCGAGGAACTGGCCAAGCGGAGAGAATGCGCGGGAGGCGCA
ATCTTTGCGAAGCGGGTCCGGATCGTGGACAACCAGGAAGCT
GTGGTGTTCAGCAACAACTTTTCCGACATCTACGGTGGTGCAA
TTTTCACCGGCTCACTCCGGGAGGAGGACAAGCTGGACGGCC
AGATTCCCGAGGTGCTCATTTCCGGCAATGCCGGCGACGTGGT
GTTCTCCGGAAACTCCTCCAAGAGGGACGAACACCTCCCGCAT
ACCGGAGGAGGAGCCATCTGCACTCAGAACCTGACGATCTCG
CAGAACACCGGCAATGTGCTGTTCTACAACAACGTCGCATGTT
CCGGTGGCGCCGTCAGAATCGAGGACCACGGAAACGTGCTGC
TGGAAGCATTCGGGGGTGATATTGTGTTCAAGGGAAACAGCA
GCTTCCGGGCCCAGGGATCAGATGCAATCTACTTCGCCGGGAA
GGAGAGCCACATTACCGCCCTGAACGCCACCGAGGGTCACGC
CATCGTGTTCCACGATGCCCTGGTGTTCGAAAACCTGAAGGAG
CGCAAGAGCGCCGAAGTGCTGCTTATCAATTCCCGCGAAAACC
CGGGCTACACCGGATCCATCCGGTTCCTCGAAGCGGAGTCGAA
GGTCCCGCAGTGTATTCATGTGCAACAGGGGTCCCTGGAACTG
CTTAACGGAGCCACCCTGTGCTCCTACGGCTTTAAGCAGGACG
CGGGCGCTAAACTGGTGCTGGCGGCCGGCTCCAAGCTTAAGAT
CCTCGACTCCGGAACCCCGGTGCAGGGGCACGCTATTAGCAA
GCCTGAAGCCGAGATTGAGTCGTCATCCGAACCCGAAGGGGC
GCACTCCCTGTGGATAGCCAAGAACGCGCAGACCACCGTGCC
AATGGTCGATATCCACACAATCTCCGTGGACCTCGCCAGCTTC
TCGTCGAGCCAGCAGGAGGGAACTGTCGAAGCGCCTCAGGTC
ATCGTGCCGGGAGGTTCCTACGTGCGCTCGGGGGAGCTCAACC
TGGAACTCGTGAATACCACTGGAACGGGATATGAGAACCACG
CCCTGCTGAAGAACGAAGCCAAAGTGCCACTGATGTCCTTCGT
CGCCTCCTCCGACGAGGCCTCCGCCGAGATTAGCAACCTGTCG
GTGTCAGATCTGCAAATTCACGTGGCCACCCCTGAGATTGAGG
AGGACACCTACGGGCACATGGGCGATTGGTCCGAGGCGAAGA
TCCAGGACGGCACACTGGTCATTTCATGGAACCCTACCGGACA TCACCACCACCATCAC
Chlamydia_Ct460_serovarD_nIgk
ATGGAAACTCCTGCCCAACTCCTGTTCTTGCTGCTGCTTTGGCT 282
CCCTGACACTACCGGAATGAGCCAGAACAAGAACTCGGCATT
CATGCAGCCGGTCAATGTGTCCGCCGATCTGGCCGCCATTGTG
GGAGCTGGGCCCATGCCACGGACCGAAATCATCAAAAAGATG
TGGGACTACATTAAGAAGAACGGCCTGCAGGACCCGACCAAC
AAGCGCAACATCAACCCGGACGATAAGCTGGCGAAGGTGTTC
GGTACCGAGAAGCCCATCGACATGTTTCAAATGACCAAGATG GTGTCCCAGCACATCATTAAG
Chlamydia_Ct460_serovarD_nIgk_cHis
ATGGAAACTCCTGCCCAACTCCTGTTCTTGCTGCTGCTTTGGCT 283
CCCTGACACTACCGGAATGAGCCAGAACAAGAACTCGGCATT
CATGCAGCCGGTCAATGTGTCCGCCGATCTGGCCGCCATTGTG
GGAGCTGGGCCCATGCCACGGACCGAAATCATCAAAAAGATG
TGGGACTACATTAAGAAGAACGGCCTGCAGGACCCGACCAAC
AAGCGCAACATCAACCCGGACGATAAGCTGGCGAAGGTGTTC
GGTACCGAGAAGCCCATCGACATGTTTCAAATGACCAAGATG
GTGTCCCAGCACATCATTAAGCACCACCACCATCACCAT
Chlamydia_Ct460_serovarL2_nIgk
ATGGAAACTCCTGCCCAACTGTTGTTCCTGCTGCTTCTCTGGCT 284
CCCTGACACTACCGGAATGTCGCAGAACAAGAACTCCGCCTTC
ATGCAACCCGTGAACGTGTCAGCGGACCTGGCAGCTATTGTCG
GTGCCGGGCCGATGCCCCGCACCGAAATCATCAAGAAGATGT
GGGACTACATCAAGGAGAACAGCCTGCAGGATCCAACCAACA
AGCGGAATATCAACCCGGACGATAAGCTGGCCAAAGTGTTCG
GCACCGAGAAGCCGATTGACATGTTTCAGATGACCAAGATGG TGTCCCAGCACATCATTAAG
Chlamydia_Ct460_serovarL2_nIgk_cHis
ATGGAAACTCCTGCCCAACTGTTGTTCCTGCTGCTTCTCTGGCT 285
CCCTGACACTACCGGAATGTCGCAGAACAAGAACTCCGCCTTC
ATGCAACCCGTGAACGTGTCAGCGGACCTGGCAGCTATTGTCG
GTGCCGGGCCGATGCCCCGCACCGAAATCATCAAGAAGATGT
GGGACTACATCAAGGAGAACAGCCTGCAGGATCCAACCAACA
AGCGGAATATCAACCCGGACGATAAGCTGGCCAAAGTGTTCG
GCACCGAGAAGCCGATTGACATGTTTCAGATGACCAAGATGG
TGTCCCAGCACATCATTAAGCACCACCACCATCATCAC
Chlamydia_Ct622_serovarE_nIgk
ATGGAAACCCCTGCCCAACTGCTTTTCTTGCTGCTGCTCTGGCT 286
CCCTGACACCACCGGAATGGAATCTGGACCCGAGTCCGTGTCA
AGCAACCAGTCCTCCATGAACCCCATCATTAATGGACAGATCG
CATCCAATTCCGAAACCAAGGAAAGCACCAAGGCATCGGAGG
CCTCCCCATCCGCCTCAAGCTCCGTGTCGTCCTGGTCGTTTCTG
TCGAGCGCGAAGAATGCCCTGATCTCACTGCGGGACGCGATTC
TGAACAAGAACAGCTCCCCAACCGACTCCCTGAGCCAACTCG
AGGCCTCAACTTCCACTTCGACTGTGACTAGGGTCGCTGCCAA
GGATTATGACGAGGCCAAGAGCAACTTCGACACCGCCAAGAG
CGGACTGGAAAACGCCAAAACCCTGGCCGAATACGAAACTAA
GATGGCCGATCTCATGGCGGCCCTGCAAGACATGGAACGGCT
GGCGAACTCCGATCCGTCCAACAACCACACTGAGGAAGTGAA
CAACATCAAGAAGGCTCTCGAGGCCCAGAAGGATACCATCGA
CAAGTTGAACAAGCTTGTGACGCTGCAGAACCAAAACAAGTC
CCTGACGGAAGTGCTCAAAACCACCGACTCGGCCGACCAGAT
TCCGGCCATCAACAGCCAGCTGGAGATTAACAAGAACTCGGC
CGATCAGATTATCAAGGACCTGGAGCGCCAGAACATTTCCTAC
GAGGCCGTCTTGACTAACGCCGGCGAAGTGATCAAGGCGTCA
TCCGAAGCCGGCATTAAGCTGGGACAGGCGCTGCAATCCATC
GTCGACGCCGGCGACCAGTCCCAGGCGGCGGTGCTGCAGGCC
CAGCAGAACAACTCCCCCGATAACATCGCTGCAACCAAGGAA
CTGATTGACGCGGCCGAAACCAAAGTCAACGAACTGAAGCAG
GAGCACACTGGTCTGACCGACTCGCCGCTCGTGAAGAAGGCC
GAAGAACAGATCAGCCAGGCTCAGAAGGATATCCAGGAAATC
AAGCCTTCGGGGAGCGACATCCCGATCGTGGGACCGTCCGGTT
CCGCCGCTTCCGCCGGGTCCGCAGCCGGGGCCCTTAAGTCGTC
GAACAATAGCGGCAGAATATCCCTGCTGCTCGACGATGTGGAT
AACGAGATGGCCGCCATTGCGCTGCAAGGATTCCGGTCCATGA
TCGAGCAGTTCAACGTGAACAACCCCGCCACCGCCAAGGAGC
TGCAGGCTATGGAGGCCCAACTCACTGCCATGTCCGACCAGCT
CGTGGGAGCGGACGGAGAACTGCCAGCCGAGATCCAGGCCAT
CAAGGACGCTCTGGCCCAGGCACTGAAGCAGCCGTCCGCGGA
TGGCCTGGCCACCGCCATGGGCCAGGTCGCGTTCGCCGCCGCT
AAAGTCGGCGGAGGTTCGGCCGGCACTGCCGGGACCGTGCAG
ATGAATGTCAAGCAGCTGTACAAGACTGCGTTCTCGTCGACCA
GCTCCAGCTCCTACGCCGCGGCCCTGTCCGACGGTTACAGCGC
GTACAAGACCCTGAACTCCCTTTACTCCGAATCGAGATCCGGG
GTCCAGTCCGCAATTTCACAAACCGCCAATCCTGCCCTGTCGC
GCTCAGTGTCACGCAGCGGCATCGAGTCACAGGGCAGAAGCG
CCGACGCTAGCCAAAGGGCCGCAGAAACCATTGTGCGGGACT
CCCAGACACTTGGAGATGTCTACAGCCGCCTCCAAGTGCTGGA
CTCCCTCATGTCCACCATCGTGTCAAACCCTCAGGCTAACCAG
GAGGAAATCATGCAGAAGCTGACCGCAAGCATTTCCAAGGCT
CCGCAGTTTGGATACCCCGCTGTGCAAAACTCCGCGGACAGCT
TGCAGAAATTCGCAGCCCAGTTGGAGAGGGAGTTCGTGGACG
GGGAGCGGTCCCTCGCGGAGTCCCAGGAGAACGCATTCCGGA
AGCAGCCCGCCTTCATTCAACAAGTGCTTGTGAACATCGCCTC CCTGTTCTCCGGTTACCTGTCT
Chlamydia_Ct622_serovarE_nIgk_cHis
ATGGAAACCCCTGCCCAACTGCTTTTCTTGCTGCTGCTCTGGCT 289
CCCTGACACCACCGGAATGGAATCTGGACCCGAGTCCGTGTCA
AGCAACCAGTCCTCCATGAACCCCATCATTAATGGACAGATCG
CATCCAATTCCGAAACCAAGGAAAGCACCAAGGCATCGGAGG
CCTCCCCATCCGCCTCAAGCTCCGTGTCGTCCTGGTCGTTTCTG
TCGAGCGCGAAGAATGCCCTGATCTCACTGCGGGACGCGATTC
TGAACAAGAACAGCTCCCCAACCGACTCCCTGAGCCAACTCG
AGGCCTCAACTTCCACTTCGACTGTGACTAGGGTCGCTGCCAA
GGATTATGACGAGGCCAAGAGCAACTTCGACACCGCCAAGAG
CGGACTGGAAAACGCCAAAACCCTGGCCGAATACGAAACTAA
GATGGCCGATCTCATGGCGGCCCTGCAAGACATGGAACGGCT
GGCGAACTCCGATCCGTCCAACAACCACACTGAGGAAGTGAA
CAACATCAAGAAGGCTCTCGAGGCCCAGAAGGATACCATCGA
CAAGTTGAACAAGCTTGTGACGCTGCAGAACCAAAACAAGTC
CCTGACGGAAGTGCTCAAAACCACCGACTCGGCCGACCAGAT
TCCGGCCATCAACAGCCAGCTGGAGATTAACAAGAACTCGGC
CGATCAGATTATCAAGGACCTGGAGCGCCAGAACATTTCCTAC
GAGGCCGTCTTGACTAACGCCGGCGAAGTGATCAAGGCGTCA
TCCGAAGCCGGCATTAAGCTGGGACAGGCGCTGCAATCCATC
GTCGACGCCGGCGACCAGTCCCAGGCGGCGGTGCTGCAGGCC
CAGCAGAACAACTCCCCCGATAACATCGCTGCAACCAAGGAA
CTGATTGACGCGGCCGAAACCAAAGTCAACGAACTGAAGCAG
GAGCACACTGGTCTGACCGACTCGCCGCTCGTGAAGAAGGCC
GAAGAACAGATCAGCCAGGCTCAGAAGGATATCCAGGAAATC
AAGCCTTCGGGGAGCGACATCCCGATCGTGGGACCGTCCGGTT
CCGCCGCTTCCGCCGGGTCCGCAGCCGGGGCCCTTAAGTCGTC
GAACAATAGCGGCAGAATATCCCTGCTGCTCGACGATGTGGAT
AACGAGATGGCCGCCATTGCGCTGCAAGGATTCCGGTCCATGA
TCGAGCAGTTCAACGTGAACAACCCCGCCACCGCCAAGGAGC
TGCAGGCTATGGAGGCCCAACTCACTGCCATGTCCGACCAGCT
CGTGGGAGCGGACGGAGAACTGCCAGCCGAGATCCAGGCCAT
CAAGGACGCTCTGGCCCAGGCACTGAAGCAGCCGTCCGCGGA
TGGCCTGGCCACCGCCATGGGCCAGGTCGCGTTCGCCGCCGCT
AAAGTCGGCGGAGGTTCGGCCGGCACTGCCGGGACCGTGCAG
ATGAATGTCAAGCAGCTGTACAAGACTGCGTTCTCGTCGACCA
GCTCCAGCTCCTACGCCGCGGCCCTGTCCGACGGTTACAGCGC
GTACAAGACCCTGAACTCCCTTTACTCCGAATCGAGATCCGGG
GTCCAGTCCGCAATTTCACAAACCGCCAATCCTGCCCTGTCGC
GCTCAGTGTCACGCAGCGGCATCGAGTCACAGGGCAGAAGCG
CCGACGCTAGCCAAAGGGCCGCAGAAACCATTGTGCGGGACT
CCCAGACACTTGGAGATGTCTACAGCCGCCTCCAAGTGCTGGA
CTCCCTCATGTCCACCATCGTGTCAAACCCTCAGGCTAACCAG
GAGGAAATCATGCAGAAGCTGACCGCAAGCATTTCCAAGGCT
CCGCAGTTTGGATACCCCGCTGTGCAAAACTCCGCGGACAGCT
TGCAGAAATTCGCAGCCCAGTTGGAGAGGGAGTTCGTGGACG
GGGAGCGGTCCCTCGCGGAGTCCCAGGAGAACGCATTCCGGA
AGCAGCCCGCCTTCATTCAACAAGTGCTTGTGAACATCGCCTC
CCTGTTCTCCGGTTACCTGTCTCATCACCACCACCATCAC Chlamydia_Ct858_nIgk
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 288
TGCCTGATACCACAGGCGTGCGGGGAGAGTCCCTCGTGTGCAA
GAATGCCCTGCAGGACCTGAGCTTCCTGGAACATCTGCTGCAA
GTGAAGTACGCCCCCAAGACCTGGAAAGAGCAGTACCTGGGC
TGGGACCTGGTGCAGTCCTCTGTGTCTGCCCAGCAGAAGCTGC
GGACCCAGGAAAACCCCTCTACCAGCTTCTGTCAGCAAGTGCT
GGCCGACTTCATCGGCGGCCTGAACGATTTCCATGCCGGCGTG
ACCTTTTTCGCCATCGAGAGCGCCTACCTGCCCTACACCGTGC
AGAAGTCCAGCGACGGCCGGTTCTACTTCGTGGACATCATGAC
CTTCAGCAGCGAGATCAGAGTGGGCGACGAGCTGCTGGAAGT
GGATGGCGCTCCTGTGCAGGATGTGCTGGCCACACTGTACGGC
AGCAACCACAAGGGCACAGCCGCCGAAGAATCTGCCGCCCTG
AGAACCCTGTTCAGCCGGATGGCCTCTCTGGGCCACAAGGTGC
CAAGCGGCAGAACCACCCTGAAGATCAGACGGCCCTTTGGCA
CCACCCGGGAAGTGCGCGTGAAGTGGCGCTATGTGCCTGAGG
GCGTGGGCGACCTGGCCACAATCGCCCCTTCTATCAGAGCCCC
CCAGCTGCAGAAATCCATGCGGTCATTCTTCCCAAAGAAGGAC
GACGCCTTCCACCGGTCCAGCAGCCTGTTCTACAGCCCTATGG
TGCCCCACTTCTGGGCCGAGCTGAGAAACCACTACGCCACCTC
CGGCCTGAAGTCCGGCTACAACATCGGCAGCACCGACGGCTTT
CTGCCCGTGATCGGACCCGTGATCTGGGAGAGCGAGGGCCTGT
TCAGAGCCTACATCAGCAGCGTGACCGACGGCGACGGCAAGA
GCCACAAAGTGGGCTTTCTGAGAATCCCCACCTACAGCTGGCA
GGACATGGAAGATTTCGACCCCAGCGGCCCACCCCCCTGGGA
GGAATTTGCCAAGATCATCCAGGTGTTCAGCAGCAACACCGA
GGCCCTGATCATCGACCAGACCAACAACCCTGGCGGCAGCGT
GCTGTACCTGTACGCCCTGCTGAGCATGCTGACCGACAGACCC
CTGGAACTGCCCAAGCACCGGATGATCCTGACCCAGGACGAG
GTGGTGGACGCCCTGGATTGGCTGACCCTGCTGGAAAACGTGG
ACACCAACGTGGAAAGCCGGCTGGCCCTGGGCGACAACATGG
AAGGCTACACAGTGGATCTGCAGGTGGCCGAGTACCTGAAAA
GCTTCGGCAGACAGGTGCTGAACTGCTGGTCCAAGGGCGACA
TCGAGCTGAGCACCCCCATCCCCCTGTTCGGCTTCGAGAAGAT
CCACCCCCACCCCAGAGTGCAGTACAGCAAGCCCATCTGCGTG
CTGATCAACGAGCAGGACTTCTCCTGCGCCGACTTCTTCCCAG
TGGTGCTGAAGGACAACGACAGAGCCCTGATCGTGGGCACCA
GAACAGCTGGCGCTGGCGGCTTCGTGTTCAACGTGCAGTTCCC
CAACCGGACCGGCATCAAGACCTGTAGCCTGACAGGCTCTCTG
GCCGTGCGGGAACACGGCGCCTTCATCGAGAACATCGGCGTG
GAACCCCACATCGACCTGCCTTTCACCGCCAACGACATCCGGT
ACAAGGGCTACTCTGAGTACCTGGACAAAGTGAAGAAACTCG
TGTGCCAGCTGATTAACAACGACGGCACCATCATCCTGGCCGA GGACGGCAGCTTC
Chlamydia_Ct858_nIgk_cHis
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 289
TGCCTGATACCACAGGCGTGCGGGGAGAGTCCCTCGTGTGCAA
GAATGCCCTGCAGGACCTGAGCTTCCTGGAACATCTGCTGCAA
GTGAAGTACGCCCCCAAGACCTGGAAAGAGCAGTACCTGGGC
TGGGACCTGGTGCAGTCCTCTGTGTCTGCCCAGCAGAAGCTGC
GGACCCAGGAAAACCCCTCTACCAGCTTCTGTCAGCAAGTGCT
GGCCGACTTCATCGGCGGCCTGAACGATTTCCATGCCGGCGTG
ACCTTTTTCGCCATCGAGAGCGCCTACCTGCCCTACACCGTGC
AGAAGTCCAGCGACGGCCGGTTCTACTTCGTGGACATCATGAC
CTTCAGCAGCGAGATCAGAGTGGGCGACGAGCTGCTGGAAGT
GGATGGCGCTCCTGTGCAGGATGTGCTGGCCACACTGTACGGC
AGCAACCACAAGGGCACAGCCGCCGAAGAATCTGCCGCCCTG
AGAACCCTGTTCAGCCGGATGGCCTCTCTGGGCCACAAGGTGC
CAAGCGGCAGAACCACCCTGAAGATCAGACGGCCCTTTGGCA
CCACCCGGGAAGTGCGCGTGAAGTGGCGCTATGTGCCTGAGG
GCGTGGGCGACCTGGCCACAATCGCCCCTTCTATCAGAGCCCC
CCAGCTGCAGAAATCCATGCGGTCATTCTTCCCAAAGAAGGAC
GACGCCTTCCACCGGTCCAGCAGCCTGTTCTACAGCCCTATGG
TGCCCCACTTCTGGGCCGAGCTGAGAAACCACTACGCCACCTC
CGGCCTGAAGTCCGGCTACAACATCGGCAGCACCGACGGCTTT
CTGCCCGTGATCGGACCCGTGATCTGGGAGAGCGAGGGCCTGT
TCAGAGCCTACATCAGCAGCGTGACCGACGGCGACGGCAAGA
GCCACAAAGTGGGCTTTCTGAGAATCCCCACCTACAGCTGGCA
GGACATGGAAGATTTCGACCCCAGCGGCCCACCCCCCTGGGA
GGAATTTGCCAAGATCATCCAGGTGTTCAGCAGCAACACCGA
GGCCCTGATCATCGACCAGACCAACAACCCTGGCGGCAGCGT
GCTGTACCTGTACGCCCTGCTGAGCATGCTGACCGACAGACCC
CTGGAACTGCCCAAGCACCGGATGATCCTGACCCAGGACGAG
GTGGTGGACGCCCTGGATTGGCTGACCCTGCTGGAAAACGTGG
ACACCAACGTGGAAAGCCGGCTGGCCCTGGGCGACAACATGG
AAGGCTACACAGTGGATCTGCAGGTGGCCGAGTACCTGAAAA
GCTTCGGCAGACAGGTGCTGAACTGCTGGTCCAAGGGCGACA
TCGAGCTGAGCACCCCCATCCCCCTGTTCGGCTTCGAGAAGAT
CCACCCCCACCCCAGAGTGCAGTACAGCAAGCCCATCTGCGTG
CTGATCAACGAGCAGGACTTCTCCTGCGCCGACTTCTTCCCAG
TGGTGCTGAAGGACAACGACAGAGCCCTGATCGTGGGCACCA
GAACAGCTGGCGCTGGCGGCTTCGTGTTCAACGTGCAGTTCCC
CAACCGGACCGGCATCAAGACCTGTAGCCTGACAGGCTCTCTG
GCCGTGCGGGAACACGGCGCCTTCATCGAGAACATCGGCGTG
GAACCCCACATCGACCTGCCTTTCACCGCCAACGACATCCGGT
ACAAGGGCTACTCTGAGTACCTGGACAAAGTGAAGAAACTCG
TGTGCCAGCTGATTAACAACGACGGCACCATCATCCTGGCCGA
GGACGGCAGCTTCCACCACCACCATCACCAC Chlamydia_Ct875_nIgk
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 290
TGCCTGACACCACCGGCATGAGCATCAGAGGCGTGGGCGGCA
ACGGCAACAGCAGAATCCCTAGCCACAACGGCGACGGCAGCA
ACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGTGGAA
GATAGAGTGTGCAGCCTGTACAGCAGCCGGTCCAACGAGAAC
CGCGAGAGCCCTTATGCCGTGGTGGACGTGTCCAGCATGATCG
AGAGCACCCCCACCAGCGGCGAGACAACCAGAGCTAGTAGAG
GCGTGCTGAGCCGGTTCCAGAGGGGCCTCGTGCGGATTGCTGA
CAAAGTGCGGAGAGCCGTGCAGTGCGCTTGGAGCAGCGTGTC
CACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAGCGGCA
GCTCTAGCAGAACAGCTAGAGGCGCCAGCAGCGGCTACAGAG
AGTACAGCCCTTCTGCCGCTCGGGGCCTGCGGCTGATGTTCAC
CGACTTTTGGCGGACCCGGGTGCTGAGACAGACCTCTCCTATG
GCCGGCGTGTTCGGCAACCTGGACGTGAACGAGGCCAGACTG
ATGGCCGCCTACACCAGCGAGTGTGCCGATCACCTGGAAGCC
AAAGAGCTGGCCGGACCTGACGGCGTGGCAGCCGCTAGAGAA
ATCGCCAAGAGATGGGAGAAGAGAGTGCGGGACCTGCAGGAC
AAGGGCGCTGCCAGAAAGCTGCTGAACGACCCCCTGGGCAGA
CGGACCCCCAACTACCAGAGCAAGAACCCCGGCGAGTACACC
GTGGGCAACTCCATGTTCTACGACGGCCCCCAGGTGGCCAACC
TGCAGAATGTGGATACCGGCTTCTGGCTGGACATGAGCAACCT
GAGCGACGTGGTGCTGTCCAGAGAGATCCAGACCGGCCTGAG
AGCCAGAGCCACCCTGGAAGAGTCCATGCCCATGCTGGAAAA
TCTGGAAGAGAGATTCCGGCGGCTGCAGGAAACCTGCGACGC
CGCCAGAACCGAGATCGAGGAAAGCGGCTGGACCCGGGAAAG
CGCCTCCAGAATGGAAGGCGACGAAGCCCAGGGCCCCAGCAG
AGTGCAGCAGGCCTTTCAGAGCTTCGTGAATGAGTGCAACAGC
ATCGAGTTCAGCTTCGGCTCCTTCGGCGAGCACGTGCGGGTGC
TGTGTGCCAGAGTGTCAAGAGGACTGGCCGCTGCCGGCGAGG
CCATCAGAAGATGCTTCAGCTGCTGCAAGGGCAGCACCCACA
GATACGCCCCCAGAGATGACCTGTCTCCTGAGGGCGCCTCTCT
GGCCGAAACCCTGGCCAGATTCGCCGACGACATGGGCATCGA
AAGAGGCGCCGACGGCACCTACGACATCCCCCTGGTGGACGA
TTGGAGAAGGGGCGTGCCATCCATCGAGGGCGAGGGCAGCGA
TAGCATCTACGAGATCATGATGCCCATCTACGAAGTGATGAAC
ATGGACCTGGAAACCCGGCGGAGCTTCGCCGTGCAGCAGGGC
CATTACCAGGACCCCAGAGCCAGCGACTACGACCTGCCTAGA
GCCTCCGATTACGATCTGCCCAGAAGCCCCTACCCCACCCCTC
CACTGCCTCCCAGATACCAGCTGCAGAACATGGATGTGGAAG
CCGGCTTTCGCGAGGCCGTGTACGCCTCTTTTGTGGCCGGCAT
GTACAACTACGTCGTGACCCAGCCCCAGGAACGGATCCCCAAT
AGCCAGCAGGTGGAAGGCATCCTGCGGGACATGCTGACCAAC
GGCAGCCAGACCTTCCGGGACCTGATGAAGCGGTGGAACAGA GAGGTGGACCGCGAG
Chlamydia_Ct875_nIgk_cHis
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 291
TGCCTGACACCACCGGCATGAGCATCAGAGGCGTGGGCGGCA
ACGGCAACAGCAGAATCCCTAGCCACAACGGCGACGGCAGCA
ACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGTGGAA
GATAGAGTGTGCAGCCTGTACAGCAGCCGGTCCAACGAGAAC
CGCGAGAGCCCTTATGCCGTGGTGGACGTGTCCAGCATGATCG
AGAGCACCCCCACCAGCGGCGAGACAACCAGAGCTAGTAGAG
GCGTGCTGAGCCGGTTCCAGAGGGGCCTCGTGCGGATTGCTGA
CAAAGTGCGGAGAGCCGTGCAGTGCGCTTGGAGCAGCGTGTC
CACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAGCGGCA
GCTCTAGCAGAACAGCTAGAGGCGCCAGCAGCGGCTACAGAG
AGTACAGCCCTTCTGCCGCTCGGGGCCTGCGGCTGATGTTCAC
CGACTTTTGGCGGACCCGGGTGCTGAGACAGACCTCTCCTATG
GCCGGCGTGTTCGGCAACCTGGACGTGAACGAGGCCAGACTG
ATGGCCGCCTACACCAGCGAGTGTGCCGATCACCTGGAAGCC
AAAGAGCTGGCCGGACCTGACGGCGTGGCAGCCGCTAGAGAA
ATCGCCAAGAGATGGGAGAAGAGAGTGCGGGACCTGCAGGAC
AAGGGCGCTGCCAGAAAGCTGCTGAACGACCCCCTGGGCAGA
CGGACCCCCAACTACCAGAGCAAGAACCCCGGCGAGTACACC
GTGGGCAACTCCATGTTCTACGACGGCCCCCAGGTGGCCAACC
TGCAGAATGTGGATACCGGCTTCTGGCTGGACATGAGCAACCT
GAGCGACGTGGTGCTGTCCAGAGAGATCCAGACCGGCCTGAG
AGCCAGAGCCACCCTGGAAGAGTCCATGCCCATGCTGGAAAA
TCTGGAAGAGAGATTCCGGCGGCTGCAGGAAACCTGCGACGC
CGCCAGAACCGAGATCGAGGAAAGCGGCTGGACCCGGGAAAG
CGCCTCCAGAATGGAAGGCGACGAAGCCCAGGGCCCCAGCAG
AGTGCAGCAGGCCTTTCAGAGCTTCGTGAATGAGTGCAACAGC
ATCGAGTTCAGCTTCGGCTCCTTCGGCGAGCACGTGCGGGTGC
TGTGTGCCAGAGTGTCAAGAGGACTGGCCGCTGCCGGCGAGG
CCATCAGAAGATGCTTCAGCTGCTGCAAGGGCAGCACCCACA
GATACGCCCCCAGAGATGACCTGTCTCCTGAGGGCGCCTCTCT
GGCCGAAACCCTGGCCAGATTCGCCGACGACATGGGCATCGA
AAGAGGCGCCGACGGCACCTACGACATCCCCCTGGTGGACGA
TTGGAGAAGGGGCGTGCCATCCATCGAGGGCGAGGGCAGCGA
TAGCATCTACGAGATCATGATGCCCATCTACGAAGTGATGAAC
ATGGACCTGGAAACCCGGCGGAGCTTCGCCGTGCAGCAGGGC
CATTACCAGGACCCCAGAGCCAGCGACTACGACCTGCCTAGA
GCCTCCGATTACGATCTGCCCAGAAGCCCCTACCCCACCCCTC
CACTGCCTCCCAGATACCAGCTGCAGAACATGGATGTGGAAG
CCGGCTTTCGCGAGGCCGTGTACGCCTCTTTTGTGGCCGGCAT
GTACAACTACGTCGTGACCCAGCCCCAGGAACGGATCCCCAAT
AGCCAGCAGGTGGAAGGCATCCTGCGGGACATGCTGACCAAC
GGCAGCCAGACCTTCCGGGACCTGATGAAGCGGTGGAACAGA
GAGGTGGACCGCGAGCACCACCATCACCACCAC Chlamydia_Ct089_nIgk
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 292
TGCCTGACACCACCGGCATGACAGCATCTGGCGGAGCTGGCG
GCCTGGGCTCTACACAGACAGTGGATGTGGCCAGGGCCCAGG
CTGCTGCCGCTACACAGGATGCCCAGGAAGTGATCGGCAGCC
AGGAAGCCAGCGAGGCCTCTATGCTGAAGGGCTGCGAGGACC
TGATCAACCCTGCCGCCGCTACCCGCATCAAGAAGAAAGAGG
AAAAGTTCGAGTCCCTGGAAGCCAGACGGAAGCCCACCGCCG
ACAAGGCCGAGAAGAAGTCCGAGAGCACCGAGGAAAAGGGC
GACACCCCCCTGGAAGATCGGTTCACCGAGGATCTGAGCGAG
GTGTCCGGCGAGGACTTCCGGGGCCTGAAGAACAGCTTCGAC
GACGACAGCAGCCCCGAGGAAATCCTGGACGCCCTGACCAGC
AAGTTCAGCGACCCCACCATCAAGGACCTGGCCCTGGACTACC
TGATCCAGACCGCCCCCAGCGACCGGAAGCTGAAGTCTGCCCT
GATTCAGGCCAAGCACCAGCTGATGAGCCAGAACCCCCAGGC
CATCGTGGGCGGCAGAAATGTGCTGCTGGCCTCCGAGACATTC
GCCAGCAGAGCCAACACCAGCCCCAGCTCCCTGCGGAGCCTG
TATCTGCAAGTGACCAGCTCCCCCAGCAACTGCGACAACCTGA
GACAGATGCTGGCTAGCTACCTGCCCTCCGAGAAAACCGCCGT
GATGGAATTCCTCGTGAACGGCATGGTGGCCGACCTGAAAAG
CGAGGGCCCTAGCATCCCTCCCGCCAAGCTGCAGGTGTACATG
ACCGAGCTGAGCAACCTGCAGGCCCTGCACAGCGTGGACAGC
TTTTTCGACCGGAACATCGGCAACCTGGAAAACAGCCTGAAGC
ACGAGGGCCACGCCCCCATCCCTTCTCTGACAACCGGCAATCT
GACCAAGACCTTCCTGCAGCTGGTGGAAGATAAGTTCCCCAGC
AGCTCCAAGGCCCAGAAGGCCCTGAACGAGCTCGTGGGCCCT
GATACCGGACCTCAGACCGAGGTGCTGAACCTGTTCTTTCGGG
CCCTGAATGGCTGCTCCCCCCGGATCTTTTCTGGCGCTGAGAA
GAAGCAGCAGCTGGCCAGCGTGATCACCAACACCCTGGATGC
CATCAACGCCGACAACGAGGACTACCCCAAGCCCGGCGACTT
CCCCAGAAGCAGCTTTAGCAGCACCCCCCCTCATGCCCCTGTG
CCCCAGTCTGAGATCCCTACCAGCCCAACCAGCACCCAGCCTC CAAGCCCT
Chlamydia_Ct089_nIgk_cHis
ATGGAAACCCCTGCCCAGCTGCTGTTCCTGCTGCTGCTGTGGC 293
TGCCTGACACCACCGGCATGACAGCATCTGGCGGAGCTGGCG
GCCTGGGCTCTACACAGACAGTGGATGTGGCCAGGGCCCAGG
CTGCTGCCGCTACACAGGATGCCCAGGAAGTGATCGGCAGCC
AGGAAGCCAGCGAGGCCTCTATGCTGAAGGGCTGCGAGGACC
TGATCAACCCTGCCGCCGCTACCCGCATCAAGAAGAAAGAGG
AAAAGTTCGAGTCCCTGGAAGCCAGACGGAAGCCCACCGCCG
ACAAGGCCGAGAAGAAGTCCGAGAGCACCGAGGAAAAGGGC
GACACCCCCCTGGAAGATCGGTTCACCGAGGATCTGAGCGAG
GTGTCCGGCGAGGACTTCCGGGGCCTGAAGAACAGCTTCGAC
GACGACAGCAGCCCCGAGGAAATCCTGGACGCCCTGACCAGC
AAGTTCAGCGACCCCACCATCAAGGACCTGGCCCTGGACTACC
TGATCCAGACCGCCCCCAGCGACCGGAAGCTGAAGTCTGCCCT
GATTCAGGCCAAGCACCAGCTGATGAGCCAGAACCCCCAGGC
CATCGTGGGCGGCAGAAATGTGCTGCTGGCCTCCGAGACATTC
GCCAGCAGAGCCAACACCAGCCCCAGCTCCCTGCGGAGCCTG
TATCTGCAAGTGACCAGCTCCCCCAGCAACTGCGACAACCTGA
GACAGATGCTGGCTAGCTACCTGCCCTCCGAGAAAACCGCCGT
GATGGAATTCCTCGTGAACGGCATGGTGGCCGACCTGAAAAG
CGAGGGCCCTAGCATCCCTCCCGCCAAGCTGCAGGTGTACATG
ACCGAGCTGAGCAACCTGCAGGCCCTGCACAGCGTGGACAGC
TTTTTCGACCGGAACATCGGCAACCTGGAAAACAGCCTGAAGC
ACGAGGGCCACGCCCCCATCCCTTCTCTGACAACCGGCAATCT
GACCAAGACCTTCCTGCAGCTGGTGGAAGATAAGTTCCCCAGC
AGCTCCAAGGCCCAGAAGGCCCTGAACGAGCTCGTGGGCCCT
GATACCGGACCTCAGACCGAGGTGCTGAACCTGTTCTTTCGGG
CCCTGAATGGCTGCTCCCCCCGGATCTTTTCTGGCGCTGAGAA
GAAGCAGCAGCTGGCCAGCGTGATCACCAACACCCTGGATGC
CATCAACGCCGACAACGAGGACTACCCCAAGCCCGGCGACTT
CCCCAGAAGCAGCTTTAGCAGCACCCCCCCTCATGCCCCTGTG
CCCCAGTCTGAGATCCCTACCAGCCCAACCAGCACCCAGCCTC
CAAGCCCTCACCACCACCATCACCAC Chlamydia_MOMP
ATGAAAAAACTCTTAAAATCGGCGTTTTTATCCGCCGCATTTTT 294
TGCTGGTCACGCCTCCTTACACGCTTTGCCTGTAGGGAACCCA
GCAGAGCCAAGTTTATTAATTGATGGAACGATATGGGAAGGT
ATGTCAGGAGATCCATGTGATCCTTGCGCTACTTGGTGCGACG
CGATTAGCTTACGCGTAGGATTTTACGGAGATTATGTTTTCGA
CAGAGTCCTCAAGACAGATGTGCCACAGAAGTTTTCAATGGG
GCCTATACCTACTTCAAGTACTTCTCCTGAAGACTCAGCTATA
CTAACAGAGAGAAATAACGCAGCGTATGGAAAACATATGCAC
GATGCGGAGTTGTTCACAAATGCAGGTTACATTGCGCTAAATA
TTTGGGACCGTTTCGACATCTTTTGTACCTTAGGAGCTACTAGT
GGGTATTTTAAAGGGAATTCTTCATCTTTCAACTTGATCGGATT
GATTGGTATTTCAGGAGCAGACCTTAACAGCAAGCTCCCAAAC
GCAAATATTTCTAACGGCGTAGTAGAGCTATATACAGACACAA
CCTTCTCTTGGAGCGTTGGAGCTCGCGGAGCTTTGTGGGAGTG
TGGTTGCGCTACTTTAGGAGCAGAATTCCAATACGCACAATCG
AAACCTCGCGTTCAAGAATTGAATGTCTTGTCTAACGTAGCAC
AATTTACTGTACACAAACCTCGGGGATATGTAGGCCAGCCTCT
ACCTCTTCCACTGACTGCAGGAACAGCAACTGATTCTAATGAT
AAATTGAAAAATGCCACGATCAACTACCATGAATGGCAAGTC
GGTGCAGCATTGTCATATAGACTGAATATGCTCGTTCCTTACA
TCGGTGTTCAGTGGTCCAGAGCTACTTTTGATGCAGATACTAT
CCAAATTGCGGAACCAAAATTAGCTTCGCCAATTTTCAACTTG
ACAACATGGAATCCAACATTATTAGGACAAGCAACTTCAGTA
GATAGCGGAAACAAGTTTGCTGACTCCCTACAAATTGTTTCTC
TTCAAATTAACAAGTTGAAGTCCAGAAAAGCTTGTGGTGTTTC
CATGGGAGCAACTTTACTTGATGCCGATAAATGGGCAATCAAT
GGGGAACTTCGTTTAATTAACGAAAGAGCTGCTCACCTTTCTG CTCAATGCAGATTC
Chlamydia mRNA coding region Sequences Cta1_E_EXT_noTM_nIgK
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 320
GCUGCCUGAUACCACCGGCCCUCCCCUGCCCAGCAGCACACA
GGACAACAGAUCCAUGGACCAGCAGGACAGCGAAGAGUUCC
UGCUGCAGAACACCCUGGAAGAUAGCGAGAUCAUCAGCAUC
CCCGACACCAUGAACCAGAUCGCCAUCGACACCGAGAAGUGG
UUCUACCUGAACAAGGACUGCACCAACGUGGGCCCCAUCUCC
AUCGUGCAGCUGACAGCCUUCCUGAAAGAGUGCAAGCACAG
CCCCGAGAAGGGCAUCGACCCCCAGGAACUGUGGGUGUGGA
AGAAAGGCAUGCCCAACUGGGAGAAAGUGAAGAACAUCCCC
GAGCUGAGCGGCACCGUGAAGGACGAG Cta1_E_EXT_noTM_nIgK_cHis
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 321
GCUGCCUGAUACCACCGGCCCUCCCCUGCCCAGCAGCACACA
GGACAACAGAUCCAUGGACCAGCAGGACAGCGAAGAGUUCC
UGCUGCAGAACACCCUGGAAGAUAGCGAGAUCAUCAGCAUC
CCCGACACCAUGAACCAGAUCGCCAUCGACACCGAGAAGUGG
UUCUACCUGAACAAGGACUGCACCAACGUGGGCCCCAUCUCC
AUCGUGCAGCUGACAGCCUUCCUGAAAGAGUGCAAGCACAG
CCCCGAGAAGGGCAUCGACCCCCAGGAACUGUGGGUGUGGA
AGAAAGGCAUGCCCAACUGGGAGAAAGUGAAGAACAUCCCC
GAGCUGAGCGGCACCGUGAAGGACGAGCACCACCACCAUCAC CAC CT875_E_NGM_nFC_cHis
AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 322
GCUGCCUGAUACAACCGGCGAGCCUAAGAGCUGCGACAAGA
CCCACACCUGUCCUCCAUGUCCUGCUCCAGAACUGCUCGGCG
GACCUUCCGUGUUCCUGUUUCCUCCAAAGCCUAAGGACACCC
UGAUGAUCAGCAGAACCCCUGAAGUGACCUGCGUGGUGGUG
GAUGUGUCCCACGAGGAUCCCGAAGUGAAGUUCAAUUGGUA
CGUGGACGGCGUGGAAGUGCACAACGCCAAGACCAAGCCUA
GAGAGGAACAGUACAACAGCACCUACAGAGUGGUGUCCGUG
CUGACCGUGCUGCACCAGGAUUGGCUGAACGGCAAAGAGUA
CAAGUGCAAGGUGUCCAACAAGGCCCUGCCUGCUCCUAUCG
AGAAGACCAUCAGCAAGGCCAAGGGCCAGCCAAGAGAACCC
CAGGUGUACACACUGCCUCCAAGCAGAGAUGAGCUGACCAA
GAACCAGGUGUCCCUGACCUGUCUGGUCAAGGGCUUCUACC
CCUCCGAUAUCGCCGUGGAAUGGGAGAGCAAUGGCCAGCCU
GAGAACAACUACAAGACAACCCCUCCUGUGCUGGACAGCGA
CGGCUCAUUCUUCCUGUACAGCAAGCUGACAGUGGACAAGA
GCAGAUGGCAGCAGGGCAACGUGUUCAGCUGCAGCGUGAUG
CACGAGGCCCUGCACAAUCACUACACCCAGAAGUCCCUGUCU
CUGAGCCCCGGCAAGAUGAGCAUCAGAGGCGUGGGCGGCAA
CGGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCAGCAA
CAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUGGAAG
AUAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGAGAAC
CGCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCAUGAU
CGAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUAGUAG
AGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGGAUUG
CUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAGCAGC
GUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAG
CGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGCU
ACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGCUG
AUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAGAC
CUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAACG
AGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCGAU
CACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUGGC
AGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUGC
GGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGAAC
GACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGAAC
CCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACGGC
CCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUCUG
GCUGGACAUGCAGCACCUGAGCGACGUGGUGCUGUCCAGAG
AGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAGAG
UCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGGCG
GCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGAGG
AAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAGGC
GACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUCA
GAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUCG
GCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGUG
UCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAUG
CUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCAG
AGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCCU
GGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCCG
ACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAGG
GGCGUGCCAUCCAUCGAGGGCGAGGGCAGCGAUAGCAUCUA
CGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGGACC
UGGAAACCCGGCGGAGCUUCGCCGUGCAGCAGGGCCAUUAC
CAGGACCCCAGAGCCAGCGACUACGACCUGCCUAGAGCCUCC
GAUUACGAUCUGCCCAGAAGCCCCUACCCCACCCCUCCACUG
CCUCCCAGAUACCAGCUGCAGAACAUGGAUGUGGAAGCCGG
CUUUCGCGAGGCCGUGUACGCCUCUUUUGUGGCCGGCAUGU
ACAACUACGUCGUGACCCAGCCCCAGGAACGGAUCCCCAAUA
GCCAGCAGGUGGAAGGCAUCCUGCGGGACAUGCUGACCAAC
GGCGACCAGACCUUCCGGGACCUGAUGAAGCGGUGGAACAG
AGAGGUGGACCGCGAGAUGAGCCCUAUCCUCGGCUACUGGA
AGAUCAAAGGCCUGGUGCAGCCCACCAGACUGCUGCUGGAA
UACCUGGAAGAGAAGUACGAGGAACACCUGUACGAGCGCGA
CGAGGGCGAUAAGUGGCGGAACAAGAAGUUCGAGCUGGGCC
UCGAGUUCCCCAACCUGCCUUACUACAUCGACGGCGACGUGA
AGCUGACCCAGAGCAUGGCCAUCAUCCGGUAUAUCGCCGAC
AAGCACAACAUGCUCGGCGGCUGCCCUAAAGAGCGGGCCGA
GAUUUCUAUGCUGGAAGGCGCCGUGCUGGACAUCAGAUACG
GCGUGUCCAGAAUCGCCUACAGCAAGGACUUCGAAACCCUG
AAGGUGGACUUCCUGAGCAAGCUGCCCGAGAUGCUGAAGAU
GUUCGAGGACCGGCUGUGCCACAAGACCUACCUGAAUGGCG
ACCACGUGACACACCCCGACUUCAUGCUGUACGACGCCCUGG
AUGUGGUGCUGUACAUGGACCCCAUGUGCCUGGACGCCUUU
CCAAAGCUCGUGUGCUUCAAGAAGCGGAUCGAGGCCAUUCC
UCAGAUCGACAAGUACCUGAAGUCCAGCAAGUAUAUCGCUU
GGCCCCUGCAAGGCUGGCAGGCCACAUUUGGAGGCGGAGAU CACCCUCCUAAG
CT875_E_nFC_cHis AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 323
GCUGCCUGAUACAACCGGCGAGCCUAAGAGCUGCGACAAGA
CCCACACCUGUCCUCCAUGUCCUGCUCCAGAACUGCUCGGCG
GACCUUCCGUGUUCCUGUUUCCUCCAAAGCCUAAGGACACCC
UGAUGAUCAGCAGAACCCCUGAAGUGACCUGCGUGGUGGUG
GAUGUGUCCCACGAGGAUCCCGAAGUGAAGUUCAAUUGGUA
CGUGGACGGCGUGGAAGUGCACAACGCCAAGACCAAGCCUA
GAGAGGAACAGUACAACAGCACCUACAGAGUGGUGUCCGUG
CUGACCGUGCUGCACCAGGAUUGGCUGAACGGCAAAGAGUA
CAAGUGCAAGGUGUCCAACAAGGCCCUGCCUGCUCCUAUCG
AGAAGACCAUCAGCAAGGCCAAGGGCCAGCCAAGAGAACCC
CAGGUGUACACACUGCCUCCAAGCAGAGAUGAGCUGACCAA
GAACCAGGUGUCCCUGACCUGUCUGGUCAAGGGCUUCUACC
CCUCCGAUAUCGCCGUGGAAUGGGAGAGCAAUGGCCAGCCU
GAGAACAACUACAAGACAACCCCUCCUGUGCUGGACAGCGA
CGGCUCAUUCUUCCUGUACAGCAAGCUGACAGUGGACAAGA
GCAGAUGGCAGCAGGGCAACGUGUUCAGCUGCAGCGUGAUG
CACGAGGCCCUGCACAAUCACUACACCCAGAAGUCCCUGUCU
CUGAGCCCCGGCAAGAUGAGCAUCAGAGGCGUGGGCGGCAA
CGGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCAGCAA
CAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUGGAAG
AUAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGAGAAC
CGCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCAUGAU
CGAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUAGUAG
AGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGGAUUG
CUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAGCAGC
GUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAG
CGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGCU
ACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGCUG
AUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAGAC
CUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAACG
AGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCGAU
CACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUGGC
AGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUGC
GGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGAAC
GACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGAAC
CCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACGGC
CCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUCUG
GCUGGACAUGAGCAACCUGAGCGACGUGGUGCUGUCCAGAG
AGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAGAG
UCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGGCG
GCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGAGG
AAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAGGC
GACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUCA
GAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUCG
GCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGUG
UCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAUG
CUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCAG
AGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCCU
GGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCCG
ACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAGG
GGCGUGCCAUCCAUCGAGGGCGAGGGCAGCGAUAGCAUCUA
CGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGGACC
UGGAAACCCGGCGGAGCUUCGCCGUGCAGCAGGGCCAUUAC
CAGGACCCCAGAGCCAGCGACUACGACCUGCCUAGAGCCUCC
GAUUACGAUCUGCCCAGAAGCCCCUACCCCACCCCUCCACUG
CCUCCCAGAUACCAGCUGCAGAACAUGGAUGUGGAAGCCGG
CUUUCGCGAGGCCGUGUACGCCUCUUUUGUGGCCGGCAUGU
ACAACUACGUCGUGACCCAGCCCCAGGAACGGAUCCCCAAUA
GCCAGCAGGUGGAAGGCAUCCUGCGGGACAUGCUGACCAAC
GGCAGCCAGACCUUCCGGGACCUGAUGAAGCGGUGGAACAG
AGAGGUGGACCGCGAGCACCACCAUCACCACCAC CT875_E_NGM_nFC
AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 324
GCUGCCUGAUACAACCGGCGAGCCUAAGAGCUGCGACAAGA
CCCACACCUGUCCUCCAUGUCCUGCUCCAGAACUGCUCGGCG
GACCUUCCGUGUUCCUGUUUCCUCCAAAGCCUAAGGACACCC
UGAUGAUCAGCAGAACCCCUGAAGUGACCUGCGUGGUGGUG
GAUGUGUCCCACGAGGAUCCCGAAGUGAAGUUCAAUUGGUA
CGUGGACGGCGUGGAAGUGCACAACGCCAAGACCAAGCCUA
GAGAGGAACAGUACAACAGCACCUACAGAGUGGUGUCCGUG
CUGACCGUGCUGCACCAGGAUUGGCUGAACGGCAAAGAGUA
CAAGUGCAAGGUGUCCAACAAGGCCCUGCCUGCUCCUAUCG
AGAAGACCAUCAGCAAGGCCAAGGGCCAGCCAAGAGAACCC
CAGGUGUACACACUGCCUCCAAGCAGAGAUGAGCUGACCAA
GAACCAGGUGUCCCUGACCUGUCUGGUCAAGGGCUUCUACC
CCUCCGAUAUCGCCGUGGAAUGGGAGAGCAAUGGCCAGCCU
GAGAACAACUACAAGACAACCCCUCCUGUGCUGGACAGCGA
CGGCUCAUUCUUCCUGUACAGCAAGCUGACAGUGGACAAGA
GCAGAUGGCAGCAGGGCAACGUGUUCAGCUGCAGCGUGAUG
CACGAGGCCCUGCACAAUCACUACACCCAGAAGUCCCUGUCU
CUGAGCCCCGGCAAGAUGAGCAUCAGAGGCGUGGGCGGCAA
CGGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCAGCAA
CAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUGGAAG
AUAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGAGAAC
CGCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCAUGAU
CGAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUAGUAG
AGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGGAUUG
CUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAGCAGC
GUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAG
CGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGCU
ACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGCUG
AUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAGAC
CUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAACG
AGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCGAU
CACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUGGC
AGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUGC
GGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGAAC
GACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGAAC
CCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACGGC
CCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUCUG
GCUGGACAUGCAGCACCUGAGCGACGUGGUGCUGUCCAGAG
AGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAGAG
UCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGGCG
GCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGAGG
AAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAGGC
GACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUCA
GAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUCG
GCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGUG
UCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAUG
CUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCAG
AGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCCU
GGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCCG
ACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAGG
GGCGUGCCAUCCAUCGAGGGCGAGGGCAGCGAUAGCAUCUA
CGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGGACC
UGGAAACCCGGCGGAGCUUCGCCGUGCAGCAGGGCCAUUAC
CAGGACCCCAGAGCCAGCGACUACGACCUGCCUAGAGCCUCC
GAUUACGAUCUGCCCAGAAGCCCCUACCCCACCCCUCCACUG
CCUCCCAGAUACCAGCUGCAGAACAUGGAUGUGGAAGCCGG
CUUUCGCGAGGCCGUGUACGCCUCUUUUGUGGCCGGCAUGU
ACAACUACGUCGUGACCCAGCCCCAGGAACGGAUCCCCAAUA
GCCAGCAGGUGGAAGGCAUCCUGCGGGACAUGCUGACCAAC
GGCGACCAGACCUUCCGGGACCUGAUGAAGCGGUGGAACAG AGAGGUGGACCGCGAG
CT875_E_nFC AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 325
GCUGCCUGAUACAACCGGCGAGCCUAAGAGCUGCGACAAGA
CCCACACCUGUCCUCCAUGUCCUGCUCCAGAACUGCUCGGCG
GACCUUCCGUGUUCCUGUUUCCUCCAAAGCCUAAGGACACCC
UGAUGAUCAGCAGAACCCCUGAAGUGACCUGCGUGGUGGUG
GAUGUGUCCCACGAGGAUCCCGAAGUGAAGUUCAAUUGGUA
CGUGGACGGCGUGGAAGUGCACAACGCCAAGACCAAGCCUA
GAGAGGAACAGUACAACAGCACCUACAGAGUGGUGUCCGUG
CUGACCGUGCUGCACCAGGAUUGGCUGAACGGCAAAGAGUA
CAAGUGCAAGGUGUCCAACAAGGCCCUGCCUGCUCCUAUCG
AGAAGACCAUCAGCAAGGCCAAGGGCCAGCCAAGAGAACCC
CAGGUGUACACACUGCCUCCAAGCAGAGAUGAGCUGACCAA
GAACCAGGUGUCCCUGACCUGUCUGGUCAAGGGCUUCUACC
CCUCCGAUAUCGCCGUGGAAUGGGAGAGCAAUGGCCAGCCU
GAGAACAACUACAAGACAACCCCUCCUGUGCUGGACAGCGA
CGGCUCAUUCUUCCUGUACAGCAAGCUGACAGUGGACAAGA
GCAGAUGGCAGCAGGGCAACGUGUUCAGCUGCAGCGUGAUG
CACGAGGCCCUGCACAAUCACUACACCCAGAAGUCCCUGUCU
CUGAGCCCCGGCAAGAUGAGCAUCAGAGGCGUGGGCGGCAA
CGGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCAGCAA
CAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUGGAAG
AUAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGAGAAC
CGCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCAUGAU
CGAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUAGUAG
AGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGGAUUG
CUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAGCAGC
GUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAG
CGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGCU
ACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGCUG
AUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAGAC
CUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAACG
AGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCGAU
CACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUGGC
AGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUGC
GGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGAAC
GACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGAAC
CCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACGGC
CCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUCUG
GCUGGACAUGAGCAACCUGAGCGACGUGGUGCUGUCCAGAG
AGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAGAG
UCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGGCG
GCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGAGG
AAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAGGC
GACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUCA
GAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUCG
GCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGUG
UCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAUG
CUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCAG
AGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCCU
GGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCCG
ACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAGG
GGCGUGCCAUCCAUCGAGGGCGAGGGCAGCGAUAGCAUCUA
CGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGGACC
UGGAAACCCGGCGGAGCUUCGCCGUGCAGCAGGGCCAUUAC
CAGGACCCCAGAGCCAGCGACUACGACCUGCCUAGAGCCUCC
GAUUACGAUCUGCCCAGAAGCCCCUACCCCACCCCUCCACUG
CCUCCCAGAUACCAGCUGCAGAACAUGGAUGUGGAAGCCGG
CUUUCGCGAGGCCGUGUACGCCUCUUUUGUGGCCGGCAUGU
ACAACUACGUCGUGACCCAGCCCCAGGAACGGAUCCCCAAUA
GCCAGCAGGUGGAAGGCAUCCUGCGGGACAUGCUGACCAAC
GGCAGCCAGACCUUCCGGGACCUGAUGAAGCGGUGGAACAG AGAGGUGGACCGCGAG
CT875_E_NGM_nIgK_nGst_cHis
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 326
GCUGCCUGACACCACCGGCAUGAGCCCUAUCCUCGGCUACUG
GAAGAUCAAAGGCCUGGUGCAGCCCACCAGACUGCUGCUGG
AAUACCUGGAAGAGAAGUACGAGGAACACCUGUACGAGCGC
GACGAGGGCGAUAAGUGGCGGAACAAGAAGUUCGAGCUGGG
CCUCGAGUUCCCCAACCUGCCUUACUACAUCGACGGCGACGU
GAAGCUGACCCAGAGCAUGGCCAUCAUCCGGUAUAUCGCCG
ACAAGCACAACAUGCUCGGCGGCUGCCCUAAAGAGCGGGCC
GAGAUUUCUAUGCUGGAAGGCGCCGUGCUGGACAUCAGAUA
CGGCGUGUCCAGAAUCGCCUACAGCAAGGACUUCGAAACCC
UGAAGGUGGACUUCCUGAGCAAGCUGCCCGAGAUGCUGAAG
AUGUUCGAGGACCGGCUGUGCCACAAGACCUACCUGAAUGG
CGACCACGUGACACACCCCGACUUCAUGCUGUACGACGCCCU
GGAUGUGGUGCUGUACAUGGACCCCAUGUGCCUGGACGCCU
UUCCAAAGCUCGUGUGCUUCAAGAAGCGGAUCGAGGCCAUU
CCUCAGAUCGACAAGUACCUGAAGUCCAGCAAGUAUAUCGC
UUGGCCCCUGCAAGGCUGGCAGGCCACAUUUGGAGGCGGAG
AUCACCCUCCUAAGAUGAGCAUCAGAGGCGUGGGCGGCAAC
GGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCAGCAAC
AGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUGGAAGA
UAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGAGAACC
GCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCAUGAUC
GAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUAGUAG
AGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGGAUUG
CUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAGCAGC
GUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAG
CGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGCU
ACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGCUG
AUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAGAC
CUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAACG
AGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCGAU
CACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUGGC
AGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUGC
GGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGAAC
GACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGAAC
CCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACGGC
CCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUCUG
GCUGGACAUGCAGCACCUGAGCGACGUGGUGCUGUCCAGAG
AGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAGAG
UCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGGCG
GCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGAGG
AAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAGGC
GACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUCA
GAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUCG
GCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGUG
UCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAUG
CUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCAG
AGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCCU
GGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCCG
ACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAGG
GGCGUGCCAUCCAUCGAGGGCGAGGGCAGCGAUAGCAUCUA
CGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGGACC
UGGAAACCCGGCGGAGCUUCGCCGUGCAGCAGGGCCAUUAC
CAGGACCCCAGAGCCAGCGACUACGACCUGCCUAGAGCCUCC
GAUUACGAUCUGCCCAGAAGCCCCUACCCCACCCCUCCACUG
CCUCCCAGAUACCAGCUGCAGAACAUGGAUGUGGAAGCCGG
CUUUCGCGAGGCCGUGUACGCCUCUUUUGUGGCCGGCAUGU
ACAACUACGUCGUGACCCAGCCCCAGGAACGGAUCCCCAAUA
GCCAGCAGGUGGAAGGCAUCCUGCGGGACAUGCUGACCAAC
GGCGACCAGACCUUCCGGGACCUGAUGAAGCGGUGGAACAG
AGAGGUGGACCGCGAGCACCACCAUCACCACCAC CT875_E_nIgK_nGst_cHis
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 327
GCUGCCUGACACCACCGGCAUGAGCCCUAUCCUCGGCUACUG
GAAGAUCAAAGGCCUGGUGCAGCCCACCAGACUGCUGCUGG
AAUACCUGGAAGAGAAGUACGAGGAACACCUGUACGAGCGC
GACGAGGGCGAUAAGUGGCGGAACAAGAAGUUCGAGCUGGG
CCUCGAGUUCCCCAACCUGCCUUACUACAUCGACGGCGACGU
GAAGCUGACCCAGAGCAUGGCCAUCAUCCGGUAUAUCGCCG
ACAAGCACAACAUGCUCGGCGGCUGCCCUAAAGAGCGGGCC
GAGAUUUCUAUGCUGGAAGGCGCCGUGCUGGACAUCAGAUA
CGGCGUGUCCAGAAUCGCCUACAGCAAGGACUUCGAAACCC
UGAAGGUGGACUUCCUGAGCAAGCUGCCCGAGAUGCUGAAG
AUGUUCGAGGACCGGCUGUGCCACAAGACCUACCUGAAUGG
CGACCACGUGACACACCCCGACUUCAUGCUGUACGACGCCCU
GGAUGUGGUGCUGUACAUGGACCCCAUGUGCCUGGACGCCU
UUCCAAAGCUCGUGUGCUUCAAGAAGCGGAUCGAGGCCAUU
CCUCAGAUCGACAAGUACCUGAAGUCCAGCAAGUAUAUCGC
UUGGCCCCUGCAAGGCUGGCAGGCCACAUUUGGAGGCGGAG
AUCACCCUCCUAAGAUGAGCAUCAGAGGCGUGGGCGGCAAC
GGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCAGCAAC
AGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUGGAAGA
UAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGAGAACC
GCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCAUGAUC
GAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUAGUAG
AGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGGAUUG
CUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAGCAGC
GUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAG
CGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGCU
ACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGCUG
AUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAGAC
CUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAACG
AGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCGAU
CACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUGGC
AGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUGC
GGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGAAC
GACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGAAC
CCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACGGC
CCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUCUG
GCUGGACAUGAGCAACCUGAGCGACGUGGUGCUGUCCAGAG
AGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAGAG
UCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGGCG
GCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGAGG
AAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAGGC
GACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUCA
GAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUCG
GCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGUG
UCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAUG
CUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCAG
AGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCCU
GGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCCG
ACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAGG
GGCGUGCCAUCCAUCGAGGGCGAGGGCAGCGAUAGCAUCUA
CGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGGACC
UGGAAACCCGGCGGAGCUUCGCCGUGCAGCAGGGCCAUUAC
CAGGACCCCAGAGCCAGCGACUACGACCUGCCUAGAGCCUCC
GAUUACGAUCUGCCCAGAAGCCCCUACCCCACCCCUCCACUG
CCUCCCAGAUACCAGCUGCAGAACAUGGAUGUGGAAGCCGG
CUUUCGCGAGGCCGUGUACGCCUCUUUUGUGGCCGGCAUGU
ACAACUACGUCGUGACCCAGCCCCAGGAACGGAUCCCCAAUA
GCCAGCAGGUGGAAGGCAUCCUGCGGGACAUGCUGACCAAC
GGCAGCCAGACCUUCCGGGACCUGAUGAAGCGGUGGAACAG
AGAGGUGGACCGCGAGCACCACCAUCACCACCAC CT875_E_NGM_nIgK_nGst
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 328
GCUGCCUGACACCACCGGCAUGAGCCCUAUCCUCGGCUACUG
GAAGAUCAAAGGCCUGGUGCAGCCCACCAGACUGCUGCUGG
AAUACCUGGAAGAGAAGUACGAGGAACACCUGUACGAGCGC
GACGAGGGCGAUAAGUGGCGGAACAAGAAGUUCGAGCUGGG
CCUCGAGUUCCCCAACCUGCCUUACUACAUCGACGGCGACGU
GAAGCUGACCCAGAGCAUGGCCAUCAUCCGGUAUAUCGCCG
ACAAGCACAACAUGCUCGGCGGCUGCCCUAAAGAGCGGGCC
GAGAUUUCUAUGCUGGAAGGCGCCGUGCUGGACAUCAGAUA
CGGCGUGUCCAGAAUCGCCUACAGCAAGGACUUCGAAACCC
UGAAGGUGGACUUCCUGAGCAAGCUGCCCGAGAUGCUGAAG
AUGUUCGAGGACCGGCUGUGCCACAAGACCUACCUGAAUGG
CGACCACGUGACACACCCCGACUUCAUGCUGUACGACGCCCU
GGAUGUGGUGCUGUACAUGGACCCCAUGUGCCUGGACGCCU
UUCCAAAGCUCGUGUGCUUCAAGAAGCGGAUCGAGGCCAUU
CCUCAGAUCGACAAGUACCUGAAGUCCAGCAAGUAUAUCGC
UUGGCCCCUGCAAGGCUGGCAGGCCACAUUUGGAGGCGGAG
AUCACCCUCCUAAGAUGAGCAUCAGAGGCGUGGGCGGCAAC
GGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCAGCAAC
AGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUGGAAGA
UAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGAGAACC
GCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCAUGAUC
GAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUAGUAG
AGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGGAUUG
CUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAGCAGC
GUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAG
CGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGCU
ACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGCUG
AUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAGAC
CUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAACG
AGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCGAU
CACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUGGC
AGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUGC
GGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGAAC
GACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGAAC
CCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACGGC
CCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUCUG
GCUGGACAUGCAGCACCUGAGCGACGUGGUGCUGUCCAGAG
AGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAGAG
UCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGGCG
GCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGAGG
AAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAGGC
GACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUCA
GAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUCG
GCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGUG
UCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAUG
CUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCAG
AGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCCU
GGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCCG
ACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAGG
GGCGUGCCAUCCAUCGAGGGCGAGGGCAGCGAUAGCAUCUA
CGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGGACC
UGGAAACCCGGCGGAGCUUCGCCGUGCAGCAGGGCCAUUAC
CAGGACCCCAGAGCCAGCGACUACGACCUGCCUAGAGCCUCC
GAUUACGAUCUGCCCAGAAGCCCCUACCCCACCCCUCCACUG
CCUCCCAGAUACCAGCUGCAGAACAUGGAUGUGGAAGCCGG
CUUUCGCGAGGCCGUGUACGCCUCUUUUGUGGCCGGCAUGU
ACAACUACGUCGUGACCCAGCCCCAGGAACGGAUCCCCAAUA
GCCAGCAGGUGGAAGGCAUCCUGCGGGACAUGCUGACCAAC
GGCGACCAGACCUUCCGGGACCUGAUGAAGCGGUGGAACAG AGAGGUGGACCGCGAG
CT875_E_nIgK_nGst AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 329
GCUGCCUGACACCACCGGCAUGAGCCCUAUCCUCGGCUACUG
GAAGAUCAAAGGCCUGGUGCAGCCCACCAGACUGCUGCUGG
AAUACCUGGAAGAGAAGUACGAGGAACACCUGUACGAGCGC
GACGAGGGCGAUAAGUGGCGGAACAAGAAGUUCGAGCUGGG
CCUCGAGUUCCCCAACCUGCCUUACUACAUCGACGGCGACGU
GAAGCUGACCCAGAGCAUGGCCAUCAUCCGGUAUAUCGCCG
ACAAGCACAACAUGCUCGGCGGCUGCCCUAAAGAGCGGGCC
GAGAUUUCUAUGCUGGAAGGCGCCGUGCUGGACAUCAGAUA
CGGCGUGUCCAGAAUCGCCUACAGCAAGGACUUCGAAACCC
UGAAGGUGGACUUCCUGAGCAAGCUGCCCGAGAUGCUGAAG
AUGUUCGAGGACCGGCUGUGCCACAAGACCUACCUGAAUGG
CGACCACGUGACACACCCCGACUUCAUGCUGUACGACGCCCU
GGAUGUGGUGCUGUACAUGGACCCCAUGUGCCUGGACGCCU
UUCCAAAGCUCGUGUGCUUCAAGAAGCGGAUCGAGGCCAUU
CCUCAGAUCGACAAGUACCUGAAGUCCAGCAAGUAUAUCGC
UUGGCCCCUGCAAGGCUGGCAGGCCACAUUUGGAGGCGGAG
AUCACCCUCCUAAGAUGAGCAUCAGAGGCGUGGGCGGCAAC
GGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCAGCAAC
AGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUGGAAGA
UAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGAGAACC
GCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCAUGAUC
GAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUAGUAG
AGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGGAUUG
CUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAGCAGC
GUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAGAG
CGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGCU
ACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGCUG
AUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAGAC
CUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAACG
AGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCGAU
CACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUGGC
AGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUGC
GGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGAAC
GACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGAAC
CCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACGGC
CCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUCUG
GCUGGACAUGAGCAACCUGAGCGACGUGGUGCUGUCCAGAG
AGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAGAG
UCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGGCG
GCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGAGG
AAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAGGC
GACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUCA
GAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUCG
GCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGUG
UCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAUG
CUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCAG
AGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCCU
GGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCCG
ACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAGG
GGCGUGCCAUCCAUCGAGGGCGAGGGCAGCGAUAGCAUCUA
CGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGGACC
UGGAAACCCGGCGGAGCUUCGCCGUGCAGCAGGGCCAUUAC
CAGGACCCCAGAGCCAGCGACUACGACCUGCCUAGAGCCUCC
GAUUACGAUCUGCCCAGAAGCCCCUACCCCACCCCUCCACUG
CCUCCCAGAUACCAGCUGCAGAACAUGGAUGUGGAAGCCGG
CUUUCGCGAGGCCGUGUACGCCUCUUUUGUGGCCGGCAUGU
ACAACUACGUCGUGACCCAGCCCCAGGAACGGAUCCCCAAUA
GCCAGCAGGUGGAAGGCAUCCUGCGGGACAUGCUGACCAAC
GGCAGCCAGACCUUCCGGGACCUGAUGAAGCGGUGGAACAG AGAGGUGGACCGCGAG
CT875_E_574_NGM_nIgK_cHis AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG
330 GCUGCCUGACACCACCGGCAUGAGCAUCAGAGGCGUGGGCG
GCAACGGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCA
GCAACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUG
GAAGAUAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGA
GAACCGCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCA
UGAUCGAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUA
GUAGAGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGG
AUUGCUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAG
CAGCGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGA
GAGCGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCG
GCUACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGC
UGAUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAG
ACCUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAA
CGAGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCG
AUCACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUG
GCAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGU
GCGGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGA
ACGACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GCCCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUC
UGGCUGGACAUGCAGCACCUGAGCGACGUGGUGCUGUCCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAG
AGUCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGG
CGGCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGA
GGAAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUC
AGAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUC
GGCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGU
GUCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAU
GCUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCA
GAGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCC
UGGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCC
GACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAG
GGGCGUGCCAUCCAUCGAGGGCGAGGGCAGCGAUAGCAUCU
ACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGGAC
CUGGAAACCCGGCGGAGCUUCGCCGUGCAGCAGGGCCAUUA
CCAGGACCCCAGAGCCAGCGACUACGACCUGCCUAGAGCCUC
CGAUUACGAUCUGCCCAGAAGCCCCUACCCCACCCCUCCACU
GCCUCCCAGAUACCAGCUGCAGAACAUGGAUGUGGAAGCCG
GCUUUCGCGAGGCCGUGUACGCCUCUUUUGUGGCCGGCAUG
UACAACUACGUCGUGACCCAGCCCCAGGAACGGAUCCCCAAU
AGCCAGCAGGUGGAAGGCAUCCUGCGGGACAUGCUGACCAA CGGCGACCACCACCAUCACCACCAC
CT875_E_458_NGM_nIgK_cHis AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG
331 GCUGCCUGACACCACCGGCAUGAGCAUCAGAGGCGUGGGCG
GCAACGGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCA
GCAACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUG
GAAGAUAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGA
GAACCGCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCA
UGAUCGAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUA
GUAGAGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGG
AUUGCUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAG
CAGCGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGA
GAGCGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCG
GCUACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGC
UGAUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAG
ACCUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAA
CGAGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCG
AUCACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUG
GCAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGU
GCGGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGA
ACGACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GCCCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUC
UGGCUGGACAUGCAGCACCUGAGCGACGUGGUGCUGUCCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAG
AGUCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGG
CGGCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGA
GGAAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUC
AGAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUC
GGCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGU
GUCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAU
GCUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCA
GAGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCC
UGGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCC
GACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAG
GGGCGUGCCAUCCAUCGAGGGCGAGGGCAGCCACCACCAUCA CCACCAC
CT875_E_574_nIgK_cHis AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 332
GCUGCCUGACACCACCGGCAUGAGCAUCAGAGGCGUGGGCG
GCAACGGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCA
GCAACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUG
GAAGAUAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGA
GAACCGCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCA
UGAUCGAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUA
GUAGAGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGG
AUUGCUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAG
CAGCGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGA
GAGCGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCG
GCUACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGC
UGAUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAG
ACCUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAA
CGAGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCG
AUCACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUG
GCAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGU
GCGGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGA
ACGACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GCCCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUC
UGGCUGGACAUGAGCAACCUGAGCGACGUGGUGCUGUCCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAG
AGUCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGG
CGGCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGA
GGAAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUC
AGAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUC
GGCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGU
GUCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAU
GCUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCA
GAGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCC
UGGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCC
GACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAG
GGGCGUGCCAUCCAUCGAGGGCGAGGGCAGCGAUAGCAUCU
ACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGGAC
CUGGAAACCCGGCGGAGCUUCGCCGUGCAGCAGGGCCAUUA
CCAGGACCCCAGAGCCAGCGACUACGACCUGCCUAGAGCCUC
CGAUUACGAUCUGCCCAGAAGCCCCUACCCCACCCCUCCACU
GCCUCCCAGAUACCAGCUGCAGAACAUGGAUGUGGAAGCCG
GCUUUCGCGAGGCCGUGUACGCCUCUUUUGUGGCCGGCAUG
UACAACUACGUCGUGACCCAGCCCCAGGAACGGAUCCCCAAU
AGCCAGCAGGUGGAAGGCAUCCUGCGGGACAUGCUGACCAA CGGCAGCCACCACCAUCACCACCAC
CT875_E_458_nIgK_cHis AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 333
GCUGCCUGACACCACCGGCAUGAGCAUCAGAGGCGUGGGCG
GCAACGGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCA
GCAACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUG
GAAGAUAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGA
GAACCGCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCA
UGAUCGAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUA
GUAGAGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGG
AUUGCUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAG
CAGCGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGA
GAGCGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCG
GCUACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGC
UGAUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAG
ACCUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAA
CGAGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCG
AUCACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUG
GCAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGU
GCGGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGA
ACGACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GCCCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUC
UGGCUGGACAUGAGCAACCUGAGCGACGUGGUGCUGUCCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAG
AGUCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGG
CGGCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGA
GGAAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUC
AGAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUC
GGCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGU
GUCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAU
GCUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCA
GAGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCC
UGGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCC
GACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAG
GGGCGUGCCAUCCAUCGAGGGCGAGGGCAGCCACCACCAUCA CCACCAC
CT875_E_574_NGM_nIgK AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 334
GCUGCCUGACACCACCGGCAUGAGCAUCAGAGGCGUGGGCG
GCAACGGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCA
GCAACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUG
GAAGAUAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGA
GAACCGCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCA
UGAUCGAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUA
GUAGAGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGG
AUUGCUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAG
CAGCGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGA
GAGCGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCG
GCUACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGC
UGAUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAG
ACCUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAA
CGAGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCG
AUCACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUG
GCAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGU
GCGGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGA
ACGACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GCCCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUC
UGGCUGGACAUGCAGCACCUGAGCGACGUGGUGCUGUCCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAG
AGUCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGG
CGGCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGA
GGAAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUC
AGAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUC
GGCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGU
GUCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAU
GCUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCA
GAGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCC
UGGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCC
GACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAG
GGGCGUGCCAUCCAUCGAGGGCGAGGGCAGCGAUAGCAUCU
ACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGGAC
CUGGAAACCCGGCGGAGCUUCGCCGUGCAGCAGGGCCAUUA
CCAGGACCCCAGAGCCAGCGACUACGACCUGCCUAGAGCCUC
CGAUUACGAUCUGCCCAGAAGCCCCUACCCCACCCCUCCACU
GCCUCCCAGAUACCAGCUGCAGAACAUGGAUGUGGAAGCCG
GCUUUCGCGAGGCCGUGUACGCCUCUUUUGUGGCCGGCAUG
UACAACUACGUCGUGACCCAGCCCCAGGAACGGAUCCCCAAU
AGCCAGCAGGUGGAAGGCAUCCUGCGGGACAUGCUGACCAA CGGCGAC
CT875_E_458_NGM_nIgK AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 335
GCUGCCUGACACCACCGGCAUGAGCAUCAGAGGCGUGGGCG
GCAACGGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCA
GCAACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUG
GAAGAUAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGA
GAACCGCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCA
UGAUCGAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUA
GUAGAGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGG
AUUGCUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAG
CAGCGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGA
GAGCGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCG
GCUACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGC
UGAUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAG
ACCUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAA
CGAGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCG
AUCACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUG
GCAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGU
GCGGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGA
ACGACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GCCCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUC
UGGCUGGACAUGCAGCACCUGAGCGACGUGGUGCUGUCCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAG
AGUCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGG
CGGCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGA
GGAAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUC
AGAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUC
GGCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGU
GUCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAU
GCUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCA
GAGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCC
UGGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCC
GACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAG
GGGCGUGCCAUCCAUCGAGGGCGAGGGCAGC CT875_E_574_nIgK
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 336
GCUGCCUGACACCACCGGCAUGAGCAUCAGAGGCGUGGGCG
GCAACGGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCA
GCAACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUG
GAAGAUAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGA
GAACCGCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCA
UGAUCGAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUA
GUAGAGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGG
AUUGCUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAG
CAGCGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGA
GAGCGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCG
GCUACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGC
UGAUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAG
ACCUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAA
CGAGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCG
AUCACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUG
GCAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGU
GCGGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGA
ACGACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GCCCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUC
UGGCUGGACAUGAGCAACCUGAGCGACGUGGUGCUGUCCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAG
AGUCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGG
CGGCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGA
GGAAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUC
AGAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUC
GGCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGU
GUCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAU
GCUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCA
GAGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCC
UGGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCC
GACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAG
GGGCGUGCCAUCCAUCGAGGGCGAGGGCAGCGAUAGCAUCU
ACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGGAC
CUGGAAACCCGGCGGAGCUUCGCCGUGCAGCAGGGCCAUUA
CCAGGACCCCAGAGCCAGCGACUACGACCUGCCUAGAGCCUC
CGAUUACGAUCUGCCCAGAAGCCCCUACCCCACCCCUCCACU
GCCUCCCAGAUACCAGCUGCAGAACAUGGAUGUGGAAGCCG
GCUUUCGCGAGGCCGUGUACGCCUCUUUUGUGGCCGGCAUG
UACAACUACGUCGUGACCCAGCCCCAGGAACGGAUCCCCAAU
AGCCAGCAGGUGGAAGGCAUCCUGCGGGACAUGCUGACCAA CGGCAGC CT875_E_458_nIgK
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 337
GCUGCCUGACACCACCGGCAUGAGCAUCAGAGGCGUGGGCG
GCAACGGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCA
GCAACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUG
GAAGAUAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGA
GAACCGCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCA
UGAUCGAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUA
GUAGAGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGG
AUUGCUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAG
CAGCGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGA
GAGCGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCG
GCUACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGC
UGAUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAG
ACCUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAA
CGAGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCG
AUCACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUG
GCAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGU
GCGGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGA
ACGACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GCCCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUC
UGGCUGGACAUGAGCAACCUGAGCGACGUGGUGCUGUCCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAG
AGUCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGG
CGGCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGA
GGAAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUC
AGAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUC
GGCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGU
GUCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAU
GCUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCA
GAGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCC
UGGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCC
GACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAG
GGGCGUGCCAUCCAUCGAGGGCGAGGGCAGC CT875_E_1_574_NGM_nIgK_cHis
AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 338
GCUGCCUGAUACCACCGGCAUGUCUAUCAGAGGCGUUGGCG
GCAACGGCAACAGCAGAAUCCCUAGCCAUAAUGGCGACGGC
AGCAACAGGCGGAGCCAGAAUACCAAGGGCAACAACAAGGU
GGAAGAUCGCGUGUGCAGCCUGUACAGCUCCAGAAGCAACG
AGAACCGCGAGAGCCCUUAUGCCGUGGUGGAUGUGUCCAGC
AUGAUCGAGAGCACCCCUACCAGCGGCGAGACAACAAGAGC
UAGUAGAGGCGUGCUGAGCCGGUUUCAGAGAGGCCUCGUUC
GGAUCGCUGACAAAGUGCGGAGAGCCGUGCAGUGUGCCUGG
UCUAGUGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGC
CGAGAGCGGAUCUUCUAGCAGAACAGCUAGAGGCGCCAGCA
GCGGCUACAGAGAGUAUUCUCCAUCUGCCGCCAGAGGCCUG
CGGCUGAUGUUUACAGAUUUCUGGCGGACCCGGGUGCUGAG
ACAGACAUCUCCUAUGGCUGGCGUGUUCGGCAACCUGGAUG
UGAAUGAGGCCAGACUGAUGGCCGCCUACACAAGCGAAUGU
GCCGAUCACCUGGAAGCCAAAGAGCUGGCUGGACCUGACGG
UGUUGCCGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGA
GAGUGCGGGACCUGCAGGAUAAGGGCGCUGCUAGAAAGCUG
CUGAACGACCCUCUGGGCAGAAGAACCCCUAACUACCAGAGC
AAGAACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUA
CGACGGACCCCAGGUGGCCAACCUGCAGAAUGUGGAUACAG
GCUUCUGGCUGGAUAUGCAGCACCUGAGCGACGUGGUGCUG
UCCAGAGAGAUCCAGACAGGCCUGAGAGCCAGAGCCACACU
GGAAGAGUCCAUGCCUAUGCUCGAGAACCUGGAAGAGAGAU
UCCGGCGGCUGCAAGAGACAUGUGACGCCGCCAGAACCGAG
AUCGAGGAAAGCGGCUGGACAAGAGAAAGCGCCUCCAGAAU
GGAAGGCGACGAAGCCCAAGGACCUAGCAGAGUGCAGCAGG
CCUUCCAGAGCUUCGUGAACGAGUGCAACAGCAUCGAGUUC
AGCUUCGGCUCCUUCGGCGAACAUGUGCGGGUGCUGUGUGC
CAGAGUUAGCAGAGGACUUGCUGCCGCUGGCGAGGCCAUCA
GAAGAUGCUUCUCUUGCUGCAAGGGCAGCACCCACAGAUAC
GCCCCUAGAGAUGAUCUGAGCCCUGAGGGCGCUUCUCUGGC
CGAAACACUGGCCAGAUUCGCCGACGAUAUGGGCAUUGAAA
GAGGCGCCGACGGAACCUACGACAUCCCUCUGGUGGACGAU
UGGAGAAGGGGCGUGCCAUCUAUCGAAGGCGAGGGCAGCGA
UAGCAUCUACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGA
ACAUGGACCUGGAAACCCGGCGGAGCUUUGCCGUGCAGCAA
GGCCAUUACCAGGAUCCUAGAGCCAGCGACUACGACCUGCCU
AGAGCCUCCGAUUAUGAUCUGCCUCGGAGCCCCUAUCCUACA
CCUCCUCUGCCUCCAAGAUACCAGCUUCAGAAUAUGGACGU
GGAAGCCGGAUUCCGCGAGGCCGUGUAUGCUAGCUUUGUGG
CCGGCAUGUACAACUACGUGGUCACCCAGCCUCAAGAGAGA
AUCCCCAACAGCCAGCAGGUCGAGGGCAUCCUGAGAGAUAU
GCUGACCAACGGCGACCACCACCAUCACCAUCAU CT875_E_NGM_nFc
AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 339
GCUGCCUGAUACAACCGGCGAGCCUAAGAGCUGCGACAAGA
CCCACACCUGUCCUCCAUGUCCUGCUCCAGAACUGCUCGGCG
GACCUUCCGUGUUCCUGUUUCCUCCAAAGCCUAAGGACACCC
UGAUGAUCAGCAGAACCCCUGAAGUGACCUGCGUGGUGGUG
GAUGUGUCCCACGAGGAUCCCGAAGUGAAGUUCAAUUGGUA
CGUGGACGGCGUGGAAGUGCACAACGCCAAGACCAAGCCUA
GAGAGGAACAGUACAACAGCACCUACAGAGUGGUGUCCGUG
CUGACCGUGCUGCACCAGGAUUGGCUGAACGGCAAAGAGUA
CAAGUGCAAGGUGUCCAACAAGGCCCUGCCUGCUCCUAUCG
AGAAGACCAUCAGCAAGGCCAAGGGCCAGCCAAGAGAACCC
CAGGUGUACACACUGCCUCCAAGCAGAGAUGAGCUGACCAA
GAACCAGGUGUCCCUGACCUGUCUGGUCAAGGGCUUCUACC
CCUCCGAUAUCGCCGUGGAAUGGGAGAGCAAUGGCCAGCCU
GAGAACAACUACAAGACAACCCCUCCUGUGCUGGACAGCGA
CGGCUCAUUCUUCCUGUACAGCAAGCUGACAGUGGACAAGA
GCAGAUGGCAGCAGGGCAACGUGUUCAGCUGCAGCGUGAUG
CACGAGGCCCUGCACAAUCACUACACCCAGAAGUCCCUGUCU
CUGAGCCCCGGCAAGAUGAGCAUCAGAGGCGUUGGCGGCAA
CGGCAACAGCAGAAUCCCUAGCCAUAAUGGCGACGGCAGCA
ACAGGCGGAGCCAGAAUACCAAGGGCAACAACAAGGUGGAA
GAUCGCGUGUGCAGCCUGUACUCCAGCAGAAGCAACGAGAA
CCGCGAGAGCCCUUAUGCCGUGGUCGACGUGUCCAGCAUGA
UCGAGAGCACACCUACCAGCGGCGAGACAACCAGAGCUAGU
AGAGGCGUGCUGAGCCGGUUUCAGAGAGGCCUCGUUCGGAU
CGCUGACAAAGUGCGGAGAGCCGUGCAGUGUGCCUGGUCUA
GUGUGUCCACCAGCAGAUCCUCUGCCACAAGAGCCGCCGAGU
CUGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGC
UACAGAGAGUAUUCUCCAUCUGCCGCCAGAGGCCUGCGGCU
GAUGUUUACAGAUUUCUGGCGGACCCGGGUGCUGAGACAGA
CAUCUCCUAUGGCUGGCGUGUUCGGCAACCUGGAUGUGAAU
GAGGCCAGACUGAUGGCCGCCUACACAAGCGAAUGUGCCGA
UCACCUGGAAGCCAAAGAGCUGGCUGGACCUGACGGUGUUG
CCGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUG
CGGGACCUGCAGGAUAAGGGCGCUGCUAGAAAGCUGCUGAA
CGACCCUCUGGGCAGAAGAACCCCUAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GACCUCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUC
UGGCUGGAUAUGCAGCACCUGUCCGAUGUGGUGCUGUCCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACACUGGAAG
AGUCCAUGCCUAUGCUCGAGAACCUGGAAGAGAGAUUCCGG
CGGCUGCAAGAGACAUGUGACGCCGCCAGAACCGAGAUCGA
GGAAAGCGGCUGGACCAGAGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAAGGACCUAGCAGAGUGCAGCAGGCCUUC
CAGAGCUUCGUGAACGAGUGCAACAGCAUCGAGUUCAGCUU
CGGCUCCUUCGGCGAACAUGUGCGGGUGCUGUGUGCCAGAG
UUAGCAGAGGACUUGCUGCCGCUGGCGAGGCCAUCAGAAGA
UGCUUCUCUUGCUGCAAGGGCAGCACCCACAGAUACGCCCCU
AGAGAUGAUCUGAGCCCUGAGGGCGCAUCUCUGGCCGAAAC
ACUGGCCAGAUUCGCCGACGAUAUGGGCAUUGAAAGAGGCG
CCGACGGAACCUACGACAUCCCUCUGGUGGACGAUUGGAGA
AGGGGCGUGCCAUCUAUCGAAGGCGAGGGCAGCGAUAGCAU
CUACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGG
ACCUGGAAACCCGGCGGAGCUUCGCUGUUCAGCAGGGCCAU
UACCAGGAUCCUAGAGCCAGCGACUACGACCUGCCUAGAGCC
UCCGAUUAUGAUCUGCCUCGGAGCCCCUAUCCUACACCUCCA
CUGCCACCUAGAUACCAGCUCCAGAAUAUGGACGUGGAAGC
CGGAUUCCGCGAGGCCGUGUAUGCUAGCUUUGUGGCCGGCA
UGUACAACUACGUGGUCACCCAGCCUCAAGAGCGGAUCCCCA
AUUCUCAGCAGGUCGAGGGCAUCCUGAGGGACAUGCUGACC
AAUGGCGACCAGACCUUCCGGGACCUGAUGAAGAGAUGGAA CAGAGAGGUGGACAGAGAG
CT875_E_NGM_nFc_cHis AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 340
GCUGCCUGAUACAACCGGCGAGCCUAAGAGCUGCGACAAGA
CCCACACCUGUCCUCCAUGUCCUGCUCCAGAACUGCUCGGCG
GACCUUCCGUGUUCCUGUUUCCUCCAAAGCCUAAGGACACCC
UGAUGAUCAGCAGAACCCCUGAAGUGACCUGCGUGGUGGUG
GAUGUGUCCCACGAGGAUCCCGAAGUGAAGUUCAAUUGGUA
CGUGGACGGCGUGGAAGUGCACAACGCCAAGACCAAGCCUA
GAGAGGAACAGUACAACAGCACCUACAGAGUGGUGUCCGUG
CUGACCGUGCUGCACCAGGAUUGGCUGAACGGCAAAGAGUA
CAAGUGCAAGGUGUCCAACAAGGCCCUGCCUGCUCCUAUCG
AGAAGACCAUCAGCAAGGCCAAGGGCCAGCCAAGAGAACCC
CAGGUGUACACACUGCCUCCAAGCAGAGAUGAGCUGACCAA
GAACCAGGUGUCCCUGACCUGUCUGGUCAAGGGCUUCUACC
CCUCCGAUAUCGCCGUGGAAUGGGAGAGCAAUGGCCAGCCU
GAGAACAACUACAAGACAACCCCUCCUGUGCUGGACAGCGA
CGGCUCAUUCUUCCUGUACAGCAAGCUGACAGUGGACAAGA
GCAGAUGGCAGCAGGGCAACGUGUUCAGCUGCAGCGUGAUG
CACGAGGCCCUGCACAAUCACUACACCCAGAAGUCCCUGUCU
CUGAGCCCCGGCAAGAUGAGCAUCAGAGGCGUUGGCGGCAA
CGGCAACAGCAGAAUCCCUAGCCAUAAUGGCGACGGCAGCA
ACAGGCGGAGCCAGAAUACCAAGGGCAACAACAAGGUGGAA
GAUCGCGUGUGCAGCCUGUACUCCAGCAGAAGCAACGAGAA
CCGCGAGAGCCCUUAUGCCGUGGUCGACGUGUCCAGCAUGA
UCGAGAGCACACCUACCAGCGGCGAGACAACCAGAGCUAGU
AGAGGCGUGCUGAGCCGGUUUCAGAGAGGCCUCGUUCGGAU
CGCUGACAAAGUGCGGAGAGCCGUGCAGUGUGCCUGGUCUA
GUGUGUCCACCAGCAGAUCCUCUGCCACAAGAGCCGCCGAGU
CUGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGC
UACAGAGAGUAUUCUCCAUCUGCCGCCAGAGGCCUGCGGCU
GAUGUUUACAGAUUUCUGGCGGACCCGGGUGCUGAGACAGA
CAUCUCCUAUGGCUGGCGUGUUCGGCAACCUGGAUGUGAAU
GAGGCCAGACUGAUGGCCGCCUACACAAGCGAAUGUGCCGA
UCACCUGGAAGCCAAAGAGCUGGCUGGACCUGACGGUGUUG
CCGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUG
CGGGACCUGCAGGAUAAGGGCGCUGCUAGAAAGCUGCUGAA
CGACCCUCUGGGCAGAAGAACCCCUAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GACCUCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUC
UGGCUGGAUAUGCAGCACCUGUCCGAUGUGGUGCUGUCCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACACUGGAAG
AGUCCAUGCCUAUGCUCGAGAACCUGGAAGAGAGAUUCCGG
CGGCUGCAAGAGACAUGUGACGCCGCCAGAACCGAGAUCGA
GGAAAGCGGCUGGACCAGAGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAAGGACCUAGCAGAGUGCAGCAGGCCUUC
CAGAGCUUCGUGAACGAGUGCAACAGCAUCGAGUUCAGCUU
CGGCUCCUUCGGCGAACAUGUGCGGGUGCUGUGUGCCAGAG
UUAGCAGAGGACUUGCUGCCGCUGGCGAGGCCAUCAGAAGA
UGCUUCUCUUGCUGCAAGGGCAGCACCCACAGAUACGCCCCU
AGAGAUGAUCUGAGCCCUGAGGGCGCAUCUCUGGCCGAAAC
ACUGGCCAGAUUCGCCGACGAUAUGGGCAUUGAAAGAGGCG
CCGACGGAACCUACGACAUCCCUCUGGUGGACGAUUGGAGA
AGGGGCGUGCCAUCUAUCGAAGGCGAGGGCAGCGAUAGCAU
CUACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGG
ACCUGGAAACCCGGCGGAGCUUCGCUGUUCAGCAGGGCCAU
UACCAGGAUCCUAGAGCCAGCGACUACGACCUGCCUAGAGCC
UCCGAUUAUGAUCUGCCUCGGAGCCCCUAUCCUACACCUCCA
CUGCCACCUAGAUACCAGCUCCAGAAUAUGGACGUGGAAGC
CGGAUUCCGCGAGGCCGUGUAUGCUAGCUUUGUGGCCGGCA
UGUACAACUACGUGGUCACCCAGCCUCAAGAGCGGAUCCCCA
AUUCUCAGCAGGUCGAGGGCAUCCUGAGGGACAUGCUGACC
AAUGGCGACCAGACCUUCCGGGACCUGAUGAAGAGAUGGAA
CAGAGAGGUGGACCGCGAGCACCACCACCAUCACCAU CT875_E_1_574_NGM_nIgK_nGST
AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 341
GCUGCCUGAUACCACAGGCAUGAGCCCUAUCCUCGGCUACUG
GAAGAUCAAAGGCCUGGUGCAGCCCACCAGACUGCUGCUGG
AAUACCUGGAAGAGAAGUACGAGGAACACCUGUACGAGCGC
GACGAGGGCGAUAAGUGGCGGAACAAGAAGUUCGAGCUGGG
CCUCGAGUUCCCCAACCUGCCUUACUACAUCGACGGCGACGU
GAAGCUGACCCAGAGCAUGGCCAUCAUCCGGUAUAUCGCCG
ACAAGCACAACAUGCUCGGCGGCUGCCCUAAAGAGCGGGCC
GAGAUUUCUAUGCUGGAAGGCGCCGUGCUGGACAUCAGAUA
CGGCGUGUCCAGAAUCGCCUACAGCAAGGACUUCGAAACCC
UGAAGGUGGACUUCCUGAGCAAGCUGCCCGAGAUGCUGAAG
AUGUUCGAGGACCGGCUGUGCCACAAGACCUACCUGAAUGG
CGACCACGUGACACACCCCGACUUCAUGCUGUACGACGCCCU
GGAUGUGGUGCUGUACAUGGACCCCAUGUGCCUGGACGCCU
UUCCAAAGCUCGUGUGCUUCAAGAAGCGGAUCGAGGCCAUU
CCUCAGAUCGACAAGUACCUGAAGUCCAGCAAGUAUAUCGC
UUGGCCCCUGCAAGGCUGGCAGGCCACAUUUGGAGGCGGAG
AUCACCCUCCUAAGAUGAGCAUCAGAGGCGUCGGCGGCAAC
GGCAACAGCAGAAUCCCUUCUCACAAUGGCGACGGCAGCAA
CAGGCGGAGCCAGAAUACCAAGGGCAACAACAAGGUGGAAG
AUCGCGUGUGCAGCCUGUACAGCUCCAGAAGCAACGAGAAC
CGCGAGAGCCCUUAUGCCGUGGUGGAUGUGUCCAGCAUGAU
CGAGAGCACCCCUACCAGCGGCGAGACAACAAGAGCUAGUA
GAGGCGUGCUGAGCCGGUUUCAGAGAGGCCUCGUUCGGAUU
GCCGACAAAGUGCGGAGAGCCGUGCAGUGUGCUUGGAGCAG
UGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAAU
CUGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGC
UACAGAGAGUAUUCUCCAUCUGCCGCCAGAGGCCUGCGGCU
GAUGUUUACAGAUUUCUGGCGGACCCGGGUGCUGAGACAGA
CAUCUCCUAUGGCUGGCGUGUUCGGCAACCUGGACGUGAAC
GAAGCCAGACUGAUGGCCGCCUACACAAGCGAGUGUGCCGA
UCACCUGGAAGCCAAAGAACUGGCCGGACCUGAUGGCGUGG
CAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUG
CGGGACCUGCAGGAUAAGGGCGCUGCUAGAAAGCUGCUGAA
CGACCCUCUGGGCAGAAGAACCCCUAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GACCCCAGGUGGCCAACCUGCAGAAUGUGGAUACAGGCUUC
UGGCUGGACAUGCAGCACCUGUCUGAUGUGGUCCUGAGCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACACUGGAAG
AGUCCAUGCCUAUGCUCGAGAAUCUGGAAGAACGGUUCAGA
CGGCUGCAAGAGACAUGCGACGCCGCCAGAACAGAGAUCGA
GGAAAGCGGCUGGACCAGAGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAAGGACCUAGCAGAGUGCAGCAGGCCUUC
CAGAGCUUCGUGAACGAGUGCAACAGCAUCGAGUUCAGCUU
CGGCUCCUUCGGCGAACAUGUGCGGGUGCUGUGUGCCAGAG
UUAGCAGAGGACUUGCUGCCGCUGGCGAGGCCAUCAGAAGA
UGCUUCUCUUGCUGCAAGGGCAGCACCCACAGAUACGCCCCU
AGAGAUGAUCUGAGCCCUGAGGGCGCAUCUCUGGCCGAAAC
ACUGGCCAGAUUUGCCGACGACAUGGGCAUUGAAAGAGGCG
CCGACGGAACCUACGACAUCCCUCUGGUGGACGAUUGGAGA
AGGGGCGUGCCAUCUAUCGAAGGCGAGGGCAGCGAUAGCAU
CUACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGG
ACCUGGAAACCCGGCGGAGCUUUGCCGUGCAACAGGGCCAU
UACCAGGAUCCUAGAGCCAGCGACUACGACCUGCCUAGAGCC
UCCGAUUAUGAUCUGCCUCGGAGCCCCUAUCCUACACCUCCU
CUGCCUCCAAGAUACCAGCUUCAGAAUAUGGACGUGGAAGC
CGGAUUCCGCGAGGCCGUGUAUGCUAGCUUUGUGGCCGGCA
UGUACAACUACGUGGUCACCCAGCCUCAAGAGAGAAUCCCC
AACAGCCAGCAGGUCGAGGGCAUCCUGAGAGAUAUGCUGAC CAACGGCGAC
CT875_E_1_574_NGM_nIgK_nGST_cHis
AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 342
GCUGCCUGAUACCACAGGCAUGAGCCCUAUCCUCGGCUACUG
GAAGAUCAAAGGCCUGGUGCAGCCCACCAGACUGCUGCUGG
AAUACCUGGAAGAGAAGUACGAGGAACACCUGUACGAGCGC
GACGAGGGCGAUAAGUGGCGGAACAAGAAGUUCGAGCUGGG
CCUCGAGUUCCCCAACCUGCCUUACUACAUCGACGGCGACGU
GAAGCUGACCCAGAGCAUGGCCAUCAUCCGGUAUAUCGCCG
ACAAGCACAACAUGCUCGGCGGCUGCCCUAAAGAGCGGGCC
GAGAUUUCUAUGCUGGAAGGCGCCGUGCUGGACAUCAGAUA
CGGCGUGUCCAGAAUCGCCUACAGCAAGGACUUCGAAACCC
UGAAGGUGGACUUCCUGAGCAAGCUGCCCGAGAUGCUGAAG
AUGUUCGAGGACCGGCUGUGCCACAAGACCUACCUGAAUGG
CGACCACGUGACACACCCCGACUUCAUGCUGUACGACGCCCU
GGAUGUGGUGCUGUACAUGGACCCCAUGUGCCUGGACGCCU
UUCCAAAGCUCGUGUGCUUCAAGAAGCGGAUCGAGGCCAUU
CCUCAGAUCGACAAGUACCUGAAGUCCAGCAAGUAUAUCGC
UUGGCCCCUGCAAGGCUGGCAGGCCACAUUUGGAGGCGGAG
AUCACCCUCCUAAGAUGAGCAUCAGAGGCGUCGGCGGCAAC
GGCAACAGCAGAAUCCCUUCUCACAAUGGCGACGGCAGCAA
CAGGCGGAGCCAGAAUACCAAGGGCAACAACAAGGUGGAAG
AUCGCGUGUGCAGCCUGUACAGCUCCAGAAGCAACGAGAAC
CGCGAGAGCCCUUAUGCCGUGGUGGAUGUGUCCAGCAUGAU
CGAGAGCACCCCUACCAGCGGCGAGACAACAAGAGCUAGUA
GAGGCGUGCUGAGCCGGUUUCAGAGAGGCCUCGUUCGGAUU
GCCGACAAAGUGCGGAGAGCCGUGCAGUGUGCUUGGAGCAG
UGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAAU
CUGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGC
UACAGAGAGUAUUCUCCAUCUGCCGCCAGAGGCCUGCGGCU
GAUGUUUACAGAUUUCUGGCGGACCCGGGUGCUGAGACAGA
CAUCUCCUAUGGCUGGCGUGUUCGGCAACCUGGACGUGAAC
GAAGCCAGACUGAUGGCCGCCUACACAAGCGAGUGUGCCGA
UCACCUGGAAGCCAAAGAACUGGCCGGACCUGAUGGCGUGG
CAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUG
CGGGACCUGCAGGAUAAGGGCGCUGCUAGAAAGCUGCUGAA
CGACCCUCUGGGCAGAAGAACCCCUAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GACCCCAGGUGGCCAACCUGCAGAAUGUGGAUACAGGCUUC
UGGCUGGACAUGCAGCACCUGUCUGAUGUGGUCCUGAGCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACACUGGAAG
AGUCCAUGCCUAUGCUCGAGAAUCUGGAAGAACGGUUCAGA
CGGCUGCAAGAGACAUGCGACGCCGCCAGAACAGAGAUCGA
GGAAAGCGGCUGGACCAGAGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAAGGACCUAGCAGAGUGCAGCAGGCCUUC
CAGAGCUUCGUGAACGAGUGCAACAGCAUCGAGUUCAGCUU
CGGCUCCUUCGGCGAACAUGUGCGGGUGCUGUGUGCCAGAG
UUAGCAGAGGACUUGCUGCCGCUGGCGAGGCCAUCAGAAGA
UGCUUCUCUUGCUGCAAGGGCAGCACCCACAGAUACGCCCCU
AGAGAUGAUCUGAGCCCUGAGGGCGCAUCUCUGGCCGAAAC
ACUGGCCAGAUUUGCCGACGACAUGGGCAUUGAAAGAGGCG
CCGACGGAACCUACGACAUCCCUCUGGUGGACGAUUGGAGA
AGGGGCGUGCCAUCUAUCGAAGGCGAGGGCAGCGAUAGCAU
CUACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGG
ACCUGGAAACCCGGCGGAGCUUUGCCGUGCAACAGGGCCAU
UACCAGGAUCCUAGAGCCAGCGACUACGACCUGCCUAGAGCC
UCCGAUUAUGAUCUGCCUCGGAGCCCCUAUCCUACACCUCCU
CUGCCUCCAAGAUACCAGCUUCAGAAUAUGGACGUGGAAGC
CGGAUUCCGCGAGGCCGUGUAUGCUAGCUUUGUGGCCGGCA
UGUACAACUACGUGGUCACCCAGCCUCAAGAGAGAAUCCCC
AACAGCCAGCAGGUCGAGGGCAUCCUGAGAGAUAUGCUGAC
CAACGGCGACCACCACCAUCACCAUCAU CT875_E_NGM_nIgK_nGST
AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 343
GCUGCCUGAUACCACAGGCAUGAGCCCUAUCCUCGGCUACUG
GAAGAUCAAAGGCCUGGUGCAGCCCACCAGACUGCUGCUGG
AAUACCUGGAAGAGAAGUACGAGGAACACCUGUACGAGCGC
GACGAGGGCGAUAAGUGGCGGAACAAGAAGUUCGAGCUGGG
CCUCGAGUUCCCCAACCUGCCUUACUACAUCGACGGCGACGU
GAAGCUGACCCAGAGCAUGGCCAUCAUCCGGUAUAUCGCCG
ACAAGCACAACAUGCUCGGCGGCUGCCCUAAAGAGCGGGCC
GAGAUUUCUAUGCUGGAAGGCGCCGUGCUGGACAUCAGAUA
CGGCGUGUCCAGAAUCGCCUACAGCAAGGACUUCGAAACCC
UGAAGGUGGACUUCCUGAGCAAGCUGCCCGAGAUGCUGAAG
AUGUUCGAGGACCGGCUGUGCCACAAGACCUACCUGAAUGG
CGACCACGUGACACACCCCGACUUCAUGCUGUACGACGCCCU
GGAUGUGGUGCUGUACAUGGACCCCAUGUGCCUGGACGCCU
UUCCAAAGCUCGUGUGCUUCAAGAAGCGGAUCGAGGCCAUU
CCUCAGAUCGACAAGUACCUGAAGUCCAGCAAGUAUAUCGC
UUGGCCCCUGCAAGGCUGGCAGGCCACAUUUGGAGGCGGAG
AUCACCCUCCUAAGAUGAGCAUCAGAGGCGUCGGCGGCAAC
GGCAACAGCAGAAUCCCUUCUCACAAUGGCGACGGCAGCAA
CAGGCGGAGCCAGAAUACCAAGGGCAACAACAAGGUGGAAG
AUCGCGUGUGCAGCCUGUACAGCUCCAGAAGCAACGAGAAC
CGCGAGAGCCCUUAUGCCGUGGUGGAUGUGUCCAGCAUGAU
CGAGAGCACCCCUACCAGCGGCGAGACAACAAGAGCUAGUA
GAGGCGUGCUGAGCCGGUUUCAGAGAGGCCUCGUUCGGAUU
GCCGACAAAGUGCGGAGAGCCGUGCAGUGUGCUUGGAGCAG
UGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAAU
CUGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGC
UACAGAGAGUAUUCUCCAUCUGCCGCCAGAGGCCUGCGGCU
GAUGUUUACAGAUUUCUGGCGGACCCGGGUGCUGAGACAGA
CAUCUCCUAUGGCUGGCGUGUUCGGCAACCUGGACGUGAAC
GAAGCCAGACUGAUGGCCGCCUACACAAGCGAGUGUGCCGA
UCACCUGGAAGCCAAAGAACUGGCCGGACCUGAUGGCGUGG
CAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUG
CGGGACCUGCAGGAUAAGGGCGCUGCUAGAAAGCUGCUGAA
CGACCCUCUGGGCAGAAGAACCCCUAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GACCCCAGGUGGCCAACCUGCAGAAUGUGGAUACAGGCUUC
UGGCUGGACAUGCAGCACCUGUCUGAUGUGGUCCUGAGCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACACUGGAAG
AGUCCAUGCCUAUGCUCGAGAAUCUGGAAGAACGGUUCAGA
CGGCUGCAAGAGACAUGCGACGCCGCCAGAACAGAGAUCGA
GGAAAGCGGCUGGACCAGAGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAAGGACCUAGCAGAGUGCAGCAGGCCUUC
CAGAGCUUCGUGAACGAGUGCAACAGCAUCGAGUUCAGCUU
CGGCUCCUUCGGCGAACAUGUGCGGGUGCUGUGUGCCAGAG
UUAGCAGAGGACUUGCUGCCGCUGGCGAGGCCAUCAGAAGA
UGCUUCUCUUGCUGCAAGGGCAGCACCCACAGAUACGCCCCU
AGAGAUGAUCUGAGCCCUGAGGGCGCAUCUCUGGCCGAAAC
ACUGGCCAGAUUUGCCGACGACAUGGGCAUUGAAAGAGGCG
CCGACGGAACCUACGACAUCCCUCUGGUGGACGAUUGGAGA
AGGGGCGUGCCAUCUAUCGAAGGCGAGGGCAGCGAUAGCAU
CUACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGG
ACCUGGAAACCCGGCGGAGCUUUGCCGUGCAACAGGGCCAU
UACCAGGAUCCUAGAGCCAGCGACUACGACCUGCCUAGAGCC
UCCGAUUAUGAUCUGCCUCGGAGCCCCUAUCCUACACCUCCU
CUGCCUCCAAGAUACCAGCUUCAGAAUAUGGACGUGGAAGC
CGGAUUCCGCGAGGCCGUGUAUGCUAGCUUUGUGGCCGGCA
UGUACAACUACGUGGUCACCCAGCCUCAAGAGAGAAUCCCC
AACAGCCAGCAGGUCGAGGGCAUCCUGAGAGAUAUGCUGAC
CAACGGCGACCAGACCUUCCGCGACCUGAUGAAGAGAUGGA ACAGAGAGGUGGACAGAGAG
CT875_E_NGM_nIgK_nGST_cHis
AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 344
GCUGCCUGAUACCACAGGCAUGAGCCCUAUCCUCGGCUACUG
GAAGAUCAAAGGCCUGGUGCAGCCCACCAGACUGCUGCUGG
AAUACCUGGAAGAGAAGUACGAGGAACACCUGUACGAGCGC
GACGAGGGCGAUAAGUGGCGGAACAAGAAGUUCGAGCUGGG
CCUCGAGUUCCCCAACCUGCCUUACUACAUCGACGGCGACGU
GAAGCUGACCCAGAGCAUGGCCAUCAUCCGGUAUAUCGCCG
ACAAGCACAACAUGCUCGGCGGCUGCCCUAAAGAGCGGGCC
GAGAUUUCUAUGCUGGAAGGCGCCGUGCUGGACAUCAGAUA
CGGCGUGUCCAGAAUCGCCUACAGCAAGGACUUCGAAACCC
UGAAGGUGGACUUCCUGAGCAAGCUGCCCGAGAUGCUGAAG
AUGUUCGAGGACCGGCUGUGCCACAAGACCUACCUGAAUGG
CGACCACGUGACACACCCCGACUUCAUGCUGUACGACGCCCU
GGAUGUGGUGCUGUACAUGGACCCCAUGUGCCUGGACGCCU
UUCCAAAGCUCGUGUGCUUCAAGAAGCGGAUCGAGGCCAUU
CCUCAGAUCGACAAGUACCUGAAGUCCAGCAAGUAUAUCGC
UUGGCCCCUGCAAGGCUGGCAGGCCACAUUUGGAGGCGGAG
AUCACCCUCCUAAGAUGAGCAUCAGAGGCGUCGGCGGCAAC
GGCAACAGCAGAAUCCCUUCUCACAAUGGCGACGGCAGCAA
CAGGCGGAGCCAGAAUACCAAGGGCAACAACAAGGUGGAAG
AUCGCGUGUGCAGCCUGUACAGCUCCAGAAGCAACGAGAAC
CGCGAGAGCCCUUAUGCCGUGGUGGAUGUGUCCAGCAUGAU
CGAGAGCACCCCUACCAGCGGCGAGACAACAAGAGCUAGUA
GAGGCGUGCUGAGCCGGUUUCAGAGAGGCCUCGUUCGGAUU
GCCGACAAAGUGCGGAGAGCCGUGCAGUGUGCUUGGAGCAG
UGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAAU
CUGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGC
UACAGAGAGUAUUCUCCAUCUGCCGCCAGAGGCCUGCGGCU
GAUGUUUACAGAUUUCUGGCGGACCCGGGUGCUGAGACAGA
CAUCUCCUAUGGCUGGCGUGUUCGGCAACCUGGACGUGAAC
GAAGCCAGACUGAUGGCCGCCUACACAAGCGAGUGUGCCGA
UCACCUGGAAGCCAAAGAACUGGCCGGACCUGAUGGCGUGG
CAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUG
CGGGACCUGCAGGAUAAGGGCGCUGCUAGAAAGCUGCUGAA
CGACCCUCUGGGCAGAAGAACCCCUAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GACCCCAGGUGGCCAACCUGCAGAAUGUGGAUACAGGCUUC
UGGCUGGACAUGCAGCACCUGUCUGAUGUGGUCCUGAGCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACACUGGAAG
AGUCCAUGCCUAUGCUCGAGAAUCUGGAAGAACGGUUCAGA
CGGCUGCAAGAGACAUGCGACGCCGCCAGAACAGAGAUCGA
GGAAAGCGGCUGGACCAGAGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAAGGACCUAGCAGAGUGCAGCAGGCCUUC
CAGAGCUUCGUGAACGAGUGCAACAGCAUCGAGUUCAGCUU
CGGCUCCUUCGGCGAACAUGUGCGGGUGCUGUGUGCCAGAG
UUAGCAGAGGACUUGCUGCCGCUGGCGAGGCCAUCAGAAGA
UGCUUCUCUUGCUGCAAGGGCAGCACCCACAGAUACGCCCCU
AGAGAUGAUCUGAGCCCUGAGGGCGCAUCUCUGGCCGAAAC
ACUGGCCAGAUUUGCCGACGACAUGGGCAUUGAAAGAGGCG
CCGACGGAACCUACGACAUCCCUCUGGUGGACGAUUGGAGA
AGGGGCGUGCCAUCUAUCGAAGGCGAGGGCAGCGAUAGCAU
CUACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGG
ACCUGGAAACCCGGCGGAGCUUUGCCGUGCAACAGGGCCAU
UACCAGGAUCCUAGAGCCAGCGACUACGACCUGCCUAGAGCC
UCCGAUUAUGAUCUGCCUCGGAGCCCCUAUCCUACACCUCCU
CUGCCUCCAAGAUACCAGCUUCAGAAUAUGGACGUGGAAGC
CGGAUUCCGCGAGGCCGUGUAUGCUAGCUUUGUGGCCGGCA
UGUACAACUACGUGGUCACCCAGCCUCAAGAGAGAAUCCCC
AACAGCCAGCAGGUCGAGGGCAUCCUGAGAGAUAUGCUGAC
CAACGGCGACCAGACCUUCCGCGACCUGAUGAAGAGAUGGA
ACAGAGAGGUGGACAGAGAGCACCACCACCAUCACCAU CT875_E_1_458_NGM_nIgK_nGST
AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 345
GCUGCCUGAUACCACAGGCAUGAGCCCUAUCCUCGGCUACUG
GAAGAUCAAAGGCCUGGUGCAGCCCACCAGACUGCUGCUGG
AAUACCUGGAAGAGAAGUACGAGGAACACCUGUACGAGCGC
GACGAGGGCGAUAAGUGGCGGAACAAGAAGUUCGAGCUGGG
CCUCGAGUUCCCCAACCUGCCUUACUACAUCGACGGCGACGU
GAAGCUGACCCAGAGCAUGGCCAUCAUCCGGUAUAUCGCCG
ACAAGCACAACAUGCUCGGCGGCUGCCCUAAAGAGCGGGCC
GAGAUUUCUAUGCUGGAAGGCGCCGUGCUGGACAUCAGAUA
CGGCGUGUCCAGAAUCGCCUACAGCAAGGACUUCGAAACCC
UGAAGGUGGACUUCCUGAGCAAGCUGCCCGAGAUGCUGAAG
AUGUUCGAGGACCGGCUGUGCCACAAGACCUACCUGAAUGG
CGACCACGUGACACACCCCGACUUCAUGCUGUACGACGCCCU
GGAUGUGGUGCUGUACAUGGACCCCAUGUGCCUGGACGCCU
UUCCAAAGCUCGUGUGCUUCAAGAAGCGGAUCGAGGCCAUU
CCUCAGAUCGACAAGUACCUGAAGUCCAGCAAGUAUAUCGC
UUGGCCCCUGCAAGGCUGGCAGGCCACAUUUGGAGGCGGAG
AUCACCCUCCUAAGAUGAGCAUCAGAGGCGUCGGCGGCAAC
GGCAACAGCAGAAUCCCUUCUCACAAUGGCGACGGCAGCAA
CAGGCGGAGCCAGAAUACCAAGGGCAACAACAAGGUGGAAG
AUCGCGUGUGCAGCCUGUACAGCUCCAGAAGCAACGAGAAC
CGCGAGAGCCCUUAUGCCGUGGUGGAUGUGUCCAGCAUGAU
CGAGAGCACCCCUACCAGCGGCGAGACAACAAGAGCUAGUA
GAGGCGUGCUGAGCCGGUUUCAGAGAGGCCUCGUUCGGAUU
GCCGACAAAGUGCGGAGAGCCGUGCAGUGUGCUUGGAGCAG
UGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAAU
CUGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGC
UACAGAGAGUAUUCUCCAUCUGCCGCCAGAGGCCUGCGGCU
GAUGUUUACAGAUUUCUGGCGGACCCGGGUGCUGAGACAGA
CAUCUCCUAUGGCUGGCGUGUUCGGCAACCUGGACGUGAAC
GAAGCCAGACUGAUGGCCGCCUACACAAGCGAGUGUGCCGA
UCACCUGGAAGCCAAAGAACUGGCCGGACCUGAUGGCGUGG
CAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUG
CGGGACCUGCAGGAUAAGGGCGCUGCUAGAAAGCUGCUGAA
CGACCCUCUGGGCAGAAGAACCCCUAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GACCCCAGGUGGCCAACCUGCAGAAUGUGGAUACAGGCUUC
UGGCUGGACAUGCAGCACCUGUCUGAUGUGGUCCUGAGCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACACUGGAAG
AGUCCAUGCCUAUGCUCGAGAAUCUGGAAGAACGGUUCAGA
CGGCUGCAAGAGACAUGCGACGCCGCCAGAACAGAGAUCGA
GGAAAGCGGCUGGACCAGAGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAAGGACCUAGCAGAGUGCAGCAGGCCUUC
CAGAGCUUCGUGAACGAGUGCAACAGCAUCGAGUUCAGCUU
CGGCUCCUUCGGCGAACAUGUGCGGGUGCUGUGUGCCAGAG
UUAGCAGAGGACUUGCUGCCGCUGGCGAGGCCAUCAGAAGA
UGCUUCUCUUGCUGCAAGGGCAGCACCCACAGAUACGCCCCU
AGAGAUGAUCUGAGCCCUGAGGGCGCAUCUCUGGCCGAAAC
ACUGGCCAGAUUUGCCGACGACAUGGGCAUUGAAAGAGGCG
CCGACGGAACCUACGACAUCCCUCUGGUGGACGAUUGGAGA
AGGGGCGUGCCAUCUAUCGAAGGCGAGGGAUCU CT875_E_1_458_NGM_nIgK_nGST_cHis
AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 346
GCUGCCUGAUACCACAGGCAUGAGCCCUAUCCUCGGCUACUG
GAAGAUCAAAGGCCUGGUGCAGCCCACCAGACUGCUGCUGG
AAUACCUGGAAGAGAAGUACGAGGAACACCUGUACGAGCGC
GACGAGGGCGAUAAGUGGCGGAACAAGAAGUUCGAGCUGGG
CCUCGAGUUCCCCAACCUGCCUUACUACAUCGACGGCGACGU
GAAGCUGACCCAGAGCAUGGCCAUCAUCCGGUAUAUCGCCG
ACAAGCACAACAUGCUCGGCGGCUGCCCUAAAGAGCGGGCC
GAGAUUUCUAUGCUGGAAGGCGCCGUGCUGGACAUCAGAUA
CGGCGUGUCCAGAAUCGCCUACAGCAAGGACUUCGAAACCC
UGAAGGUGGACUUCCUGAGCAAGCUGCCCGAGAUGCUGAAG
AUGUUCGAGGACCGGCUGUGCCACAAGACCUACCUGAAUGG
CGACCACGUGACACACCCCGACUUCAUGCUGUACGACGCCCU
GGAUGUGGUGCUGUACAUGGACCCCAUGUGCCUGGACGCCU
UUCCAAAGCUCGUGUGCUUCAAGAAGCGGAUCGAGGCCAUU
CCUCAGAUCGACAAGUACCUGAAGUCCAGCAAGUAUAUCGC
UUGGCCCCUGCAAGGCUGGCAGGCCACAUUUGGAGGCGGAG
AUCACCCUCCUAAGAUGAGCAUCAGAGGCGUCGGCGGCAAC
GGCAACAGCAGAAUCCCUUCUCACAAUGGCGACGGCAGCAA
CAGGCGGAGCCAGAAUACCAAGGGCAACAACAAGGUGGAAG
AUCGCGUGUGCAGCCUGUACAGCUCCAGAAGCAACGAGAAC
CGCGAGAGCCCUUAUGCCGUGGUGGAUGUGUCCAGCAUGAU
CGAGAGCACCCCUACCAGCGGCGAGACAACAAGAGCUAGUA
GAGGCGUGCUGAGCCGGUUUCAGAGAGGCCUCGUUCGGAUU
GCCGACAAAGUGCGGAGAGCCGUGCAGUGUGCUUGGAGCAG
UGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAAU
CUGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGC
UACAGAGAGUAUUCUCCAUCUGCCGCCAGAGGCCUGCGGCU
GAUGUUUACAGAUUUCUGGCGGACCCGGGUGCUGAGACAGA
CAUCUCCUAUGGCUGGCGUGUUCGGCAACCUGGACGUGAAC
GAAGCCAGACUGAUGGCCGCCUACACAAGCGAGUGUGCCGA
UCACCUGGAAGCCAAAGAACUGGCCGGACCUGAUGGCGUGG
CAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUG
CGGGACCUGCAGGAUAAGGGCGCUGCUAGAAAGCUGCUGAA
CGACCCUCUGGGCAGAAGAACCCCUAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GACCCCAGGUGGCCAACCUGCAGAAUGUGGAUACAGGCUUC
UGGCUGGACAUGCAGCACCUGUCUGAUGUGGUCCUGAGCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACACUGGAAG
AGUCCAUGCCUAUGCUCGAGAAUCUGGAAGAACGGUUCAGA
CGGCUGCAAGAGACAUGCGACGCCGCCAGAACAGAGAUCGA
GGAAAGCGGCUGGACCAGAGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAAGGACCUAGCAGAGUGCAGCAGGCCUUC
CAGAGCUUCGUGAACGAGUGCAACAGCAUCGAGUUCAGCUU
CGGCUCCUUCGGCGAACAUGUGCGGGUGCUGUGUGCCAGAG
UUAGCAGAGGACUUGCUGCCGCUGGCGAGGCCAUCAGAAGA
UGCUUCUCUUGCUGCAAGGGCAGCACCCACAGAUACGCCCCU
AGAGAUGAUCUGAGCCCUGAGGGCGCAUCUCUGGCCGAAAC
ACUGGCCAGAUUUGCCGACGACAUGGGCAUUGAAAGAGGCG
CCGACGGAACCUACGACAUCCCUCUGGUGGACGAUUGGAGA
AGGGGCGUGCCAUCUAUCGAAGGCGAGGGCUCUCACCACCA CCAUCACCAU
CT875_E_1_458_NGM_nIgK AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG
347 GCUGCCUGAUACCACCGGCAUGUCUAUCAGAGGCGUUGGCG
GCAACGGCAACAGCAGAAUCCCUAGCCAUAAUGGCGACGGC
AGCAACAGGCGGAGCCAGAAUACCAAGGGCAACAACAAGGU
GGAAGAUCGCGUGUGCAGCCUGUACAGCUCCAGAAGCAACG
AGAACCGCGAGAGCCCUUAUGCCGUGGUGGAUGUGUCCAGC
AUGAUCGAGAGCACCCCUACCAGCGGCGAGACAACAAGAGC
UAGUAGAGGCGUGCUGAGCCGGUUUCAGAGAGGCCUCGUUC
GGAUCGCUGACAAAGUGCGGAGAGCCGUGCAGUGUGCCUGG
UCUAGUGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGC
CGAGAGCGGAUCUUCUAGCAGAACAGCUAGAGGCGCCAGCA
GCGGCUACAGAGAGUAUUCUCCAUCUGCCGCCAGAGGCCUG
CGGCUGAUGUUUACAGAUUUCUGGCGGACCCGGGUGCUGAG
ACAGACAUCUCCUAUGGCUGGCGUGUUCGGCAACCUGGAUG
UGAAUGAGGCCAGACUGAUGGCCGCCUACACAAGCGAAUGU
GCCGAUCACCUGGAAGCCAAAGAGCUGGCUGGACCUGACGG
UGUUGCCGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGA
GAGUGCGGGACCUGCAGGAUAAGGGCGCUGCUAGAAAGCUG
CUGAACGACCCUCUGGGCAGAAGAACCCCUAACUACCAGAGC
AAGAACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUA
CGACGGACCCCAGGUGGCCAACCUGCAGAAUGUGGAUACAG
GCUUCUGGCUGGAUAUGCAGCACCUGAGCGACGUGGUGCUG
UCCAGAGAGAUCCAGACAGGCCUGAGAGCCAGAGCCACACU
GGAAGAGUCCAUGCCUAUGCUCGAGAACCUGGAAGAGAGAU
UCCGGCGGCUGCAAGAGACAUGUGACGCCGCCAGAACCGAG
AUCGAGGAAAGCGGCUGGACAAGAGAAAGCGCCUCCAGAAU
GGAAGGCGACGAAGCCCAAGGACCUAGCAGAGUGCAGCAGG
CCUUCCAGAGCUUCGUGAACGAGUGCAACAGCAUCGAGUUC
AGCUUCGGCUCCUUCGGCGAACAUGUGCGGGUGCUGUGUGC
CAGAGUUAGCAGAGGACUUGCUGCCGCUGGCGAGGCCAUCA
GAAGAUGCUUCUCUUGCUGCAAGGGCAGCACCCACAGAUAC
GCCCCUAGAGAUGAUCUGAGCCCUGAGGGCGCUUCUCUGGC
CGAAACACUGGCCAGAUUCGCCGACGAUAUGGGCAUUGAAA
GAGGCGCCGACGGAACCUACGACAUCCCUCUGGUGGACGAU
UGGAGAAGGGGCGUGCCAUCUAUCGAAGGCGAGGGAUCU CT875_E_1_458_NGM_nIgK_cHis
AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 348
GCUGCCUGAUACCACCGGCAUGUCUAUCAGAGGCGUUGGCG
GCAACGGCAACAGCAGAAUCCCUAGCCAUAAUGGCGACGGC
AGCAACAGGCGGAGCCAGAAUACCAAGGGCAACAACAAGGU
GGAAGAUCGCGUGUGCAGCCUGUACAGCUCCAGAAGCAACG
AGAACCGCGAGAGCCCUUAUGCCGUGGUGGAUGUGUCCAGC
AUGAUCGAGAGCACCCCUACCAGCGGCGAGACAACAAGAGC
UAGUAGAGGCGUGCUGAGCCGGUUUCAGAGAGGCCUCGUUC
GGAUCGCUGACAAAGUGCGGAGAGCCGUGCAGUGUGCCUGG
UCUAGUGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGC
CGAGAGCGGAUCUUCUAGCAGAACAGCUAGAGGCGCCAGCA
GCGGCUACAGAGAGUAUUCUCCAUCUGCCGCCAGAGGCCUG
CGGCUGAUGUUUACAGAUUUCUGGCGGACCCGGGUGCUGAG
ACAGACAUCUCCUAUGGCUGGCGUGUUCGGCAACCUGGAUG
UGAAUGAGGCCAGACUGAUGGCCGCCUACACAAGCGAAUGU
GCCGAUCACCUGGAAGCCAAAGAGCUGGCUGGACCUGACGG
UGUUGCCGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGA
GAGUGCGGGACCUGCAGGAUAAGGGCGCUGCUAGAAAGCUG
CUGAACGACCCUCUGGGCAGAAGAACCCCUAACUACCAGAGC
AAGAACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUA
CGACGGACCCCAGGUGGCCAACCUGCAGAAUGUGGAUACAG
GCUUCUGGCUGGAUAUGCAGCACCUGAGCGACGUGGUGCUG
UCCAGAGAGAUCCAGACAGGCCUGAGAGCCAGAGCCACACU
GGAAGAGUCCAUGCCUAUGCUCGAGAACCUGGAAGAGAGAU
UCCGGCGGCUGCAAGAGACAUGUGACGCCGCCAGAACCGAG
AUCGAGGAAAGCGGCUGGACAAGAGAAAGCGCCUCCAGAAU
GGAAGGCGACGAAGCCCAAGGACCUAGCAGAGUGCAGCAGG
CCUUCCAGAGCUUCGUGAACGAGUGCAACAGCAUCGAGUUC
AGCUUCGGCUCCUUCGGCGAACAUGUGCGGGUGCUGUGUGC
CAGAGUUAGCAGAGGACUUGCUGCCGCUGGCGAGGCCAUCA
GAAGAUGCUUCUCUUGCUGCAAGGGCAGCACCCACAGAUAC
GCCCCUAGAGAUGAUCUGAGCCCUGAGGGCGCUUCUCUGGC
CGAAACACUGGCCAGAUUCGCCGACGAUAUGGGCAUUGAAA
GAGGCGCCGACGGAACCUACGACAUCCCUCUGGUGGACGAU
UGGAGAAGGGGCGUGCCAUCUAUCGAAGGCGAGGGCUCUCA CCACCACCAUCACCAU
CT875_E_1_574_NGM_nIgK AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG
349 GCUGCCUGAUACCACCGGCAUGUCUAUCAGAGGCGUUGGCG
GCAACGGCAACAGCAGAAUCCCUAGCCAUAAUGGCGACGGC
AGCAACAGGCGGAGCCAGAAUACCAAGGGCAACAACAAGGU
GGAAGAUCGCGUGUGCAGCCUGUACAGCUCCAGAAGCAACG
AGAACCGCGAGAGCCCUUAUGCCGUGGUGGAUGUGUCCAGC
AUGAUCGAGAGCACCCCUACCAGCGGCGAGACAACAAGAGC
UAGUAGAGGCGUGCUGAGCCGGUUUCAGAGAGGCCUCGUUC
GGAUCGCUGACAAAGUGCGGAGAGCCGUGCAGUGUGCCUGG
UCUAGUGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGC
CGAGAGCGGAUCUUCUAGCAGAACAGCUAGAGGCGCCAGCA
GCGGCUACAGAGAGUAUUCUCCAUCUGCCGCCAGAGGCCUG
CGGCUGAUGUUUACAGAUUUCUGGCGGACCCGGGUGCUGAG
ACAGACAUCUCCUAUGGCUGGCGUGUUCGGCAACCUGGAUG
UGAAUGAGGCCAGACUGAUGGCCGCCUACACAAGCGAAUGU
GCCGAUCACCUGGAAGCCAAAGAGCUGGCUGGACCUGACGG
UGUUGCCGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGA
GAGUGCGGGACCUGCAGGAUAAGGGCGCUGCUAGAAAGCUG
CUGAACGACCCUCUGGGCAGAAGAACCCCUAACUACCAGAGC
AAGAACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUA
CGACGGACCCCAGGUGGCCAACCUGCAGAAUGUGGAUACAG
GCUUCUGGCUGGAUAUGCAGCACCUGAGCGACGUGGUGCUG
UCCAGAGAGAUCCAGACAGGCCUGAGAGCCAGAGCCACACU
GGAAGAGUCCAUGCCUAUGCUCGAGAACCUGGAAGAGAGAU
UCCGGCGGCUGCAAGAGACAUGUGACGCCGCCAGAACCGAG
AUCGAGGAAAGCGGCUGGACAAGAGAAAGCGCCUCCAGAAU
GGAAGGCGACGAAGCCCAAGGACCUAGCAGAGUGCAGCAGG
CCUUCCAGAGCUUCGUGAACGAGUGCAACAGCAUCGAGUUC
AGCUUCGGCUCCUUCGGCGAACAUGUGCGGGUGCUGUGUGC
CAGAGUUAGCAGAGGACUUGCUGCCGCUGGCGAGGCCAUCA
GAAGAUGCUUCUCUUGCUGCAAGGGCAGCACCCACAGAUAC
GCCCCUAGAGAUGAUCUGAGCCCUGAGGGCGCUUCUCUGGC
CGAAACACUGGCCAGAUUCGCCGACGAUAUGGGCAUUGAAA
GAGGCGCCGACGGAACCUACGACAUCCCUCUGGUGGACGAU
UGGAGAAGGGGCGUGCCAUCUAUCGAAGGCGAGGGCAGCGA
UAGCAUCUACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGA
ACAUGGACCUGGAAACCCGGCGGAGCUUUGCCGUGCAGCAA
GGCCAUUACCAGGAUCCUAGAGCCAGCGACUACGACCUGCCU
AGAGCCUCCGAUUAUGAUCUGCCUCGGAGCCCCUAUCCUACA
CCUCCUCUGCCUCCAAGAUACCAGCUUCAGAAUAUGGACGU
GGAAGCCGGAUUCCGCGAGGCCGUGUAUGCUAGCUUUGUGG
CCGGCAUGUACAACUACGUGGUCACCCAGCCUCAAGAGAGA
AUCCCCAACAGCCAGCAGGUCGAGGGCAUCCUGAGAGAUAU GCUGACCAACGGCGAC
CT875_E_1_574_nIgK_nGST AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG
350 GCUGCCUGAUACCACAGGCAUGAGCCCUAUCCUCGGCUACUG
GAAGAUCAAAGGCCUGGUGCAGCCCACCAGACUGCUGCUGG
AAUACCUGGAAGAGAAGUACGAGGAACACCUGUACGAGCGC
GACGAGGGCGAUAAGUGGCGGAACAAGAAGUUCGAGCUGGG
CCUCGAGUUCCCCAACCUGCCUUACUACAUCGACGGCGACGU
GAAGCUGACCCAGAGCAUGGCCAUCAUCCGGUAUAUCGCCG
ACAAGCACAACAUGCUCGGCGGCUGCCCUAAAGAGCGGGCC
GAGAUUUCUAUGCUGGAAGGCGCCGUGCUGGACAUCAGAUA
CGGCGUGUCCAGAAUCGCCUACAGCAAGGACUUCGAAACCC
UGAAGGUGGACUUCCUGAGCAAGCUGCCCGAGAUGCUGAAG
AUGUUCGAGGACCGGCUGUGCCACAAGACCUACCUGAAUGG
CGACCACGUGACACACCCCGACUUCAUGCUGUACGACGCCCU
GGAUGUGGUGCUGUACAUGGACCCCAUGUGCCUGGACGCCU
UUCCAAAGCUCGUGUGCUUCAAGAAGCGGAUCGAGGCCAUU
CCUCAGAUCGACAAGUACCUGAAGUCCAGCAAGUAUAUCGC
UUGGCCCCUGCAAGGCUGGCAGGCCACAUUUGGAGGCGGAG
AUCACCCUCCUAAGAUGAGCAUCAGAGGCGUCGGCGGCAAC
GGCAACAGCAGAAUCCCUUCUCACAAUGGCGACGGCAGCAA
CAGGCGGAGCCAGAAUACCAAGGGCAACAACAAGGUGGAAG
AUCGCGUGUGCAGCCUGUACAGCUCCAGAAGCAACGAGAAC
CGCGAGAGCCCUUAUGCCGUGGUGGAUGUGUCCAGCAUGAU
CGAGAGCACCCCUACCAGCGGCGAGACAACAAGAGCUAGUA
GAGGCGUGCUGAGCCGGUUUCAGAGAGGCCUCGUUCGGAUU
GCCGACAAAGUGCGGAGAGCCGUGCAGUGUGCUUGGAGCAG
UGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAAU
CUGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGC
UACAGAGAGUAUUCUCCAUCUGCCGCCAGAGGCCUGCGGCU
GAUGUUUACAGAUUUCUGGCGGACCCGGGUGCUGAGACAGA
CAUCUCCUAUGGCUGGCGUGUUCGGCAACCUGGACGUGAAC
GAAGCCAGACUGAUGGCCGCCUACACAAGCGAGUGUGCCGA
UCACCUGGAAGCCAAAGAACUGGCCGGACCUGAUGGCGUGG
CAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUG
CGGGACCUGCAGGAUAAGGGCGCUGCUAGAAAGCUGCUGAA
CGACCCUCUGGGCAGAAGAACCCCUAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GACCCCAGGUGGCCAACCUGCAGAAUGUGGAUACAGGCUUC
UGGCUGGACAUGAGCAACCUGAGCGACGUGGUCCUGAGCAG
AGAGAUCCAGACAGGCCUGAGAGCCAGAGCCACACUGGAAG
AGUCCAUGCCUAUGCUCGAGAAUCUGGAAGAACGGUUCAGA
CGGCUGCAAGAGACAUGCGACGCCGCCAGAACAGAGAUCGA
GGAAAGCGGCUGGACCAGAGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAAGGACCUAGCAGAGUGCAGCAGGCCUUC
CAGAGCUUCGUGAACGAGUGCAACAGCAUCGAGUUCAGCUU
CGGCUCCUUCGGCGAACAUGUGCGGGUGCUGUGUGCCAGAG
UUAGCAGAGGACUUGCUGCCGCUGGCGAGGCCAUCAGAAGA
UGCUUCUCUUGCUGCAAGGGCAGCACCCACAGAUACGCCCCU
AGAGAUGAUCUGAGCCCUGAGGGCGCAUCUCUGGCCGAAAC
ACUGGCCAGAUUUGCCGACGACAUGGGCAUUGAAAGAGGCG
CCGACGGAACCUACGACAUCCCUCUGGUGGACGAUUGGAGA
AGGGGCGUGCCAUCUAUCGAAGGCGAGGGCAGCGAUAGCAU
CUACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGG
ACCUGGAAACCCGGCGGAGCUUUGCCGUGCAACAGGGCCAU
UACCAGGAUCCUAGAGCCAGCGACUACGACCUGCCUAGAGCC
UCCGAUUAUGAUCUGCCUCGGAGCCCCUAUCCUACACCUCCU
CUGCCUCCAAGAUACCAGCUUCAGAAUAUGGACGUGGAAGC
CGGAUUCCGCGAGGCCGUGUAUGCUAGCUUUGUGGCCGGCA
UGUACAACUACGUGGUCACCCAGCCUCAAGAGAGAAUCCCC
AACAGCCAGCAGGUCGAGGGCAUCCUGAGAGAUAUGCUGAC CAACGGCAGC
CT875_E_1_574_nIgK_nGST_cHis
AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 351
GCUGCCUGAUACCACAGGCAUGAGCCCUAUCCUCGGCUACUG
GAAGAUCAAAGGCCUGGUGCAGCCCACCAGACUGCUGCUGG
AAUACCUGGAAGAGAAGUACGAGGAACACCUGUACGAGCGC
GACGAGGGCGAUAAGUGGCGGAACAAGAAGUUCGAGCUGGG
CCUCGAGUUCCCCAACCUGCCUUACUACAUCGACGGCGACGU
GAAGCUGACCCAGAGCAUGGCCAUCAUCCGGUAUAUCGCCG
ACAAGCACAACAUGCUCGGCGGCUGCCCUAAAGAGCGGGCC
GAGAUUUCUAUGCUGGAAGGCGCCGUGCUGGACAUCAGAUA
CGGCGUGUCCAGAAUCGCCUACAGCAAGGACUUCGAAACCC
UGAAGGUGGACUUCCUGAGCAAGCUGCCCGAGAUGCUGAAG
AUGUUCGAGGACCGGCUGUGCCACAAGACCUACCUGAAUGG
CGACCACGUGACACACCCCGACUUCAUGCUGUACGACGCCCU
GGAUGUGGUGCUGUACAUGGACCCCAUGUGCCUGGACGCCU
UUCCAAAGCUCGUGUGCUUCAAGAAGCGGAUCGAGGCCAUU
CCUCAGAUCGACAAGUACCUGAAGUCCAGCAAGUAUAUCGC
UUGGCCCCUGCAAGGCUGGCAGGCCACAUUUGGAGGCGGAG
AUCACCCUCCUAAGAUGAGCAUCAGAGGCGUCGGCGGCAAC
GGCAACAGCAGAAUCCCUUCUCACAAUGGCGACGGCAGCAA
CAGGCGGAGCCAGAAUACCAAGGGCAACAACAAGGUGGAAG
AUCGCGUGUGCAGCCUGUACAGCUCCAGAAGCAACGAGAAC
CGCGAGAGCCCUUAUGCCGUGGUGGAUGUGUCCAGCAUGAU
CGAGAGCACCCCUACCAGCGGCGAGACAACAAGAGCUAGUA
GAGGCGUGCUGAGCCGGUUUCAGAGAGGCCUCGUUCGGAUU
GCCGACAAAGUGCGGAGAGCCGUGCAGUGUGCUUGGAGCAG
UGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAAU
CUGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGC
UACAGAGAGUAUUCUCCAUCUGCCGCCAGAGGCCUGCGGCU
GAUGUUUACAGAUUUCUGGCGGACCCGGGUGCUGAGACAGA
CAUCUCCUAUGGCUGGCGUGUUCGGCAACCUGGACGUGAAC
GAAGCCAGACUGAUGGCCGCCUACACAAGCGAGUGUGCCGA
UCACCUGGAAGCCAAAGAACUGGCCGGACCUGAUGGCGUGG
CAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUG
CGGGACCUGCAGGAUAAGGGCGCUGCUAGAAAGCUGCUGAA
CGACCCUCUGGGCAGAAGAACCCCUAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GACCCCAGGUGGCCAACCUGCAGAAUGUGGAUACAGGCUUC
UGGCUGGACAUGAGCAACCUGAGCGACGUGGUCCUGAGCAG
AGAGAUCCAGACAGGCCUGAGAGCCAGAGCCACACUGGAAG
AGUCCAUGCCUAUGCUCGAGAAUCUGGAAGAACGGUUCAGA
CGGCUGCAAGAGACAUGCGACGCCGCCAGAACAGAGAUCGA
GGAAAGCGGCUGGACCAGAGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAAGGACCUAGCAGAGUGCAGCAGGCCUUC
CAGAGCUUCGUGAACGAGUGCAACAGCAUCGAGUUCAGCUU
CGGCUCCUUCGGCGAACAUGUGCGGGUGCUGUGUGCCAGAG
UUAGCAGAGGACUUGCUGCCGCUGGCGAGGCCAUCAGAAGA
UGCUUCUCUUGCUGCAAGGGCAGCACCCACAGAUACGCCCCU
AGAGAUGAUCUGAGCCCUGAGGGCGCAUCUCUGGCCGAAAC
ACUGGCCAGAUUUGCCGACGACAUGGGCAUUGAAAGAGGCG
CCGACGGAACCUACGACAUCCCUCUGGUGGACGAUUGGAGA
AGGGGCGUGCCAUCUAUCGAAGGCGAGGGCAGCGAUAGCAU
CUACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGG
ACCUGGAAACCCGGCGGAGCUUUGCCGUGCAACAGGGCCAU
UACCAGGAUCCUAGAGCCAGCGACUACGACCUGCCUAGAGCC
UCCGAUUAUGAUCUGCCUCGGAGCCCCUAUCCUACACCUCCU
CUGCCUCCAAGAUACCAGCUUCAGAAUAUGGACGUGGAAGC
CGGAUUCCGCGAGGCCGUGUAUGCUAGCUUUGUGGCCGGCA
UGUACAACUACGUGGUCACCCAGCCUCAAGAGAGAAUCCCC
AACAGCCAGCAGGUCGAGGGCAUCCUGAGAGAUAUGCUGAC
CAACGGCAGCCACCACCACCAUCACCAU CT875_E_nIgK_nGST
AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 352
GCUGCCUGAUACCACAGGCAUGAGCCCUAUCCUCGGCUACUG
GAAGAUCAAAGGCCUGGUGCAGCCCACCAGACUGCUGCUGG
AAUACCUGGAAGAGAAGUACGAGGAACACCUGUACGAGCGC
GACGAGGGCGAUAAGUGGCGGAACAAGAAGUUCGAGCUGGG
CCUCGAGUUCCCCAACCUGCCUUACUACAUCGACGGCGACGU
GAAGCUGACCCAGAGCAUGGCCAUCAUCCGGUAUAUCGCCG
ACAAGCACAACAUGCUCGGCGGCUGCCCUAAAGAGCGGGCC
GAGAUUUCUAUGCUGGAAGGCGCCGUGCUGGACAUCAGAUA
CGGCGUGUCCAGAAUCGCCUACAGCAAGGACUUCGAAACCC
UGAAGGUGGACUUCCUGAGCAAGCUGCCCGAGAUGCUGAAG
AUGUUCGAGGACCGGCUGUGCCACAAGACCUACCUGAAUGG
CGACCACGUGACACACCCCGACUUCAUGCUGUACGACGCCCU
GGAUGUGGUGCUGUACAUGGACCCCAUGUGCCUGGACGCCU
UUCCAAAGCUCGUGUGCUUCAAGAAGCGGAUCGAGGCCAUU
CCUCAGAUCGACAAGUACCUGAAGUCCAGCAAGUAUAUCGC
UUGGCCCCUGCAAGGCUGGCAGGCCACAUUUGGAGGCGGAG
AUCACCCUCCUAAGAUGAGCAUCAGAGGCGUCGGCGGCAAC
GGCAACAGCAGAAUCCCUUCUCACAAUGGCGACGGCAGCAA
CAGGCGGAGCCAGAAUACCAAGGGCAACAACAAGGUGGAAG
AUCGCGUGUGCAGCCUGUACAGCUCCAGAAGCAACGAGAAC
CGCGAGAGCCCUUAUGCCGUGGUGGAUGUGUCCAGCAUGAU
CGAGAGCACCCCUACCAGCGGCGAGACAACAAGAGCUAGUA
GAGGCGUGCUGAGCCGGUUUCAGAGAGGCCUCGUUCGGAUU
GCCGACAAAGUGCGGAGAGCCGUGCAGUGUGCUUGGAGCAG
UGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAAU
CUGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGC
UACAGAGAGUAUUCUCCAUCUGCCGCCAGAGGCCUGCGGCU
GAUGUUUACAGAUUUCUGGCGGACCCGGGUGCUGAGACAGA
CAUCUCCUAUGGCUGGCGUGUUCGGCAACCUGGACGUGAAC
GAAGCCAGACUGAUGGCCGCCUACACAAGCGAGUGUGCCGA
UCACCUGGAAGCCAAAGAACUGGCCGGACCUGAUGGCGUGG
CAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUG
CGGGACCUGCAGGAUAAGGGCGCUGCUAGAAAGCUGCUGAA
CGACCCUCUGGGCAGAAGAACCCCUAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GACCCCAGGUGGCCAACCUGCAGAAUGUGGAUACAGGCUUC
UGGCUGGACAUGAGCAACCUGAGCGACGUGGUCCUGAGCAG
AGAGAUCCAGACAGGCCUGAGAGCCAGAGCCACACUGGAAG
AGUCCAUGCCUAUGCUCGAGAAUCUGGAAGAACGGUUCAGA
CGGCUGCAAGAGACAUGCGACGCCGCCAGAACAGAGAUCGA
GGAAAGCGGCUGGACCAGAGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAAGGACCUAGCAGAGUGCAGCAGGCCUUC
CAGAGCUUCGUGAACGAGUGCAACAGCAUCGAGUUCAGCUU
CGGCUCCUUCGGCGAACAUGUGCGGGUGCUGUGUGCCAGAG
UUAGCAGAGGACUUGCUGCCGCUGGCGAGGCCAUCAGAAGA
UGCUUCUCUUGCUGCAAGGGCAGCACCCACAGAUACGCCCCU
AGAGAUGAUCUGAGCCCUGAGGGCGCAUCUCUGGCCGAAAC
ACUGGCCAGAUUUGCCGACGACAUGGGCAUUGAAAGAGGCG
CCGACGGAACCUACGACAUCCCUCUGGUGGACGAUUGGAGA
AGGGGCGUGCCAUCUAUCGAAGGCGAGGGCAGCGAUAGCAU
CUACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGG
ACCUGGAAACCCGGCGGAGCUUUGCCGUGCAACAGGGCCAU
UACCAGGAUCCUAGAGCCAGCGACUACGACCUGCCUAGAGCC
UCCGAUUAUGAUCUGCCUCGGAGCCCCUAUCCUACACCUCCU
CUGCCUCCAAGAUACCAGCUUCAGAAUAUGGACGUGGAAGC
CGGAUUCCGCGAGGCCGUGUAUGCUAGCUUUGUGGCCGGCA
UGUACAACUACGUGGUCACCCAGCCUCAAGAGAGAAUCCCC
AACAGCCAGCAGGUCGAGGGCAUCCUGAGAGAUAUGCUGAC
CAACGGCAGCCAGACCUUCCGCGACCUGAUGAAGAGAUGGA ACAGAGAGGUGGACAGAGAG
CT875_E_nIgK_nGST_cHis AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG
353 GCUGCCUGAUACCACAGGCAUGAGCCCUAUCCUCGGCUACUG
GAAGAUCAAAGGCCUGGUGCAGCCCACCAGACUGCUGCUGG
AAUACCUGGAAGAGAAGUACGAGGAACACCUGUACGAGCGC
GACGAGGGCGAUAAGUGGCGGAACAAGAAGUUCGAGCUGGG
CCUCGAGUUCCCCAACCUGCCUUACUACAUCGACGGCGACGU
GAAGCUGACCCAGAGCAUGGCCAUCAUCCGGUAUAUCGCCG
ACAAGCACAACAUGCUCGGCGGCUGCCCUAAAGAGCGGGCC
GAGAUUUCUAUGCUGGAAGGCGCCGUGCUGGACAUCAGAUA
CGGCGUGUCCAGAAUCGCCUACAGCAAGGACUUCGAAACCC
UGAAGGUGGACUUCCUGAGCAAGCUGCCCGAGAUGCUGAAG
AUGUUCGAGGACCGGCUGUGCCACAAGACCUACCUGAAUGG
CGACCACGUGACACACCCCGACUUCAUGCUGUACGACGCCCU
GGAUGUGGUGCUGUACAUGGACCCCAUGUGCCUGGACGCCU
UUCCAAAGCUCGUGUGCUUCAAGAAGCGGAUCGAGGCCAUU
CCUCAGAUCGACAAGUACCUGAAGUCCAGCAAGUAUAUCGC
UUGGCCCCUGCAAGGCUGGCAGGCCACAUUUGGAGGCGGAG
AUCACCCUCCUAAGAUGAGCAUCAGAGGCGUCGGCGGCAAC
GGCAACAGCAGAAUCCCUUCUCACAAUGGCGACGGCAGCAA
CAGGCGGAGCCAGAAUACCAAGGGCAACAACAAGGUGGAAG
AUCGCGUGUGCAGCCUGUACAGCUCCAGAAGCAACGAGAAC
CGCGAGAGCCCUUAUGCCGUGGUGGAUGUGUCCAGCAUGAU
CGAGAGCACCCCUACCAGCGGCGAGACAACAAGAGCUAGUA
GAGGCGUGCUGAGCCGGUUUCAGAGAGGCCUCGUUCGGAUU
GCCGACAAAGUGCGGAGAGCCGUGCAGUGUGCUUGGAGCAG
UGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGAAU
CUGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGC
UACAGAGAGUAUUCUCCAUCUGCCGCCAGAGGCCUGCGGCU
GAUGUUUACAGAUUUCUGGCGGACCCGGGUGCUGAGACAGA
CAUCUCCUAUGGCUGGCGUGUUCGGCAACCUGGACGUGAAC
GAAGCCAGACUGAUGGCCGCCUACACAAGCGAGUGUGCCGA
UCACCUGGAAGCCAAAGAACUGGCCGGACCUGAUGGCGUGG
CAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUG
CGGGACCUGCAGGAUAAGGGCGCUGCUAGAAAGCUGCUGAA
CGACCCUCUGGGCAGAAGAACCCCUAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GACCCCAGGUGGCCAACCUGCAGAAUGUGGAUACAGGCUUC
UGGCUGGACAUGAGCAACCUGAGCGACGUGGUCCUGAGCAG
AGAGAUCCAGACAGGCCUGAGAGCCAGAGCCACACUGGAAG
AGUCCAUGCCUAUGCUCGAGAAUCUGGAAGAACGGUUCAGA
CGGCUGCAAGAGACAUGCGACGCCGCCAGAACAGAGAUCGA
GGAAAGCGGCUGGACCAGAGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAAGGACCUAGCAGAGUGCAGCAGGCCUUC
CAGAGCUUCGUGAACGAGUGCAACAGCAUCGAGUUCAGCUU
CGGCUCCUUCGGCGAACAUGUGCGGGUGCUGUGUGCCAGAG
UUAGCAGAGGACUUGCUGCCGCUGGCGAGGCCAUCAGAAGA
UGCUUCUCUUGCUGCAAGGGCAGCACCCACAGAUACGCCCCU
AGAGAUGAUCUGAGCCCUGAGGGCGCAUCUCUGGCCGAAAC
ACUGGCCAGAUUUGCCGACGACAUGGGCAUUGAAAGAGGCG
CCGACGGAACCUACGACAUCCCUCUGGUGGACGAUUGGAGA
AGGGGCGUGCCAUCUAUCGAAGGCGAGGGCAGCGAUAGCAU
CUACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGG
ACCUGGAAACCCGGCGGAGCUUUGCCGUGCAACAGGGCCAU
UACCAGGAUCCUAGAGCCAGCGACUACGACCUGCCUAGAGCC
UCCGAUUAUGAUCUGCCUCGGAGCCCCUAUCCUACACCUCCU
CUGCCUCCAAGAUACCAGCUUCAGAAUAUGGACGUGGAAGC
CGGAUUCCGCGAGGCCGUGUAUGCUAGCUUUGUGGCCGGCA
UGUACAACUACGUGGUCACCCAGCCUCAAGAGAGAAUCCCC
AACAGCCAGCAGGUCGAGGGCAUCCUGAGAGAUAUGCUGAC
CAACGGCAGCCAGACCUUCCGCGACCUGAUGAAGAGAUGGA
ACAGAGAGGUGGACAGAGAGCACCACCACCAUCACCAU CT875_E_nFc
AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 354
GCUGCCUGAUACAACCGGCGAGCCUAAGAGCUGCGACAAGA
CCCACACCUGUCCUCCAUGUCCUGCUCCAGAACUGCUCGGCG
GACCUUCCGUGUUCCUGUUUCCUCCAAAGCCUAAGGACACCC
UGAUGAUCAGCAGAACCCCUGAAGUGACCUGCGUGGUGGUG
GAUGUGUCCCACGAGGAUCCCGAAGUGAAGUUCAAUUGGUA
CGUGGACGGCGUGGAAGUGCACAACGCCAAGACCAAGCCUA
GAGAGGAACAGUACAACAGCACCUACAGAGUGGUGUCCGUG
CUGACCGUGCUGCACCAGGAUUGGCUGAACGGCAAAGAGUA
CAAGUGCAAGGUGUCCAACAAGGCCCUGCCUGCUCCUAUCG
AGAAGACCAUCAGCAAGGCCAAGGGCCAGCCAAGAGAACCC
CAGGUGUACACACUGCCUCCAAGCAGAGAUGAGCUGACCAA
GAACCAGGUGUCCCUGACCUGUCUGGUCAAGGGCUUCUACC
CCUCCGAUAUCGCCGUGGAAUGGGAGAGCAAUGGCCAGCCU
GAGAACAACUACAAGACAACCCCUCCUGUGCUGGACAGCGA
CGGCUCAUUCUUCCUGUACAGCAAGCUGACAGUGGACAAGA
GCAGAUGGCAGCAGGGCAACGUGUUCAGCUGCAGCGUGAUG
CACGAGGCCCUGCACAAUCACUACACCCAGAAGUCCCUGUCU
CUGAGCCCCGGCAAGAUGAGCAUCAGAGGCGUUGGCGGCAA
CGGCAACAGCAGAAUCCCUAGCCAUAAUGGCGACGGCAGCA
ACAGGCGGAGCCAGAAUACCAAGGGCAACAACAAGGUGGAA
GAUCGCGUGUGCAGCCUGUACUCCAGCAGAAGCAACGAGAA
CCGCGAGAGCCCUUAUGCCGUGGUCGACGUGUCCAGCAUGA
UCGAGAGCACACCUACCAGCGGCGAGACAACCAGAGCUAGU
AGAGGCGUGCUGAGCCGGUUUCAGAGAGGCCUCGUUCGGAU
CGCUGACAAAGUGCGGAGAGCCGUGCAGUGUGCCUGGUCUA
GUGUGUCCACCAGCAGAUCCUCUGCCACAAGAGCCGCCGAGU
CUGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGC
UACAGAGAGUAUUCUCCAUCUGCCGCCAGAGGCCUGCGGCU
GAUGUUUACAGAUUUCUGGCGGACCCGGGUGCUGAGACAGA
CAUCUCCUAUGGCUGGCGUGUUCGGCAACCUGGAUGUGAAU
GAGGCCAGACUGAUGGCCGCCUACACAAGCGAAUGUGCCGA
UCACCUGGAAGCCAAAGAGCUGGCUGGACCUGACGGUGUUG
CCGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUG
CGGGACCUGCAGGAUAAGGGCGCUGCUAGAAAGCUGCUGAA
CGACCCUCUGGGCAGAAGAACCCCUAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GACCUCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUC
UGGCUGGAUAUGAGCAACCUGAGCGACGUGGUGCUGUCCAG
AGAGAUCCAGACAGGCCUGAGAGCCAGAGCCACACUGGAAG
AGUCCAUGCCUAUGCUCGAGAACCUGGAAGAGAGAUUCCGG
CGGCUGCAAGAGACAUGUGACGCCGCCAGAACCGAGAUCGA
GGAAAGCGGCUGGACCAGAGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAAGGACCUAGCAGAGUGCAGCAGGCCUUC
CAGAGCUUCGUGAACGAGUGCAACAGCAUCGAGUUCAGCUU
CGGCUCCUUCGGCGAACAUGUGCGGGUGCUGUGUGCCAGAG
UUAGCAGAGGACUUGCUGCCGCUGGCGAGGCCAUCAGAAGA
UGCUUCUCUUGCUGCAAGGGCAGCACCCACAGAUACGCCCCU
AGAGAUGAUCUGAGCCCUGAGGGCGCAUCUCUGGCCGAAAC
ACUGGCCAGAUUCGCCGACGAUAUGGGCAUUGAAAGAGGCG
CCGACGGAACCUACGACAUCCCUCUGGUGGACGAUUGGAGA
AGGGGCGUGCCAUCUAUCGAAGGCGAGGGCAGCGAUAGCAU
CUACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGG
ACCUGGAAACCCGGCGGAGCUUCGCUGUUCAGCAGGGCCAU
UACCAGGAUCCUAGAGCCAGCGACUACGACCUGCCUAGAGCC
UCCGAUUAUGAUCUGCCUCGGAGCCCCUAUCCUACACCUCCA
CUGCCACCUAGAUACCAGCUCCAGAAUAUGGACGUGGAAGC
CGGAUUCCGCGAGGCCGUGUAUGCUAGCUUUGUGGCCGGCA
UGUACAACUACGUGGUCACCCAGCCUCAAGAGCGGAUCCCCA
AUUCUCAGCAGGUCGAGGGCAUCCUGAGGGACAUGCUGACA
AAUGGCAGCCAGACCUUCCGGGACCUGAUGAAGAGAUGGAA CAGAGAGGUGGACAGAGAG
CT875_E_nFc_cHis AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 355
GCUGCCUGAUACAACCGGCGAGCCUAAGAGCUGCGACAAGA
CCCACACCUGUCCUCCAUGUCCUGCUCCAGAACUGCUCGGCG
GACCUUCCGUGUUCCUGUUUCCUCCAAAGCCUAAGGACACCC
UGAUGAUCAGCAGAACCCCUGAAGUGACCUGCGUGGUGGUG
GAUGUGUCCCACGAGGAUCCCGAAGUGAAGUUCAAUUGGUA
CGUGGACGGCGUGGAAGUGCACAACGCCAAGACCAAGCCUA
GAGAGGAACAGUACAACAGCACCUACAGAGUGGUGUCCGUG
CUGACCGUGCUGCACCAGGAUUGGCUGAACGGCAAAGAGUA
CAAGUGCAAGGUGUCCAACAAGGCCCUGCCUGCUCCUAUCG
AGAAGACCAUCAGCAAGGCCAAGGGCCAGCCAAGAGAACCC
CAGGUGUACACACUGCCUCCAAGCAGAGAUGAGCUGACCAA
GAACCAGGUGUCCCUGACCUGUCUGGUCAAGGGCUUCUACC
CCUCCGAUAUCGCCGUGGAAUGGGAGAGCAAUGGCCAGCCU
GAGAACAACUACAAGACAACCCCUCCUGUGCUGGACAGCGA
CGGCUCAUUCUUCCUGUACAGCAAGCUGACAGUGGACAAGA
GCAGAUGGCAGCAGGGCAACGUGUUCAGCUGCAGCGUGAUG
CACGAGGCCCUGCACAAUCACUACACCCAGAAGUCCCUGUCU
CUGAGCCCCGGCAAGAUGAGCAUCAGAGGCGUUGGCGGCAA
CGGCAACAGCAGAAUCCCUAGCCAUAAUGGCGACGGCAGCA
ACAGGCGGAGCCAGAAUACCAAGGGCAACAACAAGGUGGAA
GAUCGCGUGUGCAGCCUGUACUCCAGCAGAAGCAACGAGAA
CCGCGAGAGCCCUUAUGCCGUGGUCGACGUGUCCAGCAUGA
UCGAGAGCACACCUACCAGCGGCGAGACAACCAGAGCUAGU
AGAGGCGUGCUGAGCCGGUUUCAGAGAGGCCUCGUUCGGAU
CGCUGACAAAGUGCGGAGAGCCGUGCAGUGUGCCUGGUCUA
GUGUGUCCACCAGCAGAUCCUCUGCCACAAGAGCCGCCGAGU
CUGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCGGC
UACAGAGAGUAUUCUCCAUCUGCCGCCAGAGGCCUGCGGCU
GAUGUUUACAGAUUUCUGGCGGACCCGGGUGCUGAGACAGA
CAUCUCCUAUGGCUGGCGUGUUCGGCAACCUGGAUGUGAAU
GAGGCCAGACUGAUGGCCGCCUACACAAGCGAAUGUGCCGA
UCACCUGGAAGCCAAAGAGCUGGCUGGACCUGACGGUGUUG
CCGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGUG
CGGGACCUGCAGGAUAAGGGCGCUGCUAGAAAGCUGCUGAA
CGACCCUCUGGGCAGAAGAACCCCUAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GACCUCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUC
UGGCUGGAUAUGAGCAACCUGAGCGACGUGGUGCUGUCCAG
AGAGAUCCAGACAGGCCUGAGAGCCAGAGCCACACUGGAAG
AGUCCAUGCCUAUGCUCGAGAACCUGGAAGAGAGAUUCCGG
CGGCUGCAAGAGACAUGUGACGCCGCCAGAACCGAGAUCGA
GGAAAGCGGCUGGACCAGAGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAAGGACCUAGCAGAGUGCAGCAGGCCUUC
CAGAGCUUCGUGAACGAGUGCAACAGCAUCGAGUUCAGCUU
CGGCUCCUUCGGCGAACAUGUGCGGGUGCUGUGUGCCAGAG
UUAGCAGAGGACUUGCUGCCGCUGGCGAGGCCAUCAGAAGA
UGCUUCUCUUGCUGCAAGGGCAGCACCCACAGAUACGCCCCU
AGAGAUGAUCUGAGCCCUGAGGGCGCAUCUCUGGCCGAAAC
ACUGGCCAGAUUCGCCGACGAUAUGGGCAUUGAAAGAGGCG
CCGACGGAACCUACGACAUCCCUCUGGUGGACGAUUGGAGA
AGGGGCGUGCCAUCUAUCGAAGGCGAGGGCAGCGAUAGCAU
CUACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGG
ACCUGGAAACCCGGCGGAGCUUCGCUGUUCAGCAGGGCCAU
UACCAGGAUCCUAGAGCCAGCGACUACGACCUGCCUAGAGCC
UCCGAUUAUGAUCUGCCUCGGAGCCCCUAUCCUACACCUCCA
CUGCCACCUAGAUACCAGCUCCAGAAUAUGGACGUGGAAGC
CGGAUUCCGCGAGGCCGUGUAUGCUAGCUUUGUGGCCGGCA
UGUACAACUACGUGGUCACCCAGCCUCAAGAGCGGAUCCCCA
AUUCUCAGCAGGUCGAGGGCAUCCUGAGGGACAUGCUGACA
AAUGGCAGCCAGACCUUCCGGGACCUGAUGAAGAGAUGGAA
CAGAGAGGUGGACCGCGAGCACCACCACCAUCACCAU CT043_E_NGM_nIgK_no4A
AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 356
GCUGCCUGAUACCACCGGAAUGAGCAGACAGAACGCCGAGG
AGAACCUGAAGAACUUCGCCAAAGAGCUGAAGCUGCCCGAC
GUGGCCUUCGACCAGAACAAUGCCUGCAUCCUGUUCGUGGA
CGGCGAGUUCUCUCUGCACCUGACCUACGAGGAACACAGCG
ACCGGCUGUAUGUGUACGCCCCUCUGCUGGAUGGCCUGCCU
GACAACCCUCAGAGAAAGCUGGCCCUGUACGAGAAGCUGCU
GGAAGGCUCUAUGCUCGGCGGACAAAUGGCUGGUGGCGGAG
UGGGAGUUGCCACCAAAGAACAGCUGAUCCUGAUGCACUGC
GUGCUGGACAUGAAGUACGCCGAGACUAACCUGCUGAAGGC
UUUCGCCCAGCUGUUCAUCGAGACAGUGGUCAAGUGGCGGA
CCGUGUGCAGCGAUAUUAGCGCCGGCAGAGAACCCACCGUG
GACACCAUGCCUCAAAUGCCACAAGGCGGCGGAGGCGGAAU
UCAACCUCCUCCAGCCGGAAUUAGAGCC CT043_E_NGM_nIgK_cHis_no4A
AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 357
GCUGCCUGAUACCACCGGAAUGAGCAGACAGAACGCCGAGG
AGAACCUGAAGAACUUCGCCAAAGAGCUGAAGCUGCCCGAC
GUGGCCUUCGACCAGAACAAUGCCUGCAUCCUGUUCGUGGA
CGGCGAGUUCUCUCUGCACCUGACCUACGAGGAACACAGCG
ACCGGCUGUAUGUGUACGCCCCUCUGCUGGAUGGCCUGCCU
GACAACCCUCAGAGAAAGCUGGCCCUGUACGAGAAGCUGCU
GGAAGGCUCUAUGCUCGGCGGACAAAUGGCUGGUGGCGGAG
UGGGAGUUGCCACCAAAGAACAGCUGAUCCUGAUGCACUGC
GUGCUGGACAUGAAGUACGCCGAGACUAACCUGCUGAAGGC
UUUCGCCCAGCUGUUCAUCGAGACAGUGGUCAAGUGGCGGA
CCGUGUGCAGCGAUAUUAGCGCCGGCAGAGAACCCACCGUG
GACACCAUGCCUCAAAUGCCACAAGGCGGCGGAGGCGGAAU
UCAACCUCCUCCAGCCGGAAUCAGAGCCCACCACCAUCACCA UCAU CT043_E_nIgK_no4A
AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 358
GCUGCCUGAUACCACCGGAAUGAGCAGACAGAACGCCGAGG
AGAACCUGAAGAACUUCGCCAAAGAGCUGAAGCUGCCCGAC
GUGGCCUUCGACCAGAACAAUACCUGCAUCCUGUUCGUGGA
CGGCGAGUUCAGCCUGCACCUGACCUACGAGGAACACAGCG
ACCGGCUGUAUGUGUACGCCCCUCUGCUGGAUGGCCUGCCU
GACAACCCUCAGAGAAAGCUGGCCCUGUACGAGAAGCUGCU
GGAAGGCUCUAUGCUCGGCGGACAAAUGGCUGGUGGCGGAG
UGGGAGUUGCCACCAAAGAACAGCUGAUCCUGAUGCACUGC
GUGCUGGACAUGAAGUACGCCGAGACUAACCUGCUGAAGGC
UUUCGCCCAGCUGUUCAUCGAGACAGUGGUCAAGUGGCGGA
CCGUGUGCAGCGAUAUUAGCGCCGGCAGAGAACCCACCGUG
GACACCAUGCCUCAAAUGCCACAAGGCGGCGGAGGCGGAAU
UCAACCUCCUCCAGCCGGAAUUAGAGCC CT043_E_nIgK_cHis_no4A
AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 359
GCUGCCUGAUACCACCGGAAUGAGCAGACAGAACGCCGAGG
AGAACCUGAAGAACUUCGCCAAAGAGCUGAAGCUGCCCGAC
GUGGCCUUCGACCAGAACAAUACCUGCAUCCUGUUCGUGGA
CGGCGAGUUCAGCCUGCACCUGACCUACGAGGAACACAGCG
ACCGGCUGUAUGUGUACGCCCCUCUGCUGGAUGGCCUGCCU
GACAACCCUCAGAGAAAGCUGGCCCUGUACGAGAAGCUGCU
GGAAGGCUCUAUGCUCGGCGGACAAAUGGCUGGUGGCGGAG
UGGGAGUUGCCACCAAAGAACAGCUGAUCCUGAUGCACUGC
GUGCUGGACAUGAAGUACGCCGAGACUAACCUGCUGAAGGC
UUUCGCCCAGCUGUUCAUCGAGACAGUGGUCAAGUGGCGGA
CCGUGUGCAGCGAUAUUAGCGCCGGCAGAGAACCCACCGUG
GACACCAUGCCUCAAAUGCCACAAGGCGGCGGAGGCGGAAU
UCAACCUCCUCCAGCCGGAAUCAGAGCCCACCACCAUCACCA UCAU
Chlamydia_CT812_pd_serovarD_nIgK_cHis_nopolyN
AUGGAAACUCCUGCCCAACUGUUGUUCCUUCUGCUGCUCUG 360
GUUGCCCGACACCACCGGAUCGUGCGUGGAUCUCCACGCUGG
CGGCCAGUCCGUGAACGAGCUUGUGUACGUGGGCCCACAGG
CCGUGCUUCUGCUGGACCAGAUCAGAGAUCUCUUCGUGGGU
UCCAAGGACUCCCAGGCCGAGGGACAGUACCGGCUCAUCGUC
GGCGACCCUUCAAGCUUCCAAGAGAAGGAUGCCGACACUCU
UCCGGGGAAGGUGGAACAGUCCACUCUGUUUUCCGUGACCA
ACCCAGUCGUGUUUCAAGGGGUGGACCAGCAGGACCAGGUG
UCCAGCCAAGGACUGAUCUGUUCAUUCACCUCGAGCAAUUU
GGACAGCCCCCGGGACGGCGAAUCGUUCCUUGGCAUCGCAU
UCGUGGGAGACUCAUCCAAAGCAGGAAUCACCCUUACCGAU
GUGAAGGCGUCCCUGAGCGGCGCUGCUCUGUACUCCACCGA
AGAUCUCAUCUUCGAGAAGAUCAAGGGUGGACUGGAGUUCG
CCAGCUGCUCCUCACUGGAACAGGGAGGAGCCUGUGCCGCCC
AAAGCAUCCUCAUCCACGAUUGCCAGGGGCUCCAAGUGAAG
CAUUGUACCACUGCCGUGAACGCCGAGGGAUCAUCCGCUAA
CGAUCACCUCGGUUUCGGAGGGGGUGCCUUCUUCGUGACCG
GUUCGCUGUCGGGAGAGAAGUCACUGUAUAUGCCCGCGGGC
GACAUGGUGGUCGCCAACUGCGAUGGAGCCAUCUCAUUCGA
GGGAAACUCCGCCAACUUCGCAAACGGCGGCGCUAUCGCCGC
UAGCGGGAAGGUGCUGUUCGUGGCUAACGACAAGAAGACGU
CCUUCAUCGAGAACCGCGCCCUGUCGGGAGGUGCCAUUGCCG
CCAGCUCCGACAUUGCCUUCCAGAACUGUGCGGAACUGGUG
UUCAAAGGAAACUGCGCCAUCGGCACCGAAGAUAAGGGAAG
CCUGGGAGGCGGCGCCAUUUCCUCCCUCGGCACCGUGCUGCU
UCAGGGAAACCACGGCAUCACUUGUGACAAGAACGAAAGCG
CGUCCCAGGGGGGAGCGAUCUUCGGGAAGAACUGCCAGAUU
UCCGACAACGAGGGACCGGUGGUGUUCAGAGACUCCACUGC
CUGCCUGGGCGGCGGAGCGAUCGCAGCACAGGAAAUUGUCA
GCAUCCAGAACAACCAGGCCGGCAUCAGCUUCGAGGGGGGA
AAGGCUUCGUUCGGCGGAGGUAUUGCCUGCGGAUCGUUCUC
GUCCGCGGGCGGAGCCUCCGUGCUCGGAACCAUCGACAUUUC
CAAGAACCUGGGCGCUAUCUCGUUUUCUCGCACCCUGUGCAC
UACUUCCGACCUGGGUCAGAUGGAGUACCAGGGAGGCGGAG
CGCUGUUUGGAGAGAACAUCUCUCUGAGCGAGAACGCGGGA
GUGCUGACCUUCAAGGACAACAUUGUGAAGACCUUCGCCUC
AAACGGAAAGAUCCUGGGGGGAGGCGCCAUCCUGGCAACCG
GGAAGGUCGAAAUCACCAACAAUUCAGAGGGUAUCUCCUUC
ACUGGCAACGCCCGGGCCCCCCAAGCCCUGCCGACUCAGGAA
GAGUUCCCCCUGUUCUCCAAGAAGGAAGGACGCCCUUUGUC
AUCCGGCUACUCCGGUGGUGGAGCGAUUCUGGGUCGGGAAG
UGGCCAUCCUGCAUAAUGCGGCCGUGGUGUUUGAGCAGAAC
AGACUCCAAUGCUCCGAAGAAGAGGCCACCCUCCUGGGGUG
CUGCGGGGGCGGAGCAGUGCAUGGCAUGGAUUCCACUUCCA
UCGUGGGAAACUCCAGCGUCCGCUUCGGAAACAACUACGCU
AUGGGACAGGGAGUGUCAGGCGGGGCCCUGCUGUCCAAGAC
CGUCCAGUUGGCCGGAAACGGUUCGGUGGAUUUCUCACGCA
AUAUCGCCUCGCUGGGAGGCGGCGCGCUGCAGGCCUCCGAA
GGAAAUUGCGAACUGGUCGACAACGGCUACGUGCUGUUCCG
GGACAACCGCGGCAGGGUGUACGGCGGAGCAAUCUCGUGCC
UUCGGGGCGACGUCGUGAUCUCGGGAAAUAAGGGACGGGUC
GAGUUUAAGGACAACAUCGCUACCAGGCUCUACGUGGAGGA
AACUGUGGAGAAGGUGGAGGAAGUGGAGCCUGCCCCGGAAC
AGAAGGACAACAACGAGCUGUCGUUCCUCGGUCGGGCAGAA
CAGUCCUUCAUUACUGCCGCCAACCAGGCCCUGUUCGCGUCC
GAAGAUGGUGACCUCAGCCCGGAAUCCAGCAUCUCCUCCGA
GGAACUGGCCAAGCGGAGAGAAUGCGCGGGAGGCGCAAUCU
UUGCGAAGCGGGUCCGGAUCGUGGACAACCAGGAAGCUGUG
GUGUUCAGCAACAACUUUUCCGACAUCUACGGUGGUGCAAU
UUUCACCGGCUCACUCCGGGAGGAGGACAAGCUGGACGGCC
AGAUUCCCGAGGUGCUCAUUUCCGGCAAUGCCGGCGACGUG
GUGUUCUCCGGAAACUCCUCCAAGAGGGACGAACACCUCCCG
CAUACCGGAGGAGGAGCCAUCUGCACUCAGAACCUGACGAU
CUCGCAGAACACCGGCAAUGUGCUGUUCUACAACAACGUCG
CAUGUUCCGGUGGCGCCGUCAGAAUCGAGGACCACGGAAAC
GUGCUGCUGGAAGCAUUCGGGGGUGAUAUUGUGUUCAAGGG
AAACAGCAGCUUCCGGGCCCAGGGAUCAGAUGCAAUCUACU
UCGCCGGGAAGGAGAGCCACAUUACCGCCCUGAACGCCACCG
AGGGUCACGCCAUCGUGUUCCACGAUGCCCUGGUGUUCGAG
AACCUGGAGGAGCGCAAGAGCGCCGAAGUGCUGCUUAUCAA
UUCCCGCGAGAACCCGGGCUACACCGGAUCCAUCCGGUUCCU
CGAAGCGGAGUCGAAGGUCCCGCAGUGUAUUCAUGUGCAAC
AGGGGUCCCUGGAACUGCUUAACGGAGCCACCCUGUGCUCC
UACGGCUUUAAGCAGGACGCGGGCGCUAAACUGGUGCUGGC
GGCCGGCGCCAAGCUUAAGAUCCUCGACUCCGGAACCCCGGU
GCAGCAGGGGCACGCUAUUAGCAAGCCUGAAGCCGAGAUUG
AGUCGUCAUCCGAACCCGAAGGGGCGCACUCCCUGUGGAUA
GCCAAGAACGCGCAGACCACCGUGCCAAUGGUCGAUAUCCAC
ACAAUCUCCGUGGACCUCGCCAGCUUCUCGUCGAGCCAGCAG
GAGGGAACUGUCGAAGCGCCUCAGGUCAUCGUGCCGGGAGG
UUCCUACGUGCGCUCGGGGGAGCUCAACCUGGAACUCGUGA
AUACCACUGGAACGGGAUAUGAGAACCACGCCCUGCUGAAG
AACGAAGCCAAAGUGCCACUGAUGUCCUUCGUCGCCUCCGGC
GACGAGGCCUCCGCCGAGAUUAGCAACCUGUCGGUGUCAGA
UCUGCAAAUUCACGUGGUGACCCCUGAGAUUGAGGAGGACA
CCUACGGGCACAUGGGCGAUUGGUCCGAGGCGAAGAUCCAG
GACGGCACACUGGUCAUUUCAUGGAACCCUACCGGACAUCA CCACCACCAUCAC
Chlamydia_CT812_pd_serovarD_nIgK_nopolyN
AUGGAAACUCCUGCCCAACUGUUGUUCCUUCUGCUGCUCUG 361
GUUGCCCGACACCACCGGAUCGUGCGUGGAUCUCCACGCUGG
CGGCCAGUCCGUGAACGAGCUUGUGUACGUGGGCCCACAGG
CCGUGCUUCUGCUGGACCAGAUCAGAGAUCUCUUCGUGGGU
UCCAAGGACUCCCAGGCCGAGGGACAGUACCGGCUCAUCGUC
GGCGACCCUUCAAGCUUCCAAGAGAAGGAUGCCGACACUCU
UCCGGGGAAGGUGGAACAGUCCACUCUGUUUUCCGUGACCA
ACCCAGUCGUGUUUCAAGGGGUGGACCAGCAGGACCAGGUG
UCCAGCCAAGGACUGAUCUGUUCAUUCACCUCGAGCAAUUU
GGACAGCCCCCGGGACGGCGAAUCGUUCCUUGGCAUCGCAU
UCGUGGGAGACUCAUCCAAAGCAGGAAUCACCCUUACCGAU
GUGAAGGCGUCCCUGAGCGGCGCUGCUCUGUACUCCACCGA
AGAUCUCAUCUUCGAGAAGAUCAAGGGUGGACUGGAGUUCG
CCAGCUGCUCCUCACUGGAACAGGGAGGAGCCUGUGCCGCCC
AAAGCAUCCUCAUCCACGAUUGCCAGGGGCUCCAAGUGAAG
CAUUGUACCACUGCCGUGAACGCCGAGGGAUCAUCCGCUAA
CGAUCACCUCGGUUUCGGAGGGGGUGCCUUCUUCGUGACCG
GUUCGCUGUCGGGAGAGAAGUCACUGUAUAUGCCCGCGGGC
GACAUGGUGGUCGCCAACUGCGAUGGAGCCAUCUCAUUCGA
GGGAAACUCCGCCAACUUCGCAAACGGCGGCGCUAUCGCCGC
UAGCGGGAAGGUGCUGUUCGUGGCUAACGACAAGAAGACGU
CCUUCAUCGAGAACCGCGCCCUGUCGGGAGGUGCCAUUGCCG
CCAGCUCCGACAUUGCCUUCCAGAACUGUGCGGAACUGGUG
UUCAAAGGAAACUGCGCCAUCGGCACCGAAGAUAAGGGAAG
CCUGGGAGGCGGCGCCAUUUCCUCCCUCGGCACCGUGCUGCU
UCAGGGAAACCACGGCAUCACUUGUGACAAGAACGAAAGCG
CGUCCCAGGGGGGAGCGAUCUUCGGGAAGAACUGCCAGAUU
UCCGACAACGAGGGACCGGUGGUGUUCAGAGACUCCACUGC
CUGCCUGGGCGGCGGAGCGAUCGCAGCACAGGAAAUUGUCA
GCAUCCAGAACAACCAGGCCGGCAUCAGCUUCGAGGGGGGA
AAGGCUUCGUUCGGCGGAGGUAUUGCCUGCGGAUCGUUCUC
GUCCGCGGGCGGAGCCUCCGUGCUCGGAACCAUCGACAUUUC
CAAGAACCUGGGCGCUAUCUCGUUUUCUCGCACCCUGUGCAC
UACUUCCGACCUGGGUCAGAUGGAGUACCAGGGAGGCGGAG
CGCUGUUUGGAGAGAACAUCUCUCUGAGCGAGAACGCGGGA
GUGCUGACCUUCAAGGACAACAUUGUGAAGACCUUCGCCUC
AAACGGAAAGAUCCUGGGGGGAGGCGCCAUCCUGGCAACCG
GGAAGGUCGAAAUCACCAACAAUUCAGAGGGUAUCUCCUUC
ACUGGCAACGCCCGGGCCCCCCAAGCCCUGCCGACUCAGGAA
GAGUUCCCCCUGUUCUCCAAGAAGGAAGGACGCCCUUUGUC
AUCCGGCUACUCCGGUGGUGGAGCGAUUCUGGGUCGGGAAG
UGGCCAUCCUGCAUAAUGCGGCCGUGGUGUUUGAGCAGAAC
AGACUCCAAUGCUCCGAAGAAGAGGCCACCCUCCUGGGGUG
CUGCGGGGGCGGAGCAGUGCAUGGCAUGGAUUCCACUUCCA
UCGUGGGAAACUCCAGCGUCCGCUUCGGAAACAACUACGCU
AUGGGACAGGGAGUGUCAGGCGGGGCCCUGCUGUCCAAGAC
CGUCCAGUUGGCCGGAAACGGUUCGGUGGAUUUCUCACGCA
AUAUCGCCUCGCUGGGAGGCGGCGCGCUGCAGGCCUCCGAA
GGAAAUUGCGAACUGGUCGACAACGGCUACGUGCUGUUCCG
GGACAACCGCGGCAGGGUGUACGGCGGAGCAAUCUCGUGCC
UUCGGGGCGACGUCGUGAUCUCGGGAAAUAAGGGACGGGUC
GAGUUUAAGGACAACAUCGCUACCAGGCUCUACGUGGAGGA
AACUGUGGAGAAGGUGGAGGAAGUGGAGCCUGCCCCGGAAC
AGAAGGACAACAACGAGCUGUCGUUCCUCGGUCGGGCAGAA
CAGUCCUUCAUUACUGCCGCCAACCAGGCCCUGUUCGCGUCC
GAAGAUGGUGACCUCAGCCCGGAAUCCAGCAUCUCCUCCGA
GGAACUGGCCAAGCGGAGAGAAUGCGCGGGAGGCGCAAUCU
UUGCGAAGCGGGUCCGGAUCGUGGACAACCAGGAAGCUGUG
GUGUUCAGCAACAACUUUUCCGACAUCUACGGUGGUGCAAU
UUUCACCGGCUCACUCCGGGAGGAGGACAAGCUGGACGGCC
AGAUUCCCGAGGUGCUCAUUUCCGGCAAUGCCGGCGACGUG
GUGUUCUCCGGAAACUCCUCCAAGAGGGACGAACACCUCCCG
CAUACCGGAGGAGGAGCCAUCUGCACUCAGAACCUGACGAU
CUCGCAGAACACCGGCAAUGUGCUGUUCUACAACAACGUCG
CAUGUUCCGGUGGCGCCGUCAGAAUCGAGGACCACGGAAAC
GUGCUGCUGGAAGCAUUCGGGGGUGAUAUUGUGUUCAAGGG
AAACAGCAGCUUCCGGGCCCAGGGAUCAGAUGCAAUCUACU
UCGCCGGGAAGGAGAGCCACAUUACCGCCCUGAACGCCACCG
AGGGUCACGCCAUCGUGUUCCACGAUGCCCUGGUGUUCGAG
AACCUGGAGGAGCGCAAGAGCGCCGAAGUGCUGCUUAUCAA
UUCCCGCGAGAACCCGGGCUACACCGGAUCCAUCCGGUUCCU
CGAAGCGGAGUCGAAGGUCCCGCAGUGUAUUCAUGUGCAAC
AGGGGUCCCUGGAACUGCUUAACGGAGCCACCCUGUGCUCC
UACGGCUUUAAGCAGGACGCGGGCGCUAAACUGGUGCUGGC
GGCCGGCGCCAAGCUUAAGAUCCUCGACUCCGGAACCCCGGU
GCAGCAGGGGCACGCUAUUAGCAAGCCUGAAGCCGAGAUUG
AGUCGUCAUCCGAACCCGAAGGGGCGCACUCCCUGUGGAUA
GCCAAGAACGCGCAGACCACCGUGCCAAUGGUCGAUAUCCAC
ACAAUCUCCGUGGACCUCGCCAGCUUCUCGUCGAGCCAGCAG
GAGGGAACUGUCGAAGCGCCUCAGGUCAUCGUGCCGGGAGG
UUCCUACGUGCGCUCGGGGGAGCUCAACCUGGAACUCGUGA
AUACCACUGGAACGGGAUAUGAGAACCACGCCCUGCUGAAG
AACGAAGCCAAAGUGCCACUGAUGUCCUUCGUCGCCUCCGGC
GACGAGGCCUCCGCCGAGAUUAGCAACCUGUCGGUGUCAGA
UCUGCAAAUUCACGUGGUGACCCCUGAGAUUGAGGAGGACA
CCUACGGGCACAUGGGCGAUUGGUCCGAGGCGAAGAUCCAG
GACGGCACACUGGUCAUUUCAUGGAACCCUACCGGA
CT812pd_PmpD_D_NGM_nIgK_nopolyN
AUGGAAACUCCUGCCCAACUGUUGUUCCUUCUGCUGCUCUG 362
GUUGCCCGACACCACCGGAUCGUGCGUGGAUCUCCACGCUGG
CGGCCAGUCCGUGAACGAGCUUGUGUACGUGGGCCCACAGG
CCGUGCUUCUGCUGGACCAGAUCAGAGAUCUCUUCGUGGGU
UCCAAGGACUCCCAGGCCGAGGGACAGUACCGGCUCAUCGUC
GGCGACCCUUCAAGCUUCCAAGAGAAGGAUGCCGACACUCU
UCCGGGGAAGGUGGAACAGUCCACUCUGUUUUCCGUGACCA
ACCCAGUCGUGUUUCAAGGGGUGGACCAGCAGGACCAGGUG
UCCAGCCAAGGACUGAUCUGUUCAUUCACCUCGAGCAAUUU
GGACAGCCCCCGGGACGGCGAAUCGUUCCUUGGCAUCGCAU
UCGUGGGAGACUCAUCCAAAGCAGGAAUCACCCUUACCGAU
GUGAAGGCGUCCCUGAGCGGCGCUGCUCUGUACUCCACCGA
AGAUCUCAUCUUCGAGAAGAUCAAGGGUGGACUGGAGUUCG
CCAGCUGCUCCUCACUGGAACAGGGAGGAGCCUGUGCCGCCC
AAAGCAUCCUCAUCCACGAUUGCCAGGGGCUCCAAGUGAAG
CAUUGUACCACUGCCGUGAACGCCGAGGGAUCAUCCGCUAA
CGAUCACCUCGGUUUCGGAGGGGGUGCCUUCUUCGUGACCG
GUUCGCUGUCGGGAGAGAAGUCACUGUAUAUGCCCGCGGGC
GACAUGGUGGUCGCCAACUGCGAUGGAGCCAUCUCAUUCGA
GGGAAACUCCGCCAACUUCGCAAACGGCGGCGCUAUCGCCGC
UAGCGGGAAGGUGCUGUUCGUGGCUAACGACAAGAAGACGU
CCUUCAUCGAGAACCGCGCCCUGUCGGGAGGUGCCAUUGCCG
CCAGCUCCGACAUUGCCUUCCAGAACUGUGCGGAACUGGUG
UUCAAAGGAAACUGCGCCAUCGGCACCGAAGAUAAGGGAAG
CCUGGGAGGCGGCGCCAUUUCCUCCCUCGGCACCGUGCUGCU
UCAGGGAAACCACGGCAUCACUUGUGACAAGAACGAAGCAG
CGUCCCAGGGGGGAGCGAUCUUCGGGAAGAACUGCCAGAUU
UCCGACAACGAGGGACCGGUGGUGUUCAGAGACUCCACUGC
CUGCCUGGGCGGCGGAGCGAUCGCAGCACAGGAAAUUGUCA
GCAUCCAGAACAACCAGGCCGGCAUCAGCUUCGAGGGGGGA
AAGGCUUCGUUCGGCGGAGGUAUUGCCUGCGGAUCGUUCUC
GUCCGCGGGCGGAGCCUCCGUGCUCGGAACCAUCGACAUUUC
CAAGAACCUGGGCGCUAUCUCGUUUUCUCGCACCCUGUGCAC
UACUUCCGACCUGGGUCAGAUGGAGUACCAGGGAGGCGGAG
CGCUGUUUGGAGAGAACAUCGCUCUGAGCGAGAACGCGGGA
GUGCUGACCUUCAAGGACAACAUUGUGAAGACCUUCGCCUC
AAACGGAAAGAUCCUGGGGGGAGGCGCCAUCCUGGCAACCG
GGAAGGUCGAAAUCACCAACAAUGCAGAGGGUAUCUCCUUC
ACUGGCAACGCCCGGGCCCCCCAAGCCCUGCCGACUCAGGAA
GAGUUCCCCCUGUUCUCCAAGAAGGAAGGACGCCCUUUGUC
AUCCGGCUACUCCGGUGGUGGAGCGAUUCUGGGUCGGGAAG
UGGCCAUCCUGCAUAAUGCGGCCGUGGUGUUUGAGCAGAAC
AGACUCCAAUGCUCCGAAGAAGAGGCCACCCUCCUGGGGUG
CUGCGGGGGCGGAGCAGUGCAUGGCAUGGAUUCCACUUCCA
UCGUGGGAAACUCCGCAGUCCGCUUCGGAAACAACUACGCU
AUGGGACAGGGAGUGUCAGGCGGGGCCCUGCUGUCCAAGAC
CGUCCAGUUGGCCGGAAACGGUGCGGUGGAUUUCUCACGCA
AUAUCGCCUCGCUGGGAGGCGGCGCGCUGCAGGCCUCCGAA
GGAAAUUGCGAACUGGUCGACAACGGCUACGUGCUGUUCCG
GGACAACCGCGGCAGGGUGUACGGCGGAGCAAUCUCGUGCC
UUCGGGGCGACGUCGUGAUCUCGGGAAAUAAGGGACGGGUC
GAGUUUAAGGACAACAUCGCUACCAGGCUCUACGUGGAGGA
AACUGUGGAGAAGGUGGAGGAAGUGGAGCCUGCCCCGGAAC
AGAAGGACAACAACGAGCUGUCGUUCCUCGGUCGGGCAGAA
CAGUCCUUCAUUACUGCCGCCAACCAGGCCCUGUUCGCGUCC
GAAGAUGGUGACCUCAGCCCGGAAUCCAGCAUCUCCUCCGA
GGAACUGGCCAAGCGGAGAGAAUGCGCGGGAGGCGCAAUCU
UUGCGAAGCGGGUCCGGAUCGUGGACAACCAGGAAGCUGUG
GUGUUCAGCAACAACUUUGCCGACAUCUACGGUGGUGCAAU
UUUCACCGGCUCACUCCGGGAGGAGGACAAGCUGGACGGCC
AGAUUCCCGAGGUGCUCAUUUCCGGCAAUGCCGGCGACGUG
GUGUUCUCCGGAAACUCCGCCAAGAGGGACGAACACCUCCCG
CAUACCGGAGGAGGAGCCAUCUGCACUCAGAACCUGGCAAU
CUCGCAGAACACCGGCAAUGUGCUGUUCUACAACAACGUCG
CAUGUUCCGGUGGCGCCGUCAGAAUCGAGGACCACGGAAAC
GUGCUGCUGGAAGCAUUCGGGGGUGAUAUUGUGUUCAAGGG
AAACAGCGCAUUCCGGGCCCAGGGAUCAGAUGCAAUCUACU
UCGCCGGGAAGGAGAGCCACAUUACCGCCCUGAACGCCGCCG
AGGGUCACGCCAUCGUGUUCCACGAUGCCCUGGUGUUCGAG
AACCUGGAGGAGCGCAAGAGCGCCGAAGUGCUGCUUAUCAA
UUCCCGCGAGAACCCGGGCUACACCGGAUCCAUCCGGUUCCU
CGAAGCGGAGUCGAAGGUCCCGCAGUGUAUUCAUGUGCAAC
AGGGGUCCCUGGAACUGCUUAACGGAGCCACCCUGUGCUCC
UACGGCUUUAAGCAGGACGCGGGCGCUAAACUGGUGCUGGC
GGCCGGCGCCAAGCUUAAGAUCCUCGACUCCGGAACCCCGGU
GCAGCAGGGGCACGCUAUUAGCAAGCCUGAAGCCGAGAUUG
AGUCGUCAUCCGAACCCGAAGGGGCGCACUCCCUGUGGAUA
GCCAAGAACGCGCAGACCACCGUGCCAAUGGUCGAUAUCCAC
ACAAUCUCCGUGGACCUCGCCAGCUUCUCGUCGAGCCAGCAG
GAGGGAACUGUCGAAGCGCCUCAGGUCAUCGUGCCGGGAGG
UUCCUACGUGCGCUCGGGGGAGCUCAACCUGGAACUCGUGA
AUACCGCUGGAACGGGAUAUGAGAACCACGCCCUGCUGAAG
AACGAAGCCAAAGUGCCACUGAUGUCCUUCGUCGCCUCCGGC
GACGAGGCCUCCGCCGAGAUUAGCAACCUGGCGGUGUCAGA
UCUGCAAAUUCACGUGGUGACCCCUGAGAUUGAGGAGGACA
CCUACGGGCACAUGGGCGAUUGGUCCGAGGCGAAGAUCCAG
GACGGCACACUGGUCAUUUCAUGGAACCCUGCCGGA
CT812pd_PmpD_D_NGM_nIgK_cHis_nopolyN
AUGGAAACUCCUGCCCAACUGUUGUUCCUUCUGCUGCUCUG 363
GUUGCCCGACACCACCGGAUCGUGCGUGGAUCUCCACGCUGG
CGGCCAGUCCGUGAACGAGCUUGUGUACGUGGGCCCACAGG
CCGUGCUUCUGCUGGACCAGAUCAGAGAUCUCUUCGUGGGU
UCCAAGGACUCCCAGGCCGAGGGACAGUACCGGCUCAUCGUC
GGCGACCCUUCAAGCUUCCAAGAGAAGGAUGCCGACACUCU
UCCGGGGAAGGUGGAACAGUCCACUCUGUUUUCCGUGACCA
ACCCAGUCGUGUUUCAAGGGGUGGACCAGCAGGACCAGGUG
UCCAGCCAAGGACUGAUCUGUUCAUUCACCUCGAGCAAUUU
GGACAGCCCCCGGGACGGCGAAUCGUUCCUUGGCAUCGCAU
UCGUGGGAGACUCAUCCAAAGCAGGAAUCACCCUUACCGAU
GUGAAGGCGUCCCUGAGCGGCGCUGCUCUGUACUCCACCGA
AGAUCUCAUCUUCGAGAAGAUCAAGGGUGGACUGGAGUUCG
CCAGCUGCUCCUCACUGGAACAGGGAGGAGCCUGUGCCGCCC
AAAGCAUCCUCAUCCACGAUUGCCAGGGGCUCCAAGUGAAG
CAUUGUACCACUGCCGUGAACGCCGAGGGAUCAUCCGCUAA
CGAUCACCUCGGUUUCGGAGGGGGUGCCUUCUUCGUGACCG
GUUCGCUGUCGGGAGAGAAGUCACUGUAUAUGCCCGCGGGC
GACAUGGUGGUCGCCAACUGCGAUGGAGCCAUCUCAUUCGA
GGGAAACUCCGCCAACUUCGCAAACGGCGGCGCUAUCGCCGC
UAGCGGGAAGGUGCUGUUCGUGGCUAACGACAAGAAGACGU
CCUUCAUCGAGAACCGCGCCCUGUCGGGAGGUGCCAUUGCCG
CCAGCUCCGACAUUGCCUUCCAGAACUGUGCGGAACUGGUG
UUCAAAGGAAACUGCGCCAUCGGCACCGAAGAUAAGGGAAG
CCUGGGAGGCGGCGCCAUUUCCUCCCUCGGCACCGUGCUGCU
UCAGGGAAACCACGGCAUCACUUGUGACAAGAACGAAGCAG
CGUCCCAGGGGGGAGCGAUCUUCGGGAAGAACUGCCAGAUU
UCCGACAACGAGGGACCGGUGGUGUUCAGAGACUCCACUGC
CUGCCUGGGCGGCGGAGCGAUCGCAGCACAGGAAAUUGUCA
GCAUCCAGAACAACCAGGCCGGCAUCAGCUUCGAGGGGGGA
AAGGCUUCGUUCGGCGGAGGUAUUGCCUGCGGAUCGUUCUC
GUCCGCGGGCGGAGCCUCCGUGCUCGGAACCAUCGACAUUUC
CAAGAACCUGGGCGCUAUCUCGUUUUCUCGCACCCUGUGCAC
UACUUCCGACCUGGGUCAGAUGGAGUACCAGGGAGGCGGAG
CGCUGUUUGGAGAGAACAUCGCUCUGAGCGAGAACGCGGGA
GUGCUGACCUUCAAGGACAACAUUGUGAAGACCUUCGCCUC
AAACGGAAAGAUCCUGGGGGGAGGCGCCAUCCUGGCAACCG
GGAAGGUCGAAAUCACCAACAAUGCAGAGGGUAUCUCCUUC
ACUGGCAACGCCCGGGCCCCCCAAGCCCUGCCGACUCAGGAA
GAGUUCCCCCUGUUCUCCAAGAAGGAAGGACGCCCUUUGUC
AUCCGGCUACUCCGGUGGUGGAGCGAUUCUGGGUCGGGAAG
UGGCCAUCCUGCAUAAUGCGGCCGUGGUGUUUGAGCAGAAC
AGACUCCAAUGCUCCGAAGAAGAGGCCACCCUCCUGGGGUG
CUGCGGGGGCGGAGCAGUGCAUGGCAUGGAUUCCACUUCCA
UCGUGGGAAACUCCGCAGUCCGCUUCGGAAACAACUACGCU
AUGGGACAGGGAGUGUCAGGCGGGGCCCUGCUGUCCAAGAC
CGUCCAGUUGGCCGGAAACGGUGCGGUGGAUUUCUCACGCA
AUAUCGCCUCGCUGGGAGGCGGCGCGCUGCAGGCCUCCGAA
GGAAAUUGCGAACUGGUCGACAACGGCUACGUGCUGUUCCG
GGACAACCGCGGCAGGGUGUACGGCGGAGCAAUCUCGUGCC
UUCGGGGCGACGUCGUGAUCUCGGGAAAUAAGGGACGGGUC
GAGUUUAAGGACAACAUCGCUACCAGGCUCUACGUGGAGGA
AACUGUGGAGAAGGUGGAGGAAGUGGAGCCUGCCCCGGAAC
AGAAGGACAACAACGAGCUGUCGUUCCUCGGUCGGGCAGAA
CAGUCCUUCAUUACUGCCGCCAACCAGGCCCUGUUCGCGUCC
GAAGAUGGUGACCUCAGCCCGGAAUCCAGCAUCUCCUCCGA
GGAACUGGCCAAGCGGAGAGAAUGCGCGGGAGGCGCAAUCU
UUGCGAAGCGGGUCCGGAUCGUGGACAACCAGGAAGCUGUG
GUGUUCAGCAACAACUUUGCCGACAUCUACGGUGGUGCAAU
UUUCACCGGCUCACUCCGGGAGGAGGACAAGCUGGACGGCC
AGAUUCCCGAGGUGCUCAUUUCCGGCAAUGCCGGCGACGUG
GUGUUCUCCGGAAACUCCGCCAAGAGGGACGAACACCUCCCG
CAUACCGGAGGAGGAGCCAUCUGCACUCAGAACCUGGCAAU
CUCGCAGAACACCGGCAAUGUGCUGUUCUACAACAACGUCG
CAUGUUCCGGUGGCGCCGUCAGAAUCGAGGACCACGGAAAC
GUGCUGCUGGAAGCAUUCGGGGGUGAUAUUGUGUUCAAGGG
AAACAGCGCAUUCCGGGCCCAGGGAUCAGAUGCAAUCUACU
UCGCCGGGAAGGAGAGCCACAUUACCGCCCUGAACGCCGCCG
AGGGUCACGCCAUCGUGUUCCACGAUGCCCUGGUGUUCGAG
AACCUGGAGGAGCGCAAGAGCGCCGAAGUGCUGCUUAUCAA
UUCCCGCGAGAACCCGGGCUACACCGGAUCCAUCCGGUUCCU
CGAAGCGGAGUCGAAGGUCCCGCAGUGUAUUCAUGUGCAAC
AGGGGUCCCUGGAACUGCUUAACGGAGCCACCCUGUGCUCC
UACGGCUUUAAGCAGGACGCGGGCGCUAAACUGGUGCUGGC
GGCCGGCGCCAAGCUUAAGAUCCUCGACUCCGGAACCCCGGU
GCAGCAGGGGCACGCUAUUAGCAAGCCUGAAGCCGAGAUUG
AGUCGUCAUCCGAACCCGAAGGGGCGCACUCCCUGUGGAUA
GCCAAGAACGCGCAGACCACCGUGCCAAUGGUCGAUAUCCAC
ACAAUCUCCGUGGACCUCGCCAGCUUCUCGUCGAGCCAGCAG
GAGGGAACUGUCGAAGCGCCUCAGGUCAUCGUGCCGGGAGG
UUCCUACGUGCGCUCGGGGGAGCUCAACCUGGAACUCGUGA
AUACCGCUGGAACGGGAUAUGAGAACCACGCCCUGCUGAAG
AACGAAGCCAAAGUGCCACUGAUGUCCUUCGUCGCCUCCGGC
GACGAGGCCUCCGCCGAGAUUAGCAACCUGGCGGUGUCAGA
UCUGCAAAUUCACGUGGUGACCCCUGAGAUUGAGGAGGACA
CCUACGGGCACAUGGGCGAUUGGUCCGAGGCGAAGAUCCAG
GACGGCACACUGGUCAUUUCAUGGAACCCUGCCGGACAUCA CCACCACCAUCAC
Ct871pd_PmpG_D_NGM_nIgK AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG
364 GCUGCCUGAUACAACAGGCGCCGAGAUCAUGAUUCCCCAGG
GCAUCUACGACGGCGAAACCCUGACCGUGUCUUUCCCCUAUA
CCGUGAUCGGCGAUCCUAGCGGCACCACCGUGUUUUCUGCU
GGCGAGCUGACCCUGAAGAACCUGGACAACUCUAUCGCCGC
UCUGCCCCUGAGCUGCUUCGGAAAUCUGCUGGGCAGCUUCA
CCGUGCUCGGCAGAGGACACAGCCUGACCUUCGAGAACAUCC
GGACCAGCACAAAUGGCGCUGCCCUGAGCGAUAGCGCCAAU
AGCGGCCUGUUUACCAUCGAGGGCUUCAAAGAGCUGAGCUU
CAGCAACUGCAACAGCCUGCUGGCAGUGCUGCCUGCCGCCAC
AACAAAUAGCGGCAGCCAGACACCUACCACCACCAGCACACC
UUCUAACGGCGCCAUCUACAGCAAGACCGACCUGCUGCUCCU
GAACAACGAGAAGUUCAGCUUCUACUCCAACCUGGUGUCCG
GCGACGGCGGAGCCAUUGAUGCCAAAUCUCUGACCGUGCAG
GGCAUCAGCAAGCUGUGCGUGUUCCAAGAGAACACAGCCCA
GGCUGAUGGCGGAGCCUGUCAGGUGGUCACAAGCUUUAGCG
CCAUGGCCAACGAGGCCCCUAUCGCCUUUAUUGCCAAUGUG
GCCGGCGUUAGAGGCGGAGGAAUUGCCGCUGUUCAGGAUGG
ACAGCAGGGCGUGUCCAGCAGCACAAGCACUGAGGAUCCUG
UGGUGUCCUUCAGCAGAAACACCGCCGUGGAAUUCGAUGGC
AACGUGGCCAGAGUUGGCGGCGGAAUCUACAGCUACGGAAA
CGUGGCCUUUCUGAACAAUGGCAAGACCCUGUUCCUCAACA
ACGUGGCAAGCCCCGUGUAUAUCGCCGCCGAGCAGCCUACAA
AUGGCCAGGCCUCUAAUACCGCCGACAACUAUGGCGACGGU
GGCGCAAUCUUCUGCAAGAAUGGUGCUCAGGCCGCUGGCAG
CAACAAUGCCGGCUCUGUGUCCUUUGAUGGCGAAGGCGUGG
UGUUCUUCUCCUCUAACGUGGCCGCUGGAAAAGGCGGCGCU
AUCUACGCCAAGAAACUGAGCGUGGCCAACUGCGGCCCUGU
GCAGUUUCUGGGCAAUAUCGCCAAUGAUGGCGGUGCCAUCU
ACCUGGGAGAGUCCGGCGAACUGUCUCUGAGCGCCGAUUAC
