Immunoinformatic comparison of T-cell epitopes contained in novel swine-origin influenza A (H1N1) virus with epitopes in 2008-2009 conventional influenza vaccine

被引:76
作者
De Groot, Anne S. [1 ,2 ,3 ]
Ardito, Matt [1 ]
McClaine, Elizabeth M. [1 ]
Moise, Leonard [1 ,2 ]
Martina, William D. [1 ]
机构
[1] EpiVax, Providence, RI 02903 USA
[2] Univ Rhode Isl, Inst Immunol & Informat, Providence, RI 02903 USA
[3] Brown Univ, Alpert Med Sch, Providence, RI 02903 USA
关键词
H1N1; Influenza; T-cell epitope; Immunoinformatics; Algorithm; Cell-mediated; HUMAN-IMMUNODEFICIENCY-VIRUS; BINDING PREDICTION SERVERS; MHC CLASS-II; TRANSGENIC MICE; B-CELLS; ANTIBODY-RESPONSES; INFECTION; RECOGNITION; IMMUNITY; CD4(+);
D O I
10.1016/j.vaccine.2009.07.040
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In March 2009 a novel swine-origin influenza A (H1N1) virus (S-OIV) emerged in Mexico and the Western United States. Vaccination with conventional influenza vaccine (CIV) does not result in cross-reactive antibodies, however, the disproportionate number of cases (37%) occurring among persons younger than 50 years old suggested that adaptive immune memory might be responsible for the relative lack of virulence in older, healthy adults. Using EpiMatrix, a T-cell epitope prediction and comparison tool, we compared the sequences of the three hemagglutinin (HA) and neuraminidase (NA) proteins contained in 2008-2009 CIV to their counterparts in A/California/0412009 (H1N1) looking for cross-conserved T-cell epitope sequences. We found greater than 50% conservation of T helper and CTL epitopes between novel S-OIV and CIV HA for selected HLA. Conservation was lower among NA epitopes. Sixteen promiscuous helper T-cell epitopes are contained in the S-OIV H1N1 HA sequence, of which nine (56%) were 100% conserved in the 2008-2009 influenza vaccine strain; 81% were either identical or had one conservative amino acid substitution. Fifty percent of predicted CTL epitopes found in S-OIV H1N1 HA were also found in CIV HA sequences. Based on historical performance, we expect these epitope predictions to be 93-99% accurate. This in silico analysis supports the proposition that T-cell response to cross-reactive T-cell epitopes, due to vaccination or exposure, may have the capacity to attenuate the course of S-OIV H1N1 induced disease-in the absence of cross-reactive antibody response. The value of the CIV or live-attenuated influenza vaccine containing the 2008-2009 vaccine strains, as defense against H1N1, could be further tested by evaluating human immune responses to the conserved T-cell epitopes using PBMC from individuals infected with H1N1 and from CIV vaccinees. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:5740 / 5747
页数:8
相关论文
共 72 条
[1]  
[Anonymous], 2009, Wkly Epidemiol Rec, V84, P149
[2]   Immunomic Analysis of the Repertoire of T-Cell Specificities for Influenza A Virus in Humans [J].
Assarsson, Erika ;
Bui, Huynh-Hoa ;
Sidney, John ;
Zhang, Qing ;
Glenn, Jean ;
Oseroff, Carla ;
Mbawuike, Innocent N. ;
Alexander, Jeff ;
Newman, Mark J. ;
Grey, Howard ;
Sette, Alessandro .
JOURNAL OF VIROLOGY, 2008, 82 (24) :12241-12251
[3]   Compromised influenza virus-specific CD8+-T-Cell memory in CD4+-T-cell-deficient mice [J].
Belz, GT ;
Wodarz, D ;
Diaz, G ;
Nowak, MA ;
Doherty, PC .
JOURNAL OF VIROLOGY, 2002, 76 (23) :12388-12393
[4]   Antigenic and molecular analysis of influenza A (H3N2) virus strains isolated from a localised influenza outbreak in South Africa in 2003 [J].
Besselaar, TG ;
Botha, L ;
McAnerney, JM ;
Schoub, BD .
JOURNAL OF MEDICAL VIROLOGY, 2004, 73 (01) :71-78
[5]   Analysis of total human immunodeficiency virus (HIV)-specific CD4+ and CD8+ T-cell responses:: Relationship to viral load in untreated HIV infection [J].
Betts, MR ;
Ambrozak, DR ;
Douek, DC ;
Bonhoeffer, S ;
Brenchley, JM ;
Casazza, JP ;
Koup, RA ;
Picker, LJ .
JOURNAL OF VIROLOGY, 2001, 75 (24) :11983-11991
[6]   An HLA-directed molecular and bioinformatics approach identifies new HLA-A11 HIV-1 subtype E cytotoxic T lymphocyte epitopes in HIV-1-infected thais [J].
Bond, KB ;
Sriwanthana, B ;
Hodge, TW ;
De Groot, AS ;
Mastro, TD ;
Young, NL ;
Promadej, N ;
Altman, JD ;
Limpakarnjanarat, K ;
McNicholl, JM .
AIDS RESEARCH AND HUMAN RETROVIRUSES, 2001, 17 (08) :703-717
[7]   Recognition of homo- and heterosubtypic variants of influenza A viruses by human CD8+ T lymphocytes [J].
Boon, ACM ;
de Mutsert, G ;
van Baarle, D ;
Smith, DJ ;
Lapedes, AS ;
Fouchier, RAM ;
Sintnicolaas, K ;
Osterhaus, ADME ;
Rimmelzwaan, GF .
JOURNAL OF IMMUNOLOGY, 2004, 172 (04) :2453-2460
[8]   Requirement for CD40 ligand, CD4+ T cells, and B cells in an infectious mononucleosis-like syndrome [J].
Brooks, JW ;
Hamilton-Easton, AM ;
Christensen, JP ;
Cardin, RD ;
Hardy, CL ;
Doherty, PC .
JOURNAL OF VIROLOGY, 1999, 73 (11) :9650-9654
[9]   HEMAGGLUTININ-SPECIFIC ANTIBODY-RESPONSES IN IMMUNOGLOBULIN-G, IMMUNOGLOBULIN-A, AND IMMUNOGLOBULIN-M ISOTYPES AS MEASURED BY ENZYME-LINKED IMMUNOSORBENT-ASSAY AFTER PRIMARY OR SECONDARY INFECTION OF HUMANS WITH INFLUENZA-A VIRUS [J].
BURLINGTON, DB ;
CLEMENTS, ML ;
MEIKLEJOHN, G ;
PHELAN, M ;
MURPHY, BR .
INFECTION AND IMMUNITY, 1983, 41 (02) :540-545
[10]   Progressive loss of CD8(+) T cell-mediated control of a gamma-herpesvirus in the absence of CD4(+) T cells [J].
Cardin, RD ;
Brooks, JW ;
Sarawar, SR ;
Doherty, PC .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (03) :863-871