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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Lauren Levitz, Ousmane A Koita, Kotou Sangare, Matthew T Ardito, Christine M Boyle, John Rozehnal, Karamoko Tounkara, Sounkalo M Dao, Youssouf Koné, Zoumana Koty, Soren Buus, Leonard Moise, William D Martin, Anne S De Groot

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.
OriginalsprogEngelsk
TidsskriftThe Vaccine Quarterly
Vol/bind30
Udgave nummer52
Sider (fra-til)7547-7560
Antal sider14
ISSN1935-5653
DOI
StatusUdgivet - 14 dec. 2012

ID: 49594904