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61 Identification of Novel HIV-2 Epitopes and Cross-Reactive HIV-1/HIV-2 Epitopes Using a Bioinformatics Approach
N. Chinai1, A. Jaye2, A. Bosma1, A. Alabi2, S. Sabally2, C. Saint-Aubin1, H. Whittle2, and A. S. De Groot*1
1Brown Univ., Providence, RI, USA and 2Med. Res. Labs, Fajara, The Gambia
Background: Evidence suggests that the key player in the control of virus levels throughout HIV infection is the presence of circulating HIV-specific cytotoxic T-lymphocytes (CTL). MHC class I restricted CTL that are cross-reactive between HIV-1 and HIV-2 strains in Africa have been reported. We were interested in examining the role of cross-reactive CTL epitopes in protection against HIV-1 and HIV-2 in West Africa.
Methods: Using a bioinformatics approach we identified such cross-reactive epitopes in a cohort of HIV-2-infected individuals from the Gambia. Based on EpiMatrix results, we synthesized and screened twelve 9-mer peptides for reactivity in a cohort of HIV-2-infected individuals in the Gambia. Fresh and cryopreserved PBMC from HLA-matched and -mismatched HIV-2 individuals were tested in in vitro ELISpot and standard Cr51 release assays to define the immunogenicity of the predicted CTL epitopes.
Results: Two of 6 (33%) cross-conserved peptides elicited an IFN-gamma response with an effector frequency range between 1:2,500 and 1:25,000, whereas 4 of 6 (67%) HIV-2-specific peptides elicited an IFN-gamma response with an effector frequency between 1:500 and 1:200,000. Three of the 12 (25%) peptides demonstrated lytic activity in the standard Cr51 release assay (specific lysis > 10%), at a 30:1 E/T ratio. No IFN-gamma or cytotoxic killing response was elicited with HLA-mismatched peptides. An HLA-A2-predicted HIV-2-specific env peptide elicited the strongest IFN-gamma response in 4 of 6 (67%) individuals tested, with an effector frequency ranging from 1:500 to 1:6,500. In addition this env sequence demonstrated lytic activity in Cr51 release assays (peptide-specific lysis 46%) at a 20:1 E/T ratio, which progressively decreased in a dose-dependent fashion. Similar results were obtained with an HLA-A2-restricted HIV-2 gag-specific peptide sequence.
Conclusions: Such studies that map non-clade B and broadly cross-reactive CTL epitopes across diverse HIV strains will be important in the eventual goal of developing a prophylactic vaccine against HIV-1 and HIV-2.
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