Levitz, Lauren2; Koita, Ousmane A2; Sangare, Kotou2; Ardito, Matthew T2; Boyle, Christine M2; Rozehnal, John2; Tounkara, Karamoko2; Dao, Sounkalo M2; Koné, Youssouf2; Koty, Zoumana2; Buus, Soren3; Moise, Leonard2; Martin, William D2; De Groot, Anne S2
1 Department of Immunology and Microbiology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Københavns Universitet2 unknown3 Department of Immunology and Microbiology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Københavns Universitet
validation of immunogenic HLA-A2 epitopes selected for the GAIA HIV vaccine
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.
Vaccine Quarterly, 2012, Vol 30, Issue 52, p. 7547-7560
AIDS Vaccines; Antigens, Viral; Conserved Sequence; Epitopes, T-Lymphocyte; Geography; HIV-1; HLA-A2 Antigen; Humans; Leukocytes, Mononuclear; Mali; Rhode Island; Time Factors