GGCGACAUCAUCUUCGACGGCAACCUGAAGCGGACCGCCAA
AGAAAAUGCCGCCGAUGUGAAUGGCGUGACAGUGUCCAGCC
AGGCCAUCUCUAUGGGCUCUGGCGGCAAGAUCACCACACUG
AGAGCCAAGGCCGGCCACCAGAUCCUGUUCAACGACCCUAUC
GAGAUGGCCAAUGGCAACAACCAGCCUGCUCAGAGCAGCGA
GCCCCUGAAGAUUAACGAUGGCGAGGGCUACACCGGCGAUA
UCGUGUUCGCCAACGGCAACAGCGCCCUGUACCAGAAUGUG
GCCAUCGAGCAGGGCAGAAUCGUGCUGAGAGAGAAGGCCAA
GCUGAGCGUGAACAGCCUGAGUCAGACAGGCGGCAGCCUGU
AUAUGGAAGCCGGCAGCACCCUGGACUUCGUGACACCUCAA
CCUCCACAGCAACCUCCAGCCGCCAACCAGCUGAUCACCCUG
UCUAAUCUGCACCUGAGCCUGAGUUCCCUGCUGGCCAACAAC
GCCGUGACCAAUCCUCCUACCAAUCCACCAGCUCAGGACUCU
CACCCUGCCAUCAUCGGCUCUACAACAGCCGGAAGCGUGACA
AUCAGCGGCCCCAUCUUCUUCGAGGACCUGGACGAUACCGCC
UACGACAGAUACGAUUGGCUGGGCUCCAACCAGAAAAUCGA
CGUGCUGAAACUGCAGCUGGGCACCCAGCCAUCUGCCAACGC
UCCAUCUGAUCUGACCCUGGGCAACGAGAUGCCUAAGUACG
GCUACCAAGGCAGCUGGAAGCUGGCCUGGGAUCCUAACACA
GCCAACAAUGGCCCCUACACACUGAAGGCCACCUGGACCAAG ACAGGC
Ct871pd_PmpG_D_NGM_nIgK_cHis
AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 365
GCUGCCUGAUACAACAGGCGCCGAGAUCAUGAUUCCCCAGG
GCAUCUACGACGGCGAAACCCUGACCGUGUCUUUCCCCUAUA
CCGUGAUCGGCGAUCCUAGCGGCACCACCGUGUUUUCUGCU
GGCGAGCUGACCCUGAAGAACCUGGACAACUCUAUCGCCGC
UCUGCCCCUGAGCUGCUUCGGAAAUCUGCUGGGCAGCUUCA
CCGUGCUCGGCAGAGGACACAGCCUGACCUUCGAGAACAUCC
GGACCAGCACAAAUGGCGCUGCCCUGAGCGAUAGCGCCAAU
AGCGGCCUGUUUACCAUCGAGGGCUUCAAAGAGCUGAGCUU
CAGCAACUGCAACAGCCUGCUGGCAGUGCUGCCUGCCGCCAC
AACAAAUAGCGGCAGCCAGACACCUACCACCACCAGCACACC
UUCUAACGGCGCCAUCUACAGCAAGACCGACCUGCUGCUCCU
GAACAACGAGAAGUUCAGCUUCUACUCCAACCUGGUGUCCG
GCGACGGCGGAGCCAUUGAUGCCAAAUCUCUGACCGUGCAG
GGCAUCAGCAAGCUGUGCGUGUUCCAAGAGAACACAGCCCA
GGCUGAUGGCGGAGCCUGUCAGGUGGUCACAAGCUUUAGCG
CCAUGGCCAACGAGGCCCCUAUCGCCUUUAUUGCCAAUGUG
GCCGGCGUUAGAGGCGGAGGAAUUGCCGCUGUUCAGGAUGG
ACAGCAGGGCGUGUCCAGCAGCACAAGCACUGAGGAUCCUG
UGGUGUCCUUCAGCAGAAACACCGCCGUGGAAUUCGAUGGC
AACGUGGCCAGAGUUGGCGGCGGAAUCUACAGCUACGGAAA
CGUGGCCUUUCUGAACAAUGGCAAGACCCUGUUCCUCAACA
ACGUGGCAAGCCCCGUGUAUAUCGCCGCCGAGCAGCCUACAA
AUGGCCAGGCCUCUAAUACCGCCGACAACUAUGGCGACGGU
GGCGCAAUCUUCUGCAAGAAUGGUGCUCAGGCCGCUGGCAG
CAACAAUGCCGGCUCUGUGUCCUUUGAUGGCGAAGGCGUGG
UGUUCUUCUCCUCUAACGUGGCCGCUGGAAAAGGCGGCGCU
AUCUACGCCAAGAAACUGAGCGUGGCCAACUGCGGCCCUGU
GCAGUUUCUGGGCAAUAUCGCCAAUGAUGGCGGUGCCAUCU
ACCUGGGAGAGUCCGGCGAACUGUCUCUGAGCGCCGAUUAC
GGCGACAUCAUCUUCGACGGCAACCUGAAGCGGACCGCCAA
AGAAAAUGCCGCCGAUGUGAAUGGCGUGACAGUGUCCAGCC
AGGCCAUCUCUAUGGGCUCUGGCGGCAAGAUCACCACACUG
AGAGCCAAGGCCGGCCACCAGAUCCUGUUCAACGACCCUAUC
GAGAUGGCCAAUGGCAACAACCAGCCUGCUCAGAGCAGCGA
GCCCCUGAAGAUUAACGAUGGCGAGGGCUACACCGGCGAUA
UCGUGUUCGCCAACGGCAACAGCGCCCUGUACCAGAAUGUG
GCCAUCGAGCAGGGCAGAAUCGUGCUGAGAGAGAAGGCCAA
GCUGAGCGUGAACAGCCUGAGUCAGACAGGCGGCAGCCUGU
AUAUGGAAGCCGGCAGCACCCUGGACUUCGUGACACCUCAA
CCUCCACAGCAACCUCCAGCCGCCAACCAGCUGAUCACCCUG
UCUAAUCUGCACCUGAGCCUGAGUUCCCUGCUGGCCAACAAC
GCCGUGACCAAUCCUCCUACCAAUCCACCAGCUCAGGACUCU
CACCCUGCCAUCAUCGGCUCUACAACAGCCGGAAGCGUGACA
AUCAGCGGCCCCAUCUUCUUCGAGGACCUGGACGAUACCGCC
UACGACAGAUACGAUUGGCUGGGCUCCAACCAGAAAAUCGA
CGUGCUGAAACUGCAGCUGGGCACCCAGCCAUCUGCCAACGC
UCCAUCUGAUCUGACCCUGGGCAACGAGAUGCCUAAGUACG
GCUACCAAGGCAGCUGGAAGCUGGCCUGGGAUCCUAACACA
GCCAACAAUGGCCCCUACACACUGAAGGCCACCUGGACCAAG ACAGGCCACCACCAUCACCAUCAC
CT460_D_S16A_nIgK AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 366
GCUGCCUGAUACCACAGGCAUGAGCCAGAACAAGAACAGCG
CCUUCAUGCAGCCCGUGAACGUGGCAGCUGAUCUGGCCGCU
AUAGUUGGCGCUGGCCCUAUGCCUAGAACCGAGAUCAUCAA
GAAGAUGUGGGACUACAUUAAGAAGAACGGCCUGCAGGACC
CCACCAACAAGCGGAACAUCAACCCCGACGACAAGCUGGCCA
AGGUGUUCGGCACAGAGAAGCCCAUCGACAUGUUCCAGAUG
ACCAAGAUGGUGUCCCAGCACAUCAUCAAG CT460_D_S16A_nIgK_cHis
AUGGAAACCCCUGCUCAGCUGCUGUUCCUGCUGCUGCUGUG 367
GCUGCCUGAUACCACAGGCAUGAGCCAGAACAAGAACAGCG
CCUUCAUGCAGCCCGUGAACGUGGCAGCUGAUCUGGCCGCU
AUAGUUGGCGCUGGCCCUAUGCCUAGAACCGAGAUCAUCAA
GAAGAUGUGGGACUACAUUAAGAAGAACGGCCUGCAGGACC
CCACCAACAAGCGGAACAUCAACCCCGACGACAAGCUGGCCA
AGGUGUUCGGCACAGAGAAGCCCAUCGACAUGUUCCAGAUG
ACCAAGAUGGUGUCCCAGCACAUCAUCAAGCACCACCACCAU CACCAC
CT875_E_S274Q_N275H_S574D_nIgK
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 368
GCUGCCUGACACCACCGGCAUGAGCAUCAGAGGCGUGGGCG
GCAACGGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCA
GCAACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUG
GAAGAUAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGA
GAACCGCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCA
UGAUCGAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUA
GUAGAGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGG
AUUGCUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAG
CAGCGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGA
GAGCGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCG
GCUACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGC
UGAUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAG
ACCUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAA
CGAGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCG
AUCACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUG
GCAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGU
GCGGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGA
ACGACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GCCCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUC
UGGCUGGACAUGCAGCACCUGAGCGACGUGGUGCUGUCCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAG
AGUCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGG
CGGCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGA
GGAAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUC
AGAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUC
GGCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGU
GUCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAU
GCUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCA
GAGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCC
UGGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCC
GACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAG
GGGCGUGCCAUCCAUCGAGGGCGAGGGCAGCGAUAGCAUCU
ACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGGAC
CUGGAAACCCGGCGGAGCUUCGCCGUGCAGCAGGGCCAUUA
CCAGGACCCCAGAGCCAGCGACUACGACCUGCCUAGAGCCUC
CGAUUACGAUCUGCCCAGAAGCCCCUACCCCACCCCUCCACU
GCCUCCCAGAUACCAGCUGCAGAACAUGGAUGUGGAAGCCG
GCUUUCGCGAGGCCGUGUACGCCUCUUUUGUGGCCGGCAUG
UACAACUACGUCGUGACCCAGCCCCAGGAACGGAUCCCCAAU
AGCCAGCAGGUGGAAGGCAUCCUGCGGGACAUGCUGACCAA
CGGCGAUCAGACCUUCCGGGACCUGAUGAAGCGGUGGAACA GAGAGGUGGACCGCGAG
CT875_E_S274Q_N275H_S574D_nIgK_cHis
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 369
GCUGCCUGACACCACCGGCAUGAGCAUCAGAGGCGUGGGCG
GCAACGGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCA
GCAACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUG
GAAGAUAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGA
GAACCGCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCA
UGAUCGAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUA
GUAGAGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGG
AUUGCUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAG
CAGCGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGA
GAGCGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCG
GCUACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGC
UGAUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAG
ACCUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAA
CGAGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCG
AUCACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUG
GCAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGU
GCGGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGA
ACGACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GCCCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUC
UGGCUGGACAUGCAGCACCUGAGCGACGUGGUGCUGUCCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAG
AGUCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGG
CGGCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGA
GGAAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUC
AGAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUC
GGCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGU
GUCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAU
GCUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCA
GAGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCC
UGGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCC
GACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAG
GGGCGUGCCAUCCAUCGAGGGCGAGGGCAGCGAUAGCAUCU
ACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGGAC
CUGGAAACCCGGCGGAGCUUCGCCGUGCAGCAGGGCCAUUA
CCAGGACCCCAGAGCCAGCGACUACGACCUGCCUAGAGCCUC
CGAUUACGAUCUGCCCAGAAGCCCCUACCCCACCCCUCCACU
GCCUCCCAGAUACCAGCUGCAGAACAUGGAUGUGGAAGCCG
GCUUUCGCGAGGCCGUGUACGCCUCUUUUGUGGCCGGCAUG
UACAACUACGUCGUGACCCAGCCCCAGGAACGGAUCCCCAAU
AGCCAGCAGGUGGAAGGCAUCCUGCGGGACAUGCUGACCAA
CGGCGAUCAGACCUUCCGGGACCUGAUGAAGCGGUGGAACA
GAGAGGUGGACCGCGAGCACCACCAUCACCACCAC CT622_E_S13N_S179A_S220N_nIgK
AUGGAAACCCCUGCCCAACUGCUUUUCUUGCUGCUGCUCUG 370
GCUCCCUGACACCACCGGAAUGGAAUCUGGACCCGAGUCCGU
GUCAAGCAACCAGAACUCCAUGAACCCCAUCAUUAAUGGAC
AGAUCGCAUCCAAUUCCGAAACCAAGGAAAGCACCAAGGCA
UCGGAGGCCUCCCCAUCCGCCUCAAGCUCCGUGUCGUCCUGG
UCGUUUCUGUCGAGCGCGAAGAAUGCCCUGAUCUCACUGCG
GGACGCGAUUCUGAACAAGAACAGCUCCCCAACCGACUCCCU
GAGCCAACUCGAGGCCUCAACUUCCACUUCGACUGUGACUA
GGGUCGCUGCCAAGGAUUAUGACGAGGCCAAGAGCAACUUC
GACACCGCCAAGAGCGGACUGGAAAACGCCAAAACCCUGGCC
GAAUACGAAACUAAGAUGGCCGAUCUCAUGGCGGCCCUGCA
AGACAUGGAACGGCUGGCGAACUCCGAUCCGUCCAACAACC
ACACUGAGGAAGUGAACAACAUCAAGAAGGCUCUCGAGGCC
CAGAAGGAUACCAUCGACAAGUUGAACAAGCUUGUGACGCU
GCAGAACCAAAACAAGGCCCUGACGGAAGUGCUCAAAACCA
CCGACUCGGCCGACCAGAUUCCGGCCAUCAACAGCCAGCUGG
AGAUUAACAAGAACUCGGCCGAUCAGAUUAUCAAGGACCUG
GAGCGCCAGAACAUUAACUACGAGGCCGUCUUGACUAACGC
CGGCGAAGUGAUCAAGGCGUCAUCCGAAGCCGGCAUUAAGC
UGGGACAGGCGCUGCAAUCCAUCGUCGACGCCGGCGACCAG
UCCCAGGCGGCGGUGCUGCAGGCCCAGCAGAACAACUCCCCC
GAUAACAUCGCUGCAACCAAGGAACUGAUUGACGCGGCCGA
AACCAAAGUCAACGAACUGAAGCAGGAGCACACUGGUCUGA
CCGACUCGCCGCUCGUGAAGAAGGCCGAAGAACAGAUCAGC
CAGGCUCAGAAGGAUAUCCAGGAAAUCAAGCCUUCGGGGAG
CGACAUCCCGAUCGUGGGACCGUCCGGUUCCGCCGCUUCCGC
CGGGUCCGCAGCCGGGGCCCUUAAGUCGUCGAACAAUAGCG
GCAGAAUAUCCCUGCUGCUCGACGAUGUGGAUAACGAGAUG
GCCGCCAUUGCGCUGCAAGGAUUCCGGUCCAUGAUCGAGCA
GUUCAACGUGAACAACCCCGCCACCGCCAAGGAGCUGCAGGC
UAUGGAGGCCCAACUCACUGCCAUGUCCGACCAGCUCGUGG
GAGCGGACGGAGAACUGCCAGCCGAGAUCCAGGCCAUCAAG
GACGCUCUGGCCCAGGCACUGAAGCAGCCGUCCGCGGAUGGC
CUGGCCACCGCCAUGGGCCAGGUCGCGUUCGCCGCCGCUAAA
GUCGGCGGAGGUUCGGCCGGCACUGCCGGGACCGUGCAGAU
GAAUGUCAAGCAGCUGUACAAGACUGCGUUCUCGUCGACCA
GCUCCAGCUCCUACGCCGCGGCCCUGUCCGACGGUUACAGCG
CGUACAAGACCCUGAACUCCCUUUACUCCGAAUCGAGAUCCG
GGGUCCAGUCCGCAAUUUCACAAACCGCCAAUCCUGCCCUGU
CGCGCUCAGUGUCACGCAGCGGCAUCGAGUCACAGGGCAGA
AGCGCCGACGCUAGCCAAAGGGCCGCAGAAACCAUUGUGCG
GGACUCCCAGACACUUGGAGAUGUCUACAGCCGCCUCCAAG
UGCUGGACUCCCUCAUGUCCACCAUCGUGUCAAACCCUCAGG
CUAACCAGGAGGAAAUCAUGCAGAAGCUGACCGCAAGCAUU
UCCAAGGCUCCGCAGUUUGGAUACCCCGCUGUGCAAAACUCC
GCGGACAGCUUGCAGAAAUUCGCAGCCCAGUUGGAGAGGGA
GUUCGUGGACGGGGAGCGGUCCCUCGCGGAGUCCCAGGAGA
ACGCAUUCCGGAAGCAGCCCGCCUUCAUUCAACAAGUGCUU
GUGAACAUCGCCUCCCUGUUCUCCGGUUACCUGUCU
CT622_E_S13N_S179A_S220N_nIgK_cHis
AUGGAAACCCCUGCCCAACUGCUUUUCUUGCUGCUGCUCUG 371
GCUCCCUGACACCACCGGAAUGGAAUCUGGACCCGAGUCCGU
GUCAAGCAACCAGAACUCCAUGAACCCCAUCAUUAAUGGAC
AGAUCGCAUCCAAUUCCGAAACCAAGGAAAGCACCAAGGCA
UCGGAGGCCUCCCCAUCCGCCUCAAGCUCCGUGUCGUCCUGG
UCGUUUCUGUCGAGCGCGAAGAAUGCCCUGAUCUCACUGCG
GGACGCGAUUCUGAACAAGAACAGCUCCCCAACCGACUCCCU
GAGCCAACUCGAGGCCUCAACUUCCACUUCGACUGUGACUA
GGGUCGCUGCCAAGGAUUAUGACGAGGCCAAGAGCAACUUC
GACACCGCCAAGAGCGGACUGGAAAACGCCAAAACCCUGGCC
GAAUACGAAACUAAGAUGGCCGAUCUCAUGGCGGCCCUGCA
AGACAUGGAACGGCUGGCGAACUCCGAUCCGUCCAACAACC
ACACUGAGGAAGUGAACAACAUCAAGAAGGCUCUCGAGGCC
CAGAAGGAUACCAUCGACAAGUUGAACAAGCUUGUGACGCU
GCAGAACCAAAACAAGGCCCUGACGGAAGUGCUCAAAACCA
CCGACUCGGCCGACCAGAUUCCGGCCAUCAACAGCCAGCUGG
AGAUUAACAAGAACUCGGCCGAUCAGAUUAUCAAGGACCUG
GAGCGCCAGAACAUUAACUACGAGGCCGUCUUGACUAACGC
CGGCGAAGUGAUCAAGGCGUCAUCCGAAGCCGGCAUUAAGC
UGGGACAGGCGCUGCAAUCCAUCGUCGACGCCGGCGACCAG
UCCCAGGCGGCGGUGCUGCAGGCCCAGCAGAACAACUCCCCC
GAUAACAUCGCUGCAACCAAGGAACUGAUUGACGCGGCCGA
AACCAAAGUCAACGAACUGAAGCAGGAGCACACUGGUCUGA
CCGACUCGCCGCUCGUGAAGAAGGCCGAAGAACAGAUCAGC
CAGGCUCAGAAGGAUAUCCAGGAAAUCAAGCCUUCGGGGAG
CGACAUCCCGAUCGUGGGACCGUCCGGUUCCGCCGCUUCCGC
CGGGUCCGCAGCCGGGGCCCUUAAGUCGUCGAACAAUAGCG
GCAGAAUAUCCCUGCUGCUCGACGAUGUGGAUAACGAGAUG
GCCGCCAUUGCGCUGCAAGGAUUCCGGUCCAUGAUCGAGCA
GUUCAACGUGAACAACCCCGCCACCGCCAAGGAGCUGCAGGC
UAUGGAGGCCCAACUCACUGCCAUGUCCGACCAGCUCGUGG
GAGCGGACGGAGAACUGCCAGCCGAGAUCCAGGCCAUCAAG
GACGCUCUGGCCCAGGCACUGAAGCAGCCGUCCGCGGAUGGC
CUGGCCACCGCCAUGGGCCAGGUCGCGUUCGCCGCCGCUAAA
GUCGGCGGAGGUUCGGCCGGCACUGCCGGGACCGUGCAGAU
GAAUGUCAAGCAGCUGUACAAGACUGCGUUCUCGUCGACCA
GCUCCAGCUCCUACGCCGCGGCCCUGUCCGACGGUUACAGCG
CGUACAAGACCCUGAACUCCCUUUACUCCGAAUCGAGAUCCG
GGGUCCAGUCCGCAAUUUCACAAACCGCCAAUCCUGCCCUGU
CGCGCUCAGUGUCACGCAGCGGCAUCGAGUCACAGGGCAGA
AGCGCCGACGCUAGCCAAAGGGCCGCAGAAACCAUUGUGCG
GGACUCCCAGACACUUGGAGAUGUCUACAGCCGCCUCCAAG
UGCUGGACUCCCUCAUGUCCACCAUCGUGUCAAACCCUCAGG
CUAACCAGGAGGAAAUCAUGCAGAAGCUGACCGCAAGCAUU
UCCAAGGCUCCGCAGUUUGGAUACCCCGCUGUGCAAAACUCC
GCGGACAGCUUGCAGAAAUUCGCAGCCCAGUUGGAGAGGGA
GUUCGUGGACGGGGAGCGGUCCCUCGCGGAGUCCCAGGAGA
ACGCAUUCCGGAAGCAGCCCGCCUUCAUUCAACAAGUGCUU
GUGAACAUCGCCUCCCUGUUCUCCGGUUACCUGUCUCAUCAC CACCACCAUCAC
Cta1_E_noTM_nIgK_cHis AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 372
GCUGCCUGAUACCACCGGCCCUAGCAGCACCCAGGACAACAG
AUCCAUGGACCAGCAGGACAGCGAGGAAUUUCUGCUGCAGA
ACACCCUGGAAGAUAGCGAGAUCAUCAGCAUCCCCGACACCA
UGAACCAGAUCGCCAUCGACACCGAGAAGUGGUUCUACCUG
AACAAGGACUGCACCAACGUGGGCCCCAUCUCCAUCGUGCAG
CUGACCGCCUUCCUGAAAGAGUGCAAGCACAGCCCCGAGAA
GGGCAUCGACCCCCAGGAACUGUGGGUGUGGAAGAAAGGCA
UGCCCAACUGGGAGAAAGUGAAGAACAUCCCCGAGCUGAGC
GGCACCGUGAAGGACGAGCACCACCACCAUCACCAC Cta1_E_noTM_nIgK
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 373
GCUGCCUGAUACCACCGGCCCUAGCAGCACCCAGGACAACAG
AUCCAUGGACCAGCAGGACAGCGAGGAAUUUCUGCUGCAGA
ACACCCUGGAAGAUAGCGAGAUCAUCAGCAUCCCCGACACCA
UGAACCAGAUCGCCAUCGACACCGAGAAGUGGUUCUACCUG
AACAAGGACUGCACCAACGUGGGCCCCAUCUCCAUCGUGCAG
CUGACCGCCUUCCUGAAAGAGUGCAAGCACAGCCCCGAGAA
GGGCAUCGACCCCCAGGAACUGUGGGUGUGGAAGAAAGGCA
UGCCCAACUGGGAGAAAGUGAAGAACAUCCCCGAGCUGAGC GGCACCGUGAAGGACGAA
Cta1_E_cHis AUGAACAGCGGGAUGUUCCCCUUCACCUUCUUUCUGCUGUA 374
CAUCUGCCUGGGCAUGCUGACCGCCUACCUGGCCAACAAGAA
GAACCGGAACCUGAUCGGCUGGUUCCUGGCCGGCAUGUUCU
UCGGAAUCUUCGCCAUCAUUUUUCUGCUGAUCCUGCCCCCCC
UGCCCAGCAGCACACAGGACAACAGAUCCAUGGACCAGCAG
GACAGCGAAGAGUUCCUGCUGCAGAACACCCUGGAAGAUAG
CGAGAUCAUCAGCAUCCCCGACACCAUGAACCAGAUCGCCAU
CGACACCGAGAAGUGGUUCUACCUGAACAAGGACUGCACCA
ACGUGGGCCCCAUCUCCAUCGUGCAGCUGACAGCCUUCCUGA
AAGAGUGCAAGCACAGCCCCGAGAAGGGCAUCGACCCCCAG
GAACUGUGGGUGUGGAAGAAAGGCAUGCCCAACUGGGAGAA
AGUGAAGAACAUCCCCGAGCUGAGCGGCACCGUGAAGGACG AGCACCACCACCAUCACCAC
Cta1_E AUGAACAGCGGGAUGUUCCCCUUCACCUUCUUUCUGCUGUA 375
CAUCUGCCUGGGCAUGCUGACCGCCUACCUGGCCAACAAGAA
GAACCGGAACCUGAUCGGCUGGUUCCUGGCCGGCAUGUUCU
UCGGAAUCUUCGCCAUCAUUUUUCUGCUGAUCCUGCCCCCCC
UGCCCAGCAGCACACAGGACAACAGAUCCAUGGACCAGCAG
GACAGCGAAGAGUUCCUGCUGCAGAACACCCUGGAAGAUAG
CGAGAUCAUCAGCAUCCCCGACACCAUGAACCAGAUCGCCAU
CGACACCGAGAAGUGGUUCUACCUGAACAAGGACUGCACCA
ACGUGGGCCCCAUCUCCAUCGUGCAGCUGACAGCCUUCCUGA
AAGAGUGCAAGCACAGCCCCGAGAAGGGCAUCGACCCCCAG
GAACUGUGGGUGUGGAAGAAAGGCAUGCCCAACUGGGAGAA
AGUGAAGAACAUCCCCGAGCUGAGCGGCACCGUGAAGGACG AA CT443_E_nIgK_cHis_mod
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUCCUGCUGUGG 376
CUGCCUGAUACCACAGGCAGCGGCGUGCUGGAAACCAGCAU
GGCCGAGAGCCUGAGCACCAACGUGAUCAGCCUGGCCGACAC
CAAGGCCAAGGACAACACCAGCCACAAGAGCAAGAAGGCCC
GGAAGAACCACAGCAAAGAAACCCUGGUGGACCGGAAAGAG
GUGGCCCCUGUGCACGAGUCUAAGGCCACAGGCCCCAAGCAG
GACAGCUGCUUCGGCCGGAUGUACACCGUGAAAGUGAACGA
CGACCGGAACGUGGAAAUCACCCAGGCCGUGCCUGAGUACG
CCACAGUGGGCAGCCCUUACCCCAUCGAGAUCACCGCCACCG
GCAAGAGGGAUUGCGUGGAUGUGAUCAUUACCCAACAGCUG
CCUUGCGAGGCCGAGUUCGUGCGCUCUGAUCCUGCCACCACC
CCUACCGCCGAUGGCAAGCUCGUGUGGAAGAUCGACAGACU
GGGCCAGGGCGAGAAGUCCAAAAUCACUGUGUGGGUCAAGC
CCCUGAAAGAGGGGUGCUGCUUUACCGCAGCCACCGUGUGU
GCCUGCCCCGAGAUUAGAAGCGUGACCAAGUGUGGCCAGCC
CGCCAUCUGCGUGAAGCAGGAAGGACCUGAGAACGCCUGCC
UGAGAUGCCCCGUGGUGUACAAGAUCAACGUCGUGAACCAG
GGCACCGCCAUUGCCAGAAACGUGGUGGUGGAAAACCCCGU
GCCCGACGGCUACGCCCACAGCUCUGGACAGAGAGUGCUGAC
CUUCACCCUGGGCGACAUGCAGCCCGGCGAGCACAGAACCAU
CACCGUGGAAUUCUGCCCCCUGAAGCGGGGCAGAGCCACCAA
CAUUGCGACAGUGUCCUACUGUGGCGGGCACAAGAACACCG
CCUCCGUGACCACCGUGAUCAACGAGCCUUGCGUGCAGGUG
UCCAUUGCCGGCGCUGACUGGUCCUACGUGUGCAAGCCAGU
GGAGUACGUGAUCUCCGUGUCCAACCCCGGCGACCUGGUGC
UGAGAGAUGUGGUGGUUGAGGAUACCCUGAGCCCUGGCGUG
ACAGUCCUGGAAGCUGCUGGCGCCCAGAUCAGCUGCAACAA
GGUGGUGUGGACAGUGAAAGAGCUGAACCCCGGGGAGUCCC
UGCAGUACAAGGUGCUCGUGCGGGCCCAGACCCCUGGCCAG
UUCACCAACAAUGUGGUCGUGAAGUCCUGCAGCGACUGCGG
CACCUGUACCUCUUGUGCCGAGGCCACCACGUACUGGAAAG
GCGUGGCCGCUACCCAUAUGUGCGUGGUGGAUACCUGCGAC
CCCGUCUGCGUGGGCGAAAACACCGUGUACCGGAUCUGUGU
GACCAACCGGGGCAGCGCCGAGGACACCAAUGUGUCCCUGA
UGCUGAAGUUCUCCAAAGAACUGCAACCCGUGAGCUUCAGC
GGCCCCACCAAGGGAACAAUCACUGGCAACACCGUCGUUUUC
GACAGCCUGCCUCGGCUGGGCUCUAAGGAAACUGUGGAGUU
CAGCGUGACACUGAAGGCCGUGUCUGCCGGGGAUGCUAGAG
GCGAGGCCAUCCUGAGCAGCGACACACUGACGGUCCCUGUG
UCCGACACCGAGAAUACCCACAUCUACCACCACCAUCAUCAC CAU CT443_E_nIgK_mod
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUCCUGCUGUGG 377
CUGCCUGAUACCACAGGCAGCGGCGUGCUGGAAACCAGCAU
GGCCGAGAGCCUGAGCACCAACGUGAUCAGCCUGGCCGACAC
CAAGGCCAAGGACAACACCAGCCACAAGAGCAAGAAGGCCC
GGAAGAACCACAGCAAAGAAACCCUGGUGGACCGGAAAGAG
GUGGCCCCUGUGCACGAGUCUAAGGCCACAGGCCCCAAGCAG
GACAGCUGCUUCGGCCGGAUGUACACCGUGAAAGUGAACGA
CGACCGGAACGUGGAAAUCACCCAGGCCGUGCCUGAGUACG
CCACAGUGGGCAGCCCUUACCCCAUCGAGAUCACCGCCACCG
GCAAGAGGGAUUGCGUGGAUGUGAUCAUUACCCAACAGCUG
CCUUGCGAGGCCGAGUUCGUGCGCUCUGAUCCUGCCACCACC
CCUACCGCCGAUGGCAAGCUCGUGUGGAAGAUCGACAGACU
GGGCCAGGGCGAGAAGUCCAAAAUCACUGUGUGGGUCAAGC
CCCUGAAAGAGGGGUGCUGCUUUACCGCAGCCACCGUGUGU
GCCUGCCCCGAGAUUAGAAGCGUGACCAAGUGUGGCCAGCC
CGCCAUCUGCGUGAAGCAGGAAGGACCUGAGAACGCCUGCC
UGAGAUGCCCCGUGGUGUACAAGAUCAACGUCGUGAACCAG
GGCACCGCCAUUGCCAGAAACGUGGUGGUGGAAAACCCCGU
GCCCGACGGCUACGCCCACAGCUCUGGACAGAGAGUGCUGAC
CUUCACCCUGGGCGACAUGCAGCCCGGCGAGCACAGAACCAU
CACCGUGGAAUUCUGCCCCCUGAAGCGGGGCAGAGCCACCAA
CAUUGCGACAGUGUCCUACUGUGGCGGGCACAAGAACACCG
CCUCCGUGACCACCGUGAUCAACGAGCCUUGCGUGCAGGUG
UCCAUUGCCGGCGCUGACUGGUCCUACGUGUGCAAGCCAGU
GGAGUACGUGAUCUCCGUGUCCAACCCCGGCGACCUGGUGC
UGAGAGAUGUGGUGGUUGAGGAUACCCUGAGCCCUGGCGUG
ACAGUCCUGGAAGCUGCUGGCGCCCAGAUCAGCUGCAACAA
GGUGGUGUGGACAGUGAAAGAGCUGAACCCCGGGGAGUCCC
UGCAGUACAAGGUGCUCGUGCGGGCCCAGACCCCUGGCCAG
UUCACCAACAAUGUGGUCGUGAAGUCCUGCAGCGACUGCGG
CACCUGUACCUCUUGUGCCGAGGCCACCACGUACUGGAAAG
GCGUGGCCGCUACCCAUAUGUGCGUGGUGGAUACCUGCGAC
CCCGUCUGCGUGGGCGAAAACACCGUGUACCGGAUCUGUGU
GACCAACCGGGGCAGCGCCGAGGACACCAAUGUGUCCCUGA
UGCUGAAGUUCUCCAAAGAACUGCAACCCGUGAGCUUCAGC
GGCCCCACCAAGGGAACAAUCACUGGCAACACCGUCGUUUUC
GACAGCCUGCCUCGGCUGGGCUCUAAGGAAACUGUGGAGUU
CAGCGUGACACUGAAGGCCGUGUCUGCCGGGGAUGCUAGAG
GCGAGGCCAUCCUGAGCAGCGACACACUGACGGUCCCUGUG
UCCGACACCGAGAAUACCCACAUCUAC CT875_E_nIgK_CO004
AUGGAAACUCCCGCACAGUUACUUUUCUUGUUGCUUCUAUG 378
GCUCCCCGAUACCACCGGGAUGAGCAUCAGAGGCGUCGGCG
GGAACGGCAACAGCAGAAUUCCCUCCCACAACGGCGACGGCA
GCAACAGAAGAUCCCAGAACACAAAGGGCAAUAAUAAGGUC
GAGGACAGAGUGUGCAGCCUCUACUCCAGCAGGUCUAACGA
GAAUAGGGAGUCCCCGUACGCCGUUGUCGACGUGAGUUCUA
UGAUAGAGAGCACGCCCACGUCCGGAGAAACAACUAGAGCA
AGCAGGGGCGUCCUGAGCCGGUUCCAGAGAGGUCUGGUGCG
AAUUGCCGACAAGGUGAGACGGGCAGUGCAAUGCGCCUGGA
GCAGCGUCUCCACCAGCAGAAGCAGCGCCACCCGCGCUGCCG
AAUCAGGCAGCAGCUCCAGAACGGCACGGGGCGCCUCCUCCG
GCUACCGAGAGUACUCCCCUAGCGCCGCCAGAGGCCUGAGAC
UGAUGUUCACCGAUUUUUGGAGGACACGGGUUCUGAGACAG
ACCUCCCCCAUGGCUGGGGUGUUCGGCAACCUGGACGUCAA
UGAAGCCAGACUCAUGGCCGCAUAUACUUCUGAGUGCGCUG
ACCACCUGGAAGCUAAGGAACUGGCGGGCCCCGAUGGCGUG
GCCGCGGCCCGGGAGAUCGCCAAGAGAUGGGAGAAGAGAGU
GCGGGACCUGCAAGACAAGGGGGCCGCCCGGAAGCUGCUGA
ACGAUCCCUUGGGCCGCCGGACACCGAACUAUCAGAGCAAG
AACCCGGGCGAGUACACCGUGGGAAACAGCAUGUUCUAUGA
CGGACCUCAGGUGGCAAACCUGCAGAACGUGGACACUGGAU
UUUGGCUCGACAUGAGUAACCUCUCCGAUGUCGUUCUGUCU
CGUGAGAUACAGACAGGUCUGCGGGCUAGAGCCACCCUUGA
GGAGAGCAUGCCUAUGUUGGAGAAUCUGGAGGAGCGGUUCA
GAAGACUGCAGGAGACUUGCGAUGCCGCCAGGACCGAGAUU
GAGGAGAGCGGCUGGACCCGGGAAAGCGCCUCAAGGAUGGA
GGGAGACGAGGCCCAGGGACCCUCCAGGGUUCAGCAGGCCU
UCCAGUCGUUCGUGAAUGAAUGCAACAGCAUCGAGUUCAGC
UUCGGAAGCUUCGGAGAGCACGUGCGAGUGCUGUGCGCCAG
AGUAUCCAGAGGUCUGGCCGCUGCAGGCGAGGCCAUCCGGA
GAUGCUUCUCCUGCUGCAAAGGCAGCACCCACAGGUAUGCU
CCCAGGGAUGAUCUUUCUCCCGAGGGAGCCAGCCUGGCUGA
GACUCUUGCAAGAUUCGCCGAUGACAUGGGGAUCGAGCGGG
GCGCUGACGGCACCUACGACAUUCCCCUGGUGGACGACUGG
AGGAGGGGAGUGCCCUCCAUCGAGGGCGAGGGCUCCGAUUC
AAUCUAUGAGAUCAUGAUGCCUAUUUACGAGGUGAUGAACA
UGGACCUGGAGACAAGAAGAAGUUUCGCCGUCCAGCAGGGU
CAUUACCAGGACCCCCGAGCAAGCGACUACGAUCUGCCUCGC
GCCAGCGAUUACGACCUGCCUAGAAGCCCCUACCCUACACCU
CCACUGCCCCCAAGAUAUCAGCUCCAGAACAUGGACGUGGA
GGCCGGCUUCAGGGAGGCCGUGUACGCCAGCUUUGUGGCCG
GCAUGUACAACUAUGUCGUGACACAGCCUCAGGAACGCAUU
CCCAAUAGCCAACAGGUGGAGGGCAUCCUGAGAGACAUGCU
GACCAACGGCUCUCAGACUUUUAGAGAUCUGAUGAAAAGAU GGAACAGAGAAGUGGACAGGGAG
CT875_E_nIgK_CO003 AUGGAAACACCAGCUCAGCUCCUUUUCUUACUCCUCUUGUG 379
GUUGCCGGAUACCACAGGCAUGAGCAUCCGGGGCGUCGGCG
GCAACGGAAACAGCCGGAUCCCCAGCCACAACGGAGACGGCU
CUAAUAGAAGAUCACAGAAUACCAAGGGAAAUAACAAGGUC
GAAGAUAGAGUCUGCAGCUUAUAUUCCAGCAGAUCCAACGA
GAAUAGGGAAAGCCCCUACGCCGUCGUUGACGUGAGCUCCA
UGAUCGAAAGCACCCCAACAAGUGGCGAGACUACAAGAGCC
UCAAGGGGCGUCCUGUCAAGAUUCCAAAGAGGCCUGGUGAG
GAUCGCAGACAAGGUGCGGCGGGCCGUGCAGUGCGCCUGGA
GCUCUGUGUCGACAAGCAGAUCAAGUGCCACCAGGGCCGCC
GAGAGCGGAUCCUCCAGUCGGACCGCCCGCGGCGCCUCUAGU
GGGUACAGAGAAUAUAGUCCCAGCGCCGCUAGGGGGCUGCG
CCUCAUGUUCACCGACUUCUGGAGAACCCGCGUGCUCAGGCA
GACAUCCCCUAUGGCCGGGGUGUUCGGCAACCUGGACGUGA
ACGAGGCCCGGCUUAUGGCCGCAUAUACAAGCGAGUGUGCC
GACCACCUGGAGGCCAAGGAGCUGGCUGGCCCCGACGGCGU
GGCCGCCGCACGCGAGAUUGCCAAGAGGUGGGAAAAGAGGG
UGAGAGAUCUGCAGGAUAAGGGCGCCGCCAGAAAACUGCUG
AAUGACCCCCUGGGGAGGAGGACACCCAAUUACCAGUCAAA
GAAUCCAGGGGAGUACACUGUUGGAAAUUCUAUGUUUUAUG
ACGGCCCUCAGGUGGCCAACCUUCAGAAUGUGGACACAGGC
UUCUGGCUUGACAUGAGCAACCUCAGCGACGUGGUGCUGUC
UAGGGAGAUCCAGACAGGCUUAAGAGCACGGGCUACCCUGG
AAGAGUCGAUGCCCAUGCUCGAAAAUCUGGAGGAGAGGUUC
AGACGCCUGCAAGAGACAUGCGACGCCGCGAGGACUGAAAU
CGAGGAGAGCGGCUGGACCAGGGAGUCCGCUUCUCGCAUGG
AAGGGGACGAGGCUCAGGGCCCCAGCAGGGUGCAGCAGGCC
UUCCAGAGCUUUGUGAACGAGUGCAACUCCAUUGAGUUCAG
CUUUGGAAGCUUCGGAGAGCACGUGCGGGUGCUGUGCGCCC
GCGUGUCCAGGGGCCUGGCCGCAGCUGGCGAGGCUAUACGU
CGCUGCUUCAGCUGUUGUAAGGGAAGCACCCAUAGGUACGC
CCCUCGUGACGAUCUGUCUCCCGAAGGGGCCAGCCUGGCUGA
GACACUGGCCCGCUUCGCCGAUGAUAUGGGGAUUGAACGGG
GCGCCGACGGAACCUACGACAUCCCUCUUGUGGACGACUGG
AGGAGAGGCGUCCCCUCUAUCGAGGGCGAGGGCUCUGACUC
CAUCUACGAGAUUAUGAUGCCUAUCUACGAGGUCAUGAACA
UGGACCUGGAAACCAGAAGAAGCUUCGCAGUUCAGCAGGGA
CACUACCAAGACCCACGGGCUAGUGAUUAUGACCUCCCAAG
AGCAUCCGACUAUGAUCUGCCAAGGUCACCUUACCCUACCCC
ACCCCUGCCCCCACGGUACCAGUUACAGAACAUGGAUGUGG
AGGCCGGCUUCAGGGAAGCCGUCUAUGCAUCCUUCGUGGCC
GGCAUGUACAACUACGUGGUGACUCAACCUCAGGAACGGAU
CCCCAACAGUCAGCAGGUGGAGGGGAUCCUUAGGGAUAUGC
UGACUAAUGGAAGCCAGACCUUCAGAGAUCUGAUGAAGCGG UGGAAUAGGGAGGUGGACAGGGAG
CT875_E_nIgK_CO002 AUGGAGACACCCGCACAGCUCCUCUUCUUAUUGCUCUUGUG 380
GCUACCGGACACCACAGGCAUGUCUAUCCGGGGCGUUGGCG
GGAACGGCAACUCUAGGAUCCCCUCUCACAACGGCGACGGG
AGCAACAGGAGAAGCCAGAACACCAAAGGCAAUAACAAAGU
CGAGGACAGAGUUUGUUCUCUCUAUAGCUCUAGGAGCAACG
AAAACCGCGAAUCUCCUUACGCCGUCGUCGACGUCAGCAGCA
UGAUAGAGUCAACCCCUACCUCUGGAGAAACAACACGCGCC
UCCAGAGGCGUUCUGUCCAGGUUCCAGAGGGGCCUGGUGAG
AAUUGCCGACAAGGUCAGACGAGCCGUGCAGUGUGCCUGGU
CCAGCGUCUCUACCAGCAGAAGCUCCGCCACCAGAGCCGCUG
AGAGUGGCAGCUCCAGCAGGACAGCCAGGGGGGCUUCCAGC
GGCUAUAGAGAGUAUAGCCCUUCAGCCGCCAGAGGCCUGCG
GCUGAUGUUCACAGACUUUUGGAGAACAAGGGUGCUGCGGC
AGACCAGCCCCAUGGCCGGCGUGUUUGGCAAUCUGGACGUG
AACGAGGCCCGGCUGAUGGCCGCAUACACCAGCGAGUGUGC
GGACCACCUGGAGGCAAAGGAGCUGGCUGGACCCGACGGUG
UGGCCGCUGCCCGAGAAAUUGCCAAGAGGUGGGAGAAGAGA
GUUCGCGACCUGCAGGAUAAGGGCGCCGCACGGAAACUCCU
GAACGACCCACUCGGCAGAAGAACCCCCAACUACCAGUCAAA
GAACCCUGGGGAGUAUACCGUGGGAAAUUCAAUGUUCUACG
AUGGCCCUCAGGUUGCUAAUCUCCAGAACGUGGACACUGGG
UUCUGGCUGGACAUGAGCAACCUGAGUGACGUGGUGCUGUC
UCGGGAAAUUCAGACAGGCCUGCGGGCCAGAGCCACCCUGG
AAGAGUCCAUGCCUAUGCUUGAGAACCUGGAGGAGCGCUUU
AGGCGACUCCAAGAAACCUGCGAUGCUGCCAGGACCGAGAU
CGAGGAGUCUGGAUGGACCAGAGAAAGCGCCUCCAGGAUGG
AGGGCGAUGAGGCCCAGGGCCCCAGCAGGGUGCAGCAGGCU
UUCCAGAGCUUCGUGAACGAAUGUAACAGUAUCGAAUUCUC
UUUCGGUAGCUUCGGCGAGCACGUGCGGGUGUUAUGCGCCA
GGGUCAGCAGGGGCCUGGCGGCCGCCGGCGAGGCCAUCAGA
AGAUGCUUCAGCUGUUGCAAAGGCUCAACCCACAGAUAUGC
CCCUAGGGACGAUCUGUCUCCAGAGGGCGCUAGCUUGGCCG
AGACACUAGCAAGGUUCGCCGACGAUAUGGGUAUCGAGAGG
GGCGCCGACGGUACCUACGACAUCCCCCUGGUGGACGACUGG
AGGAGAGGCGUGCCCAGUAUUGAGGGCGAGGGAUCCGACAG
CAUCUACGAGAUCAUGAUGCCGAUCUACGAGGUGAUGAAUA
UGGAUCUGGAGACUCGUAGAUCAUUCGCUGUCCAGCAGGGC
CACUACCAGGAUCCUAGAGCCUCGGACUACGACUUGCCCAGG
GCUAGCGAUUACGACCUGCCUAGAUCCCCCUACCCCACUCCC
CCUCUUCCCCCUCGGUAUCAGCUGCAGAACAUGGACGUGGA
GGCCGGUUUCCGAGAGGCUGUGUACGCCUCCUUCGUGGCCG
GGAUGUACAACUACGUCGUGACCCAGCCCCAGGAGAGAAUC
CCUAAUUCCCAGCAGGUGGAGGGCAUCUUGAGAGAUAUGCU
CACAAACGGGAGCCAGACCUUUCGUGACUUAAUGAAGCGAU GGAACAGAGAGGUGGAUAGGGAG
CT875_E_nIgK_CO001 AUGGAAACCCCCGCCCAGCUUCUCUUCCUCCUCUUGCUUUGG 381
CUCCCAGACACAACCGGCAUGAGUAUCAGAGGCGUAGGAGG
CAACGGCAAUAGCCGUAUCCCCUCACACAACGGCGACGGCUC
CAACAGACGGAGCCAGAACACCAAGGGGAAUAAUAAGGUGG
AGGACCGGGUCUGUUCACUUUACAGCUCCAGGUCUAACGAG
AAUCGGGAAAGCCCUUACGCCGUAGUCGACGUUAGCAGUAU
GAUCGAAAGCACCCCCACCAGCGGCGAGACAACAAGGGCCUC
UCGAGGAGUUCUGAGCAGAUUUCAGAGAGGCCUGGUGCGGA
UCGCCGACAAGGUGCGGAGAGCCGUGCAGUGCGCCUGGAGC
AGCGUGAGUACAUCUCGGAGCAGCGCCACCAGAGCAGCCGA
AAGCGGCUCAUCUAGCAGGACCGCUAGAGGCGCCAGCUCGG
GGUACAGGGAAUAUUCACCCUCCGCCGCAAGGGGGCUGAGA
CUGAUGUUUACAGACUUCUGGAGAACCAGGGUGCUGCGCCA
GACAAGCCCAAUGGCAGGGGUGUUUGGUAACCUGGAUGUGA
AUGAGGCCAGACUGAUGGCCGCCUACACUUCUGAGUGCGCG
GAUCAUCUUGAGGCCAAGGAACUGGCAGGCCCCGACGGCGU
GGCCGCCGCCCGGGAGAUUGCUAAGAGAUGGGAGAAGCGGG
UCAGAGAUCUGCAGGAUAAGGGGGCCGCUAGGAAACUCCUG
AAUGACCCCCUAGGCAGGAGAACCCCUAACUACCAGAGCAA
AAAUCCUGGGGAAUACACCGUGGGCAAUUCCAUGUUUUACG
AUGGCCCCCAAGUCGCAAACCUCCAGAAUGUGGACACCGGCU
UCUGGCUGGACAUGUCCAACUUGAGCGACGUGGUUCUAAGC
AGAGAAAUCCAGACCGGACUCCGCGCGAGAGCUACACUCGA
GGAAAGCAUGCCUAUGCUGGAGAAUCUGGAGGAGCGAUUCC
GUCGUCUACAGGAGACUUGUGACGCCGCUAGGACCGAGAUC
GAGGAGAGCGGCUGGACAAGAGAAAGCGCCUCUCGAAUGGA
GGGCGAUGAGGCCCAGGGCCCCUCCCGGGUGCAGCAGGCCUU
UCAGAGCUUCGUGAAUGAGUGCAAUUCUAUUGAGUUCAGCU
UCGGCUCUUUUGGCGAGCACGUGCGGGUGCUUUGCGCCAGG
GUGUCCCGGGGACUGGCAGCCGCCGGCGAGGCCAUAAGAAG
AUGUUUCUCCUGCUGCAAGGGCAGCACCCACCGGUAUGCUCC
CAGAGACGACCUGUCUCCAGAAGGGGCAUCGCUGGCCGAGA
CACUGGCACGGUUCGCCGACGAUAUGGGCAUUGAGAGGGGA
GCCGACGGCACUUAUGAUAUCCCUCUCGUGGACGACUGGAG
AAGAGGAGUCCCCUCAAUUGAGGGCGAAGGAUCCGAUUCUA
UCUAUGAGAUCAUGAUGCCUAUCUACGAAGUGAUGAAUAUG
GACCUGGAAACCAGGAGAUCUUUCGCUGUGCAGCAGGGCCA
UUACCAGGAUCCCCGCGCCAGCGAUUAUGACCUGCCCAGAGC
CUCAGACUACGAUUUGCCCAGAAGCCCCUACCCCACCCCUCC
GCUGCCCCCUAGAUACCAGCUGCAGAAUAUGGACGUGGAGG
CUGGCUUUAGGGAGGCUGUGUACGCUAGCUUCGUGGCCGGC
AUGUACAACUACGUGGUGACACAGCCCCAGGAGAGAAUUCC
CAAUUCUCAACAAGUAGAGGGCAUCCUGAGAGACAUGUUAA
CAAACGGAUCUCAGACCUUCCGCGACCUGAUGAAGCGGUGG AACCGGGAAGUGGACCGCGAG
CT875_E_nIgK_cHis_CO005 AUGGAAACACCCGCCCAGCUCCUCUUUCUACUUCUCCUUUGG
382 CUUCCCGACACCACCGGUAUGAGCAUUAGAGGAGUCGGCGG
GAACGGGAAUAGCCGUAUCCCCUCCCACAACGGCGACGGCAG
CAACCGCAGAAGCCAGAAUACUAAGGGAAACAAUAAGGUUG
AGGACCGCGUCUGUAGCUUGUACAGCUCAAGAAGUAACGAG
AACAGAGAGAGCCCCUACGCCGUGGUCGACGUUUCCAGCAU
GAUCGAGUCAACGCCCACAAGCGGCGAAACCACCCGCGCGUC
AAGGGGGGUCCUGUCCCGGUUCCAGAGAGGCCUGGUGAGGA
UCGCCGACAAGGUGAGACGGGCCGUGCAGUGCGCCUGGUCC
AGCGUCAGCACAUCACGGUCCUCCGCUACCAGGGCCGCCGAG
UCAGGCAGCAGCUCUCGUACCGCCCGGGGAGCCUCAAGCGGG
UACAGAGAGUACAGCCCUUCUGCCGCUAGAGGCCUGAGACU
CAUGUUUACAGACUUCUGGCGGACAAGGGUUCUCAGGCAGA
CUAGCCCUAUGGCUGGCGUGUUUGGCAAUCUUGAUGUUAAC
GAAGCCAGGCUGAUGGCUGCAUAUACAAGCGAAUGCGCCGA
CCAUCUGGAAGCUAAGGAGCUGGCCGGGCCCGACGGCGUGG
CCGCUGCCAGGGAGAUCGCCAAGAGGUGGGAGAAAAGGGUG
CGAGAUCUCCAGGAUAAGGGAGCAGCUAGAAAGCUGCUGAA
CGACCCCCUGGGCAGGCGGACCCCUAACUACCAGAGCAAAAA
UCCGGGCGAGUACACCGUCGGCAACAGCAUGUUUUACGAUG
GCCCUCAGGUGGCCAACCUUCAGAACGUGGACACCGGCUUCU
GGCUCGAUAUGUCUAAUCUUUCCGACGUCGUGCUCAGCCGG
GAAAUCCAGACUGGUCUGCGCGCCAGAGCUACCUUGGAAGA
GAGCAUGCCCAUGCUGGAGAACCUGGAGGAGAGAUUUCGGC
GCUUACAGGAAACAUGUGACGCUGCUAGGACCGAGAUUGAA
GAGAGCGGGUGGACAAGGGAGUCGGCGAGCAGGAUGGAGGG
GGACGAGGCCCAGGGCCCCAGCAGGGUGCAACAGGCUUUUC
AGUCCUUCGUGAACGAGUGCAACAGCAUCGAGUUCUCCUUC
GGCAGCUUCGGGGAGCACGUGAGAGUGUUGUGCGCCCGCGU
GUCUAGGGGAUUAGCCGCCGCAGGCGAAGCCAUCCGGCGCU
GCUUCAGCUGCUGCAAGGGCUCCACCCAUCGCUACGCCCCUA
GAGACGACCUGUCUCCCGAAGGCGCCUCCCUGGCCGAGACUC
UGGCCCGAUUCGCCGAUGACAUGGGCAUCGAGCGGGGGGCC
GAUGGCACCUACGACAUCCCUCUGGUCGAUGACUGGCGGAG
GGGCGUUCCCUCUAUUGAGGGCGAGGGCUCUGACUCUAUUU
ACGAGAUUAUGAUGCCCAUCUACGAAGUGAUGAACAUGGAC
UUGGAAACUCGCAGAUCGUUUGCAGUGCAACAGGGUCAUUA
CCAGGACCCUAGAGCCUCCGAUUAUGACCUGCCAAGAGCUA
GCGAUUAUGACCUCCCUAGAUCACCCUACCCCACACCUCCUC
UCCCUCCACGGUAUCAGCUGCAGAACAUGGACGUUGAGGCA
GGGUUUAGGGAGGCCGUGUACGCCAGCUUCGUGGCAGGCAU
GUAUAAUUAUGUGGUAACCCAGCCACAGGAGCGAAUUCCCA
ACUCUCAACAGGUGGAGGGCAUCCUGAGAGACAUGCUCACC
AACGGCAGCCAAACCUUCAGGGACCUUAUGAAACGGUGGAA
UAGAGAAGUUGAUCGCGAGCACCACCACCACCACCAC CT875_E_nIgK_cHis_CO004
AUGGAAACUCCCGCACAGUUACUUUUCUUGUUGCUUCUAUG 383
GCUCCCCGAUACCACCGGGAUGAGCAUCAGAGGCGUCGGCG
GGAACGGCAACAGCAGAAUUCCCUCCCACAACGGCGACGGCA
GCAACAGAAGAUCCCAGAACACAAAGGGCAAUAAUAAGGUC
GAGGACAGAGUGUGCAGCCUCUACUCCAGCAGGUCUAACGA
GAAUAGGGAGUCCCCGUACGCCGUUGUCGACGUGAGUUCUA
UGAUAGAGAGCACGCCCACGUCCGGAGAAACAACUAGAGCA
AGCAGGGGCGUCCUGAGCCGGUUCCAGAGAGGUCUGGUGCG
AAUUGCCGACAAGGUGAGACGGGCAGUGCAAUGCGCCUGGA
GCAGCGUCUCCACCAGCAGAAGCAGCGCCACCCGCGCUGCCG
AAUCAGGCAGCAGCUCCAGAACGGCACGGGGCGCCUCCUCCG
GCUACCGAGAGUACUCCCCUAGCGCCGCCAGAGGCCUGAGAC
UGAUGUUCACCGAUUUUUGGAGGACACGGGUUCUGAGACAG
ACCUCCCCCAUGGCUGGGGUGUUCGGCAACCUGGACGUCAA
UGAAGCCAGACUCAUGGCCGCAUAUACUUCUGAGUGCGCUG
ACCACCUGGAAGCUAAGGAACUGGCGGGCCCCGAUGGCGUG
GCCGCGGCCCGGGAGAUCGCCAAGAGAUGGGAGAAGAGAGU
GCGGGACCUGCAAGACAAGGGGGCCGCCCGGAAGCUGCUGA
ACGAUCCCUUGGGCCGCCGGACACCGAACUAUCAGAGCAAG
AACCCGGGCGAGUACACCGUGGGAAACAGCAUGUUCUAUGA
CGGACCUCAGGUGGCAAACCUGCAGAACGUGGACACUGGAU
UUUGGCUCGACAUGAGUAACCUCUCCGAUGUCGUUCUGUCU
CGUGAGAUACAGACAGGUCUGCGGGCUAGAGCCACCCUUGA
GGAGAGCAUGCCUAUGUUGGAGAAUCUGGAGGAGCGGUUCA
GAAGACUGCAGGAGACUUGCGAUGCCGCCAGGACCGAGAUU
GAGGAGAGCGGCUGGACCCGGGAAAGCGCCUCAAGGAUGGA
GGGAGACGAGGCCCAGGGACCCUCCAGGGUUCAGCAGGCCU
UCCAGUCGUUCGUGAAUGAAUGCAACAGCAUCGAGUUCAGC
UUCGGAAGCUUCGGAGAGCACGUGCGAGUGCUGUGCGCCAG
AGUAUCCAGAGGUCUGGCCGCUGCAGGCGAGGCCAUCCGGA
GAUGCUUCUCCUGCUGCAAAGGCAGCACCCACAGGUAUGCU
CCCAGGGAUGAUCUUUCUCCCGAGGGAGCCAGCCUGGCUGA
GACUCUUGCAAGAUUCGCCGAUGACAUGGGGAUCGAGCGGG
GCGCUGACGGCACCUACGACAUUCCCCUGGUGGACGACUGG
AGGAGGGGAGUGCCCUCCAUCGAGGGCGAGGGCUCCGAUUC
AAUCUAUGAGAUCAUGAUGCCUAUUUACGAGGUGAUGAACA
UGGACCUGGAGACAAGAAGAAGUUUCGCCGUCCAGCAGGGU
CAUUACCAGGACCCCCGAGCAAGCGACUACGAUCUGCCUCGC
GCCAGCGAUUACGACCUGCCUAGAAGCCCCUACCCUACACCU
CCACUGCCCCCAAGAUAUCAGCUCCAGAACAUGGACGUGGA
GGCCGGCUUCAGGGAGGCCGUGUACGCCAGCUUUGUGGCCG
GCAUGUACAACUAUGUCGUGACACAGCCUCAGGAACGCAUU
CCCAAUAGCCAACAGGUGGAGGGCAUCCUGAGAGACAUGCU
GACCAACGGCUCUCAGACUUUUAGAGAUCUGAUGAAAAGAU
GGAACAGAGAAGUGGACAGGGAGCACCACCACCACCACCAC CT875_E_nIgK_cHis_CO003
AUGGAAACACCAGCUCAGCUCCUUUUCUUACUCCUCUUGUG 384
GUUGCCGGAUACCACAGGCAUGAGCAUCCGGGGCGUCGGCG
GCAACGGAAACAGCCGGAUCCCCAGCCACAACGGAGACGGCU
CUAAUAGAAGAUCACAGAAUACCAAGGGAAAUAACAAGGUC
GAAGAUAGAGUCUGCAGCUUAUAUUCCAGCAGAUCCAACGA
GAAUAGGGAAAGCCCCUACGCCGUCGUUGACGUGAGCUCCA
UGAUCGAAAGCACCCCAACAAGUGGCGAGACUACAAGAGCC
UCAAGGGGCGUCCUGUCAAGAUUCCAAAGAGGCCUGGUGAG
GAUCGCAGACAAGGUGCGGCGGGCCGUGCAGUGCGCCUGGA
GCUCUGUGUCGACAAGCAGAUCAAGUGCCACCAGGGCCGCC
GAGAGCGGAUCCUCCAGUCGGACCGCCCGCGGCGCCUCUAGU
GGGUACAGAGAAUAUAGUCCCAGCGCCGCUAGGGGGCUGCG
CCUCAUGUUCACCGACUUCUGGAGAACCCGCGUGCUCAGGCA
GACAUCCCCUAUGGCCGGGGUGUUCGGCAACCUGGACGUGA
ACGAGGCCCGGCUUAUGGCCGCAUAUACAAGCGAGUGUGCC
GACCACCUGGAGGCCAAGGAGCUGGCUGGCCCCGACGGCGU
GGCCGCCGCACGCGAGAUUGCCAAGAGGUGGGAAAAGAGGG
UGAGAGAUCUGCAGGAUAAGGGCGCCGCCAGAAAACUGCUG
AAUGACCCCCUGGGGAGGAGGACACCCAAUUACCAGUCAAA
GAAUCCAGGGGAGUACACUGUUGGAAAUUCUAUGUUUUAUG
ACGGCCCUCAGGUGGCCAACCUUCAGAAUGUGGACACAGGC
UUCUGGCUUGACAUGAGCAACCUCAGCGACGUGGUGCUGUC
UAGGGAGAUCCAGACAGGCUUAAGAGCACGGGCUACCCUGG
AAGAGUCGAUGCCCAUGCUCGAAAAUCUGGAGGAGAGGUUC
AGACGCCUGCAAGAGACAUGCGACGCCGCGAGGACUGAAAU
CGAGGAGAGCGGCUGGACCAGGGAGUCCGCUUCUCGCAUGG
AAGGGGACGAGGCUCAGGGCCCCAGCAGGGUGCAGCAGGCC
UUCCAGAGCUUUGUGAACGAGUGCAACUCCAUUGAGUUCAG
CUUUGGAAGCUUCGGAGAGCACGUGCGGGUGCUGUGCGCCC
GCGUGUCCAGGGGCCUGGCCGCAGCUGGCGAGGCUAUACGU
CGCUGCUUCAGCUGUUGUAAGGGAAGCACCCAUAGGUACGC
CCCUCGUGACGAUCUGUCUCCCGAAGGGGCCAGCCUGGCUGA
GACACUGGCCCGCUUCGCCGAUGAUAUGGGGAUUGAACGGG
GCGCCGACGGAACCUACGACAUCCCUCUUGUGGACGACUGG
AGGAGAGGCGUCCCCUCUAUCGAGGGCGAGGGCUCUGACUC
CAUCUACGAGAUUAUGAUGCCUAUCUACGAGGUCAUGAACA
UGGACCUGGAAACCAGAAGAAGCUUCGCAGUUCAGCAGGGA
CACUACCAAGACCCACGGGCUAGUGAUUAUGACCUCCCAAG
AGCAUCCGACUAUGAUCUGCCAAGGUCACCUUACCCUACCCC
ACCCCUGCCCCCACGGUACCAGUUACAGAACAUGGAUGUGG
AGGCCGGCUUCAGGGAAGCCGUCUAUGCAUCCUUCGUGGCC
