title: Conservation of HIV-1 T cell epitopes across time and clades: validation of immunogenic HLA-A2 epitopes selected for the GAIA HIV vaccine.
abstract: 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.
authors.affiliation: EpiVax, Inc., Providence, Rhode Island, United States.
authors.forename: Lauren
authors.initials: L
authors.lastname: Levitz
authors.forename: Ousmane A
authors.initials: OA
authors.lastname: Koita
authors.forename: Kotou
authors.initials: K
authors.lastname: Sangare
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Ardito
authors.forename: Christine M
authors.initials: CM
authors.lastname: Boyle
authors.forename: John
authors.initials: J
authors.lastname: Rozehnal
authors.forename: Karamoko
authors.initials: K
authors.lastname: Tounkara
authors.forename: Sounkalo M
authors.initials: SM
authors.lastname: Dao
authors.forename: Youssouf
authors.initials: Y
authors.lastname: Koné
authors.forename: Zoumana
authors.initials: Z
authors.lastname: Koty
authors.forename: Soren
authors.initials: S
authors.lastname: Buus
authors.forename: Leonard
authors.initials: L
authors.lastname: Moise
authors.forename: William D
authors.initials: WD
authors.lastname: Martin
authors.forename: Anne S
authors.initials: AS
authors.lastname: De Groot
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D017124:Conserved Sequence; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005843:Geography; D015497:HIV-1 / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008302:Mali; D012237:Rhode Island; D013997:Time Factors
chemical_list: D016915:AIDS Vaccines; D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen