Conservation of HIV-1 T cell epitopes across time and clades: validation of immunogenic HLA-A2 epitopes selected for the GAIA HIV vaccine
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Conservation of HIV-1 T cell epitopes across time and clades : validation of immunogenic HLA-A2 epitopes selected for the GAIA HIV vaccine. / Levitz, Lauren; Koita, Ousmane A; Sangare, Kotou; Ardito, Matthew T; Boyle, Christine M; Rozehnal, John; Tounkara, Karamoko; Dao, Sounkalo M; Koné, Youssouf; Koty, Zoumana; Buus, Soren; Moise, Leonard; Martin, William D; De Groot, Anne S.
I: The Vaccine Quarterly, Bind 30, Nr. 52, 14.12.2012, s. 7547-7560.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Conservation of HIV-1 T cell epitopes across time and clades
T2 - validation of immunogenic HLA-A2 epitopes selected for the GAIA HIV vaccine
AU - Levitz, Lauren
AU - Koita, Ousmane A
AU - Sangare, Kotou
AU - Ardito, Matthew T
AU - Boyle, Christine M
AU - Rozehnal, John
AU - Tounkara, Karamoko
AU - Dao, Sounkalo M
AU - Koné, Youssouf
AU - Koty, Zoumana
AU - Buus, Soren
AU - Moise, Leonard
AU - Martin, William D
AU - De Groot, Anne S
N1 - Copyright © 2012 Elsevier Ltd. All rights reserved.
PY - 2012/12/14
Y1 - 2012/12/14
N2 - HIV genomic sequence variability has complicated efforts to generate an effective globally relevant vaccine. Regions of the viral genome conserved in sequence and across time may represent the "Achilles' heel" of HIV. In this study, highly conserved T-cell epitopes were selected using immunoinformatics tools combining HLA-A2 supertype binding predictions with relative global conservation. Analysis performed in 2002 on 10,803 HIV-1 sequences, and again in 2009, on 43,822 sequences, yielded 38 HLA-A2 epitopes. These epitopes were experimentally validated for HLA binding and immunogenicity with PBMCs from HIV-infected patients in Providence, Rhode Island, and/or Bamako, Mali. Thirty-five (92%) stimulated an IFNγ response in PBMCs from at least one subject. Eleven of fourteen peptides (79%) were confirmed as HLA-A2 epitopes in both locations. Validation of these HLA-A2 epitopes conserved across time, clades, and geography supports the hypothesis that such epitopes could provide effective coverage of virus diversity and would be appropriate for inclusion in a globally relevant HIV vaccine.
AB - HIV genomic sequence variability has complicated efforts to generate an effective globally relevant vaccine. Regions of the viral genome conserved in sequence and across time may represent the "Achilles' heel" of HIV. In this study, highly conserved T-cell epitopes were selected using immunoinformatics tools combining HLA-A2 supertype binding predictions with relative global conservation. Analysis performed in 2002 on 10,803 HIV-1 sequences, and again in 2009, on 43,822 sequences, yielded 38 HLA-A2 epitopes. These epitopes were experimentally validated for HLA binding and immunogenicity with PBMCs from HIV-infected patients in Providence, Rhode Island, and/or Bamako, Mali. Thirty-five (92%) stimulated an IFNγ response in PBMCs from at least one subject. Eleven of fourteen peptides (79%) were confirmed as HLA-A2 epitopes in both locations. Validation of these HLA-A2 epitopes conserved across time, clades, and geography supports the hypothesis that such epitopes could provide effective coverage of virus diversity and would be appropriate for inclusion in a globally relevant HIV vaccine.
KW - AIDS Vaccines
KW - Antigens, Viral
KW - Conserved Sequence
KW - Epitopes, T-Lymphocyte
KW - Geography
KW - HIV-1
KW - HLA-A2 Antigen
KW - Humans
KW - Leukocytes, Mononuclear
KW - Mali
KW - Rhode Island
KW - Time Factors
U2 - 10.1016/j.vaccine.2012.10.042
DO - 10.1016/j.vaccine.2012.10.042
M3 - Journal article
C2 - 23102976
VL - 30
SP - 7547
EP - 7560
JO - The Vaccine Quarterly
JF - The Vaccine Quarterly
SN - 1935-5653
IS - 52
ER -
ID: 49594904