GGCAUGUACAACUACGUGGUGACUCAACCUCAGGAACGGAU
CCCCAACAGUCAGCAGGUGGAGGGGAUCCUUAGGGAUAUGC
UGACUAAUGGAAGCCAGACCUUCAGAGAUCUGAUGAAGCGG
UGGAAUAGGGAGGUGGACAGGGAGCACCAUCACCAUCACCAC CT875_E_nIgK_cHis_CO002
AUGGAGACACCCGCACAGCUCCUCUUCUUAUUGCUCUUGUG 385
GCUACCGGACACCACAGGCAUGUCUAUCCGGGGCGUUGGCG
GGAACGGCAACUCUAGGAUCCCCUCUCACAACGGCGACGGG
AGCAACAGGAGAAGCCAGAACACCAAAGGCAAUAACAAAGU
CGAGGACAGAGUUUGUUCUCUCUAUAGCUCUAGGAGCAACG
AAAACCGCGAAUCUCCUUACGCCGUCGUCGACGUCAGCAGCA
UGAUAGAGUCAACCCCUACCUCUGGAGAAACAACACGCGCC
UCCAGAGGCGUUCUGUCCAGGUUCCAGAGGGGCCUGGUGAG
AAUUGCCGACAAGGUCAGACGAGCCGUGCAGUGUGCCUGGU
CCAGCGUCUCUACCAGCAGAAGCUCCGCCACCAGAGCCGCUG
AGAGUGGCAGCUCCAGCAGGACAGCCAGGGGGGCUUCCAGC
GGCUAUAGAGAGUAUAGCCCUUCAGCCGCCAGAGGCCUGCG
GCUGAUGUUCACAGACUUUUGGAGAACAAGGGUGCUGCGGC
AGACCAGCCCCAUGGCCGGCGUGUUUGGCAAUCUGGACGUG
AACGAGGCCCGGCUGAUGGCCGCAUACACCAGCGAGUGUGC
GGACCACCUGGAGGCAAAGGAGCUGGCUGGACCCGACGGUG
UGGCCGCUGCCCGAGAAAUUGCCAAGAGGUGGGAGAAGAGA
GUUCGCGACCUGCAGGAUAAGGGCGCCGCACGGAAACUCCU
GAACGACCCACUCGGCAGAAGAACCCCCAACUACCAGUCAAA
GAACCCUGGGGAGUAUACCGUGGGAAAUUCAAUGUUCUACG
AUGGCCCUCAGGUUGCUAAUCUCCAGAACGUGGACACUGGG
UUCUGGCUGGACAUGAGCAACCUGAGUGACGUGGUGCUGUC
UCGGGAAAUUCAGACAGGCCUGCGGGCCAGAGCCACCCUGG
AAGAGUCCAUGCCUAUGCUUGAGAACCUGGAGGAGCGCUUU
AGGCGACUCCAAGAAACCUGCGAUGCUGCCAGGACCGAGAU
CGAGGAGUCUGGAUGGACCAGAGAAAGCGCCUCCAGGAUGG
AGGGCGAUGAGGCCCAGGGCCCCAGCAGGGUGCAGCAGGCU
UUCCAGAGCUUCGUGAACGAAUGUAACAGUAUCGAAUUCUC
UUUCGGUAGCUUCGGCGAGCACGUGCGGGUGUUAUGCGCCA
GGGUCAGCAGGGGCCUGGCGGCCGCCGGCGAGGCCAUCAGA
AGAUGCUUCAGCUGUUGCAAAGGCUCAACCCACAGAUAUGC
CCCUAGGGACGAUCUGUCUCCAGAGGGCGCUAGCUUGGCCG
AGACACUAGCAAGGUUCGCCGACGAUAUGGGUAUCGAGAGG
GGCGCCGACGGUACCUACGACAUCCCCCUGGUGGACGACUGG
AGGAGAGGCGUGCCCAGUAUUGAGGGCGAGGGAUCCGACAG
CAUCUACGAGAUCAUGAUGCCGAUCUACGAGGUGAUGAAUA
UGGAUCUGGAGACUCGUAGAUCAUUCGCUGUCCAGCAGGGC
CACUACCAGGAUCCUAGAGCCUCGGACUACGACUUGCCCAGG
GCUAGCGAUUACGACCUGCCUAGAUCCCCCUACCCCACUCCC
CCUCUUCCCCCUCGGUAUCAGCUGCAGAACAUGGACGUGGA
GGCCGGUUUCCGAGAGGCUGUGUACGCCUCCUUCGUGGCCG
GGAUGUACAACUACGUCGUGACCCAGCCCCAGGAGAGAAUC
CCUAAUUCCCAGCAGGUGGAGGGCAUCUUGAGAGAUAUGCU
CACAAACGGGAGCCAGACCUUUCGUGACUUAAUGAAGCGAU
GGAACAGAGAGGUGGAUAGGGAGCACCACCAUCACCACCAC CT875_E_nIgK_cHis_CO001
AUGGAAACCCCCGCCCAGCUUCUCUUCCUCCUCUUGCUUUGG 386
CUCCCAGACACAACCGGCAUGAGUAUCAGAGGCGUAGGAGG
CAACGGCAAUAGCCGUAUCCCCUCACACAACGGCGACGGCUC
CAACAGACGGAGCCAGAACACCAAGGGGAAUAAUAAGGUGG
AGGACCGGGUCUGUUCACUUUACAGCUCCAGGUCUAACGAG
AAUCGGGAAAGCCCUUACGCCGUAGUCGACGUUAGCAGUAU
GAUCGAAAGCACCCCCACCAGCGGCGAGACAACAAGGGCCUC
UCGAGGAGUUCUGAGCAGAUUUCAGAGAGGCCUGGUGCGGA
UCGCCGACAAGGUGCGGAGAGCCGUGCAGUGCGCCUGGAGC
AGCGUGAGUACAUCUCGGAGCAGCGCCACCAGAGCAGCCGA
AAGCGGCUCAUCUAGCAGGACCGCUAGAGGCGCCAGCUCGG
GGUACAGGGAAUAUUCACCCUCCGCCGCAAGGGGGCUGAGA
CUGAUGUUUACAGACUUCUGGAGAACCAGGGUGCUGCGCCA
GACAAGCCCAAUGGCAGGGGUGUUUGGUAACCUGGAUGUGA
AUGAGGCCAGACUGAUGGCCGCCUACACUUCUGAGUGCGCG
GAUCAUCUUGAGGCCAAGGAACUGGCAGGCCCCGACGGCGU
GGCCGCCGCCCGGGAGAUUGCUAAGAGAUGGGAGAAGCGGG
UCAGAGAUCUGCAGGAUAAGGGGGCCGCUAGGAAACUCCUG
AAUGACCCCCUAGGCAGGAGAACCCCUAACUACCAGAGCAA
AAAUCCUGGGGAAUACACCGUGGGCAAUUCCAUGUUUUACG
AUGGCCCCCAAGUCGCAAACCUCCAGAAUGUGGACACCGGCU
UCUGGCUGGACAUGUCCAACUUGAGCGACGUGGUUCUAAGC
AGAGAAAUCCAGACCGGACUCCGCGCGAGAGCUACACUCGA
GGAAAGCAUGCCUAUGCUGGAGAAUCUGGAGGAGCGAUUCC
GUCGUCUACAGGAGACUUGUGACGCCGCUAGGACCGAGAUC
GAGGAGAGCGGCUGGACAAGAGAAAGCGCCUCUCGAAUGGA
GGGCGAUGAGGCCCAGGGCCCCUCCCGGGUGCAGCAGGCCUU
UCAGAGCUUCGUGAAUGAGUGCAAUUCUAUUGAGUUCAGCU
UCGGCUCUUUUGGCGAGCACGUGCGGGUGCUUUGCGCCAGG
GUGUCCCGGGGACUGGCAGCCGCCGGCGAGGCCAUAAGAAG
AUGUUUCUCCUGCUGCAAGGGCAGCACCCACCGGUAUGCUCC
CAGAGACGACCUGUCUCCAGAAGGGGCAUCGCUGGCCGAGA
CACUGGCACGGUUCGCCGACGAUAUGGGCAUUGAGAGGGGA
GCCGACGGCACUUAUGAUAUCCCUCUCGUGGACGACUGGAG
AAGAGGAGUCCCCUCAAUUGAGGGCGAAGGAUCCGAUUCUA
UCUAUGAGAUCAUGAUGCCUAUCUACGAAGUGAUGAAUAUG
GACCUGGAAACCAGGAGAUCUUUCGCUGUGCAGCAGGGCCA
UUACCAGGAUCCCCGCGCCAGCGAUUAUGACCUGCCCAGAGC
CUCAGACUACGAUUUGCCCAGAAGCCCCUACCCCACCCCUCC
GCUGCCCCCUAGAUACCAGCUGCAGAAUAUGGACGUGGAGG
CUGGCUUUAGGGAGGCUGUGUACGCUAGCUUCGUGGCCGGC
AUGUACAACUACGUGGUGACACAGCCCCAGGAGAGAAUUCC
CAAUUCUCAACAAGUAGAGGGCAUCCUGAGAGACAUGUUAA
CAAACGGAUCUCAGACCUUCCGCGACCUGAUGAAGCGGUGG
AACCGGGAAGUGGACCGCGAGCACCACCACCACCAUCAU CT875_E_nIgK_nFLAG
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 387
GCUGCCUGACACCACCGGCGACUAUAAAGACCACGAUGGCG
AUUACAAAGAUCACGACAUCGAUUACAAGGAUGACGACGAC
AAAAUGAGCAUCAGAGGCGUGGGCGGCAACGGCAACAGCAG
AAUCCCUAGCCACAACGGCGACGGCAGCAACAGGCGGAGCCA
GAACACCAAGGGCAACAACAAGGUGGAAGAUAGAGUGUGCA
GCCUGUACAGCAGCCGGUCCAACGAGAACCGCGAGAGCCCUU
AUGCCGUGGUGGACGUGUCCAGCAUGAUCGAGAGCACCCCC
ACCAGCGGCGAGACAACCAGAGCUAGUAGAGGCGUGCUGAG
CCGGUUCCAGAGGGGCCUCGUGCGGAUUGCUGACAAAGUGC
GGAGAGCCGUGCAGUGCGCUUGGAGCAGCGUGUCCACAAGC
AGAAGCAGCGCCACAAGAGCCGCCGAGAGCGGCAGCUCUAG
CAGAACAGCUAGAGGCGCCAGCAGCGGCUACAGAGAGUACA
GCCCUUCUGCCGCUCGGGGCCUGCGGCUGAUGUUCACCGACU
UUUGGCGGACCCGGGUGCUGAGACAGACCUCUCCUAUGGCC
GGCGUGUUCGGCAACCUGGACGUGAACGAGGCCAGACUGAU
GGCCGCCUACACCAGCGAGUGUGCCGAUCACCUGGAAGCCAA
AGAGCUGGCCGGACCUGACGGCGUGGCAGCCGCUAGAGAAA
UCGCCAAGAGAUGGGAGAAGAGAGUGCGGGACCUGCAGGAC
AAGGGCGCUGCCAGAAAGCUGCUGAACGACCCCCUGGGCAG
ACGGACCCCCAACUACCAGAGCAAGAACCCCGGCGAGUACAC
CGUGGGCAACUCCAUGUUCUACGACGGCCCCCAGGUGGCCAA
CCUGCAGAAUGUGGAUACCGGCUUCUGGCUGGACAUGAGCA
ACCUGAGCGACGUGGUGCUGUCCAGAGAGAUCCAGACCGGC
CUGAGAGCCAGAGCCACCCUGGAAGAGUCCAUGCCCAUGCU
GGAAAAUCUGGAAGAGAGAUUCCGGCGGCUGCAGGAAACCU
GCGACGCCGCCAGAACCGAGAUCGAGGAAAGCGGCUGGACC
CGGGAAAGCGCCUCCAGAAUGGAAGGCGACGAAGCCCAGGG
CCCCAGCAGAGUGCAGCAGGCCUUUCAGAGCUUCGUGAAUG
AGUGCAACAGCAUCGAGUUCAGCUUCGGCUCCUUCGGCGAG
CACGUGCGGGUGCUGUGUGCCAGAGUGUCAAGAGGACUGGC
CGCUGCCGGCGAGGCCAUCAGAAGAUGCUUCAGCUGCUGCA
AGGGCAGCACCCACAGAUACGCCCCCAGAGAUGACCUGUCUC
CUGAGGGCGCCUCUCUGGCCGAAACCCUGGCCAGAUUCGCCG
ACGACAUGGGCAUCGAAAGAGGCGCCGACGGCACCUACGAC
AUCCCCCUGGUGGACGAUUGGAGAAGGGGCGUGCCAUCCAU
CGAGGGCGAGGGCAGCGAUAGCAUCUACGAGAUCAUGAUGC
CCAUCUACGAAGUGAUGAACAUGGACCUGGAAACCCGGCGG
AGCUUCGCCGUGCAGCAGGGCCAUUACCAGGACCCCAGAGCC
AGCGACUACGACCUGCCUAGAGCCUCCGAUUACGAUCUGCCC
AGAAGCCCCUACCCCACCCCUCCACUGCCUCCCAGAUACCAG
CUGCAGAACAUGGAUGUGGAAGCCGGCUUUCGCGAGGCCGU
GUACGCCUCUUUUGUGGCCGGCAUGUACAACUACGUCGUGA
CCCAGCCCCAGGAACGGAUCCCCAAUAGCCAGCAGGUGGAAG
GCAUCCUGCGGGACAUGCUGACCAACGGCAGCCAGACCUUCC
GGGACCUGAUGAAGCGGUGGAACAGAGAGGUGGACCGCGAG CT875_E_nIgK_cFLAG
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 388
GCUGCCUGACACCACCGGCAUGAGCAUCAGAGGCGUGGGCG
GCAACGGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCA
GCAACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUG
GAAGAUAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGA
GAACCGCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCA
UGAUCGAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUA
GUAGAGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGG
AUUGCUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAG
CAGCGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGA
GAGCGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCG
GCUACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGC
UGAUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAG
ACCUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAA
CGAGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCG
AUCACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUG
GCAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGU
GCGGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGA
ACGACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GCCCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUC
UGGCUGGACAUGAGCAACCUGAGCGACGUGGUGCUGUCCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAG
AGUCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGG
CGGCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGA
GGAAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUC
AGAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUC
GGCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGU
GUCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAU
GCUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCA
GAGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCC
UGGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCC
GACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAG
GGGCGUGCCAUCCAUCGAGGGCGAGGGCAGCGAUAGCAUCU
ACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGGAC
CUGGAAACCCGGCGGAGCUUCGCCGUGCAGCAGGGCCAUUA
CCAGGACCCCAGAGCCAGCGACUACGACCUGCCUAGAGCCUC
CGAUUACGAUCUGCCCAGAAGCCCCUACCCCACCCCUCCACU
GCCUCCCAGAUACCAGCUGCAGAACAUGGAUGUGGAAGCCG
GCUUUCGCGAGGCCGUGUACGCCUCUUUUGUGGCCGGCAUG
UACAACUACGUCGUGACCCAGCCCCAGGAACGGAUCCCCAAU
AGCCAGCAGGUGGAAGGCAUCCUGCGGGACAUGCUGACCAA
CGGCAGCCAGACCUUCCGGGACCUGAUGAAGCGGUGGAACA
GAGAGGUGGACCGCGAGGACUAUAAAGACCACGAUGGCGAU
UACAAAGAUCACGACAUCGAUUACAAGGAUGACGACGACAAA CT875_E_nIgK_nHis
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 389
GCUGCCUGACACCACCGGCCACCACCAUCACCACCACAUGAG
CAUCAGAGGCGUGGGCGGCAACGGCAACAGCAGAAUCCCUA
GCCACAACGGCGACGGCAGCAACAGGCGGAGCCAGAACACCA
AGGGCAACAACAAGGUGGAAGAUAGAGUGUGCAGCCUGUAC
AGCAGCCGGUCCAACGAGAACCGCGAGAGCCCUUAUGCCGU
GGUGGACGUGUCCAGCAUGAUCGAGAGCACCCCCACCAGCG
GCGAGACAACCAGAGCUAGUAGAGGCGUGCUGAGCCGGUUC
CAGAGGGGCCUCGUGCGGAUUGCUGACAAAGUGCGGAGAGC
CGUGCAGUGCGCUUGGAGCAGCGUGUCCACAAGCAGAAGCA
GCGCCACAAGAGCCGCCGAGAGCGGCAGCUCUAGCAGAACA
GCUAGAGGCGCCAGCAGCGGCUACAGAGAGUACAGCCCUUC
UGCCGCUCGGGGCCUGCGGCUGAUGUUCACCGACUUUUGGC
GGACCCGGGUGCUGAGACAGACCUCUCCUAUGGCCGGCGUG
UUCGGCAACCUGGACGUGAACGAGGCCAGACUGAUGGCCGC
CUACACCAGCGAGUGUGCCGAUCACCUGGAAGCCAAAGAGC
UGGCCGGACCUGACGGCGUGGCAGCCGCUAGAGAAAUCGCC
AAGAGAUGGGAGAAGAGAGUGCGGGACCUGCAGGACAAGGG
CGCUGCCAGAAAGCUGCUGAACGACCCCCUGGGCAGACGGAC
CCCCAACUACCAGAGCAAGAACCCCGGCGAGUACACCGUGGG
CAACUCCAUGUUCUACGACGGCCCCCAGGUGGCCAACCUGCA
GAAUGUGGAUACCGGCUUCUGGCUGGACAUGAGCAACCUGA
GCGACGUGGUGCUGUCCAGAGAGAUCCAGACCGGCCUGAGA
GCCAGAGCCACCCUGGAAGAGUCCAUGCCCAUGCUGGAAAA
UCUGGAAGAGAGAUUCCGGCGGCUGCAGGAAACCUGCGACG
CCGCCAGAACCGAGAUCGAGGAAAGCGGCUGGACCCGGGAA
AGCGCCUCCAGAAUGGAAGGCGACGAAGCCCAGGGCCCCAGC
AGAGUGCAGCAGGCCUUUCAGAGCUUCGUGAAUGAGUGCAA
CAGCAUCGAGUUCAGCUUCGGCUCCUUCGGCGAGCACGUGC
GGGUGCUGUGUGCCAGAGUGUCAAGAGGACUGGCCGCUGCC
GGCGAGGCCAUCAGAAGAUGCUUCAGCUGCUGCAAGGGCAG
CACCCACAGAUACGCCCCCAGAGAUGACCUGUCUCCUGAGGG
CGCCUCUCUGGCCGAAACCCUGGCCAGAUUCGCCGACGACAU
GGGCAUCGAAAGAGGCGCCGACGGCACCUACGACAUCCCCCU
GGUGGACGAUUGGAGAAGGGGCGUGCCAUCCAUCGAGGGCG
AGGGCAGCGAUAGCAUCUACGAGAUCAUGAUGCCCAUCUAC
GAAGUGAUGAACAUGGACCUGGAAACCCGGCGGAGCUUCGC
CGUGCAGCAGGGCCAUUACCAGGACCCCAGAGCCAGCGACUA
CGACCUGCCUAGAGCCUCCGAUUACGAUCUGCCCAGAAGCCC
CUACCCCACCCCUCCACUGCCUCCCAGAUACCAGCUGCAGAA
CAUGGAUGUGGAAGCCGGCUUUCGCGAGGCCGUGUACGCCU
CUUUUGUGGCCGGCAUGUACAACUACGUCGUGACCCAGCCCC
AGGAACGGAUCCCCAAUAGCCAGCAGGUGGAAGGCAUCCUG
CGGGACAUGCUGACCAACGGCAGCCAGACCUUCCGGGACCUG
AUGAAGCGGUGGAACAGAGAGGUGGACCGCGAG MOMP_E_nTMEM149
AUGGGCCCUGGCAGAUGUCUGCUGACAGCCCUGCUGCUGCU 390
GGCCCUGGCUCCUCCACCUGAAGCUCUGCCCGUGGGAAAUCC
UGCCGAGCCCAGCCUGAUGAUCGACGGCAUUCUGUGGGAGG
GCUUCGGCGGCGACCCUUGCGAUCCUUGUACCACUUGGUGC
GACGCCAUCAGCAUGAGAAUGGGCUACUACGGCGACUUCGU
GUUCGACCGGGUGCUGAAAACCGACGUGAACAAAGAAUUCC
AGAUGGGCGACAAGCCCACCAGCACCACCGGAAAUGCCACCG
CCCCUACCACCCUGACCGCCAGAGAAAAUCCCGCCUACGGCC
GGCACAUGCAGGACGCCGAGAUGUUCACCAACGCCGCCUGCA
UGGCCCUGAACAUCUGGGACAGAUUCGACGUGUUCUGCACC
CUGGGCGCCAGCAGCGGCUACCUGAAGGGCAAUAGCGCCAG
CUUCAACCUCGUGGGCCUGUUCGGCGACAACGAGAACCAGA
GCACCGUGAAAACAAACAGCGUGCCCAACAUGAGCCUGGAC
CAGAGCGUGGUGGAACUGUACACCGACACCGCAUUCUCUUG
GAGCGUGGGAGCCAGAGCUGCCCUGUGGGAGUGUGGAUGUG
CCACACUGGGCGCUAGCUUCCAGUACGCCCAGAGCAAGCCCA
AGGUGGAAGAACUGAACGUGCUGUGCAAUGCCGCCGAGUUC
ACCAUCAACAAGCCUAAGGGCUACGUGGGCCAGGAAUUCCC
CCUGGCCCUGAUCGCCGGAACAGAUGCCGCCACCGGAACAAA
GGACGCCAGCAUCGACUACCACGAGUGGCAGGCUUCUCUGG
CCCUGUCCUACCGGCUGAAUAUGUUCACCCCCUACAUCGGCG
UGAAGUGGUCCCGGGCCAGCUUCGAUGCCGACACCAUCAGA
AUCGCCCAGCCCAAGAGCGCCACCGCCAUCUUCGAUACCACC
ACACUGAACCCCACCAUUGCCGGCGCUGGCGACGUGAAAGCC
UCUGCCGAAGGACAGCUGGGCGACACAAUGCAGAUCGUGUC
CCUGCAGCUGAACAAGAUGAAGUCCCGGAAGUCCUGCGGAA
UCGCCGUGGGCACCACAAUCGUGGACGCCGAUAAGUACGCC
GUGACCGUGGAAACCCGGCUGAUCGAUGAGAGGGCCGCUCA CGUGAACGCCCAGUUCAGAUUC
MOMP_E_nTMEM149_cHis AUGGGCCCUGGCAGAUGUCUGCUGACAGCCCUGCUGCUGCU 391
GGCCCUGGCUCCUCCACCUGAAGCUCUGCCCGUGGGAAAUCC
UGCCGAGCCCAGCCUGAUGAUCGACGGCAUUCUGUGGGAGG
GCUUCGGCGGCGACCCUUGCGAUCCUUGUACCACUUGGUGC
GACGCCAUCAGCAUGAGAAUGGGCUACUACGGCGACUUCGU
GUUCGACCGGGUGCUGAAAACCGACGUGAACAAAGAAUUCC
AGAUGGGCGACAAGCCCACCAGCACCACCGGAAAUGCCACCG
CCCCUACCACCCUGACCGCCAGAGAAAAUCCCGCCUACGGCC
GGCACAUGCAGGACGCCGAGAUGUUCACCAACGCCGCCUGCA
UGGCCCUGAACAUCUGGGACAGAUUCGACGUGUUCUGCACC
CUGGGCGCCAGCAGCGGCUACCUGAAGGGCAAUAGCGCCAG
CUUCAACCUCGUGGGCCUGUUCGGCGACAACGAGAACCAGA
GCACCGUGAAAACAAACAGCGUGCCCAACAUGAGCCUGGAC
CAGAGCGUGGUGGAACUGUACACCGACACCGCAUUCUCUUG
GAGCGUGGGAGCCAGAGCUGCCCUGUGGGAGUGUGGAUGUG
CCACACUGGGCGCUAGCUUCCAGUACGCCCAGAGCAAGCCCA
AGGUGGAAGAACUGAACGUGCUGUGCAAUGCCGCCGAGUUC
ACCAUCAACAAGCCUAAGGGCUACGUGGGCCAGGAAUUCCC
CCUGGCCCUGAUCGCCGGAACAGAUGCCGCCACCGGAACAAA
GGACGCCAGCAUCGACUACCACGAGUGGCAGGCUUCUCUGG
CCCUGUCCUACCGGCUGAAUAUGUUCACCCCCUACAUCGGCG
UGAAGUGGUCCCGGGCCAGCUUCGAUGCCGACACCAUCAGA
AUCGCCCAGCCCAAGAGCGCCACCGCCAUCUUCGAUACCACC
ACACUGAACCCCACCAUUGCCGGCGCUGGCGACGUGAAAGCC
UCUGCCGAAGGACAGCUGGGCGACACAAUGCAGAUCGUGUC
CCUGCAGCUGAACAAGAUGAAGUCCCGGAAGUCCUGCGGAA
UCGCCGUGGGCACCACAAUCGUGGACGCCGAUAAGUACGCC
GUGACCGUGGAAACCCGGCUGAUCGAUGAGAGGGCCGCUCA
CGUGAACGCCCAGUUCAGAUUCCACCACCACCAUCACCAC MOMP_E_nFLRU2
AUGGGCCUGCAGACCACCAAGUGGCCUAGCCACGGCGCAUUC 392
UUUCUGAAGUCCUGGCUGAUCAUCUCCCUGGGCCUGUACAG
CCAGGUGUCCAAGCUGCUGGCUCUGCCCGUGGGAAAUCCUG
CCGAGCCCAGCCUGAUGAUCGACGGCAUUCUGUGGGAGGGC
UUCGGCGGCGACCCUUGCGAUCCUUGUACCACUUGGUGCGA
CGCCAUCAGCAUGAGAAUGGGCUACUACGGCGACUUCGUGU
UCGACCGGGUGCUGAAAACCGACGUGAACAAAGAAUUCCAG
AUGGGCGACAAGCCCACCAGCACCACCGGAAAUGCCACCGCC
CCUACCACCCUGACCGCCAGAGAAAAUCCCGCCUACGGCCGG
CACAUGCAGGACGCCGAGAUGUUCACCAACGCCGCCUGCAUG
GCCCUGAACAUCUGGGACAGAUUCGACGUGUUCUGCACCCU
GGGCGCCAGCAGCGGCUACCUGAAGGGCAAUAGCGCCAGCU
UCAACCUCGUGGGCCUGUUCGGCGACAACGAGAACCAGAGC
ACCGUGAAAACAAACAGCGUGCCCAACAUGAGCCUGGACCA
GAGCGUGGUGGAACUGUACACCGACACCGCAUUCUCUUGGA
GCGUGGGAGCCAGAGCUGCCCUGUGGGAGUGUGGAUGUGCC
ACACUGGGCGCUAGCUUCCAGUACGCCCAGAGCAAGCCCAAG
GUGGAAGAACUGAACGUGCUGUGCAAUGCCGCCGAGUUCAC
CAUCAACAAGCCUAAGGGCUACGUGGGCCAGGAAUUCCCCC
UGGCCCUGAUCGCCGGAACAGAUGCCGCCACCGGAACAAAG
GACGCCAGCAUCGACUACCACGAGUGGCAGGCUUCUCUGGCC
CUGUCCUACCGGCUGAAUAUGUUCACCCCCUACAUCGGCGUG
AAGUGGUCCCGGGCCAGCUUCGAUGCCGACACCAUCAGAAU
CGCCCAGCCCAAGAGCGCCACCGCCAUCUUCGAUACCACCAC
ACUGAACCCCACCAUUGCCGGCGCUGGCGACGUGAAAGCCUC
UGCCGAAGGACAGCUGGGCGACACAAUGCAGAUCGUGUCCC
UGCAGCUGAACAAGAUGAAGUCCCGGAAGUCCUGCGGAAUC
GCCGUGGGCACCACAAUCGUGGACGCCGAUAAGUACGCCGU
GACCGUGGAAACCCGGCUGAUCGAUGAGAGGGCCGCUCACG UGAACGCCCAGUUCAGAUUC
MOMP_E_nFLRU2_cHis AUGGGCCUGCAGACCACCAAGUGGCCUAGCCACGGCGCAUUC 393
UUUCUGAAGUCCUGGCUGAUCAUCUCCCUGGGCCUGUACAG
CCAGGUGUCCAAGCUGCUGGCUCUGCCCGUGGGAAAUCCUG
CCGAGCCCAGCCUGAUGAUCGACGGCAUUCUGUGGGAGGGC
UUCGGCGGCGACCCUUGCGAUCCUUGUACCACUUGGUGCGA
CGCCAUCAGCAUGAGAAUGGGCUACUACGGCGACUUCGUGU
UCGACCGGGUGCUGAAAACCGACGUGAACAAAGAAUUCCAG
AUGGGCGACAAGCCCACCAGCACCACCGGAAAUGCCACCGCC
CCUACCACCCUGACCGCCAGAGAAAAUCCCGCCUACGGCCGG
CACAUGCAGGACGCCGAGAUGUUCACCAACGCCGCCUGCAUG
GCCCUGAACAUCUGGGACAGAUUCGACGUGUUCUGCACCCU
GGGCGCCAGCAGCGGCUACCUGAAGGGCAAUAGCGCCAGCU
UCAACCUCGUGGGCCUGUUCGGCGACAACGAGAACCAGAGC
ACCGUGAAAACAAACAGCGUGCCCAACAUGAGCCUGGACCA
GAGCGUGGUGGAACUGUACACCGACACCGCAUUCUCUUGGA
GCGUGGGAGCCAGAGCUGCCCUGUGGGAGUGUGGAUGUGCC
ACACUGGGCGCUAGCUUCCAGUACGCCCAGAGCAAGCCCAAG
GUGGAAGAACUGAACGUGCUGUGCAAUGCCGCCGAGUUCAC
CAUCAACAAGCCUAAGGGCUACGUGGGCCAGGAAUUCCCCC
UGGCCCUGAUCGCCGGAACAGAUGCCGCCACCGGAACAAAG
GACGCCAGCAUCGACUACCACGAGUGGCAGGCUUCUCUGGCC
CUGUCCUACCGGCUGAAUAUGUUCACCCCCUACAUCGGCGUG
AAGUGGUCCCGGGCCAGCUUCGAUGCCGACACCAUCAGAAU
CGCCCAGCCCAAGAGCGCCACCGCCAUCUUCGAUACCACCAC
ACUGAACCCCACCAUUGCCGGCGCUGGCGACGUGAAAGCCUC
UGCCGAAGGACAGCUGGGCGACACAAUGCAGAUCGUGUCCC
UGCAGCUGAACAAGAUGAAGUCCCGGAAGUCCUGCGGAAUC
GCCGUGGGCACCACAAUCGUGGACGCCGAUAAGUACGCCGU
GACCGUGGAAACCCGGCUGAUCGAUGAGAGGGCCGCUCACG
UGAACGCCCAGUUCAGAUUCCACCACCACCAUCACCAC MOMP_E_nIgK
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 394
GCUGCCUGACACCACCGGCCUGCCCGUGGGAAAUCCUGCCGA
GCCCAGCCUGAUGAUCGACGGCAUUCUGUGGGAGGGCUUCG
GCGGCGACCCUUGCGAUCCUUGUACCACUUGGUGCGACGCCA
UCAGCAUGAGAAUGGGCUACUACGGCGACUUCGUGUUCGAC
CGGGUGCUGAAAACCGACGUGAACAAAGAAUUCCAGAUGGG
CGACAAGCCCACCAGCACCACCGGAAAUGCCACCGCCCCUAC
CACCCUGACCGCCAGAGAAAAUCCCGCCUACGGCCGGCACAU
GCAGGACGCCGAGAUGUUCACCAACGCCGCCUGCAUGGCCCU
GAACAUCUGGGACAGAUUCGACGUGUUCUGCACCCUGGGCG
CCAGCAGCGGCUACCUGAAGGGCAAUAGCGCCAGCUUCAACC
UCGUGGGCCUGUUCGGCGACAACGAGAACCAGAGCACCGUG
AAAACAAACAGCGUGCCCAACAUGAGCCUGGACCAGAGCGU
GGUGGAACUGUACACCGACACCGCAUUCUCUUGGAGCGUGG
GAGCCAGAGCUGCCCUGUGGGAGUGUGGAUGUGCCACACUG
GGCGCUAGCUUCCAGUACGCCCAGAGCAAGCCCAAGGUGGA
AGAACUGAACGUGCUGUGCAAUGCCGCCGAGUUCACCAUCA
ACAAGCCUAAGGGCUACGUGGGCCAGGAAUUCCCCCUGGCCC
UGAUCGCCGGAACAGAUGCCGCCACCGGAACAAAGGACGCC
AGCAUCGACUACCACGAGUGGCAGGCUUCUCUGGCCCUGUCC
UACCGGCUGAAUAUGUUCACCCCCUACAUCGGCGUGAAGUG
GUCCCGGGCCAGCUUCGAUGCCGACACCAUCAGAAUCGCCCA
GCCCAAGAGCGCCACCGCCAUCUUCGAUACCACCACACUGAA
CCCCACCAUUGCCGGCGCUGGCGACGUGAAAGCCUCUGCCGA
AGGACAGCUGGGCGACACAAUGCAGAUCGUGUCCCUGCAGC
UGAACAAGAUGAAGUCCCGGAAGUCCUGCGGAAUCGCCGUG
GGCACCACAAUCGUGGACGCCGAUAAGUACGCCGUGACCGU
GGAAACCCGGCUGAUCGAUGAGAGGGCCGCUCACGUGAACG CCCAGUUCAGAUUC
MOMP_E_nIgK_cHis AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 395
GCUGCCUGACACCACCGGCCUGCCCGUGGGAAAUCCUGCCGA
GCCCAGCCUGAUGAUCGACGGCAUUCUGUGGGAGGGCUUCG
GCGGCGACCCUUGCGAUCCUUGUACCACUUGGUGCGACGCCA
UCAGCAUGAGAAUGGGCUACUACGGCGACUUCGUGUUCGAC
CGGGUGCUGAAAACCGACGUGAACAAAGAAUUCCAGAUGGG
CGACAAGCCCACCAGCACCACCGGAAAUGCCACCGCCCCUAC
CACCCUGACCGCCAGAGAAAAUCCCGCCUACGGCCGGCACAU
GCAGGACGCCGAGAUGUUCACCAACGCCGCCUGCAUGGCCCU
GAACAUCUGGGACAGAUUCGACGUGUUCUGCACCCUGGGCG
CCAGCAGCGGCUACCUGAAGGGCAAUAGCGCCAGCUUCAACC
UCGUGGGCCUGUUCGGCGACAACGAGAACCAGAGCACCGUG
AAAACAAACAGCGUGCCCAACAUGAGCCUGGACCAGAGCGU
GGUGGAACUGUACACCGACACCGCAUUCUCUUGGAGCGUGG
GAGCCAGAGCUGCCCUGUGGGAGUGUGGAUGUGCCACACUG
GGCGCUAGCUUCCAGUACGCCCAGAGCAAGCCCAAGGUGGA
AGAACUGAACGUGCUGUGCAAUGCCGCCGAGUUCACCAUCA
ACAAGCCUAAGGGCUACGUGGGCCAGGAAUUCCCCCUGGCCC
UGAUCGCCGGAACAGAUGCCGCCACCGGAACAAAGGACGCC
AGCAUCGACUACCACGAGUGGCAGGCUUCUCUGGCCCUGUCC
UACCGGCUGAAUAUGUUCACCCCCUACAUCGGCGUGAAGUG
GUCCCGGGCCAGCUUCGAUGCCGACACCAUCAGAAUCGCCCA
GCCCAAGAGCGCCACCGCCAUCUUCGAUACCACCACACUGAA
CCCCACCAUUGCCGGCGCUGGCGACGUGAAAGCCUCUGCCGA
AGGACAGCUGGGCGACACAAUGCAGAUCGUGUCCCUGCAGC
UGAACAAGAUGAAGUCCCGGAAGUCCUGCGGAAUCGCCGUG
GGCACCACAAUCGUGGACGCCGAUAAGUACGCCGUGACCGU
GGAAACCCGGCUGAUCGAUGAGAGGGCCGCUCACGUGAACG
CCCAGUUCAGAUUCCACCACCACCAUCACCAC MOMP_E_nOsteo
AUGUGGUGGCGGCUGUGGUGGCUUCUCCUUCUCCUCCUGCU 396
GCUGUGGCCCAUGGUGUGGGCCCUGCCCGUGGGAAAUCCUG
CCGAGCCCAGCCUGAUGAUCGACGGCAUUCUGUGGGAGGGC
UUCGGCGGCGACCCUUGCGAUCCUUGUACCACUUGGUGCGA
CGCCAUCAGCAUGAGAAUGGGCUACUACGGCGACUUCGUGU
UCGACCGGGUGCUGAAAACCGACGUGAACAAAGAAUUCCAG
AUGGGCGACAAGCCCACCAGCACCACCGGAAAUGCCACCGCC
CCUACCACCCUGACCGCCAGAGAAAAUCCCGCCUACGGCCGG
CACAUGCAGGACGCCGAGAUGUUCACCAACGCCGCCUGCAUG
GCCCUGAACAUCUGGGACAGAUUCGACGUGUUCUGCACCCU
GGGCGCCAGCAGCGGCUACCUGAAGGGCAAUAGCGCCAGCU
UCAACCUCGUGGGCCUGUUCGGCGACAACGAGAACCAGAGC
ACCGUGAAAACAAACAGCGUGCCCAACAUGAGCCUGGACCA
GAGCGUGGUGGAACUGUACACCGACACCGCAUUCUCUUGGA
GCGUGGGAGCCAGAGCUGCCCUGUGGGAGUGUGGAUGUGCC
ACACUGGGCGCUAGCUUCCAGUACGCCCAGAGCAAGCCCAAG
GUGGAAGAACUGAACGUGCUGUGCAAUGCCGCCGAGUUCAC
CAUCAACAAGCCUAAGGGCUACGUGGGCCAGGAAUUCCCCC
UGGCCCUGAUCGCCGGAACAGAUGCCGCCACCGGAACAAAG
GACGCCAGCAUCGACUACCACGAGUGGCAGGCUUCUCUGGCC
CUGUCCUACCGGCUGAAUAUGUUCACCCCCUACAUCGGCGUG
AAGUGGUCCCGGGCCAGCUUCGAUGCCGACACCAUCAGAAU
CGCCCAGCCCAAGAGCGCCACCGCCAUCUUCGAUACCACCAC
ACUGAACCCCACCAUUGCCGGCGCUGGCGACGUGAAAGCCUC
UGCCGAAGGACAGCUGGGCGACACAAUGCAGAUCGUGUCCC
UGCAGCUGAACAAGAUGAAGUCCCGGAAGUCCUGCGGAAUC
GCCGUGGGCACCACAAUCGUGGACGCCGAUAAGUACGCCGU
GACCGUGGAAACCCGGCUGAUCGAUGAGAGGGCCGCUCACG UGAACGCCCAGUUCAGAUUC
MOMP_E_nOsteo_cHis AUGUGGUGGCGGCUGUGGUGGCUUCUCCUUCUCCUCCUGCU 397
GCUGUGGCCCAUGGUGUGGGCCCUGCCCGUGGGAAAUCCUG
CCGAGCCCAGCCUGAUGAUCGACGGCAUUCUGUGGGAGGGC
UUCGGCGGCGACCCUUGCGAUCCUUGUACCACUUGGUGCGA
CGCCAUCAGCAUGAGAAUGGGCUACUACGGCGACUUCGUGU
UCGACCGGGUGCUGAAAACCGACGUGAACAAAGAAUUCCAG
AUGGGCGACAAGCCCACCAGCACCACCGGAAAUGCCACCGCC
CCUACCACCCUGACCGCCAGAGAAAAUCCCGCCUACGGCCGG
CACAUGCAGGACGCCGAGAUGUUCACCAACGCCGCCUGCAUG
GCCCUGAACAUCUGGGACAGAUUCGACGUGUUCUGCACCCU
GGGCGCCAGCAGCGGCUACCUGAAGGGCAAUAGCGCCAGCU
UCAACCUCGUGGGCCUGUUCGGCGACAACGAGAACCAGAGC
ACCGUGAAAACAAACAGCGUGCCCAACAUGAGCCUGGACCA
GAGCGUGGUGGAACUGUACACCGACACCGCAUUCUCUUGGA
GCGUGGGAGCCAGAGCUGCCCUGUGGGAGUGUGGAUGUGCC
ACACUGGGCGCUAGCUUCCAGUACGCCCAGAGCAAGCCCAAG
GUGGAAGAACUGAACGUGCUGUGCAAUGCCGCCGAGUUCAC
CAUCAACAAGCCUAAGGGCUACGUGGGCCAGGAAUUCCCCC
UGGCCCUGAUCGCCGGAACAGAUGCCGCCACCGGAACAAAG
GACGCCAGCAUCGACUACCACGAGUGGCAGGCUUCUCUGGCC
CUGUCCUACCGGCUGAAUAUGUUCACCCCCUACAUCGGCGUG
AAGUGGUCCCGGGCCAGCUUCGAUGCCGACACCAUCAGAAU
CGCCCAGCCCAAGAGCGCCACCGCCAUCUUCGAUACCACCAC
ACUGAACCCCACCAUUGCCGGCGCUGGCGACGUGAAAGCCUC
UGCCGAAGGACAGCUGGGCGACACAAUGCAGAUCGUGUCCC
UGCAGCUGAACAAGAUGAAGUCCCGGAAGUCCUGCGGAAUC
GCCGUGGGCACCACAAUCGUGGACGCCGAUAAGUACGCCGU
GACCGUGGAAACCCGGCUGAUCGAUGAGAGGGCCGCUCACG
UGAACGCCCAGUUCAGAUUCCACCACCACCAUCACCAC CT-858_E_H97A_nIgK
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 398
GCUGCCUGAUACCACAGGCGUGCGGGGAGAGUCCCUCGUGU
GCAAGAAUGCCCUGCAGGACCUGAGCUUCCUGGAACAUCUG
CUGCAAGUGAAGUACGCCCCCAAGACCUGGAAAGAGCAGUA
CCUGGGCUGGGACCUGGUGCAGUCCUCUGUGUCUGCCCAGC
AGAAGCUGCGGACCCAGGAAAACCCCUCUACCAGCUUCUGUC
AGCAAGUGCUGGCCGACUUCAUCGGCGGCCUGAACGAUUUC
GCCGCCGGCGUGACCUUUUUCGCCAUCGAGAGCGCCUACCUG
CCCUACACCGUGCAGAAGUCCAGCGACGGCCGGUUCUACUUC
GUGGACAUCAUGACCUUCAGCAGCGAGAUCAGAGUGGGCGA
CGAGCUGCUGGAAGUGGAUGGCGCUCCUGUGCAGGAUGUGC
UGGCCACACUGUACGGCAGCAACCACAAGGGCACAGCCGCCG
AAGAAUCUGCCGCCCUGAGAACCCUGUUCAGCCGGAUGGCC
UCUCUGGGCCACAAGGUGCCAAGCGGCAGAACCACCCUGAA
GAUCAGACGGCCCUUUGGCACCACCCGGGAAGUGCGCGUGA
AGUGGCGCUAUGUGCCUGAGGGCGUGGGCGACCUGGCCACA
AUCGCCCCUUCUAUCAGAGCCCCCCAGCUGCAGAAAUCCAUG
CGGUCAUUCUUCCCAAAGAAGGACGACGCCUUCCACCGGUCC
AGCAGCCUGUUCUACAGCCCUAUGGUGCCCCACUUCUGGGCC
GAGCUGAGAAACCACUACGCCACCUCCGGCCUGAAGUCCGGC
UACAACAUCGGCAGCACCGACGGCUUUCUGCCCGUGAUCGG
ACCCGUGAUCUGGGAGAGCGAGGGCCUGUUCAGAGCCUACA
UCAGCAGCGUGACCGACGGCGACGGCAAGAGCCACAAAGUG
GGCUUUCUGAGAAUCCCCACCUACAGCUGGCAGGACAUGGA
AGAUUUCGACCCCAGCGGCCCACCCCCCUGGGAGGAAUUUGC
CAAGAUCAUCCAGGUGUUCAGCAGCAACACCGAGGCCCUGA
UCAUCGACCAGACCAACAACCCUGGCGGCAGCGUGCUGUACC
UGUACGCCCUGCUGAGCAUGCUGACCGACAGACCCCUGGAAC
UGCCCAAGCACCGGAUGAUCCUGACCCAGGACGAGGUGGUG
GACGCCCUGGAUUGGCUGACCCUGCUGGAAAACGUGGACAC
CAACGUGGAAAGCCGGCUGGCCCUGGGCGACAACAUGGAAG
GCUACACAGUGGAUCUGCAGGUGGCCGAGUACCUGAAAAGC
UUCGGCAGACAGGUGCUGAACUGCUGGUCCAAGGGCGACAU
CGAGCUGAGCACCCCCAUCCCCCUGUUCGGCUUCGAGAAGAU
CCACCCCCACCCCAGAGUGCAGUACAGCAAGCCCAUCUGCGU
GCUGAUCAACGAGCAGGACUUCUCCUGCGCCGACUUCUUCCC
AGUGGUGCUGAAGGACAACGACAGAGCCCUGAUCGUGGGCA
CCAGAACAGCUGGCGCUGGCGGCUUCGUGUUCAACGUGCAG
UUCCCCAACCGGACCGGCAUCAAGACCUGUAGCCUGACAGGC
UCUCUGGCCGUGCGGGAACACGGCGCCUUCAUCGAGAACAU
CGGCGUGGAACCCCACAUCGACCUGCCUUUCACCGCCAACGA
CAUCCGGUACAAGGGCUACUCUGAGUACCUGGACAAAGUGA
AGAAACUCGUGUGCCAGCUGAUUAACAACGACGGCACCAUC AUCCUGGCCGAGGACGGCAGCUUC
CT858_E_H97A_nIgK_cHis AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG
399 GCUGCCUGAUACCACAGGCGUGCGGGGAGAGUCCCUCGUGU
GCAAGAAUGCCCUGCAGGACCUGAGCUUCCUGGAACAUCUG
CUGCAAGUGAAGUACGCCCCCAAGACCUGGAAAGAGCAGUA
CCUGGGCUGGGACCUGGUGCAGUCCUCUGUGUCUGCCCAGC
AGAAGCUGCGGACCCAGGAAAACCCCUCUACCAGCUUCUGUC
AGCAAGUGCUGGCCGACUUCAUCGGCGGCCUGAACGAUUUC
GCCGCCGGCGUGACCUUUUUCGCCAUCGAGAGCGCCUACCUG
CCCUACACCGUGCAGAAGUCCAGCGACGGCCGGUUCUACUUC
GUGGACAUCAUGACCUUCAGCAGCGAGAUCAGAGUGGGCGA
CGAGCUGCUGGAAGUGGAUGGCGCUCCUGUGCAGGAUGUGC
UGGCCACACUGUACGGCAGCAACCACAAGGGCACAGCCGCCG
AAGAAUCUGCCGCCCUGAGAACCCUGUUCAGCCGGAUGGCC
UCUCUGGGCCACAAGGUGCCAAGCGGCAGAACCACCCUGAA
GAUCAGACGGCCCUUUGGCACCACCCGGGAAGUGCGCGUGA
AGUGGCGCUAUGUGCCUGAGGGCGUGGGCGACCUGGCCACA
AUCGCCCCUUCUAUCAGAGCCCCCCAGCUGCAGAAAUCCAUG
CGGUCAUUCUUCCCAAAGAAGGACGACGCCUUCCACCGGUCC
AGCAGCCUGUUCUACAGCCCUAUGGUGCCCCACUUCUGGGCC
GAGCUGAGAAACCACUACGCCACCUCCGGCCUGAAGUCCGGC
UACAACAUCGGCAGCACCGACGGCUUUCUGCCCGUGAUCGG
ACCCGUGAUCUGGGAGAGCGAGGGCCUGUUCAGAGCCUACA
UCAGCAGCGUGACCGACGGCGACGGCAAGAGCCACAAAGUG
GGCUUUCUGAGAAUCCCCACCUACAGCUGGCAGGACAUGGA
AGAUUUCGACCCCAGCGGCCCACCCCCCUGGGAGGAAUUUGC
CAAGAUCAUCCAGGUGUUCAGCAGCAACACCGAGGCCCUGA
UCAUCGACCAGACCAACAACCCUGGCGGCAGCGUGCUGUACC
UGUACGCCCUGCUGAGCAUGCUGACCGACAGACCCCUGGAAC
UGCCCAAGCACCGGAUGAUCCUGACCCAGGACGAGGUGGUG
GACGCCCUGGAUUGGCUGACCCUGCUGGAAAACGUGGACAC
CAACGUGGAAAGCCGGCUGGCCCUGGGCGACAACAUGGAAG
GCUACACAGUGGAUCUGCAGGUGGCCGAGUACCUGAAAAGC
UUCGGCAGACAGGUGCUGAACUGCUGGUCCAAGGGCGACAU
CGAGCUGAGCACCCCCAUCCCCCUGUUCGGCUUCGAGAAGAU
CCACCCCCACCCCAGAGUGCAGUACAGCAAGCCCAUCUGCGU
GCUGAUCAACGAGCAGGACUUCUCCUGCGCCGACUUCUUCCC
AGUGGUGCUGAAGGACAACGACAGAGCCCUGAUCGUGGGCA
CCAGAACAGCUGGCGCUGGCGGCUUCGUGUUCAACGUGCAG
UUCCCCAACCGGACCGGCAUCAAGACCUGUAGCCUGACAGGC
UCUCUGGCCGUGCGGGAACACGGCGCCUUCAUCGAGAACAU
CGGCGUGGAACCCCACAUCGACCUGCCUUUCACCGCCAACGA
CAUCCGGUACAAGGGCUACUCUGAGUACCUGGACAAAGUGA
AGAAACUCGUGUGCCAGCUGAUUAACAACGACGGCACCAUC
AUCCUGGCCGAGGACGGCAGCUUCCACCACCACCAUCACCAC CT858_E_S491A_nIgK
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 400
GCUGCCUGAUACCACAGGCGUGCGGGGAGAGUCCCUCGUGU
GCAAGAAUGCCCUGCAGGACCUGAGCUUCCUGGAACAUCUG
CUGCAAGUGAAGUACGCCCCCAAGACCUGGAAAGAGCAGUA
CCUGGGCUGGGACCUGGUGCAGUCCUCUGUGUCUGCCCAGC
AGAAGCUGCGGACCCAGGAAAACCCCUCUACCAGCUUCUGUC
AGCAAGUGCUGGCCGACUUCAUCGGCGGCCUGAACGAUUUC
CAUGCCGGCGUGACCUUUUUCGCCAUCGAGAGCGCCUACCUG
CCCUACACCGUGCAGAAGUCCAGCGACGGCCGGUUCUACUUC
GUGGACAUCAUGACCUUCAGCAGCGAGAUCAGAGUGGGCGA
CGAGCUGCUGGAAGUGGAUGGCGCUCCUGUGCAGGAUGUGC
UGGCCACACUGUACGGCAGCAACCACAAGGGCACAGCCGCCG
AAGAAUCUGCCGCCCUGAGAACCCUGUUCAGCCGGAUGGCC
UCUCUGGGCCACAAGGUGCCAAGCGGCAGAACCACCCUGAA
GAUCAGACGGCCCUUUGGCACCACCCGGGAAGUGCGCGUGA
AGUGGCGCUAUGUGCCUGAGGGCGUGGGCGACCUGGCCACA
AUCGCCCCUUCUAUCAGAGCCCCCCAGCUGCAGAAAUCCAUG
CGGUCAUUCUUCCCAAAGAAGGACGACGCCUUCCACCGGUCC
AGCAGCCUGUUCUACAGCCCUAUGGUGCCCCACUUCUGGGCC
GAGCUGAGAAACCACUACGCCACCUCCGGCCUGAAGUCCGGC
UACAACAUCGGCAGCACCGACGGCUUUCUGCCCGUGAUCGG
ACCCGUGAUCUGGGAGAGCGAGGGCCUGUUCAGAGCCUACA
UCAGCAGCGUGACCGACGGCGACGGCAAGAGCCACAAAGUG
GGCUUUCUGAGAAUCCCCACCUACAGCUGGCAGGACAUGGA
AGAUUUCGACCCCAGCGGCCCACCCCCCUGGGAGGAAUUUGC
CAAGAUCAUCCAGGUGUUCAGCAGCAACACCGAGGCCCUGA
UCAUCGACCAGACCAACAACCCUGGCGGCAGCGUGCUGUACC
UGUACGCCCUGCUGAGCAUGCUGACCGACAGACCCCUGGAAC
UGCCCAAGCACCGGAUGAUCCUGACCCAGGACGAGGUGGUG
GACGCCCUGGAUUGGCUGACCCUGCUGGAAAACGUGGACAC
CAACGUGGAAAGCCGGCUGGCCCUGGGCGACAACAUGGAAG
GCUACACAGUGGAUCUGCAGGUGGCCGAGUACCUGAAAAGC
UUCGGCAGACAGGUGCUGAACUGCUGGUCCAAGGGCGACAU
CGAGCUGAGCACCCCCAUCCCCCUGUUCGGCUUCGAGAAGAU
CCACCCCCACCCCAGAGUGCAGUACAGCAAGCCCAUCUGCGU
GCUGAUCAACGAGCAGGACUUCGCCUGCGCCGACUUCUUCCC
AGUGGUGCUGAAGGACAACGACAGAGCCCUGAUCGUGGGCA
CCAGAACAGCUGGCGCUGGCGGCUUCGUGUUCAACGUGCAG
UUCCCCAACCGGACCGGCAUCAAGACCUGUAGCCUGACAGGC
UCUCUGGCCGUGCGGGAACACGGCGCCUUCAUCGAGAACAU
CGGCGUGGAACCCCACAUCGACCUGCCUUUCACCGCCAACGA
CAUCCGGUACAAGGGCUACUCUGAGUACCUGGACAAAGUGA
AGAAACUCGUGUGCCAGCUGAUUAACAACGACGGCACCAUC AUCCUGGCCGAGGACGGCAGCUUC
CT858_E_S491A_nIgK_cHis AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG
401 GCUGCCUGAUACCACAGGCGUGCGGGGAGAGUCCCUCGUGU
GCAAGAAUGCCCUGCAGGACCUGAGCUUCCUGGAACAUCUG
CUGCAAGUGAAGUACGCCCCCAAGACCUGGAAAGAGCAGUA
CCUGGGCUGGGACCUGGUGCAGUCCUCUGUGUCUGCCCAGC
AGAAGCUGCGGACCCAGGAAAACCCCUCUACCAGCUUCUGUC
AGCAAGUGCUGGCCGACUUCAUCGGCGGCCUGAACGAUUUC
CAUGCCGGCGUGACCUUUUUCGCCAUCGAGAGCGCCUACCUG
CCCUACACCGUGCAGAAGUCCAGCGACGGCCGGUUCUACUUC
GUGGACAUCAUGACCUUCAGCAGCGAGAUCAGAGUGGGCGA
CGAGCUGCUGGAAGUGGAUGGCGCUCCUGUGCAGGAUGUGC
UGGCCACACUGUACGGCAGCAACCACAAGGGCACAGCCGCCG
AAGAAUCUGCCGCCCUGAGAACCCUGUUCAGCCGGAUGGCC
UCUCUGGGCCACAAGGUGCCAAGCGGCAGAACCACCCUGAA
GAUCAGACGGCCCUUUGGCACCACCCGGGAAGUGCGCGUGA
AGUGGCGCUAUGUGCCUGAGGGCGUGGGCGACCUGGCCACA
AUCGCCCCUUCUAUCAGAGCCCCCCAGCUGCAGAAAUCCAUG
CGGUCAUUCUUCCCAAAGAAGGACGACGCCUUCCACCGGUCC
AGCAGCCUGUUCUACAGCCCUAUGGUGCCCCACUUCUGGGCC
GAGCUGAGAAACCACUACGCCACCUCCGGCCUGAAGUCCGGC
UACAACAUCGGCAGCACCGACGGCUUUCUGCCCGUGAUCGG
ACCCGUGAUCUGGGAGAGCGAGGGCCUGUUCAGAGCCUACA
UCAGCAGCGUGACCGACGGCGACGGCAAGAGCCACAAAGUG
GGCUUUCUGAGAAUCCCCACCUACAGCUGGCAGGACAUGGA
AGAUUUCGACCCCAGCGGCCCACCCCCCUGGGAGGAAUUUGC
CAAGAUCAUCCAGGUGUUCAGCAGCAACACCGAGGCCCUGA
UCAUCGACCAGACCAACAACCCUGGCGGCAGCGUGCUGUACC
UGUACGCCCUGCUGAGCAUGCUGACCGACAGACCCCUGGAAC
UGCCCAAGCACCGGAUGAUCCUGACCCAGGACGAGGUGGUG
GACGCCCUGGAUUGGCUGACCCUGCUGGAAAACGUGGACAC
CAACGUGGAAAGCCGGCUGGCCCUGGGCGACAACAUGGAAG
GCUACACAGUGGAUCUGCAGGUGGCCGAGUACCUGAAAAGC
UUCGGCAGACAGGUGCUGAACUGCUGGUCCAAGGGCGACAU
CGAGCUGAGCACCCCCAUCCCCCUGUUCGGCUUCGAGAAGAU
CCACCCCCACCCCAGAGUGCAGUACAGCAAGCCCAUCUGCGU
GCUGAUCAACGAGCAGGACUUCGCCUGCGCCGACUUCUUCCC
AGUGGUGCUGAAGGACAACGACAGAGCCCUGAUCGUGGGCA
CCAGAACAGCUGGCGCUGGCGGCUUCGUGUUCAACGUGCAG
UUCCCCAACCGGACCGGCAUCAAGACCUGUAGCCUGACAGGC
UCUCUGGCCGUGCGGGAACACGGCGCCUUCAUCGAGAACAU
CGGCGUGGAACCCCACAUCGACCUGCCUUUCACCGCCAACGA
CAUCCGGUACAAGGGCUACUCUGAGUACCUGGACAAAGUGA
AGAAACUCGUGUGCCAGCUGAUUAACAACGACGGCACCAUC
AUCCUGGCCGAGGACGGCAGCUUCCACCACCACCAUCACCAC CT089_E_T306A_nIgK
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 402
GCUGCCUGACACCACCGGCAUGACAGCAUCUGGCGGAGCUG
GCGGCCUGGGCUCUACACAGACAGUGGAUGUGGCCAGGGCC
CAGGCUGCUGCCGCUACACAGGAUGCCCAGGAAGUGAUCGG
CAGCCAGGAAGCCAGCGAGGCCUCUAUGCUGAAGGGCUGCG
AGGACCUGAUCAACCCUGCCGCCGCUACCCGCAUCAAGAAGA
AAGAGGAAAAGUUCGAGUCCCUGGAAGCCAGACGGAAGCCC
ACCGCCGACAAGGCCGAGAAGAAGUCCGAGAGCACCGAGGA
AAAGGGCGACACCCCCCUGGAAGAUCGGUUCACCGAGGAUC
UGAGCGAGGUGUCCGGCGAGGACUUCCGGGGCCUGAAGAAC
AGCUUCGACGACGACAGCAGCCCCGAGGAAAUCCUGGACGCC
CUGACCAGCAAGUUCAGCGACCCCACCAUCAAGGACCUGGCC
CUGGACUACCUGAUCCAGACCGCCCCCAGCGACCGGAAGCUG
AAGUCUGCCCUGAUUCAGGCCAAGCACCAGCUGAUGAGCCA
GAACCCCCAGGCCAUCGUGGGCGGCAGAAAUGUGCUGCUGG
CCUCCGAGACAUUCGCCAGCAGAGCCAACACCAGCCCCAGCU
CCCUGCGGAGCCUGUAUCUGCAAGUGACCAGCUCCCCCAGCA
ACUGCGACAACCUGAGACAGAUGCUGGCUAGCUACCUGCCC
UCCGAGAAAACCGCCGUGAUGGAAUUCCUCGUGAACGGCAU
GGUGGCCGACCUGAAAAGCGAGGGCCCUAGCAUCCCUCCCGC
CAAGCUGCAGGUGUACAUGACCGAGCUGAGCAACCUGCAGG
CCCUGCACAGCGUGGACAGCUUUUUCGACCGGAACAUCGGC
AACCUGGAAAACAGCCUGAAGCACGAGGGCCACGCCCCCAUC
CCUUCUCUGACAACCGGCAAUCUGGCCAAGACCUUCCUGCAG
CUGGUGGAAGAUAAGUUCCCCAGCAGCUCCAAGGCCCAGAA
GGCCCUGAACGAGCUCGUGGGCCCUGAUACCGGACCUCAGAC
CGAGGUGCUGAACCUGUUCUUUCGGGCCCUGAAUGGCUGCU
CCCCCCGGAUCUUUUCUGGCGCUGAGAAGAAGCAGCAGCUG
GCCAGCGUGAUCACCAACACCCUGGAUGCCAUCAACGCCGAC
AACGAGGACUACCCCAAGCCCGGCGACUUCCCCAGAAGCAGC
UUUAGCAGCACCCCCCCUCAUGCCCCUGUGCCCCAGUCUGAG
AUCCCUACCAGCCCAACCAGCACCCAGCCUCCAAGCCCU CT089_E_T306A_nIgK_cHis
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 403
GCUGCCUGACACCACCGGCAUGACAGCAUCUGGCGGAGCUG
GCGGCCUGGGCUCUACACAGACAGUGGAUGUGGCCAGGGCC
CAGGCUGCUGCCGCUACACAGGAUGCCCAGGAAGUGAUCGG
CAGCCAGGAAGCCAGCGAGGCCUCUAUGCUGAAGGGCUGCG
AGGACCUGAUCAACCCUGCCGCCGCUACCCGCAUCAAGAAGA
AAGAGGAAAAGUUCGAGUCCCUGGAAGCCAGACGGAAGCCC
ACCGCCGACAAGGCCGAGAAGAAGUCCGAGAGCACCGAGGA
AAAGGGCGACACCCCCCUGGAAGAUCGGUUCACCGAGGAUC
UGAGCGAGGUGUCCGGCGAGGACUUCCGGGGCCUGAAGAAC
AGCUUCGACGACGACAGCAGCCCCGAGGAAAUCCUGGACGCC
CUGACCAGCAAGUUCAGCGACCCCACCAUCAAGGACCUGGCC
CUGGACUACCUGAUCCAGACCGCCCCCAGCGACCGGAAGCUG
AAGUCUGCCCUGAUUCAGGCCAAGCACCAGCUGAUGAGCCA
GAACCCCCAGGCCAUCGUGGGCGGCAGAAAUGUGCUGCUGG
CCUCCGAGACAUUCGCCAGCAGAGCCAACACCAGCCCCAGCU
CCCUGCGGAGCCUGUAUCUGCAAGUGACCAGCUCCCCCAGCA
ACUGCGACAACCUGAGACAGAUGCUGGCUAGCUACCUGCCC
UCCGAGAAAACCGCCGUGAUGGAAUUCCUCGUGAACGGCAU
GGUGGCCGACCUGAAAAGCGAGGGCCCUAGCAUCCCUCCCGC
CAAGCUGCAGGUGUACAUGACCGAGCUGAGCAACCUGCAGG
CCCUGCACAGCGUGGACAGCUUUUUCGACCGGAACAUCGGC
AACCUGGAAAACAGCCUGAAGCACGAGGGCCACGCCCCCAUC
CCUUCUCUGACAACCGGCAAUCUGGCCAAGACCUUCCUGCAG
CUGGUGGAAGAUAAGUUCCCCAGCAGCUCCAAGGCCCAGAA
GGCCCUGAACGAGCUCGUGGGCCCUGAUACCGGACCUCAGAC
CGAGGUGCUGAACCUGUUCUUUCGGGCCCUGAAUGGCUGCU
CCCCCCGGAUCUUUUCUGGCGCUGAGAAGAAGCAGCAGCUG
GCCAGCGUGAUCACCAACACCCUGGAUGCCAUCAACGCCGAC
AACGAGGACUACCCCAAGCCCGGCGACUUCCCCAGAAGCAGC
UUUAGCAGCACCCCCCCUCAUGCCCCUGUGCCCCAGUCUGAG
AUCCCUACCAGCCCAACCAGCACCCAGCCUCCAAGCCCUCAC CACCACCAUCACCAC
CT089_E_S198A_T306A_nIgK AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG
404 GCUGCCUGACACCACCGGCAUGACAGCAUCUGGCGGAGCUG
GCGGCCUGGGCUCUACACAGACAGUGGAUGUGGCCAGGGCC
CAGGCUGCUGCCGCUACACAGGAUGCCCAGGAAGUGAUCGG
CAGCCAGGAAGCCAGCGAGGCCUCUAUGCUGAAGGGCUGCG
AGGACCUGAUCAACCCUGCCGCCGCUACCCGCAUCAAGAAGA
AAGAGGAAAAGUUCGAGUCCCUGGAAGCCAGACGGAAGCCC
ACCGCCGACAAGGCCGAGAAGAAGUCCGAGAGCACCGAGGA
AAAGGGCGACACCCCCCUGGAAGAUCGGUUCACCGAGGAUC
UGAGCGAGGUGUCCGGCGAGGACUUCCGGGGCCUGAAGAAC
AGCUUCGACGACGACAGCAGCCCCGAGGAAAUCCUGGACGCC
CUGACCAGCAAGUUCAGCGACCCCACCAUCAAGGACCUGGCC
CUGGACUACCUGAUCCAGACCGCCCCCAGCGACCGGAAGCUG
AAGUCUGCCCUGAUUCAGGCCAAGCACCAGCUGAUGAGCCA
GAACCCCCAGGCCAUCGUGGGCGGCAGAAAUGUGCUGCUGG
CCUCCGAGACAUUCGCCAGCAGAGCCAACACCGCCCCCAGCU
CCCUGCGGAGCCUGUAUCUGCAAGUGACCAGCUCCCCCAGCA
ACUGCGACAACCUGAGACAGAUGCUGGCUAGCUACCUGCCC
UCCGAGAAAACCGCCGUGAUGGAAUUCCUCGUGAACGGCAU
GGUGGCCGACCUGAAAAGCGAGGGCCCUAGCAUCCCUCCCGC
CAAGCUGCAGGUGUACAUGACCGAGCUGAGCAACCUGCAGG
CCCUGCACAGCGUGGACAGCUUUUUCGACCGGAACAUCGGC
AACCUGGAAAACAGCCUGAAGCACGAGGGCCACGCCCCCAUC
CCUUCUCUGACAACCGGCAAUCUGGCCAAGACCUUCCUGCAG
CUGGUGGAAGAUAAGUUCCCCAGCAGCUCCAAGGCCCAGAA
GGCCCUGAACGAGCUCGUGGGCCCUGAUACCGGACCUCAGAC
CGAGGUGCUGAACCUGUUCUUUCGGGCCCUGAAUGGCUGCU
CCCCCCGGAUCUUUUCUGGCGCUGAGAAGAAGCAGCAGCUG
GCCAGCGUGAUCACCAACACCCUGGAUGCCAUCAACGCCGAC
AACGAGGACUACCCCAAGCCCGGCGACUUCCCCAGAAGCAGC
UUUAGCAGCACCCCCCCUCAUGCCCCUGUGCCCCAGUCUGAG
AUCCCUACCAGCCCAACCAGCACCCAGCCUCCAAGCCCU
CT089_E_S198A_T306A_nIgK_cHis
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 405
GCUGCCUGACACCACCGGCAUGACAGCAUCUGGCGGAGCUG
GCGGCCUGGGCUCUACACAGACAGUGGAUGUGGCCAGGGCC
CAGGCUGCUGCCGCUACACAGGAUGCCCAGGAAGUGAUCGG
CAGCCAGGAAGCCAGCGAGGCCUCUAUGCUGAAGGGCUGCG
AGGACCUGAUCAACCCUGCCGCCGCUACCCGCAUCAAGAAGA
AAGAGGAAAAGUUCGAGUCCCUGGAAGCCAGACGGAAGCCC
ACCGCCGACAAGGCCGAGAAGAAGUCCGAGAGCACCGAGGA
AAAGGGCGACACCCCCCUGGAAGAUCGGUUCACCGAGGAUC
UGAGCGAGGUGUCCGGCGAGGACUUCCGGGGCCUGAAGAAC
AGCUUCGACGACGACAGCAGCCCCGAGGAAAUCCUGGACGCC
CUGACCAGCAAGUUCAGCGACCCCACCAUCAAGGACCUGGCC
CUGGACUACCUGAUCCAGACCGCCCCCAGCGACCGGAAGCUG
AAGUCUGCCCUGAUUCAGGCCAAGCACCAGCUGAUGAGCCA
GAACCCCCAGGCCAUCGUGGGCGGCAGAAAUGUGCUGCUGG
CCUCCGAGACAUUCGCCAGCAGAGCCAACACCGCCCCCAGCU
CCCUGCGGAGCCUGUAUCUGCAAGUGACCAGCUCCCCCAGCA
ACUGCGACAACCUGAGACAGAUGCUGGCUAGCUACCUGCCC
UCCGAGAAAACCGCCGUGAUGGAAUUCCUCGUGAACGGCAU
GGUGGCCGACCUGAAAAGCGAGGGCCCUAGCAUCCCUCCCGC
CAAGCUGCAGGUGUACAUGACCGAGCUGAGCAACCUGCAGG
CCCUGCACAGCGUGGACAGCUUUUUCGACCGGAACAUCGGC
AACCUGGAAAACAGCCUGAAGCACGAGGGCCACGCCCCCAUC
CCUUCUCUGACAACCGGCAAUCUGGCCAAGACCUUCCUGCAG
CUGGUGGAAGAUAAGUUCCCCAGCAGCUCCAAGGCCCAGAA
GGCCCUGAACGAGCUCGUGGGCCCUGAUACCGGACCUCAGAC
CGAGGUGCUGAACCUGUUCUUUCGGGCCCUGAAUGGCUGCU
CCCCCCGGAUCUUUUCUGGCGCUGAGAAGAAGCAGCAGCUG
GCCAGCGUGAUCACCAACACCCUGGAUGCCAUCAACGCCGAC
AACGAGGACUACCCCAAGCCCGGCGACUUCCCCAGAAGCAGC
UUUAGCAGCACCCCCCCUCAUGCCCCUGUGCCCCAGUCUGAG
AUCCCUACCAGCCCAACCAGCACCCAGCCUCCAAGCCCUCAC CACCACCAUCACCAC
CT089_E_S198A_nIgK AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 406
GCUGCCUGACACCACCGGCAUGACAGCAUCUGGCGGAGCUG
GCGGCCUGGGCUCUACACAGACAGUGGAUGUGGCCAGGGCC
CAGGCUGCUGCCGCUACACAGGAUGCCCAGGAAGUGAUCGG
CAGCCAGGAAGCCAGCGAGGCCUCUAUGCUGAAGGGCUGCG
AGGACCUGAUCAACCCUGCCGCCGCUACCCGCAUCAAGAAGA
AAGAGGAAAAGUUCGAGUCCCUGGAAGCCAGACGGAAGCCC
ACCGCCGACAAGGCCGAGAAGAAGUCCGAGAGCACCGAGGA
AAAGGGCGACACCCCCCUGGAAGAUCGGUUCACCGAGGAUC
UGAGCGAGGUGUCCGGCGAGGACUUCCGGGGCCUGAAGAAC
AGCUUCGACGACGACAGCAGCCCCGAGGAAAUCCUGGACGCC
CUGACCAGCAAGUUCAGCGACCCCACCAUCAAGGACCUGGCC
CUGGACUACCUGAUCCAGACCGCCCCCAGCGACCGGAAGCUG
AAGUCUGCCCUGAUUCAGGCCAAGCACCAGCUGAUGAGCCA
GAACCCCCAGGCCAUCGUGGGCGGCAGAAAUGUGCUGCUGG
CCUCCGAGACAUUCGCCAGCAGAGCCAACACCGCCCCCAGCU
CCCUGCGGAGCCUGUAUCUGCAAGUGACCAGCUCCCCCAGCA
ACUGCGACAACCUGAGACAGAUGCUGGCUAGCUACCUGCCC
UCCGAGAAAACCGCCGUGAUGGAAUUCCUCGUGAACGGCAU
GGUGGCCGACCUGAAAAGCGAGGGCCCUAGCAUCCCUCCCGC
CAAGCUGCAGGUGUACAUGACCGAGCUGAGCAACCUGCAGG
CCCUGCACAGCGUGGACAGCUUUUUCGACCGGAACAUCGGC
AACCUGGAAAACAGCCUGAAGCACGAGGGCCACGCCCCCAUC
CCUUCUCUGACAACCGGCAAUCUGACCAAGACCUUCCUGCAG
CUGGUGGAAGAUAAGUUCCCCAGCAGCUCCAAGGCCCAGAA
GGCCCUGAACGAGCUCGUGGGCCCUGAUACCGGACCUCAGAC
CGAGGUGCUGAACCUGUUCUUUCGGGCCCUGAAUGGCUGCU
CCCCCCGGAUCUUUUCUGGCGCUGAGAAGAAGCAGCAGCUG
GCCAGCGUGAUCACCAACACCCUGGAUGCCAUCAACGCCGAC
AACGAGGACUACCCCAAGCCCGGCGACUUCCCCAGAAGCAGC
UUUAGCAGCACCCCCCCUCAUGCCCCUGUGCCCCAGUCUGAG
AUCCCUACCAGCCCAACCAGCACCCAGCCUCCAAGCCCU CT089_E_S198A_nIgK_cHis
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 407
GCUGCCUGACACCACCGGCAUGACAGCAUCUGGCGGAGCUG
GCGGCCUGGGCUCUACACAGACAGUGGAUGUGGCCAGGGCC
CAGGCUGCUGCCGCUACACAGGAUGCCCAGGAAGUGAUCGG
CAGCCAGGAAGCCAGCGAGGCCUCUAUGCUGAAGGGCUGCG
AGGACCUGAUCAACCCUGCCGCCGCUACCCGCAUCAAGAAGA
AAGAGGAAAAGUUCGAGUCCCUGGAAGCCAGACGGAAGCCC
ACCGCCGACAAGGCCGAGAAGAAGUCCGAGAGCACCGAGGA
AAAGGGCGACACCCCCCUGGAAGAUCGGUUCACCGAGGAUC
UGAGCGAGGUGUCCGGCGAGGACUUCCGGGGCCUGAAGAAC
AGCUUCGACGACGACAGCAGCCCCGAGGAAAUCCUGGACGCC
CUGACCAGCAAGUUCAGCGACCCCACCAUCAAGGACCUGGCC
CUGGACUACCUGAUCCAGACCGCCCCCAGCGACCGGAAGCUG
AAGUCUGCCCUGAUUCAGGCCAAGCACCAGCUGAUGAGCCA
GAACCCCCAGGCCAUCGUGGGCGGCAGAAAUGUGCUGCUGG
CCUCCGAGACAUUCGCCAGCAGAGCCAACACCGCCCCCAGCU
CCCUGCGGAGCCUGUAUCUGCAAGUGACCAGCUCCCCCAGCA
ACUGCGACAACCUGAGACAGAUGCUGGCUAGCUACCUGCCC
UCCGAGAAAACCGCCGUGAUGGAAUUCCUCGUGAACGGCAU
GGUGGCCGACCUGAAAAGCGAGGGCCCUAGCAUCCCUCCCGC
CAAGCUGCAGGUGUACAUGACCGAGCUGAGCAACCUGCAGG
CCCUGCACAGCGUGGACAGCUUUUUCGACCGGAACAUCGGC
AACCUGGAAAACAGCCUGAAGCACGAGGGCCACGCCCCCAUC
CCUUCUCUGACAACCGGCAAUCUGACCAAGACCUUCCUGCAG
CUGGUGGAAGAUAAGUUCCCCAGCAGCUCCAAGGCCCAGAA
GGCCCUGAACGAGCUCGUGGGCCCUGAUACCGGACCUCAGAC
CGAGGUGCUGAACCUGUUCUUUCGGGCCCUGAAUGGCUGCU
CCCCCCGGAUCUUUUCUGGCGCUGAGAAGAAGCAGCAGCUG
GCCAGCGUGAUCACCAACACCCUGGAUGCCAUCAACGCCGAC
AACGAGGACUACCCCAAGCCCGGCGACUUCCCCAGAAGCAGC
UUUAGCAGCACCCCCCCUCAUGCCCCUGUGCCCCAGUCUGAG
AUCCCUACCAGCCCAACCAGCACCCAGCCUCCAAGCCCUCAC CACCACCAUCACCAC
Chlamydia_CT875_nIgk_cHis AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG
408 GCUGCCUGACACCACCGGCAUGAGCAUCAGAGGCGUGGGCG
GCAACGGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCA
GCAACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUG
GAAGAUAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGA
GAACCGCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCA
UGAUCGAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUA
GUAGAGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGG
AUUGCUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAG
CAGCGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGA
GAGCGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCG
GCUACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGC
UGAUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAG
ACCUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAA
CGAGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCG
AUCACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUG
GCAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGU
GCGGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGA
ACGACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GCCCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUC
UGGCUGGACAUGAGCAACCUGAGCGACGUGGUGCUGUCCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAG
AGUCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGG
CGGCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGA
GGAAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUC
AGAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUC
GGCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGU
GUCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAU
GCUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCA
GAGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCC
UGGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCC
GACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAG
GGGCGUGCCAUCCAUCGAGGGCGAGGGCAGCGAUAGCAUCU
ACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGGAC
CUGGAAACCCGGCGGAGCUUCGCCGUGCAGCAGGGCCAUUA
CCAGGACCCCAGAGCCAGCGACUACGACCUGCCUAGAGCCUC
CGAUUACGAUCUGCCCAGAAGCCCCUACCCCACCCCUCCACU
GCCUCCCAGAUACCAGCUGCAGAACAUGGAUGUGGAAGCCG
GCUUUCGCGAGGCCGUGUACGCCUCUUUUGUGGCCGGCAUG
UACAACUACGUCGUGACCCAGCCCCAGGAACGGAUCCCCAAU
AGCCAGCAGGUGGAAGGCAUCCUGCGGGACAUGCUGACCAA
CGGCAGCCAGACCUUCCGGGACCUGAUGAAGCGGUGGAACA
GAGAGGUGGACCGCGAGCACCACCAUCACCACCAC MOMP_serovarD
AUGAAGAAACUGCUGAAGUCCGUGCUGGUGUUCGCCGCCCU 409
GUCUAGCGCAAGCUCUCUGCAGGCUCUGCCCGUGGGAAAUC
CUGCCGAGCCCAGCCUGAUGAUCGACGGCAUUCUGUGGGAG
GGCUUCGGCGGCGACCCUUGCGAUCCUUGUGCUACUUGGUG
CGACGCCAUCAGCAUGAGAGUGGGCUACUACGGCGACUUCG
UGUUCGACCGGGUGCUGAAAACCGACGUGAACAAAGAAUUC
CAGAUGGGCGCCAAGCCCACCACCGACACCGGAAAUUCUGCC
GCCCCUAGCACCCUGACCGCCAGAGAGAAUCCUGCCUACGGC
CGGCACAUGCAGGACGCCGAGAUGUUCACCAACGCCGCCUGC
AUGGCCCUGAACAUCUGGGACAGAUUCGACGUGUUCUGCAC
CCUGGGCGCCACCAGCGGCUACCUGAAAGGCAAUAGCGCCAG
CUUCAACCUCGUGGGCCUGUUCGGCGACAACGAGAACCAGA
AAACCGUGAAGGCCGAGAGCGUGCCCAACAUGAGCUUCGAC
CAGAGCGUGGUGGAACUGUACACCGAUACCACCUUCGCUUG
GAGCGUGGGAGCCAGAGCCGCUCUGUGGGAAUGUGGCUGUG
CCACACUGGGGGCCAGCUUCCAGUACGCCCAGAGCAAGCCCA
AGGUGGAAGAACUGAACGUGCUGUGCAAUGCCGCCGAGUUC
ACCAUCAACAAGCCUAAGGGCUACGUGGGCAAAGAGUUCCC
CCUGGAUCUGACCGCCGGAACCGAUGCCGCCACCGGAACAAA
GGACGCCAGCAUCGACUACCACGAGUGGCAGGCUUCUCUGG
CCCUGAGCUACCGGCUGAAUAUGUUCACCCCCUACAUCGGCG
UGAAGUGGUCCAGAGCCAGCUUCGACGCCGACACCAUCAGA
AUCGCCCAGCCCAAGAGCGCCACCGCCAUCUUUGAUACCACC
ACCCUGAACCCCACCAUUGCCGGCGCUGGCGACGUGAAAACA
GGCGCCGAAGGACAGCUGGGCGACACAAUGCAGAUCGUGUC
CCUGCAGCUGAACAAGAUGAAGUCCCGGAAGUCCUGCGGAA
UCGCCGUGGGCACCACAAUCGUGGACGCCGAUAAGUACGCC
GUGACCGUGGAAACCCGGCUGAUCGAUGAGAGGGCCGCUCA CGUGAACGCCCAGUUCAGAUUC
Chlamydia_CT871_pd_serovarD_nIgK
AUGGAAACCCCCGCCCAACUCCUGUUCCUUCUUCUGCUCUGG 410
CUCCCUGACACUACUGGUGCUGAGAUUAUGAUACCUCAGGG
AAUCUACGACGGAGAGACUCUGACUGUCUCGUUCCCGUAUA
CCGUGAUCGGCGACCCCUCUGGCACCACCGUCUUUUCCGCCG
GGGAGCUGACCCUGAAAAACCUGGACAACAGCAUCGCGGCC
CUGCCCCUGAGCUGUUUCGGAAACUUGUUGGGUUCCUUCAC
UGUGCUCGGACGGGGUCACUCCCUGACCUUUGAGAAUAUCC
GGACUUCGACUAACGGCGCCGCCCUGUCGGAUUCAGCCAACU
CCGGACUCUUCACCAUCGAAGGCUUCAAGGAACUCAGCUUU
AGCAAUUGCAACUCGCUGCUGGCGGUGCUGCCAGCGGCUAC
CACUAACAACGGAUCCCAAACUCCCACCACCACUUCGACUCC
GUCCAAUGGGACCAUCUACUCCAAGACCGAUCUCCUUCUCCU
GAACAACGAGAAGUUCUCCUUCUACUCCAACCUGGUGUCCG
GGGAUGGGGGUGCCAUUGACGCCAAGUCACUGACAGUGCAG
GGCAUCUCCAAGCUCUGUGUGUUCCAAGAAAACACCGCCCA
GGCCGAUGGGGGAGCGUGCCAGGUCGUCACCUCCUUCUCUG
CAAUGGCCAACGAGGCCCCCAUCGCCUUCAUUGCAAACGUGG
CGGGCGUGCGCGGCGGCGGCAUUGCCGCGGUGCAAGACGGC
CAGCAGGGAGUGUCGUCCUCAACCUCGACCGAAGAUCCGGU
CGUGUCCUUCUCCCGGAAUACUGCCGUGGAAUUCGACGGAA
ACGUGGCUCGCGUGGGAGGCGGAAUCUACAGCUAUGGAAAC
GUCGCCUUUCUGAACAACGGCAAAACGCUUUUCCUGAACAA
UGUCGCUAGCCCUGUGUACAUCGCUGCCGAACAGCCGACCAA
CGGACAGGCAUCCAACACCAGCGACAACUAUGGCGAUGGCG
GCGCGAUCUUCUGCAAGAACGGGGCCCAGGCGGCCGGGAGC
AACAACUCAGGAUCCGUGUCCUUCGACGGAGAAGGCGUCGU
GUUCUUCUCCUCAAACGUGGCUGCCGGAAAGGGUGGAGCCA
UCUACGCGAAGAAGCUCUCCGUGGCCAAUUGCGGACCGGUC
CAGUUCCUGGGAAACAUUGCCAACGACGGAGGUGCAAUCUA
CCUGGGAGAAAGCGGAGAACUGUCGCUCUCCGCCGACUACG
GCGAUAUCAUCUUCGACGGCAACCUCAAGCGGACCGCAAAG
GAGAACGCGGCAGACGUCAAUGGAGUGACCGUGUCGAGCCA
AGCCAUUUCAAUGGGUUCCGGCGGGAAGAUCACCACCUUGA
GGGCCAAGGCCGGCCACCAGAUUCUGUUCAACGAUCCUAUU
GAGAUGGCCAACGGGAACAACCAGCCUGCGCAGUCCUCGGA
ACCCCUGAAGAUCAAUGACGGAGAGGGCUACACUGGAGACA
UCGUGUUCGCCAACGGAAACUCCACCUUGUACCAGAACGUG
ACGAUUGAGCAGGGGAGAAUUGUGCUGAGAGAAAAAGCGAA
GCUGUCCGUGAAUAGCUUGAGCCAGACCGGGGGCUCACUGU
ACAUGGAGGCCGGAUCCACCCUGGACUUCGUGACACCGCAGC
CACCGCAGCAGCCUCCCGCCGCGAACCAACUGAUUACCCUCU
CGAACCUUCACCUGAGCCUGUCCUCACUGCUGGCAAACAACG
CUGUGACUAACCCUCCAACCAACCCGCCGGCCCAGGACAGCC
AUCCGGCCAUUAUCGGCUCCACCACCGCCGGUUCUGUGACCA
UCAGCGGCCCAAUCUUUUUCGAGGAUCUGGACGACACCGCU
UACGACCGCUACGAUUGGCUGGGAUCCAACCAGAAGAUCGA
CGUGCUUAAGCUGCAACUGGGAACGCAACCCUCCGCCAACGC
CCCGUCGGACCUGACCCUGGGGAACGAAAUGCCUAAGUACG
GAUACCAGGGGAGCUGGAAGCUCGCCUGGGAUCCCAACACC
GCCAACAACGGUCCGUACACUCUGAAGGCCACCUGGACUAA GACUGGU
Chlamydia_CT871_pd_serovarD_nIgK_cHis
AUGGAAACCCCCGCCCAACUCCUGUUCCUUCUUCUGCUCUGG 411
CUCCCUGACACUACUGGUGCUGAGAUUAUGAUACCUCAGGG
AAUCUACGACGGAGAGACUCUGACUGUCUCGUUCCCGUAUA
CCGUGAUCGGCGACCCCUCUGGCACCACCGUCUUUUCCGCCG
GGGAGCUGACCCUGAAAAACCUGGACAACAGCAUCGCGGCC
CUGCCCCUGAGCUGUUUCGGAAACUUGUUGGGUUCCUUCAC
UGUGCUCGGACGGGGUCACUCCCUGACCUUUGAGAAUAUCC
GGACUUCGACUAACGGCGCCGCCCUGUCGGAUUCAGCCAACU
CCGGACUCUUCACCAUCGAAGGCUUCAAGGAACUCAGCUUU
AGCAAUUGCAACUCGCUGCUGGCGGUGCUGCCAGCGGCUAC
CACUAACAACGGAUCCCAAACUCCCACCACCACUUCGACUCC
GUCCAAUGGGACCAUCUACUCCAAGACCGAUCUCCUUCUCCU
GAACAACGAGAAGUUCUCCUUCUACUCCAACCUGGUGUCCG
GGGAUGGGGGUGCCAUUGACGCCAAGUCACUGACAGUGCAG
GGCAUCUCCAAGCUCUGUGUGUUCCAAGAAAACACCGCCCA
GGCCGAUGGGGGAGCGUGCCAGGUCGUCACCUCCUUCUCUG
CAAUGGCCAACGAGGCCCCCAUCGCCUUCAUUGCAAACGUGG
CGGGCGUGCGCGGCGGCGGCAUUGCCGCGGUGCAAGACGGC
CAGCAGGGAGUGUCGUCCUCAACCUCGACCGAAGAUCCGGU
CGUGUCCUUCUCCCGGAAUACUGCCGUGGAAUUCGACGGAA
ACGUGGCUCGCGUGGGAGGCGGAAUCUACAGCUAUGGAAAC
GUCGCCUUUCUGAACAACGGCAAAACGCUUUUCCUGAACAA
UGUCGCUAGCCCUGUGUACAUCGCUGCCGAACAGCCGACCAA
CGGACAGGCAUCCAACACCAGCGACAACUAUGGCGAUGGCG
GCGCGAUCUUCUGCAAGAACGGGGCCCAGGCGGCCGGGAGC
AACAACUCAGGAUCCGUGUCCUUCGACGGAGAAGGCGUCGU
GUUCUUCUCCUCAAACGUGGCUGCCGGAAAGGGUGGAGCCA
UCUACGCGAAGAAGCUCUCCGUGGCCAAUUGCGGACCGGUC
CAGUUCCUGGGAAACAUUGCCAACGACGGAGGUGCAAUCUA
CCUGGGAGAAAGCGGAGAACUGUCGCUCUCCGCCGACUACG
GCGAUAUCAUCUUCGACGGCAACCUCAAGCGGACCGCAAAG
GAGAACGCGGCAGACGUCAAUGGAGUGACCGUGUCGAGCCA
AGCCAUUUCAAUGGGUUCCGGCGGGAAGAUCACCACCUUGA
GGGCCAAGGCCGGCCACCAGAUUCUGUUCAACGAUCCUAUU
GAGAUGGCCAACGGGAACAACCAGCCUGCGCAGUCCUCGGA
ACCCCUGAAGAUCAAUGACGGAGAGGGCUACACUGGAGACA
UCGUGUUCGCCAACGGAAACUCCACCUUGUACCAGAACGUG
ACGAUUGAGCAGGGGAGAAUUGUGCUGAGAGAAAAAGCGAA
GCUGUCCGUGAAUAGCUUGAGCCAGACCGGGGGCUCACUGU
ACAUGGAGGCCGGAUCCACCCUGGACUUCGUGACACCGCAGC
CACCGCAGCAGCCUCCCGCCGCGAACCAACUGAUUACCCUCU
CGAACCUUCACCUGAGCCUGUCCUCACUGCUGGCAAACAACG
CUGUGACUAACCCUCCAACCAACCCGCCGGCCCAGGACAGCC
AUCCGGCCAUUAUCGGCUCCACCACCGCCGGUUCUGUGACCA
UCAGCGGCCCAAUCUUUUUCGAGGAUCUGGACGACACCGCU
UACGACCGCUACGAUUGGCUGGGAUCCAACCAGAAGAUCGA
CGUGCUUAAGCUGCAACUGGGAACGCAACCCUCCGCCAACGC
CCCGUCGGACCUGACCCUGGGGAACGAAAUGCCUAAGUACG
GAUACCAGGGGAGCUGGAAGCUCGCCUGGGAUCCCAACACC
GCCAACAACGGUCCGUACACUCUGAAGGCCACCUGGACUAA GACUGGUCACCAUCAUCACCACCAC
Chlamydia_CT871_pd_serovarL2_nIgK
AUGGAAACCCCUGCCCAACUUCUGUUCCUCCUUCUGCUCUGG 412
CUCCCCGACACUACCGGUGCUGAGAUCAUGAUUCCGCAAGGC
AUCUACGACGGGGAAACUCUGACCGUGUCCUUUCCAUACAC
CGUCAUUGGUGAUCCUUCCGGAACUACCGUGUUCUCCGCGG
GCGAACUGACCUUGAAGAAUCUUGACAAUUCCAUCGCGGCC
CUGCCCCUGAGCUGCUUCGGCAACUUGCUGGGAUCGUUCAC
UGUGCUGGGGCGCGGACAUUCGCUGACUUUCGAAAACAUUA
GAACCAGCACCAACGGUGCUGCGCUUUCGAAUAGCGCCGCU
GAUGGCUUGUUCACCAUCGAGGGUUUCAAGGAACUGAGCUU
CUCCAACUGCAACUCGCUGCUCGCCGUGCUGCCGGCCGCUAC
UACGAACAAGGGCAGCCAGACUCCGACGACAACCUCCACUCC
CUCAAACGGCACCAUCUACUCCAAGACCGAUCUGCUGCUGCU
CAACAACGAGAAGUUCUCAUUCUACUCCAACCUCGUGUCCG
GCGACGGAGGCGCAAUUGACGCCAAGAGCCUGACCGUGCAG
GGAAUCUCAAAGCUGUGCGUCUUUCAAGAGAACACUGCGCA
GGCAGACGGAGGAGCCUGUCAGGUCGUGACCUCCUUUUCCG
CCAUGGCCAACGAGGCCCCUAUCGCCUUCGUGGCCAACGUGG
CCGGCGUGCGGGGUGGAGGAAUCGCAGCCGUGCAAGACGGC
CAGCAGGGAGUGUCUAGCAGCACUUCCACCGAGGACCCCGU
GGUGUCGUUCUCCCGGAACACCGCCGUGGAGUUCGAUGGAA
ACGUGGCGCGCGUGGGGGGAGGCAUCUACUCCUACGGGAAC
GUCGCCUUUCUUAACAACGGAAAGACCCUGUUCCUGAACAA
UGUGGCCUCGCCGGUGUACAUCGCCGCCAAGCAGCCAACUAG
CGGCCAGGCCUCCAACACCUCCAACAACUAUGGCGACGGCGG
AGCCAUCUUCUGCAAGAACGGCGCUCAAGCUGGAUCGAACA
ACAGCGGUUCUGUCUCCUUCGACGGCGAAGGAGUCGUGUUU
UUCUCCUCCAACGUCGCGGCCGGCAAAGGGGGGGCCAUAUA
CGCGAAGAAACUGUCAGUGGCGAACUGCGGACCCGUGCAGU
UCCUCCGGAACAUUGCCAACGACGGGGGUGCAAUCUACCUG
GGAGAGUCAGGAGAACUGAGCCUCUCGGCGGAUUACGGCGA
CAUCAUUUUCGACGGAAAUCUGAAGCGGACCGCCAAGGAAA
ACGCGGCAGAUGUGAACGGGGUCACCGUGUCAAGCCAGGCC
AUUUCUAUGGGGUCCGGAGGGAAGAUUACCACCCUGCGCGC
CAAGGCCGGCCAUCAGAUUCUCUUCAACGACCCUAUCGAGA
UGGCUAAUGGAAACAAUCAGCCCGCCCAGUCCUCCAAGCUGC
UGAAAAUCAACGACGGAGAGGGGUACACCGGGGAUAUCGUG
UUCGCCAACGGAAGCUCGACUCUCUACCAAAACGUGACCAU
UGAGCAGGGGAGGAUCGUGCUGAGGGAAAAGGCUAAGCUGU
CCGUCAACUCGCUGAGCCAGACCGGAGGCUCCCUCUACAUGG
AAGCAGGAUCGACGCUGGACUUCGUGACUCCGCAACCACCGC
AGCAGCCUCCCGCCGCCAACCAGCUGAUCACCUUGUCCAAUC
UGCACCUGAGCCUGUCGUCCUUGCUCGCCAACAACGCCGUGA
CUAACCCUCCUACUAACCCGCCGGCCCAGGACUCGCACCCGG
CCGUCAUCGGAUCAACCACAGCAGGAAGCGUGACUAUCUCC
GGUCCUAUCUUCUUCGAGGACCUGGAUGACACCGCCUACGA
UAGAUACGAUUGGUUGGGUUCCAACCAGAAGAUUAACGUGC
UGAAGCUGCAGCUGGGAACCAAGCCACCGGCGAACGCCCCGU
CCGACCUGACCCUCGGCAACGAAAUGCCCAAAUACGGAUACC
AGGGCUCCUGGAAGCUCGCGUGGGACCCCAAUACCGCGAAC
AACGGUCCCUAUACACUCAAGGCCACUUGGACCAAGACCGGC
Chlamydia_CT871_pd_serovarL2_nIgK_cHis
AUGGAAACCCCUGCCCAACUUCUGUUCCUCCUUCUGCUCUGG 413
CUCCCCGACACUACCGGUGCUGAGAUCAUGAUUCCGCAAGGC
AUCUACGACGGGGAAACUCUGACCGUGUCCUUUCCAUACAC
CGUCAUUGGUGAUCCUUCCGGAACUACCGUGUUCUCCGCGG
GCGAACUGACCUUGAAGAAUCUUGACAAUUCCAUCGCGGCC
CUGCCCCUGAGCUGCUUCGGCAACUUGCUGGGAUCGUUCAC
UGUGCUGGGGCGCGGACAUUCGCUGACUUUCGAAAACAUUA
GAACCAGCACCAACGGUGCUGCGCUUUCGAAUAGCGCCGCU
GAUGGCUUGUUCACCAUCGAGGGUUUCAAGGAACUGAGCUU
CUCCAACUGCAACUCGCUGCUCGCCGUGCUGCCGGCCGCUAC
UACGAACAAGGGCAGCCAGACUCCGACGACAACCUCCACUCC
CUCAAACGGCACCAUCUACUCCAAGACCGAUCUGCUGCUGCU
CAACAACGAGAAGUUCUCAUUCUACUCCAACCUCGUGUCCG
GCGACGGAGGCGCAAUUGACGCCAAGAGCCUGACCGUGCAG
GGAAUCUCAAAGCUGUGCGUCUUUCAAGAGAACACUGCGCA
GGCAGACGGAGGAGCCUGUCAGGUCGUGACCUCCUUUUCCG
CCAUGGCCAACGAGGCCCCUAUCGCCUUCGUGGCCAACGUGG
CCGGCGUGCGGGGUGGAGGAAUCGCAGCCGUGCAAGACGGC
CAGCAGGGAGUGUCUAGCAGCACUUCCACCGAGGACCCCGU
GGUGUCGUUCUCCCGGAACACCGCCGUGGAGUUCGAUGGAA
ACGUGGCGCGCGUGGGGGGAGGCAUCUACUCCUACGGGAAC
GUCGCCUUUCUUAACAACGGAAAGACCCUGUUCCUGAACAA
UGUGGCCUCGCCGGUGUACAUCGCCGCCAAGCAGCCAACUAG
CGGCCAGGCCUCCAACACCUCCAACAACUAUGGCGACGGCGG
AGCCAUCUUCUGCAAGAACGGCGCUCAAGCUGGAUCGAACA
ACAGCGGUUCUGUCUCCUUCGACGGCGAAGGAGUCGUGUUU
UUCUCCUCCAACGUCGCGGCCGGCAAAGGGGGGGCCAUAUA
CGCGAAGAAACUGUCAGUGGCGAACUGCGGACCCGUGCAGU
UCCUCCGGAACAUUGCCAACGACGGGGGUGCAAUCUACCUG
GGAGAGUCAGGAGAACUGAGCCUCUCGGCGGAUUACGGCGA
CAUCAUUUUCGACGGAAAUCUGAAGCGGACCGCCAAGGAAA
ACGCGGCAGAUGUGAACGGGGUCACCGUGUCAAGCCAGGCC
AUUUCUAUGGGGUCCGGAGGGAAGAUUACCACCCUGCGCGC
CAAGGCCGGCCAUCAGAUUCUCUUCAACGACCCUAUCGAGA
UGGCUAAUGGAAACAAUCAGCCCGCCCAGUCCUCCAAGCUGC
UGAAAAUCAACGACGGAGAGGGGUACACCGGGGAUAUCGUG
UUCGCCAACGGAAGCUCGACUCUCUACCAAAACGUGACCAU
UGAGCAGGGGAGGAUCGUGCUGAGGGAAAAGGCUAAGCUGU
CCGUCAACUCGCUGAGCCAGACCGGAGGCUCCCUCUACAUGG
AAGCAGGAUCGACGCUGGACUUCGUGACUCCGCAACCACCGC
AGCAGCCUCCCGCCGCCAACCAGCUGAUCACCUUGUCCAAUC
UGCACCUGAGCCUGUCGUCCUUGCUCGCCAACAACGCCGUGA
CUAACCCUCCUACUAACCCGCCGGCCCAGGACUCGCACCCGG
CCGUCAUCGGAUCAACCACAGCAGGAAGCGUGACUAUCUCC
GGUCCUAUCUUCUUCGAGGACCUGGAUGACACCGCCUACGA
UAGAUACGAUUGGUUGGGUUCCAACCAGAAGAUUAACGUGC
UGAAGCUGCAGCUGGGAACCAAGCCACCGGCGAACGCCCCGU
CCGACCUGACCCUCGGCAACGAAAUGCCCAAAUACGGAUACC
AGGGCUCCUGGAAGCUCGCGUGGGACCCCAAUACCGCGAAC
AACGGUCCCUAUACACUCAAGGCCACUUGGACCAAGACCGGC CACCACCAUCACCACCAC
Chlamydia_CT812_pd_serovarD_nIgK
AUGGAAACUCCUGCCCAACUGUUGUUCCUUCUGCUGCUCUG 414
GUUGCCCGACACCACCGGAUCGUGCGUGGAUCUCCACGCUGG
CGGCCAGUCCGUGAACGAGCUUGUGUACGUGGGCCCACAGG
CCGUGCUUCUGCUGGACCAGAUCAGAGAUCUCUUCGUGGGU
UCCAAGGACUCCCAGGCCGAGGGACAGUACCGGCUCAUCGUC
GGCGACCCUUCAAGCUUCCAAGAGAAGGAUGCCGACACUCU
UCCGGGGAAGGUGGAACAGUCCACUCUGUUUUCCGUGACCA
ACCCAGUCGUGUUUCAAGGGGUGGACCAGCAGGACCAGGUG
UCCAGCCAAGGACUGAUCUGUUCAUUCACCUCGAGCAAUUU
GGACAGCCCCCGGGACGGCGAAUCGUUCCUUGGCAUCGCAU
UCGUGGGAGACUCAUCCAAAGCAGGAAUCACCCUUACCGAU
GUGAAGGCGUCCCUGAGCGGCGCUGCUCUGUACUCCACCGA
AGAUCUCAUCUUCGAGAAGAUCAAGGGUGGACUGGAGUUCG
CCAGCUGCUCCUCACUGGAACAGGGAGGAGCCUGUGCCGCCC
AAAGCAUCCUCAUCCACGAUUGCCAGGGGCUCCAAGUGAAG
CAUUGUACCACUGCCGUGAACGCCGAGGGAUCAUCCGCUAA
CGAUCACCUCGGUUUCGGAGGGGGUGCCUUCUUCGUGACCG
GUUCGCUGUCGGGAGAAAAGUCACUGUAUAUGCCCGCGGGC
GACAUGGUGGUCGCCAACUGCGAUGGAGCCAUCUCAUUCGA
GGGAAACUCCGCCAACUUCGCAAACGGCGGCGCUAUCGCCGC
UAGCGGGAAGGUGCUGUUCGUGGCUAACGACAAGAAAACGU
CCUUCAUCGAAAACCGCGCCCUGUCGGGAGGUGCCAUUGCCG
CCAGCUCCGACAUUGCCUUCCAAAACUGUGCGGAACUGGUG
UUCAAAGGAAACUGCGCCAUCGGCACCGAAGAUAAGGGAAG
CCUGGGGGGGGGCGCCAUUUCCUCCCUCGGCACCGUGCUGCU
UCAGGGAAACCACGGCAUCACUUGUGACAAGAACGAAAGCG
CGUCCCAGGGGGGAGCGAUCUUCGGGAAAAACUGCCAGAUU
UCCGACAACGAGGGACCGGUGGUGUUCAGAGACUCCACUGC
CUGCCUGGGCGGCGGAGCGAUCGCAGCACAGGAAAUUGUCA
GCAUCCAGAACAACCAGGCCGGCAUCAGCUUCGAGGGGGGA
AAGGCUUCGUUCGGCGGAGGUAUUGCCUGCGGAUCGUUCUC
GUCCGCGGGCGGAGCCUCCGUGCUCGGAACCAUCGACAUUUC
CAAGAACCUGGGCGCUAUCUCGUUUUCUCGCACCCUGUGCAC
UACUUCCGACCUGGGUCAGAUGGAGUACCAGGGAGGCGGAG
CGCUGUUUGGAGAGAACAUCUCUCUGAGCGAGAACGCGGGA
GUGCUGACCUUCAAGGACAACAUUGUGAAAACCUUCGCCUC
AAACGGAAAGAUCCUGGGGGGAGGCGCCAUCCUGGCAACCG
GGAAGGUCGAAAUCACCAACAAUUCAGAGGGUAUCUCCUUC
ACUGGCAACGCCCGGGCCCCCCAAGCCCUGCCGACUCAGGAA
GAGUUCCCCCUGUUCUCCAAGAAGGAAGGACGCCCUUUGUC
AUCCGGCUACUCCGGUGGUGGAGCGAUUCUGGGUCGGGAAG
UGGCCAUCCUGCAUAAUGCGGCCGUGGUGUUUGAGCAAAAC
AGACUCCAAUGCUCCGAAGAAGAGGCCACCCUCCUGGGGUG
CUGCGGGGGCGGAGCAGUGCAUGGCAUGGAUUCCACUUCCA
UCGUGGGAAACUCCAGCGUCCGCUUCGGAAACAACUACGCU
AUGGGACAGGGAGUGUCAGGGGGGGCCCUGCUGUCCAAGAC
CGUCCAGUUGGCCGGAAACGGUUCGGUGGAUUUCUCACGCA
AUAUCGCCUCGCUGGGAGGCGGCGCGCUGCAGGCCUCCGAA
GGAAAUUGCGAACUGGUCGACAACGGCUACGUGCUGUUCCG
GGACAACCGCGGCAGGGUGUACGGCGGAGCAAUCUCGUGCC
UUCGGGGCGACGUCGUGAUCUCGGGAAAUAAGGGACGGGUC
GAGUUUAAGGACAACAUCGCUACCAGGCUCUACGUGGAGGA
AACUGUGGAGAAGGUGGAGGAAGUGGAGCCUGCCCCGGAAC
AGAAGGACAACAACGAGCUGUCGUUCCUCGGUCGGGCAGAA
CAGUCCUUCAUUACUGCCGCCAACCAGGCCCUGUUCGCGUCC
GAAGAUGGUGACCUCAGCCCGGAAUCCAGCAUCUCCUCCGA
GGAACUGGCCAAGCGGAGAGAAUGCGCGGGAGGCGCAAUCU
UUGCGAAGCGGGUCCGGAUCGUGGACAACCAGGAAGCUGUG
GUGUUCAGCAACAACUUUUCCGACAUCUACGGUGGUGCAAU
UUUCACCGGCUCACUCCGGGAGGAGGACAAGCUGGACGGCC
AGAUUCCCGAGGUGCUCAUUUCCGGCAAUGCCGGCGACGUG
GUGUUCUCCGGAAACUCCUCCAAGAGGGACGAACACCUCCCG
CAUACCGGAGGAGGAGCCAUCUGCACUCAGAACCUGACGAU
CUCGCAGAACACCGGCAAUGUGCUGUUCUACAACAACGUCG
CAUGUUCCGGUGGCGCCGUCAGAAUCGAGGACCACGGAAAC
GUGCUGCUGGAAGCAUUCGGGGGUGAUAUUGUGUUCAAGGG
AAACAGCAGCUUCCGGGCCCAGGGAUCAGAUGCAAUCUACU
UCGCCGGGAAGGAGAGCCACAUUACCGCCCUGAACGCCACCG
AGGGUCACGCCAUCGUGUUCCACGAUGCCCUGGUGUUCGAA
AACCUGGAGGAGCGCAAGAGCGCCGAAGUGCUGCUUAUCAA
UUCCCGCGAAAACCCGGGCUACACCGGAUCCAUCCGGUUCCU
CGAAGCGGAGUCGAAGGUCCCGCAGUGUAUUCAUGUGCAAC
AGGGGUCCCUGGAACUGCUUAACGGAGCCACCCUGUGCUCC
UACGGCUUUAAGCAGGACGCGGGCGCUAAACUGGUGCUGGC
GGCCGGCGCCAAGCUUAAGAUCCUCGACUCCGGAACCCCGGU
GCAGCAGGGGCACGCUAUUAGCAAGCCUGAAGCCGAGAUUG
AGUCGUCAUCCGAACCCGAAGGGGCGCACUCCCUGUGGAUA
GCCAAGAACGCGCAGACCACCGUGCCAAUGGUCGAUAUCCAC
ACAAUCUCCGUGGACCUCGCCAGCUUCUCGUCGAGCCAGCAG
GAGGGAACUGUCGAAGCGCCUCAGGUCAUCGUGCCGGGAGG
UUCCUACGUGCGCUCGGGGGAGCUCAACCUGGAACUCGUGA
AUACCACUGGAACGGGAUAUGAGAACCACGCCCUGCUGAAG
AACGAAGCCAAAGUGCCACUGAUGUCCUUCGUCGCCUCCGGC
GACGAGGCCUCCGCCGAGAUUAGCAACCUGUCGGUGUCAGA
UCUGCAAAUUCACGUGGUGACCCCUGAGAUUGAGGAGGACA
CCUACGGGCACAUGGGCGAUUGGUCCGAGGCGAAGAUCCAG
GACGGCACACUGGUCAUUUCAUGGAACCCUACCGGA
Chlamydia_CT812_pd_serovarD_nIgK_cHis
AUGGAAACUCCUGCCCAACUGUUGUUCCUUCUGCUGCUCUG 415
GUUGCCCGACACCACCGGAUCGUGCGUGGAUCUCCACGCUGG
CGGCCAGUCCGUGAACGAGCUUGUGUACGUGGGCCCACAGG
CCGUGCUUCUGCUGGACCAGAUCAGAGAUCUCUUCGUGGGU
UCCAAGGACUCCCAGGCCGAGGGACAGUACCGGCUCAUCGUC
GGCGACCCUUCAAGCUUCCAAGAGAAGGAUGCCGACACUCU
UCCGGGGAAGGUGGAACAGUCCACUCUGUUUUCCGUGACCA
ACCCAGUCGUGUUUCAAGGGGUGGACCAGCAGGACCAGGUG
UCCAGCCAAGGACUGAUCUGUUCAUUCACCUCGAGCAAUUU
GGACAGCCCCCGGGACGGCGAAUCGUUCCUUGGCAUCGCAU
UCGUGGGAGACUCAUCCAAAGCAGGAAUCACCCUUACCGAU
GUGAAGGCGUCCCUGAGCGGCGCUGCUCUGUACUCCACCGA
AGAUCUCAUCUUCGAGAAGAUCAAGGGUGGACUGGAGUUCG
CCAGCUGCUCCUCACUGGAACAGGGAGGAGCCUGUGCCGCCC
AAAGCAUCCUCAUCCACGAUUGCCAGGGGCUCCAAGUGAAG
CAUUGUACCACUGCCGUGAACGCCGAGGGAUCAUCCGCUAA
CGAUCACCUCGGUUUCGGAGGGGGUGCCUUCUUCGUGACCG
GUUCGCUGUCGGGAGAAAAGUCACUGUAUAUGCCCGCGGGC
GACAUGGUGGUCGCCAACUGCGAUGGAGCCAUCUCAUUCGA
GGGAAACUCCGCCAACUUCGCAAACGGCGGCGCUAUCGCCGC
UAGCGGGAAGGUGCUGUUCGUGGCUAACGACAAGAAAACGU
CCUUCAUCGAAAACCGCGCCCUGUCGGGAGGUGCCAUUGCCG
CCAGCUCCGACAUUGCCUUCCAAAACUGUGCGGAACUGGUG
UUCAAAGGAAACUGCGCCAUCGGCACCGAAGAUAAGGGAAG
CCUGGGGGGGGGCGCCAUUUCCUCCCUCGGCACCGUGCUGCU
UCAGGGAAACCACGGCAUCACUUGUGACAAGAACGAAAGCG
CGUCCCAGGGGGGAGCGAUCUUCGGGAAAAACUGCCAGAUU
UCCGACAACGAGGGACCGGUGGUGUUCAGAGACUCCACUGC
CUGCCUGGGCGGCGGAGCGAUCGCAGCACAGGAAAUUGUCA
GCAUCCAGAACAACCAGGCCGGCAUCAGCUUCGAGGGGGGA
AAGGCUUCGUUCGGCGGAGGUAUUGCCUGCGGAUCGUUCUC
GUCCGCGGGCGGAGCCUCCGUGCUCGGAACCAUCGACAUUUC
CAAGAACCUGGGCGCUAUCUCGUUUUCUCGCACCCUGUGCAC
UACUUCCGACCUGGGUCAGAUGGAGUACCAGGGAGGCGGAG
CGCUGUUUGGAGAGAACAUCUCUCUGAGCGAGAACGCGGGA
GUGCUGACCUUCAAGGACAACAUUGUGAAAACCUUCGCCUC
AAACGGAAAGAUCCUGGGGGGAGGCGCCAUCCUGGCAACCG
GGAAGGUCGAAAUCACCAACAAUUCAGAGGGUAUCUCCUUC
ACUGGCAACGCCCGGGCCCCCCAAGCCCUGCCGACUCAGGAA
GAGUUCCCCCUGUUCUCCAAGAAGGAAGGACGCCCUUUGUC
AUCCGGCUACUCCGGUGGUGGAGCGAUUCUGGGUCGGGAAG
UGGCCAUCCUGCAUAAUGCGGCCGUGGUGUUUGAGCAAAAC
AGACUCCAAUGCUCCGAAGAAGAGGCCACCCUCCUGGGGUG
CUGCGGGGGCGGAGCAGUGCAUGGCAUGGAUUCCACUUCCA
UCGUGGGAAACUCCAGCGUCCGCUUCGGAAACAACUACGCU
AUGGGACAGGGAGUGUCAGGGGGGGCCCUGCUGUCCAAGAC
CGUCCAGUUGGCCGGAAACGGUUCGGUGGAUUUCUCACGCA
AUAUCGCCUCGCUGGGAGGCGGCGCGCUGCAGGCCUCCGAA
GGAAAUUGCGAACUGGUCGACAACGGCUACGUGCUGUUCCG
GGACAACCGCGGCAGGGUGUACGGCGGAGCAAUCUCGUGCC
UUCGGGGCGACGUCGUGAUCUCGGGAAAUAAGGGACGGGUC
GAGUUUAAGGACAACAUCGCUACCAGGCUCUACGUGGAGGA
AACUGUGGAGAAGGUGGAGGAAGUGGAGCCUGCCCCGGAAC
AGAAGGACAACAACGAGCUGUCGUUCCUCGGUAGAGCCGAA
CAGUCCUUCAUUACUGCCGCCAACCAGGCCCUGUUCGCGUCC
GAAGAUGGUGACCUCAGCCCGGAAUCCAGCAUCUCCUCCGA
GGAACUGGCCAAGCGGAGAGAAUGCGCGGGAGGCGCAAUCU
UUGCGAAGCGGGUCCGGAUCGUGGACAACCAGGAAGCUGUG
GUGUUCAGCAACAACUUUUCCGACAUCUACGGUGGUGCAAU
UUUCACCGGCUCACUCCGGGAGGAGGACAAGCUGGACGGCC
AGAUUCCCGAGGUGCUCAUUUCCGGCAAUGCCGGCGACGUG
GUGUUCUCCGGAAACUCCUCCAAGAGGGACGAACACCUCCCG
CAUACCGGAGGAGGAGCCAUCUGCACUCAGAACCUGACGAU
CUCGCAGAACACCGGCAAUGUGCUGUUCUACAACAACGUCG
CAUGUUCCGGUGGCGCCGUCAGAAUCGAGGACCACGGAAAC
GUGCUGCUGGAAGCAUUCGGGGGUGAUAUUGUGUUCAAGGG
AAACAGCAGCUUCCGGGCCCAGGGAUCAGAUGCAAUCUACU
UCGCCGGGAAGGAGAGCCACAUUACCGCCCUGAACGCCACCG
AGGGUCACGCCAUCGUGUUCCACGAUGCCCUGGUGUUCGAA
AACCUGGAGGAGCGCAAGAGCGCCGAAGUGCUGCUUAUCAA
UUCCCGCGAAAACCCGGGCUACACCGGAUCCAUCCGGUUCCU
CGAAGCGGAGUCGAAGGUCCCGCAGUGUAUUCAUGUGCAAC
AGGGGUCCCUGGAACUGCUUAACGGAGCCACCCUGUGCUCC
UACGGCUUUAAGCAGGACGCGGGCGCUAAACUGGUGCUGGC
GGCCGGCGCCAAGCUUAAGAUCCUCGACUCCGGAACCCCGGU
GCAGCAGGGGCACGCUAUUAGCAAGCCUGAAGCCGAGAUUG
AGUCGUCAUCCGAACCCGAAGGGGCGCACUCCCUGUGGAUA
GCCAAGAACGCGCAGACCACCGUGCCAAUGGUCGAUAUCCAC
ACAAUCUCCGUGGACCUCGCCAGCUUCUCGUCGAGCCAGCAG
GAGGGAACUGUCGAAGCGCCUCAGGUCAUCGUGCCGGGAGG
UUCCUACGUGCGCUCGGGGGAGCUCAACCUGGAACUCGUGA
AUACCACUGGAACGGGAUAUGAGAACCACGCCCUGCUGAAG
AACGAAGCCAAAGUGCCACUGAUGUCCUUCGUCGCCUCCGG
GGACGAGGCCUCCGCCGAGAUUAGCAACCUGUCGGUGUCAG
AUCUGCAAAUUCACGUGGUCACCCCUGAGAUUGAGGAGGAC
ACCUACGGGCACAUGGGCGAUUGGUCCGAGGCGAAGAUCCA
GGACGGCACACUGGUCAUUUCAUGGAACCCUACCGGACAUC ACCACCACCAUCAC
Chlamydia_CT812_pd_serovarL2_nIgk
AUGGAAACUCCUGCCCAACUGUUGUUCCUUCUGCUGCUCUG 416
GUUGCCCGACACCACCGGAUCGUGCGUGGAUCUCCACGCUGG
CGGCCAGUCCGUGAACGAGCUUGUGUACGUGGGCCCACAGG
CCGUGCUUCUGCUGGACCAGAUCAGAGAUCUCUUCGUGGGU
UCCAAGGACUCCCAGGCCGAGGGACAGUACCGGCUCAUCGUC
GGCGACCCUUCAAGCUUCCAAGAGAAGGAUGCCGACACUCU
UCCGGGGAAGGUGGAACAGUCCACUCUGUUUUCCGUGACCA
ACCCAGUCGUGUUUCAAGGGGUGGACCAGCAGGACCAGGUG
UCCAGCCAAGGACUGAUCUGUUCAUUCACCUCGAGCAAUUU
GGACAGCCCCCGGGACGGCGAAUCGUUCCUUGGCAUCGCAU
UCGUGGGAGACUCAUCCAAAGCAGGAAUCACCCUUACCGAU
GUGAAGGCGUCCCUGAGCGGCGCUGCUCUGUACUCCACCGA
AGAUCUCAUCUUCGAGAAGAUCAAGGGUGGACUGGAGUUCG
CCAGCUGCUCCUCACUGGAACAGGGAGGAGCCUGUGCCGCCC
AAAGCAUCCUCAUCCACGAUUGCCAGGGGCUCCAAGUGAAG
CAUUGUACCACUGCCGUGAACGCCGAGGGAUCAUCCGCUAA
CGAUCACCUCGGUUUCGGAGGGGGUGCCUUCUUCGUGACCG
GUUCGCUGUCGGGAGAAAAGUCACUGUAUAUGCCCGCGGGC
GACAUGGUGGUCGCCAACUGCGAUGGAGCCAUCUCAUUCGA
GGGAAACUCCGCCAACUUCGCAAACGGCGGCGCUAUCGCCGC
UAGCGGGAAGGUGCUGUUCGUGGCUAACGACAAGAAAACGU
CCUUCAUCGAAAACCGCGCCCUGUCGGGAGGUGCCAUUGCCG
CCAGCUCCGACAUUGCCUUCCAAAACUGUGCGGAACUGGUG
UUCAAAGGAAACUGCGCCAUCGGCACCGAAGAUAAGGGAAG
CCUGGGGGGGGGCGCCAUUUCCUCCCUCGGCACCGUGCUGCU
UCAGGGAAACCACGGCAUCACUUGUGACAAGAACGAAAGCG
CGUCCCAGGGGGGAGCGAUCUUCGGGAAAAACUGCCAGAUU
UCCGACAACGAGGGACCGGUGGUGUUCAGAGACUCCACUGC
CUGCCUGGGCGGCGGAGCGAUCGCAGCACAGGAAAUUGUCA
GCAUCCAGAACAACCAGGCCGGCAUCAGCUUCGAGGGGGGA
AAGGCUUCGUUCGGCGGAGGUAUUGCCUGCGGAUCGUUCUC
GUCCGCGGGCGGAGCCUCCGUGCUCGGAACCAUCGACAUUUC
CAAGAACCUGGGCGCUAUCUCGUUUUCUCGCACCCUGUGCAC
UACUUCCGACCUGGGUCAGAUGGAGUACCAGGGAGGCGGAG
CGCUGUUUGGAGAGAACAUCUCUCUGAGCGAGAACGCGGGA
GUGCUGACCUUCAAGGACAACAUUGUGAAAACCUUCGCCUC
AAACGGAAAGAUCCUGGGGGGAGGCGCCAUCCUGGCAACCG
GGAAGGUCGAAAUCACCAACAAUUCAGGCGGUAUCUCCUUC
ACUGGCAACGCCCGGGCCCCCCAAGCCCUGCCGACUCAGGAA
GAGUUCCCCCUGUUCUCCAAGAAGGAAGGACGCCCUUUGUC
AUCCGGCUACUCCGGUGGUGGAGCGAUUCUGGGUCGGGAAG
UGGCCAUCCUGCAUAAUGCGGCCGUGGUGUUUGAGCAAAAC
AGACUCCAAUGCUCCGAAGAAGAGGCCACCCUCCUGGGGUG
CUGCGGGGGCGGAGCAGUGCAUGGCAUGGAUUCCACUUCCA
UCGUGGGAAACUCCAGCGUCCGCUUCGGAAACAACUACGCU
AUGGGACAGGGAGUGUCAGGGGGGGCCCUGCUGUCCAAGAC
CGUCCAGUUGGCCGGAAACGGUUCGGUGGAUUUCUCACGCA
AUAUCGCCUCGCUGGGAGGCGGCGCGCUGCAGGCCUCCGAA
GGAAAUUGCGAACUGGUCGACAACGGCUACGUGCUGUUCCG
GGACAACCGCGGCAGGGUGUACGGCGGAGCAAUCUCGUGCC
UUCGGGGCGACGUCGUGAUCUCGGGAAAUAAGGGACGGGUC
GAGUUUAAGGACAACAUCGCUACCAGGCUCUACGUGGAGGA
AACUGUGGAGAAGGUGGAGGAAGUGGAGCCUGCCCCGGAAC
AGAAGGACAACAACGAGCUGUCGUUCCUCGGUUCCGUCGAA
CAGUCCUUCAUUACUGCCGCCAACCAGGCCCUGUUCGCGUCC
GAAGAUGGUGACCUCAGCCCGGAAUCCAGCAUCUCCUCCGA
GGAACUGGCCAAGCGGAGAGAAUGCGCGGGAGGCGCAAUCU
UUGCGAAGCGGGUCCGGAUCGUGGACAACCAGGAAGCUGUG
GUGUUCAGCAACAACUUUUCCGACAUCUACGGUGGUGCAAU
UUUCACCGGCUCACUCCGGGAGGAGGACAAGCUGGACGGCC
AGAUUCCCGAGGUGCUCAUUUCCGGCAAUGCCGGCGACGUG
GUGUUCUCCGGAAACUCCUCCAAGAGGGACGAACACCUCCCG
CAUACCGGAGGAGGAGCCAUCUGCACUCAGAACCUGACGAU
CUCGCAGAACACCGGCAAUGUGCUGUUCUACAACAACGUCG
CAUGUUCCGGUGGCGCCGUCAGAAUCGAGGACCACGGAAAC
GUGCUGCUGGAAGCAUUCGGGGGUGAUAUUGUGUUCAAGGG
AAACAGCAGCUUCCGGGCCCAGGGAUCAGAUGCAAUCUACU
UCGCCGGGAAGGAGAGCCACAUUACCGCCCUGAACGCCACCG
AGGGUCACGCCAUCGUGUUCCACGAUGCCCUGGUGUUCGAA
AACCUGAAGGAGCGCAAGAGCGCCGAAGUGCUGCUUAUCAA
UUCCCGCGAAAACCCGGGCUACACCGGAUCCAUCCGGUUCCU
CGAAGCGGAGUCGAAGGUCCCGCAGUGUAUUCAUGUGCAAC
AGGGGUCCCUGGAACUGCUUAACGGAGCCACCCUGUGCUCC
UACGGCUUUAAGCAGGACGCGGGCGCUAAACUGGUGCUGGC
GGCCGGCUCCAAGCUUAAGAUCCUCGACUCCGGAACCCCGGU
GCAGGGGCACGCUAUUAGCAAGCCUGAAGCCGAGAUUGAGU
CGUCAUCCGAACCCGAAGGGGCGCACUCCCUGUGGAUAGCCA
AGAACGCGCAGACCACCGUGCCAAUGGUCGAUAUCCACACA
AUCUCCGUGGACCUCGCCAGCUUCUCGUCGAGCCAGCAGGAG
GGAACUGUCGAAGCGCCUCAGGUCAUCGUGCCGGGAGGUUC
CUACGUGCGCUCGGGGGAGCUCAACCUGGAACUCGUGAAUA
CCACUGGAACGGGAUAUGAGAACCACGCCCUGCUGAAGAAC
GAAGCCAAAGUGCCACUGAUGUCCUUCGUCGCCUCCUCCGAC
GAGGCCUCCGCCGAGAUUAGCAACCUGUCGGUGUCAGAUCU
GCAAAUUCACGUGGCCACCCCUGAGAUUGAGGAGGACACCU
ACGGGCACAUGGGCGAUUGGUCCGAGGCGAAGAUCCAGGAC
GGCACACUGGUCAUUUCAUGGAACCCUACCGGA
Chlamydia_CT812_pd_serovarL2_nIgk_cHis
AUGGAAACUCCUGCCCAACUGUUGUUCCUUCUGCUGCUCUG 417
GUUGCCCGACACCACCGGAUCGUGCGUGGAUCUCCACGCUGG
CGGCCAGUCCGUGAACGAGCUUGUGUACGUGGGCCCACAGG
CCGUGCUUCUGCUGGACCAGAUCAGAGAUCUCUUCGUGGGU
UCCAAGGACUCCCAGGCCGAGGGACAGUACCGGCUCAUCGUC
GGCGACCCUUCAAGCUUCCAAGAGAAGGAUGCCGACACUCU
UCCGGGGAAGGUGGAACAGUCCACUCUGUUUUCCGUGACCA
ACCCAGUCGUGUUUCAAGGGGUGGACCAGCAGGACCAGGUG
UCCAGCCAAGGACUGAUCUGUUCAUUCACCUCGAGCAAUUU
GGACAGCCCCCGGGACGGCGAAUCGUUCCUUGGCAUCGCAU
UCGUGGGAGACUCAUCCAAAGCAGGAAUCACCCUUACCGAU
GUGAAGGCGUCCCUGAGCGGCGCUGCUCUGUACUCCACCGA
AGAUCUCAUCUUCGAGAAGAUCAAGGGUGGACUGGAGUUCG
CCAGCUGCUCCUCACUGGAACAGGGAGGAGCCUGUGCCGCCC
AAAGCAUCCUCAUCCACGAUUGCCAGGGGCUCCAAGUGAAG
CAUUGUACCACUGCCGUGAACGCCGAGGGAUCAUCCGCUAA
CGAUCACCUCGGUUUCGGAGGGGGUGCCUUCUUCGUGACCG
GUUCGCUGUCGGGAGAAAAGUCACUGUAUAUGCCCGCGGGC
GACAUGGUGGUCGCCAACUGCGAUGGAGCCAUCUCAUUCGA
GGGAAACUCCGCCAACUUCGCAAACGGCGGCGCUAUCGCCGC
UAGCGGGAAGGUGCUGUUCGUGGCUAACGACAAGAAAACGU
CCUUCAUCGAAAACCGCGCCCUGUCGGGAGGUGCCAUUGCCG
CCAGCUCCGACAUUGCCUUCCAAAACUGUGCGGAACUGGUG
UUCAAAGGAAACUGCGCCAUCGGCACCGAAGAUAAGGGAAG
CCUGGGGGGGGGCGCCAUUUCCUCCCUCGGCACCGUGCUGCU
UCAGGGAAACCACGGCAUCACUUGUGACAAGAACGAAAGCG
CGUCCCAGGGGGGAGCGAUCUUCGGGAAAAACUGCCAGAUU
UCCGACAACGAGGGACCGGUGGUGUUCAGAGACUCCACUGC
CUGCCUGGGCGGCGGAGCGAUCGCAGCACAGGAAAUUGUCA
GCAUCCAGAACAACCAGGCCGGCAUCAGCUUCGAGGGGGGA
AAGGCUUCGUUCGGCGGAGGUAUUGCCUGCGGAUCGUUCUC
GUCCGCGGGCGGAGCCUCCGUGCUCGGAACCAUCGACAUUUC
CAAGAACCUGGGCGCUAUCUCGUUUUCUCGCACCCUGUGCAC
UACUUCCGACCUGGGUCAGAUGGAGUACCAGGGAGGCGGAG
CGCUGUUUGGAGAGAACAUCUCUCUGAGCGAGAACGCGGGA
GUGCUGACCUUCAAGGACAACAUUGUGAAAACCUUCGCCUC
AAACGGAAAGAUCCUGGGGGGAGGCGCCAUCCUGGCAACCG
GGAAGGUCGAAAUCACCAACAAUUCAGGCGGUAUCUCCUUC
ACUGGCAACGCCCGGGCCCCCCAAGCCCUGCCGACUCAGGAA
GAGUUCCCCCUGUUCUCCAAGAAGGAAGGACGCCCUUUGUC
AUCCGGCUACUCCGGUGGUGGAGCGAUUCUGGGUCGGGAAG
UGGCCAUCCUGCAUAAUGCGGCCGUGGUGUUUGAGCAAAAC
AGACUCCAAUGCUCCGAAGAAGAGGCCACCCUCCUGGGGUG
CUGCGGGGGCGGAGCAGUGCAUGGCAUGGAUUCCACUUCCA
UCGUGGGAAACUCCAGCGUCCGCUUCGGAAACAACUACGCU
AUGGGACAGGGAGUGUCAGGGGGGGCCCUGCUGUCCAAGAC
CGUCCAGUUGGCCGGAAACGGUUCGGUGGAUUUCUCACGCA
AUAUCGCCUCGCUGGGAGGCGGCGCGCUGCAGGCCUCCGAA
GGAAAUUGCGAACUGGUCGACAACGGCUACGUGCUGUUCCG
GGACAACCGCGGCAGGGUGUACGGCGGAGCAAUCUCGUGCC
UUCGGGGCGACGUCGUGAUCUCGGGAAAUAAGGGACGGGUC
GAGUUUAAGGACAACAUCGCUACCAGGCUCUACGUGGAGGA
AACUGUGGAGAAGGUGGAGGAAGUGGAGCCUGCCCCGGAAC
AGAAGGACAACAACGAGCUGUCGUUCCUCGGUUCCGUCGAA
CAGUCCUUCAUUACUGCCGCCAACCAGGCCCUGUUCGCGUCC
GAAGAUGGUGACCUCAGCCCGGAAUCCAGCAUCUCCUCCGA
GGAACUGGCCAAGCGGAGAGAAUGCGCGGGAGGCGCAAUCU
UUGCGAAGCGGGUCCGGAUCGUGGACAACCAGGAAGCUGUG
GUGUUCAGCAACAACUUUUCCGACAUCUACGGUGGUGCAAU
UUUCACCGGCUCACUCCGGGAGGAGGACAAGCUGGACGGCC
AGAUUCCCGAGGUGCUCAUUUCCGGCAAUGCCGGCGACGUG
GUGUUCUCCGGAAACUCCUCCAAGAGGGACGAACACCUCCCG
CAUACCGGAGGAGGAGCCAUCUGCACUCAGAACCUGACGAU
CUCGCAGAACACCGGCAAUGUGCUGUUCUACAACAACGUCG
CAUGUUCCGGUGGCGCCGUCAGAAUCGAGGACCACGGAAAC
GUGCUGCUGGAAGCAUUCGGGGGUGAUAUUGUGUUCAAGGG
AAACAGCAGCUUCCGGGCCCAGGGAUCAGAUGCAAUCUACU
UCGCCGGGAAGGAGAGCCACAUUACCGCCCUGAACGCCACCG
AGGGUCACGCCAUCGUGUUCCACGAUGCCCUGGUGUUCGAA
AACCUGAAGGAGCGCAAGAGCGCCGAAGUGCUGCUUAUCAA
