Conservation of HIV-1 T cell epitopes across time and clades: validation of immunogenic HLA-A2 epitopes selected for the GAIA HIV vaccine

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

SN - 1935-5653

VL - 30

SP - 7547

EP - 7560

JO - The Vaccine Quarterly

JF - The Vaccine Quarterly

IS - 52

ER -