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207 Designing an HIV World Clade Vaccine Using a Bioinformatics-Based Approach
H. Sbai*1, J. Frost1, A. Bosma1, G. Skowron3, K. Mayer4, W. Martin2, and A. S. De Groot1,2
1TB/HIV Res. Lab, Brown Univ., Providence, RI, USA; 2EpiVax, Inc., Providence, RI, USA; 3 Roger Williams Hosp., Providence, RI, USA; and 4 Brown AIDS Program, Providence, RI, USA
Objective: We are using a bioinformatics approach to design a "world clade" HIV vaccine that will induce T-cell responses against the broadest range of HIV isolates possible.
Methods: T-cell epitopes were selected for their conservation across HIV-1 isolates by Conservatrix and screened for potential MHC class I binding using EpiMatrix. Peptides were selected based on their restriction by the following MHC-I alleles: A2, A11, A3, or B7. T-cell responses of PBMCs derived from healthy HIV-infected individuals were measured using ELIspot assay.
Results: ELIspot results obtained from PBMC derived from HIV-infected patients indicated that 60% of the B7 peptides, 40% of the A11 peptides, 24% of the A2 peptides, and 60% of the A3 peptides elicit IFN-g secretion. These novel T epitopes are conserved in as many as 1238 HIV-1 strains, including strains from Africa, Asia, and the Americas. These epitopes have been cloned into DNA vaccine constructs and expressed in vitro.
Conclusions: Conservatrix and EpiMatrix provide a rapid and accurate means of MHC ligand/epitope selection for HIV vaccine design. We have identified several novel, highly conserved HIV immunogenic peptides from the sequences of available HIV-1 isolates. Additional CTL assays and CD4 depletion studies are required to confirm the MHC Class I-restriction of these epitopes.
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