UUCCCGCGAAAACCCGGGCUACACCGGAUCCAUCCGGUUCCU
CGAAGCGGAGUCGAAGGUCCCGCAGUGUAUUCAUGUGCAAC
AGGGGUCCCUGGAACUGCUUAACGGAGCCACCCUGUGCUCC
UACGGCUUUAAGCAGGACGCGGGCGCUAAACUGGUGCUGGC
GGCCGGCUCCAAGCUUAAGAUCCUCGACUCCGGAACCCCGGU
GCAGGGGCACGCUAUUAGCAAGCCUGAAGCCGAGAUUGAGU
CGUCAUCCGAACCCGAAGGGGCGCACUCCCUGUGGAUAGCCA
AGAACGCGCAGACCACCGUGCCAAUGGUCGAUAUCCACACA
AUCUCCGUGGACCUCGCCAGCUUCUCGUCGAGCCAGCAGGAG
GGAACUGUCGAAGCGCCUCAGGUCAUCGUGCCGGGAGGUUC
CUACGUGCGCUCGGGGGAGCUCAACCUGGAACUCGUGAAUA
CCACUGGAACGGGAUAUGAGAACCACGCCCUGCUGAAGAAC
GAAGCCAAAGUGCCACUGAUGUCCUUCGUCGCCUCCUCCGAC
GAGGCCUCCGCCGAGAUUAGCAACCUGUCGGUGUCAGAUCU
GCAAAUUCACGUGGCCACCCCUGAGAUUGAGGAGGACACCU
ACGGGCACAUGGGCGAUUGGUCCGAGGCGAAGAUCCAGGAC
GGCACACUGGUCAUUUCAUGGAACCCUACCGGACAUCACCAC CACCAUCAC
Chlamydia_CT460_serovarD_nIgk
AUGGAAACUCCUGCCCAACUCCUGUUCUUGCUGCUGCUUUG 418
GCUCCCUGACACUACCGGAAUGAGCCAGAACAAGAACUCGG
CAUUCAUGCAGCCGGUCAAUGUGUCCGCCGAUCUGGCCGCCA
UUGUGGGAGCUGGGCCCAUGCCACGGACCGAAAUCAUCAAA
AAGAUGUGGGACUACAUUAAGAAGAACGGCCUGCAGGACCC
GACCAACAAGCGCAACAUCAACCCGGACGAUAAGCUGGCGA
AGGUGUUCGGUACCGAGAAGCCCAUCGACAUGUUUCAAAUG
ACCAAGAUGGUGUCCCAGCACAUCAUUAAG Chlamydia_CT460_serovarD_nIgk_cHis
AUGGAAACUCCUGCCCAACUCCUGUUCUUGCUGCUGCUUUG 419
GCUCCCUGACACUACCGGAAUGAGCCAGAACAAGAACUCGG
CAUUCAUGCAGCCGGUCAAUGUGUCCGCCGAUCUGGCCGCCA
UUGUGGGAGCUGGGCCCAUGCCACGGACCGAAAUCAUCAAA
AAGAUGUGGGACUACAUUAAGAAGAACGGCCUGCAGGACCC
GACCAACAAGCGCAACAUCAACCCGGACGAUAAGCUGGCGA
AGGUGUUCGGUACCGAGAAGCCCAUCGACAUGUUUCAAAUG
ACCAAGAUGGUGUCCCAGCACAUCAUUAAGCACCACCACCAU CACCAU
Chlamydia_CT460_serovarL2_nIgk
AUGGAAACUCCUGCCCAACUGUUGUUCCUGCUGCUUCUCUG 420
GCUCCCUGACACUACCGGAAUGUCGCAGAACAAGAACUCCGC
CUUCAUGCAACCCGUGAACGUGUCAGCGGACCUGGCAGCUA
UUGUCGGUGCCGGGCCGAUGCCCCGCACCGAAAUCAUCAAG
AAGAUGUGGGACUACAUCAAGGAGAACAGCCUGCAGGAUCC
AACCAACAAGCGGAAUAUCAACCCGGACGAUAAGCUGGCCA
AAGUGUUCGGCACCGAGAAGCCGAUUGACAUGUUUCAGAUG
ACCAAGAUGGUGUCCCAGCACAUCAUUAAG Chlamydia_CT460_serovarL2_nIgk_cHis
AUGGAAACUCCUGCCCAACUGUUGUUCCUGCUGCUUCUCUG 421
GCUCCCUGACACUACCGGAAUGUCGCAGAACAAGAACUCCGC
CUUCAUGCAACCCGUGAACGUGUCAGCGGACCUGGCAGCUA
UUGUCGGUGCCGGGCCGAUGCCCCGCACCGAAAUCAUCAAG
AAGAUGUGGGACUACAUCAAGGAGAACAGCCUGCAGGAUCC
AACCAACAAGCGGAAUAUCAACCCGGACGAUAAGCUGGCCA
AAGUGUUCGGCACCGAGAAGCCGAUUGACAUGUUUCAGAUG
ACCAAGAUGGUGUCCCAGCACAUCAUUAAGCACCACCACCAU CAUCAC
Chlamydia_CT622_serovarE_nIgk
AUGGAAACCCCUGCCCAACUGCUUUUCUUGCUGCUGCUCUG 422
GCUCCCUGACACCACCGGAAUGGAAUCUGGACCCGAGUCCGU
GUCAAGCAACCAGUCCUCCAUGAACCCCAUCAUUAAUGGAC
AGAUCGCAUCCAAUUCCGAAACCAAGGAAAGCACCAAGGCA
UCGGAGGCCUCCCCAUCCGCCUCAAGCUCCGUGUCGUCCUGG
UCGUUUCUGUCGAGCGCGAAGAAUGCCCUGAUCUCACUGCG
GGACGCGAUUCUGAACAAGAACAGCUCCCCAACCGACUCCCU
GAGCCAACUCGAGGCCUCAACUUCCACUUCGACUGUGACUA
GGGUCGCUGCCAAGGAUUAUGACGAGGCCAAGAGCAACUUC
GACACCGCCAAGAGCGGACUGGAAAACGCCAAAACCCUGGCC
GAAUACGAAACUAAGAUGGCCGAUCUCAUGGCGGCCCUGCA
AGACAUGGAACGGCUGGCGAACUCCGAUCCGUCCAACAACC
ACACUGAGGAAGUGAACAACAUCAAGAAGGCUCUCGAGGCC
CAGAAGGAUACCAUCGACAAGUUGAACAAGCUUGUGACGCU
GCAGAACCAAAACAAGUCCCUGACGGAAGUGCUCAAAACCA
CCGACUCGGCCGACCAGAUUCCGGCCAUCAACAGCCAGCUGG
AGAUUAACAAGAACUCGGCCGAUCAGAUUAUCAAGGACCUG
GAGCGCCAGAACAUUUCCUACGAGGCCGUCUUGACUAACGC
CGGCGAAGUGAUCAAGGCGUCAUCCGAAGCCGGCAUUAAGC
UGGGACAGGCGCUGCAAUCCAUCGUCGACGCCGGCGACCAG
UCCCAGGCGGCGGUGCUGCAGGCCCAGCAGAACAACUCCCCC
GAUAACAUCGCUGCAACCAAGGAACUGAUUGACGCGGCCGA
AACCAAAGUCAACGAACUGAAGCAGGAGCACACUGGUCUGA
CCGACUCGCCGCUCGUGAAGAAGGCCGAAGAACAGAUCAGC
CAGGCUCAGAAGGAUAUCCAGGAAAUCAAGCCUUCGGGGAG
CGACAUCCCGAUCGUGGGACCGUCCGGUUCCGCCGCUUCCGC
CGGGUCCGCAGCCGGGGCCCUUAAGUCGUCGAACAAUAGCG
GCAGAAUAUCCCUGCUGCUCGACGAUGUGGAUAACGAGAUG
GCCGCCAUUGCGCUGCAAGGAUUCCGGUCCAUGAUCGAGCA
GUUCAACGUGAACAACCCCGCCACCGCCAAGGAGCUGCAGGC
UAUGGAGGCCCAACUCACUGCCAUGUCCGACCAGCUCGUGG
GAGCGGACGGAGAACUGCCAGCCGAGAUCCAGGCCAUCAAG
GACGCUCUGGCCCAGGCACUGAAGCAGCCGUCCGCGGAUGGC
CUGGCCACCGCCAUGGGCCAGGUCGCGUUCGCCGCCGCUAAA
GUCGGCGGAGGUUCGGCCGGCACUGCCGGGACCGUGCAGAU
GAAUGUCAAGCAGCUGUACAAGACUGCGUUCUCGUCGACCA
GCUCCAGCUCCUACGCCGCGGCCCUGUCCGACGGUUACAGCG
CGUACAAGACCCUGAACUCCCUUUACUCCGAAUCGAGAUCCG
GGGUCCAGUCCGCAAUUUCACAAACCGCCAAUCCUGCCCUGU
CGCGCUCAGUGUCACGCAGCGGCAUCGAGUCACAGGGCAGA
AGCGCCGACGCUAGCCAAAGGGCCGCAGAAACCAUUGUGCG
GGACUCCCAGACACUUGGAGAUGUCUACAGCCGCCUCCAAG
UGCUGGACUCCCUCAUGUCCACCAUCGUGUCAAACCCUCAGG
CUAACCAGGAGGAAAUCAUGCAGAAGCUGACCGCAAGCAUU
UCCAAGGCUCCGCAGUUUGGAUACCCCGCUGUGCAAAACUCC
GCGGACAGCUUGCAGAAAUUCGCAGCCCAGUUGGAGAGGGA
GUUCGUGGACGGGGAGCGGUCCCUCGCGGAGUCCCAGGAGA
ACGCAUUCCGGAAGCAGCCCGCCUUCAUUCAACAAGUGCUU
GUGAACAUCGCCUCCCUGUUCUCCGGUUACCUGUCU
Chlamydia_CT622_serovarE_nIgk_cHis
AUGGAAACCCCUGCCCAACUGCUUUUCUUGCUGCUGCUCUG 423
GCUCCCUGACACCACCGGAAUGGAAUCUGGACCCGAGUCCGU
GUCAAGCAACCAGUCCUCCAUGAACCCCAUCAUUAAUGGAC
AGAUCGCAUCCAAUUCCGAAACCAAGGAAAGCACCAAGGCA
UCGGAGGCCUCCCCAUCCGCCUCAAGCUCCGUGUCGUCCUGG
UCGUUUCUGUCGAGCGCGAAGAAUGCCCUGAUCUCACUGCG
GGACGCGAUUCUGAACAAGAACAGCUCCCCAACCGACUCCCU
GAGCCAACUCGAGGCCUCAACUUCCACUUCGACUGUGACUA
GGGUCGCUGCCAAGGAUUAUGACGAGGCCAAGAGCAACUUC
GACACCGCCAAGAGCGGACUGGAAAACGCCAAAACCCUGGCC
GAAUACGAAACUAAGAUGGCCGAUCUCAUGGCGGCCCUGCA
AGACAUGGAACGGCUGGCGAACUCCGAUCCGUCCAACAACC
ACACUGAGGAAGUGAACAACAUCAAGAAGGCUCUCGAGGCC
CAGAAGGAUACCAUCGACAAGUUGAACAAGCUUGUGACGCU
GCAGAACCAAAACAAGUCCCUGACGGAAGUGCUCAAAACCA
CCGACUCGGCCGACCAGAUUCCGGCCAUCAACAGCCAGCUGG
AGAUUAACAAGAACUCGGCCGAUCAGAUUAUCAAGGACCUG
GAGCGCCAGAACAUUUCCUACGAGGCCGUCUUGACUAACGC
CGGCGAAGUGAUCAAGGCGUCAUCCGAAGCCGGCAUUAAGC
UGGGACAGGCGCUGCAAUCCAUCGUCGACGCCGGCGACCAG
UCCCAGGCGGCGGUGCUGCAGGCCCAGCAGAACAACUCCCCC
GAUAACAUCGCUGCAACCAAGGAACUGAUUGACGCGGCCGA
AACCAAAGUCAACGAACUGAAGCAGGAGCACACUGGUCUGA
CCGACUCGCCGCUCGUGAAGAAGGCCGAAGAACAGAUCAGC
CAGGCUCAGAAGGAUAUCCAGGAAAUCAAGCCUUCGGGGAG
CGACAUCCCGAUCGUGGGACCGUCCGGUUCCGCCGCUUCCGC
CGGGUCCGCAGCCGGGGCCCUUAAGUCGUCGAACAAUAGCG
GCAGAAUAUCCCUGCUGCUCGACGAUGUGGAUAACGAGAUG
GCCGCCAUUGCGCUGCAAGGAUUCCGGUCCAUGAUCGAGCA
GUUCAACGUGAACAACCCCGCCACCGCCAAGGAGCUGCAGGC
UAUGGAGGCCCAACUCACUGCCAUGUCCGACCAGCUCGUGG
GAGCGGACGGAGAACUGCCAGCCGAGAUCCAGGCCAUCAAG
GACGCUCUGGCCCAGGCACUGAAGCAGCCGUCCGCGGAUGGC
CUGGCCACCGCCAUGGGCCAGGUCGCGUUCGCCGCCGCUAAA
GUCGGCGGAGGUUCGGCCGGCACUGCCGGGACCGUGCAGAU
GAAUGUCAAGCAGCUGUACAAGACUGCGUUCUCGUCGACCA
GCUCCAGCUCCUACGCCGCGGCCCUGUCCGACGGUUACAGCG
CGUACAAGACCCUGAACUCCCUUUACUCCGAAUCGAGAUCCG
GGGUCCAGUCCGCAAUUUCACAAACCGCCAAUCCUGCCCUGU
CGCGCUCAGUGUCACGCAGCGGCAUCGAGUCACAGGGCAGA
AGCGCCGACGCUAGCCAAAGGGCCGCAGAAACCAUUGUGCG
GGACUCCCAGACACUUGGAGAUGUCUACAGCCGCCUCCAAG
UGCUGGACUCCCUCAUGUCCACCAUCGUGUCAAACCCUCAGG
CUAACCAGGAGGAAAUCAUGCAGAAGCUGACCGCAAGCAUU
UCCAAGGCUCCGCAGUUUGGAUACCCCGCUGUGCAAAACUCC
GCGGACAGCUUGCAGAAAUUCGCAGCCCAGUUGGAGAGGGA
GUUCGUGGACGGGGAGCGGUCCCUCGCGGAGUCCCAGGAGA
ACGCAUUCCGGAAGCAGCCCGCCUUCAUUCAACAAGUGCUU
GUGAACAUCGCCUCCCUGUUCUCCGGUUACCUGUCUCAUCAC CACCACCAUCAC
Chlamydia_CT858_nIgk AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 424
GCUGCCUGAUACCACAGGCGUGCGGGGAGAGUCCCUCGUGU
GCAAGAAUGCCCUGCAGGACCUGAGCUUCCUGGAACAUCUG
CUGCAAGUGAAGUACGCCCCCAAGACCUGGAAAGAGCAGUA
CCUGGGCUGGGACCUGGUGCAGUCCUCUGUGUCUGCCCAGC
AGAAGCUGCGGACCCAGGAAAACCCCUCUACCAGCUUCUGUC
AGCAAGUGCUGGCCGACUUCAUCGGCGGCCUGAACGAUUUC
CAUGCCGGCGUGACCUUUUUCGCCAUCGAGAGCGCCUACCUG
CCCUACACCGUGCAGAAGUCCAGCGACGGCCGGUUCUACUUC
GUGGACAUCAUGACCUUCAGCAGCGAGAUCAGAGUGGGCGA
CGAGCUGCUGGAAGUGGAUGGCGCUCCUGUGCAGGAUGUGC
UGGCCACACUGUACGGCAGCAACCACAAGGGCACAGCCGCCG
AAGAAUCUGCCGCCCUGAGAACCCUGUUCAGCCGGAUGGCC
UCUCUGGGCCACAAGGUGCCAAGCGGCAGAACCACCCUGAA
GAUCAGACGGCCCUUUGGCACCACCCGGGAAGUGCGCGUGA
AGUGGCGCUAUGUGCCUGAGGGCGUGGGCGACCUGGCCACA
AUCGCCCCUUCUAUCAGAGCCCCCCAGCUGCAGAAAUCCAUG
CGGUCAUUCUUCCCAAAGAAGGACGACGCCUUCCACCGGUCC
AGCAGCCUGUUCUACAGCCCUAUGGUGCCCCACUUCUGGGCC
GAGCUGAGAAACCACUACGCCACCUCCGGCCUGAAGUCCGGC
UACAACAUCGGCAGCACCGACGGCUUUCUGCCCGUGAUCGG
ACCCGUGAUCUGGGAGAGCGAGGGCCUGUUCAGAGCCUACA
UCAGCAGCGUGACCGACGGCGACGGCAAGAGCCACAAAGUG
GGCUUUCUGAGAAUCCCCACCUACAGCUGGCAGGACAUGGA
AGAUUUCGACCCCAGCGGCCCACCCCCCUGGGAGGAAUUUGC
CAAGAUCAUCCAGGUGUUCAGCAGCAACACCGAGGCCCUGA
UCAUCGACCAGACCAACAACCCUGGCGGCAGCGUGCUGUACC
UGUACGCCCUGCUGAGCAUGCUGACCGACAGACCCCUGGAAC
UGCCCAAGCACCGGAUGAUCCUGACCCAGGACGAGGUGGUG
GACGCCCUGGAUUGGCUGACCCUGCUGGAAAACGUGGACAC
CAACGUGGAAAGCCGGCUGGCCCUGGGCGACAACAUGGAAG
GCUACACAGUGGAUCUGCAGGUGGCCGAGUACCUGAAAAGC
UUCGGCAGACAGGUGCUGAACUGCUGGUCCAAGGGCGACAU
CGAGCUGAGCACCCCCAUCCCCCUGUUCGGCUUCGAGAAGAU
CCACCCCCACCCCAGAGUGCAGUACAGCAAGCCCAUCUGCGU
GCUGAUCAACGAGCAGGACUUCUCCUGCGCCGACUUCUUCCC
AGUGGUGCUGAAGGACAACGACAGAGCCCUGAUCGUGGGCA
CCAGAACAGCUGGCGCUGGCGGCUUCGUGUUCAACGUGCAG
UUCCCCAACCGGACCGGCAUCAAGACCUGUAGCCUGACAGGC
UCUCUGGCCGUGCGGGAACACGGCGCCUUCAUCGAGAACAU
CGGCGUGGAACCCCACAUCGACCUGCCUUUCACCGCCAACGA
CAUCCGGUACAAGGGCUACUCUGAGUACCUGGACAAAGUGA
AGAAACUCGUGUGCCAGCUGAUUAACAACGACGGCACCAUC AUCCUGGCCGAGGACGGCAGCUUC
Chlamydia_CT858_nIgk_cHis AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG
425 GCUGCCUGAUACCACAGGCGUGCGGGGAGAGUCCCUCGUGU
GCAAGAAUGCCCUGCAGGACCUGAGCUUCCUGGAACAUCUG
CUGCAAGUGAAGUACGCCCCCAAGACCUGGAAAGAGCAGUA
CCUGGGCUGGGACCUGGUGCAGUCCUCUGUGUCUGCCCAGC
AGAAGCUGCGGACCCAGGAAAACCCCUCUACCAGCUUCUGUC
AGCAAGUGCUGGCCGACUUCAUCGGCGGCCUGAACGAUUUC
CAUGCCGGCGUGACCUUUUUCGCCAUCGAGAGCGCCUACCUG
CCCUACACCGUGCAGAAGUCCAGCGACGGCCGGUUCUACUUC
GUGGACAUCAUGACCUUCAGCAGCGAGAUCAGAGUGGGCGA
CGAGCUGCUGGAAGUGGAUGGCGCUCCUGUGCAGGAUGUGC
UGGCCACACUGUACGGCAGCAACCACAAGGGCACAGCCGCCG
AAGAAUCUGCCGCCCUGAGAACCCUGUUCAGCCGGAUGGCC
UCUCUGGGCCACAAGGUGCCAAGCGGCAGAACCACCCUGAA
GAUCAGACGGCCCUUUGGCACCACCCGGGAAGUGCGCGUGA
AGUGGCGCUAUGUGCCUGAGGGCGUGGGCGACCUGGCCACA
AUCGCCCCUUCUAUCAGAGCCCCCCAGCUGCAGAAAUCCAUG
CGGUCAUUCUUCCCAAAGAAGGACGACGCCUUCCACCGGUCC
AGCAGCCUGUUCUACAGCCCUAUGGUGCCCCACUUCUGGGCC
GAGCUGAGAAACCACUACGCCACCUCCGGCCUGAAGUCCGGC
UACAACAUCGGCAGCACCGACGGCUUUCUGCCCGUGAUCGG
ACCCGUGAUCUGGGAGAGCGAGGGCCUGUUCAGAGCCUACA
UCAGCAGCGUGACCGACGGCGACGGCAAGAGCCACAAAGUG
GGCUUUCUGAGAAUCCCCACCUACAGCUGGCAGGACAUGGA
AGAUUUCGACCCCAGCGGCCCACCCCCCUGGGAGGAAUUUGC
CAAGAUCAUCCAGGUGUUCAGCAGCAACACCGAGGCCCUGA
UCAUCGACCAGACCAACAACCCUGGCGGCAGCGUGCUGUACC
UGUACGCCCUGCUGAGCAUGCUGACCGACAGACCCCUGGAAC
UGCCCAAGCACCGGAUGAUCCUGACCCAGGACGAGGUGGUG
GACGCCCUGGAUUGGCUGACCCUGCUGGAAAACGUGGACAC
CAACGUGGAAAGCCGGCUGGCCCUGGGCGACAACAUGGAAG
GCUACACAGUGGAUCUGCAGGUGGCCGAGUACCUGAAAAGC
UUCGGCAGACAGGUGCUGAACUGCUGGUCCAAGGGCGACAU
CGAGCUGAGCACCCCCAUCCCCCUGUUCGGCUUCGAGAAGAU
CCACCCCCACCCCAGAGUGCAGUACAGCAAGCCCAUCUGCGU
GCUGAUCAACGAGCAGGACUUCUCCUGCGCCGACUUCUUCCC
AGUGGUGCUGAAGGACAACGACAGAGCCCUGAUCGUGGGCA
CCAGAACAGCUGGCGCUGGCGGCUUCGUGUUCAACGUGCAG
UUCCCCAACCGGACCGGCAUCAAGACCUGUAGCCUGACAGGC
UCUCUGGCCGUGCGGGAACACGGCGCCUUCAUCGAGAACAU
CGGCGUGGAACCCCACAUCGACCUGCCUUUCACCGCCAACGA
CAUCCGGUACAAGGGCUACUCUGAGUACCUGGACAAAGUGA
AGAAACUCGUGUGCCAGCUGAUUAACAACGACGGCACCAUC
AUCCUGGCCGAGGACGGCAGCUUCCACCACCACCAUCACCAC Chlamydia_CT875_nIgk
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 426
GCUGCCUGACACCACCGGCAUGAGCAUCAGAGGCGUGGGCG
GCAACGGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCA
GCAACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUG
GAAGAUAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGA
GAACCGCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCA
UGAUCGAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUA
GUAGAGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGG
AUUGCUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAG
CAGCGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGA
GAGCGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCG
GCUACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGC
UGAUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAG
ACCUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAA
CGAGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCG
AUCACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUG
GCAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGU
GCGGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGA
ACGACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GCCCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUC
UGGCUGGACAUGAGCAACCUGAGCGACGUGGUGCUGUCCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAG
AGUCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGG
CGGCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGA
GGAAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUC
AGAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUC
GGCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGU
GUCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAU
GCUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCA
GAGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCC
UGGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCC
GACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAG
GGGCGUGCCAUCCAUCGAGGGCGAGGGCAGCGAUAGCAUCU
ACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGGAC
CUGGAAACCCGGCGGAGCUUCGCCGUGCAGCAGGGCCAUUA
CCAGGACCCCAGAGCCAGCGACUACGACCUGCCUAGAGCCUC
CGAUUACGAUCUGCCCAGAAGCCCCUACCCCACCCCUCCACU
GCCUCCCAGAUACCAGCUGCAGAACAUGGAUGUGGAAGCCG
GCUUUCGCGAGGCCGUGUACGCCUCUUUUGUGGCCGGCAUG
UACAACUACGUCGUGACCCAGCCCCAGGAACGGAUCCCCAAU
AGCCAGCAGGUGGAAGGCAUCCUGCGGGACAUGCUGACCAA
CGGCAGCCAGACCUUCCGGGACCUGAUGAAGCGGUGGAACA GAGAGGUGGACCGCGAG
Chlamydia_CT875_nIgk_cHis AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG
427 GCUGCCUGACACCACCGGCAUGAGCAUCAGAGGCGUGGGCG
GCAACGGCAACAGCAGAAUCCCUAGCCACAACGGCGACGGCA
GCAACAGGCGGAGCCAGAACACCAAGGGCAACAACAAGGUG
GAAGAUAGAGUGUGCAGCCUGUACAGCAGCCGGUCCAACGA
GAACCGCGAGAGCCCUUAUGCCGUGGUGGACGUGUCCAGCA
UGAUCGAGAGCACCCCCACCAGCGGCGAGACAACCAGAGCUA
GUAGAGGCGUGCUGAGCCGGUUCCAGAGGGGCCUCGUGCGG
AUUGCUGACAAAGUGCGGAGAGCCGUGCAGUGCGCUUGGAG
CAGCGUGUCCACAAGCAGAAGCAGCGCCACAAGAGCCGCCGA
GAGCGGCAGCUCUAGCAGAACAGCUAGAGGCGCCAGCAGCG
GCUACAGAGAGUACAGCCCUUCUGCCGCUCGGGGCCUGCGGC
UGAUGUUCACCGACUUUUGGCGGACCCGGGUGCUGAGACAG
ACCUCUCCUAUGGCCGGCGUGUUCGGCAACCUGGACGUGAA
CGAGGCCAGACUGAUGGCCGCCUACACCAGCGAGUGUGCCG
AUCACCUGGAAGCCAAAGAGCUGGCCGGACCUGACGGCGUG
GCAGCCGCUAGAGAAAUCGCCAAGAGAUGGGAGAAGAGAGU
GCGGGACCUGCAGGACAAGGGCGCUGCCAGAAAGCUGCUGA
ACGACCCCCUGGGCAGACGGACCCCCAACUACCAGAGCAAGA
ACCCCGGCGAGUACACCGUGGGCAACUCCAUGUUCUACGACG
GCCCCCAGGUGGCCAACCUGCAGAAUGUGGAUACCGGCUUC
UGGCUGGACAUGAGCAACCUGAGCGACGUGGUGCUGUCCAG
AGAGAUCCAGACCGGCCUGAGAGCCAGAGCCACCCUGGAAG
AGUCCAUGCCCAUGCUGGAAAAUCUGGAAGAGAGAUUCCGG
CGGCUGCAGGAAACCUGCGACGCCGCCAGAACCGAGAUCGA
GGAAAGCGGCUGGACCCGGGAAAGCGCCUCCAGAAUGGAAG
GCGACGAAGCCCAGGGCCCCAGCAGAGUGCAGCAGGCCUUUC
AGAGCUUCGUGAAUGAGUGCAACAGCAUCGAGUUCAGCUUC
GGCUCCUUCGGCGAGCACGUGCGGGUGCUGUGUGCCAGAGU
GUCAAGAGGACUGGCCGCUGCCGGCGAGGCCAUCAGAAGAU
GCUUCAGCUGCUGCAAGGGCAGCACCCACAGAUACGCCCCCA
GAGAUGACCUGUCUCCUGAGGGCGCCUCUCUGGCCGAAACCC
UGGCCAGAUUCGCCGACGACAUGGGCAUCGAAAGAGGCGCC
GACGGCACCUACGACAUCCCCCUGGUGGACGAUUGGAGAAG
GGGCGUGCCAUCCAUCGAGGGCGAGGGCAGCGAUAGCAUCU
ACGAGAUCAUGAUGCCCAUCUACGAAGUGAUGAACAUGGAC
CUGGAAACCCGGCGGAGCUUCGCCGUGCAGCAGGGCCAUUA
CCAGGACCCCAGAGCCAGCGACUACGACCUGCCUAGAGCCUC
CGAUUACGAUCUGCCCAGAAGCCCCUACCCCACCCCUCCACU
GCCUCCCAGAUACCAGCUGCAGAACAUGGAUGUGGAAGCCG
GCUUUCGCGAGGCCGUGUACGCCUCUUUUGUGGCCGGCAUG
UACAACUACGUCGUGACCCAGCCCCAGGAACGGAUCCCCAAU
AGCCAGCAGGUGGAAGGCAUCCUGCGGGACAUGCUGACCAA
CGGCAGCCAGACCUUCCGGGACCUGAUGAAGCGGUGGAACA
GAGAGGUGGACCGCGAGCACCACCAUCACCACCAC Chlamydia_CT089_nIgk
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 428
GCUGCCUGACACCACCGGCAUGACAGCAUCUGGCGGAGCUG
GCGGCCUGGGCUCUACACAGACAGUGGAUGUGGCCAGGGCC
CAGGCUGCUGCCGCUACACAGGAUGCCCAGGAAGUGAUCGG
CAGCCAGGAAGCCAGCGAGGCCUCUAUGCUGAAGGGCUGCG
AGGACCUGAUCAACCCUGCCGCCGCUACCCGCAUCAAGAAGA
AAGAGGAAAAGUUCGAGUCCCUGGAAGCCAGACGGAAGCCC
ACCGCCGACAAGGCCGAGAAGAAGUCCGAGAGCACCGAGGA
AAAGGGCGACACCCCCCUGGAAGAUCGGUUCACCGAGGAUC
UGAGCGAGGUGUCCGGCGAGGACUUCCGGGGCCUGAAGAAC
AGCUUCGACGACGACAGCAGCCCCGAGGAAAUCCUGGACGCC
CUGACCAGCAAGUUCAGCGACCCCACCAUCAAGGACCUGGCC
CUGGACUACCUGAUCCAGACCGCCCCCAGCGACCGGAAGCUG
AAGUCUGCCCUGAUUCAGGCCAAGCACCAGCUGAUGAGCCA
GAACCCCCAGGCCAUCGUGGGCGGCAGAAAUGUGCUGCUGG
CCUCCGAGACAUUCGCCAGCAGAGCCAACACCAGCCCCAGCU
CCCUGCGGAGCCUGUAUCUGCAAGUGACCAGCUCCCCCAGCA
ACUGCGACAACCUGAGACAGAUGCUGGCUAGCUACCUGCCC
UCCGAGAAAACCGCCGUGAUGGAAUUCCUCGUGAACGGCAU
GGUGGCCGACCUGAAAAGCGAGGGCCCUAGCAUCCCUCCCGC
CAAGCUGCAGGUGUACAUGACCGAGCUGAGCAACCUGCAGG
CCCUGCACAGCGUGGACAGCUUUUUCGACCGGAACAUCGGC
AACCUGGAAAACAGCCUGAAGCACGAGGGCCACGCCCCCAUC
CCUUCUCUGACAACCGGCAAUCUGACCAAGACCUUCCUGCAG
CUGGUGGAAGAUAAGUUCCCCAGCAGCUCCAAGGCCCAGAA
GGCCCUGAACGAGCUCGUGGGCCCUGAUACCGGACCUCAGAC
CGAGGUGCUGAACCUGUUCUUUCGGGCCCUGAAUGGCUGCU
CCCCCCGGAUCUUUUCUGGCGCUGAGAAGAAGCAGCAGCUG
GCCAGCGUGAUCACCAACACCCUGGAUGCCAUCAACGCCGAC
AACGAGGACUACCCCAAGCCCGGCGACUUCCCCAGAAGCAGC
UUUAGCAGCACCCCCCCUCAUGCCCCUGUGCCCCAGUCUGAG
AUCCCUACCAGCCCAACCAGCACCCAGCCUCCAAGCCCU Chlamydia_CT089_nIgk_cHis
AUGGAAACCCCUGCCCAGCUGCUGUUCCUGCUGCUGCUGUG 429
GCUGCCUGACACCACCGGCAUGACAGCAUCUGGCGGAGCUG
GCGGCCUGGGCUCUACACAGACAGUGGAUGUGGCCAGGGCC
CAGGCUGCUGCCGCUACACAGGAUGCCCAGGAAGUGAUCGG
CAGCCAGGAAGCCAGCGAGGCCUCUAUGCUGAAGGGCUGCG
AGGACCUGAUCAACCCUGCCGCCGCUACCCGCAUCAAGAAGA
AAGAGGAAAAGUUCGAGUCCCUGGAAGCCAGACGGAAGCCC
ACCGCCGACAAGGCCGAGAAGAAGUCCGAGAGCACCGAGGA
AAAGGGCGACACCCCCCUGGAAGAUCGGUUCACCGAGGAUC
UGAGCGAGGUGUCCGGCGAGGACUUCCGGGGCCUGAAGAAC
AGCUUCGACGACGACAGCAGCCCCGAGGAAAUCCUGGACGCC
CUGACCAGCAAGUUCAGCGACCCCACCAUCAAGGACCUGGCC
CUGGACUACCUGAUCCAGACCGCCCCCAGCGACCGGAAGCUG
AAGUCUGCCCUGAUUCAGGCCAAGCACCAGCUGAUGAGCCA
GAACCCCCAGGCCAUCGUGGGCGGCAGAAAUGUGCUGCUGG
CCUCCGAGACAUUCGCCAGCAGAGCCAACACCAGCCCCAGCU
CCCUGCGGAGCCUGUAUCUGCAAGUGACCAGCUCCCCCAGCA
ACUGCGACAACCUGAGACAGAUGCUGGCUAGCUACCUGCCC
UCCGAGAAAACCGCCGUGAUGGAAUUCCUCGUGAACGGCAU
GGUGGCCGACCUGAAAAGCGAGGGCCCUAGCAUCCCUCCCGC
CAAGCUGCAGGUGUACAUGACCGAGCUGAGCAACCUGCAGG
CCCUGCACAGCGUGGACAGCUUUUUCGACCGGAACAUCGGC
AACCUGGAAAACAGCCUGAAGCACGAGGGCCACGCCCCCAUC
CCUUCUCUGACAACCGGCAAUCUGACCAAGACCUUCCUGCAG
CUGGUGGAAGAUAAGUUCCCCAGCAGCUCCAAGGCCCAGAA
GGCCCUGAACGAGCUCGUGGGCCCUGAUACCGGACCUCAGAC
CGAGGUGCUGAACCUGUUCUUUCGGGCCCUGAAUGGCUGCU
CCCCCCGGAUCUUUUCUGGCGCUGAGAAGAAGCAGCAGCUG
GCCAGCGUGAUCACCAACACCCUGGAUGCCAUCAACGCCGAC
AACGAGGACUACCCCAAGCCCGGCGACUUCCCCAGAAGCAGC
UUUAGCAGCACCCCCCCUCAUGCCCCUGUGCCCCAGUCUGAG
AUCCCUACCAGCCCAACCAGCACCCAGCCUCCAAGCCCUCAC CACCACCAUCACCAC
Chlamydia_MOMP AUGAAAAAACUCUUAAAAUCGGCGUUUUUAUCCGCCGCAUU 430
UUUUGCUGGUCACGCCUCCUUACACGCUUUGCCUGUAGGGA
ACCCAGCAGAGCCAAGUUUAUUAAUUGAUGGAACGAUAUGG
GAAGGUAUGUCAGGAGAUCCAUGUGAUCCUUGCGCUACUUG
GUGCGACGCGAUUAGCUUACGCGUAGGAUUUUACGGAGAUU
AUGUUUUCGACAGAGUCCUCAAGACAGAUGUGCCACAGAAG
UUUUCAAUGGGGCCUAUACCUACUUCAAGUACUUCUCCUGA
AGACUCAGCUAUACUAACAGAGAGAAAUAACGCAGCGUAUG
GAAAACAUAUGCACGAUGCGGAGUUGUUCACAAAUGCAGGU
UACAUUGCGCUAAAUAUUUGGGACCGUUUCGACAUCUUUUG
UACCUUAGGAGCUACUAGUGGGUAUUUUAAAGGGAAUUCUU
CAUCUUUCAACUUGAUCGGAUUGAUUGGUAUUUCAGGAGCA
GACCUUAACAGCAAGCUCCCAAACGCAAAUAUUUCUAACGG
CGUAGUAGAGCUAUAUACAGACACAACCUUCUCUUGGAGCG
UUGGAGCUCGCGGAGCUUUGUGGGAGUGUGGUUGCGCUACU
UUAGGAGCAGAAUUCCAAUACGCACAAUCGAAACCUCGCGU
UCAAGAAUUGAAUGUCUUGUCUAACGUAGCACAAUUUACUG
UACACAAACCUCGGGGAUAUGUAGGCCAGCCUCUACCUCUU
CCACUGACUGCAGGAACAGCAACUGAUUCUAAUGAUAAAUU
GAAAAAUGCCACGAUCAACUACCAUGAAUGGCAAGUCGGUG
CAGCAUUGUCAUAUAGACUGAAUAUGCUCGUUCCUUACAUC
GGUGUUCAGUGGUCCAGAGCUACUUUUGAUGCAGAUACUAU
CCAAAUUGCGGAACCAAAAUUAGCUUCGCCAAUUUUCAACU
UGACAACAUGGAAUCCAACAUUAUUAGGACAAGCAACUUCA
GUAGAUAGCGGAAACAAGUUUGCUGACUCCCUACAAAUUGU
UUCUCUUCAAAUUAACAAGUUGAAGUCCAGAAAAGCUUGUG
GUGUUUCCAUGGGAGCAACUUUACUUGAUGCCGAUAAAUGG
GCAAUCAAUGGGGAACUUCGUUUAAUUAACGAAAGAGCUGC UCACCUUUCUGCUCAAUGCAGAUUC
* All Chlamydia mRNA vaccines contain standard 5'UTR and 3'UTR
sequences and G5 Cap 5'UTR: (SEQ ID NO: 295)
TCAAGCTTTTGGACCCTCGTACAGAAGCTAATACGACTCACTATAGGGAAATAAGAGAGAAAAGA
AGAGTAAGAAGAAATATAAGAGCCACC 5'UTR without promoter sequence: (SEQ
ID NO: 296 GGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACC 3'UTR:
(SEQ ID NO: 297)
TGATAATAGGCTGGAGCCTCGGTGGCCATGCTTCTTGCCCCTTGGGCCTCCCCCCAGCCCCTCCTCC
CCTTCCTGCACCCGTACCCCCGTGGTCTTTGAATAAAGTCTGAGTGGGCGGC
TABLE-US-00010 TABLE 9 Chlamydia mRNA Vaccine Expression Test In
vitro expression (IF = immunofluorescence; L = lysate, S =
supernatant; mRNA Name cS = Concentrated supernatant)
Chlamydia_Ct089_nIgk_cHis yes, (L, S, cS) high expression, evidence
of glycosylation Chlamydia_Ct460_serovarD_nIgk_cHis yes (L, cS)
medium expression, likely glycosylated
Chlamydia_Ct622_serovarE_nIgk_cHis yes (cS only), low expression
secreted, evidence of Glycosylation Chlamydia_Ct858_nIgk_cHis yes,
(L only by WB and LCMS -exp4, 7). In exp 15 saw band (ran a bit
small in both L and cSup (weak))
Chlamydia_Ct871_pd_serovarD_nIgK_cHis yes (L, cS), medium
expression, possibly glycosylated Chlamydia_Ct875_nIgk_cHis yes (L,
cS), very weak expression Ct089_E_S198A_nIgK_cHis yes, (L, S, cS)
high expression, evidence of glycosylation
Ct089_E_S198A_T306A_nIgK_cHis yes, (L, S, cS) high expression,
evidence of residual glycosylation, looks similar to T306A single
mutant Ct089_E_T306A_nIgK_cHis yes, (L, S, cS) high expression,
evidence of residual glycosylation Ct443_E_nIgK_cHis_mod yes (L,
cS), v weak in sup, maybe glycosylated
Ct622_E_S13N_S179A_S220N_nIgK_cHis yes, mostly in cS. Evidence of
N-linked gly and possible other modifications as multiple sizes
present in mutant Ct858_E_S491A_nIgK_cHis yes, (L and cS) v. weakly
secreted. Comparable to wt in same exp. Size looks a bit small.
Ct875_E_nIgK_cHis_CO002 yes (L, cS), very very weak expression
Ct875_E_nIgK_cHis_CO003 yes (L, cS), very weak expression, maybe
slightly better then original but not dramatic
Ct875_E_nIgK_cHis_CO004 yes (L, cS), very very weak expression
Ct875_E_nIgK_cHis_CO005 yes, similar to 1707458 Ct875_E_nIgK_nHis
no expression Ct875_E_S274Q_N275H_5574D_nIgK_cHis well expressed in
L, not in sup. Possible evidence of minor N-linked glycosylation
but would need confirming Ctal_E_cHis yes (strong in L, weak in cS)
Ctal_E_noTM_nIgK_cHis multiple bands in L, weak in sup MOMP_E_
nTMEM149 yes, surface expression (IF) MOMP_E_nFLRT2 yes, surface
expression (IF) MOMP_E_nIgK yes, surface expression (IF)
MOMP_E_nOsteo yes, surface expression (IF) MOMP_serovarE yes,
surface expression (IF) MOMP_serovarF yes, surface expression (IF)
MOMP_serovarG yes, surface expression (IF) OMPA_H_CO yes, surface
expression (IF)
TABLE-US-00011 TABLE 10 Flagellin Nucleic Acid Sequences SEQ ID
Name Sequence NO: NT (5'
TCAAGCTTTTGGACCCTCGTACAGAAGCTAATACGACTCACTAT 298 UTR, ORF,
AGGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAG 3' UTR)
AGCCACCATGGCACAAGTCATTAATACAAACAGCCTGTCGCTG
TTGACCCAGAATAACCTGAACAAATCCCAGTCCGCACTGGGCA
CTGCTATCGAGCGTTTGTCTTCCGGTCTGCGTATCAACAGCGCG
AAAGACGATGCGGCAGGACAGGCGATTGCTAACCGTTTTACCG
CGAACATCAAAGGTCTGACTCAGGCTTCCCGTAACGCTAACGA
CGGTATCTCCATTGCGCAGACCACTGAAGGCGCGCTGAACGAA
ATCAACAACAACCTGCAGCGTGTGCGTGAACTGGCGGTTCAGT
CTGCGAATGGTACTAACTCCCAGTCTGACCTCGACTCCATCCAG
GCTGAAATCACCCAGCGCCTGAACGAAATCGACCGTGTATCCG
GCCAGACTCAGTTCAACGGCGTGAAAGTCCTGGCGCAGGACAA
CACCCTGACCATCCAGGTTGGTGCCAACGACGGTGAAACTATC
GATATTGATTTAAAAGAAATCAGCTCTAAAACACTGGGACTTG
ATAAGCTTAATGTCCAAGATGCCTACACCCCGAAAGAAACTGC
TGTAACCGTTGATAAAACTACCTATAAAAATGGTACAGATCCT
ATTACAGCCCAGAGCAATACTGATATCCAAACTGCAATTGGCG
GTGGTGCAACGGGGGTTACTGGGGCTGATATCAAATTTAAAGA
TGGTCAATACTATTTAGATGTTAAAGGCGGTGCTTCTGCTGGTG
TTTATAAAGCCACTTATGATGAAACTACAAAGAAAGTTAATAT
TGATACGACTGATAAAACTCCGTTGGCAACTGCGGAAGCTACA
GCTATTCGGGGAACGGCCACTATAACCCACAACCAAATTGCTG
AAGTAACAAAAGAGGGTGTTGATACGACCACAGTTGCGGCTCA
ACTTGCTGCAGCAGGGGTTACTGGCGCCGATAAGGACAATACT
AGCCTTGTAAAACTATCGTTTGAGGATAAAAACGGTAAGGTTA
TTGATGGTGGCTATGCAGTGAAAATGGGCGACGATTTCTATGC
CGCTACATATGATGAGAAAACAGGTGCAATTACTGCTAAAACC
ACTACTTATACAGATGGTACTGGCGTTGCTCAAACTGGAGCTGT
GAAATTTGGTGGCGCAAATGGTAAATCTGAAGTTGTTACTGCT
ACCGATGGTAAGACTTACTTAGCAAGCGACCTTGACAAACATA
ACTTCAGAACAGGCGGTGAGCTTAAAGAGGTTAATACAGATAA
GACTGAAAACCCACTGCAGAAAATTGATGCTGCCTTGGCACAG
GTTGATACACTTCGTTCTGACCTGGGTGCGGTTCAGAACCGTTT
CAACTCCGCTATCACCAACCTGGGCAATACCGTAAATAACCTG
TCTTCTGCCCGTAGCCGTATCGAAGATTCCGACTACGCAACCGA
AGTCTCCAACATGTCTCGCGCGCAGATTCTGCAGCAGGCCGGT
ACCTCCGTTCTGGCGCAGGCGAACCAGGTTCCGCAAAACGTCC
TCTCTTTACTGCGTTGATAATAGGCTGGAGCCTCGGTGGCCATG
CTTCTTGCCCCTTGGGCCTCCCCCCAGCCCCTCCTCCCCTTCCTG
CACCCGTACCCCCGTGGTCTTTGAATAAAGTCTGAGTGGGCGGC ORF
ATGGCACAAGTCATTAATACAAACAGCCTGTCGCTGTTGACCC 299 Sequence,
AGAATAACCTGAACAAATCCCAGTCCGCACTGGGCACTGCTAT NT
CGAGCGTTTGTCTTCCGGTCTGCGTATCAACAGCGCGAAAGAC
GATGCGGCAGGACAGGCGATTGCTAACCGTTTTACCGCGAACA
TCAAAGGTCTGACTCAGGCTTCCCGTAACGCTAACGACGGTAT
CTCCATTGCGCAGACCACTGAAGGCGCGCTGAACGAAATCAAC
AACAACCTGCAGCGTGTGCGTGAACTGGCGGTTCAGTCTGCGA
ATGGTACTAACTCCCAGTCTGACCTCGACTCCATCCAGGCTGAA
ATCACCCAGCGCCTGAACGAAATCGACCGTGTATCCGGCCAGA
CTCAGTTCAACGGCGTGAAAGTCCTGGCGCAGGACAACACCCT
GACCATCCAGGTTGGTGCCAACGACGGTGAAACTATCGATATT
GATTTAAAAGAAATCAGCTCTAAAACACTGGGACTTGATAAGC
TTAATGTCCAAGATGCCTACACCCCGAAAGAAACTGCTGTAAC
CGTTGATAAAACTACCTATAAAAATGGTACAGATCCTATTACA
GCCCAGAGCAATACTGATATCCAAACTGCAATTGGCGGTGGTG
CAACGGGGGTTACTGGGGCTGATATCAAATTTAAAGATGGTCA
ATACTATTTAGATGTTAAAGGCGGTGCTTCTGCTGGTGTTTATA
AAGCCACTTATGATGAAACTACAAAGAAAGTTAATATTGATAC
GACTGATAAAACTCCGTTGGCAACTGCGGAAGCTACAGCTATT
CGGGGAACGGCCACTATAACCCACAACCAAATTGCTGAAGTAA
CAAAAGAGGGTGTTGATACGACCACAGTTGCGGCTCAACTTGC
TGCAGCAGGGGTTACTGGCGCCGATAAGGACAATACTAGCCTT
GTAAAACTATCGTTTGAGGATAAAAACGGTAAGGTTATTGATG
GTGGCTATGCAGTGAAAATGGGCGACGATTTCTATGCCGCTAC
ATATGATGAGAAAACAGGTGCAATTACTGCTAAAACCACTACT
TATACAGATGGTACTGGCGTTGCTCAAACTGGAGCTGTGAAAT
TTGGTGGCGCAAATGGTAAATCTGAAGTTGTTACTGCTACCGAT
GGTAAGACTTACTTAGCAAGCGACCTTGACAAACATAACTTCA
GAACAGGCGGTGAGCTTAAAGAGGTTAATACAGATAAGACTG
AAAACCCACTGCAGAAAATTGATGCTGCCTTGGCACAGGTTGA
TACACTTCGTTCTGACCTGGGTGCGGTTCAGAACCGTTTCAACT
CCGCTATCACCAACCTGGGCAATACCGTAAATAACCTGTCTTCT
GCCCGTAGCCGTATCGAAGATTCCGACTACGCAACCGAAGTCT
CCAACATGTCTCGCGCGCAGATTCTGCAGCAGGCCGGTACCTC
CGTTCTGGCGCAGGCGAACCAGGTTCCGCAAAACGTCCTCTCTT TACTGCGT mRNA
G*GGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAA 300 Sequence
GAGCCACCAUGGCACAAGUCAUUAAUACAAACAGCCUGUCGC (assumes
UGUUGACCCAGAAUAACCUGAACAAAUCCCAGUCCGCACUGG T100 tail)
GCACUGCUAUCGAGCGUUUGUCUUCCGGUCUGCGUAUCAACA
GCGCGAAAGACGAUGCGGCAGGACAGGCGAUUGCUAACCGUU
UUACCGCGAACAUCAAAGGUCUGACUCAGGCUUCCCGUAACG
CUAACGACGGUAUCUCCAUUGCGCAGACCACUGAAGGCGCGC
UGAACGAAAUCAACAACAACCUGCAGCGUGUGCGUGAACUGG
CGGUUCAGUCUGCGAAUGGUACUAACUCCCAGUCUGACCUCG
ACUCCAUCCAGGCUGAAAUCACCCAGCGCCUGAACGAAAUCG
ACCGUGUAUCCGGCCAGACUCAGUUCAACGGCGUGAAAGUCC
UGGCGCAGGACAACACCCUGACCAUCCAGGUUGGUGCCAACG
ACGGUGAAACUAUCGAUAUUGAUUUAAAAGAAAUCAGCUCU
AAAACACUGGGACUUGAUAAGCUUAAUGUCCAAGAUGCCUAC
ACCCCGAAAGAAACUGCUGUAACCGUUGAUAAAACUACCUAU
AAAAAUGGUACAGAUCCUAUUACAGCCCAGAGCAAUACUGAU
AUCCAAACUGCAAUUGGCGGUGGUGCAACGGGGGUUACUGG
GGCUGAUAUCAAAUUUAAAGAUGGUCAAUACUAUUUAGAUG
UUAAAGGCGGUGCUUCUGCUGGUGUUUAUAAAGCCACUUAU
GAUGAAACUACAAAGAAAGUUAAUAUUGAUACGACUGAUAA
AACUCCGUUGGCAACUGCGGAAGCUACAGCUAUUCGGGGAAC
GGCCACUAUAACCCACAACCAAAUUGCUGAAGUAACAAAAGA
GGGUGUUGAUACGACCACAGUUGCGGCUCAACUUGCUGCAGC
AGGGGUUACUGGCGCCGAUAAGGACAAUACUAGCCUUGUAA
AACUAUCGUUUGAGGAUAAAAACGGUAAGGUUAUUGAUGGU
GGCUAUGCAGUGAAAAUGGGCGACGAUUUCUAUGCCGCUACA
UAUGAUGAGAAAACAGGUGCAAUUACUGCUAAAACCACUAC
UUAUACAGAUGGUACUGGCGUUGCUCAAACUGGAGCUGUGA
AAUUUGGUGGCGCAAAUGGUAAAUCUGAAGUUGUUACUGCU
ACCGAUGGUAAGACUUACUUAGCAAGCGACCUUGACAAACAU
AACUUCAGAACAGGCGGUGAGCUUAAAGAGGUUAAUACAGA
UAAGACUGAAAACCCACUGCAGAAAAUUGAUGCUGCCUUGGC
ACAGGUUGAUACACUUCGUUCUGACCUGGGUGCGGUUCAGAA
CCGUUUCAACUCCGCUAUCACCAACCUGGGCAAUACCGUAAA
UAACCUGUCUUCUGCCCGUAGCCGUAUCGAAGAUUCCGACUA
CGCAACCGAAGUCUCCAACAUGUCUCGCGCGCAGAUUCUGCA
GCAGGCCGGUACCUCCGUUCUGGCGCAGGCGAACCAGGUUCC
GCAAAACGUCCUCUCUUUACUGCGUUGAUAAUAGGCUGGAGC
CUCGGUGGCCAUGCUUCUUGCCCCUUGGGCCUCCCCCCAGCC
CCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAU
AAAGUCUGAGUGGGCGGCAAAAAAAAAAAAAAAAAAAAAAA
AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAUCUAG
TABLE-US-00012 TABLE 11 Flagellin Amino Acid Sequences SEQ ID Name
Sequence NO: ORF MAQVINTNSLSLLTQNNLNKSQSALGTAIERLSSGLRINSAKDDAA 301
Sequence, GQAIANRFTANIKGLTQASRNANDGISIAQTTEGALNEINNNLQRV AA
RELAVQSANGTNSQSDLDSIQAEITQRLNEIDRVSGQTQFNGVKVL
AQDNTLTIQVGANDGETIDIDLKEISSKTLGLDKLNVQDAYTPKET
AVTVDKTTYKNGTDPITAQSNTDIQTAIGGGATGVTGADIKFKDG
QYYLDVKGGASAGVYKATYDETTKKVNIDTTDKTPLATAEATAI
RGTATITHNQIAEVTKEGVDTTTVAAQLAAAGVTGADKDNTSLV
KLSFEDKNGKVIDGGYAVKMGDDFYAATYDEKTGAITAKTTTYT
DGTGVAQTGAVKFGGANGKSEVVTATDGKTYLASDLDKHNFRT
GGELKEVNTDKTENPLQKIDAALAQVDTLRSDLGAVQNRFNSAIT
NLGNTVNNLSSARSRIEDSDYATEVSNMSRAQILQQAGTSVLAQA NQVPQNVLSLLR
Flagellin- MAQVINTNSLSLLTQNNLNKSQSALGTAIERLSSGLRINSAKDDAA 302 GS
linker- GQAIANRFTANIKGLTQASRNANDGISIAQTTEGALNEINNNLQRV
circumsporozoite RELAVQSANSTNSQSDLDSIQAEITQRLNEIDRVSGQTQFNGVKVL
protein AQDNTLTIQVGANDGETIDIDLKQINSQTLGLDTLNVQQKYKVSD (CSP)
TAATVTGYADTTIALDNSTFKASATGLGGTDQKIDGDLKFDDTTG
KYYAKVTVTGGTGKDGYYEVSVDKTNGEVTLAGGATSPLTGGLP
ATATEDVKNVQVANADLTEAKAALTAAGVTGTASVVKMSYTDN
NGKTIDGGLAVKVGDDYYSATQNKDGSISINTTKYTADDGTSKTA
LNKLGGADGKTEVVSIGGKTYAASKAEGHNFKAQPDLAEAAATT
TENPLQKIDAALAQVDTLRSDLGAVQNRFNSAITNLGNTVNNLTS
ARSRIEDSDYATEVSNMSRAQILQQAGTSVLAQANQVPQNVLSLL
RGGGGSGGGGSMMAPDPNANPNANPNANPNANPNANPNANPNA
NPNANPNANPNANPNANPNANPNANPNANPNANPNANPNANPN
ANPNANPNKNNQGNGQGHNMPNDPNRNVDENANANNAVKNNN
NEEPSDKHIEQYLKKIKNSISTEWSPCSVTCGNGIQVRIKPGSANKP
KDELDYENDIEKKICKMEKCSSVFNVVNS Flagellin-
MMAPDPNANPNANPNANPNANPNANPNANPNANPNANPNANPN 303 RPVT
ANPNANPNANPNANPNANPNANPNANPNANPNANPNANPNKNN linker-
QGNGQGHNMPNDPNRNVDENANANNAVKNNNNEEPSDKHIEQY circumsporozoite
LKKIKNSISTEWSPCSVTCGNGIQVRIKPGSANKPKDELDYENDIEK protein
KICKMEKCSSVFNVVNSRPVTMAQVINTNSLSLLTQNNLNKSQSA (CSP)
LGTAIERLSSGLRINSAKDDAAGQAIANRFTANIKGLTQASRNAND
GISIAQTTEGALNEINNNLQRVRELAVQSANSTNSQSDLDSIQAEIT
QRLNEIDRVSGQTQFNGVKVLAQDNTLTIQVGANDGETIDIDLKQI
NSQTLGLDTLNVQQKYKVSDTAATVTGYADTTIALDNSTFKASAT
GLGGTDQKIDGDLKFDDTTGKYYAKVTVTGGTGKDGYYEVSVD
KTNGEVTLAGGATSPLTGGLPATATEDVKNVQVANADLTEAKAA
LTAAGVTGTASVVKMSYTDNNGKTIDGGLAVKVGDDYYSATQN
KDGSISINTTKYTADDGTSKTALNKLGGADGKTEVVSIGGKTYAA
SKAEGHNFKAQPDLAEAAATTTENPLQKIDAALAQVDTLRSDLG
AVQNRFNSAITNLGNTVNNLTSARSRIEDSDYATEVSNMSRAQILQ
QAGTSVLAQANQVPQNVLSLLR
TABLE-US-00013 TABLE 12 Signal Peptides SEQ ID Description Sequence
NO: HuIgG.sub.k signal METPAQLLFLLLLWLPDTTG 304 peptide IgE heavy
chain MDWTWILFLVAAATRVHS 305 epsilon-1 signal peptide Japanese
MLGSNSGQRVVFTILLLLVAPAYS 306 encephalitis PRM signal sequence VSVg
protein MKCLLYLAFLFIGVNCA 307 signal sequence Japanese
MWLVSLAIVTACAGA 308 encephalitis JEV signal sequence
TABLE-US-00014 TABLE 13 Leader Sequences SEQ ID Leader Amino Acid
Sequence NO: Native Cm-MOMP MKKLLKSVLAFAVLGSASSLHA 309 Native
CtD/CtE-MOMP MKKLLKSVLVFAALGSASSLQA 310 Shigella flexneri
MKSKFLVLALCVPAIFTTHA 311 (SopA) Salmonella enterica
MKTHVIAVMIIAVFSESVYA 312 (PgtE) Yersinia pestis (Pla)
MKKSSIVATIITILSGSANA 313 E. coli OmpP MQTKLLAIMLAAPVVFSSQEASA 314
E. coli OmpA MKKTAIAIAVALAGFATVAQA 315 pectate lyase B of
MKYLLPTAAAGLLLLAAQPAMA 316 Erwinia carotovora CE (PelB)
TABLE-US-00015 TABLE 14 In Vitro Expression of Chlamydia
Trachomatic Antigens from Candidate mRNA Vaccines Observed Expected
Observed Size in Observed Size Size in cell Size in Antigen (kDa)
in vitro QC supernatants cell lysates Ct-089 48.37 56.34 ~60-75
~55, 70, 75 Ct-858 68.02 75.65 -- ~70 (zymogen) Ct-875 69.08 71.84
~70 -- Ct-622 71.9 ~79 ~90 80 Ct-460 12.7 11-12 11-13 ~13 PmPG_pd
72 ~80 ~85 ~80 Cta1 19.9 20.5 19 19-27 Ct-443 59.3 -- ~60 60
(diffused and weak) Ct821pd_D 124 -- no band ~125
EQUIVALENTS
[0664] Those skilled in the art will recognize, or be able to
ascertain using no more than routine experimentation, many
equivalents to the specific embodiments of the disclosure described
herein. Such equivalents are intended to be encompassed by the
following claims.
[0665] All references, including patent documents, disclosed herein
are incorporated by reference in their entirety.
Sequence CWU 0 SQTB SEQUENCE LISTING The patent application
contains a lengthy "Sequence Listing" section. A copy of the
"Sequence Listing" is available in electronic form from the USPTO
web site
(http://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US20180289792A1).
An electronic copy of the "Sequence Listing" will also be available
from the USPTO upon request and payment of the fee set forth in 37
CFR 1.19(b)(3).
0 SQTB SEQUENCE LISTING The patent application contains a lengthy
"Sequence Listing" section. A copy of the "Sequence Listing" is
available in electronic form from the USPTO web site
(http://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US20180289792A1).
An electronic copy of the "Sequence Listing" will also be available
from the USPTO upon request and payment of the fee set forth in 37
CFR 1.19(b)(3).
* * * * *
References