These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Mapping cross-clade HIV-1 vaccine epitopes using a bioinformatics approach.
    Author: De Groot AS, Jesdale B, Martin W, Saint Aubin C, Sbai H, Bosma A, Lieberman J, Skowron G, Mansourati F, Mayer KH.
    Journal: Vaccine; 2003 Oct 01; 21(27-30):4486-504. PubMed ID: 14505932.
    Abstract:
    UNLABELLED: The genomic variability of HIV viruses circulating in different regions of the world has impeded the development of a globally relevant HIV vaccine. Broadly conserved HIV-1 cytotoxic T cell (CTL) epitopes were identified by screening protein sequences in the Los Alamos National Laboratory (LANL) HIV sequence database with a sequence parsing and matching algorithm (Conservatrix). Putative HIV-1 CTL epitopes were selected from this list using the epitope prediction tool EpiMatrix. METHODS: One hundred peptides representing putative HLA A*0201, HLA A*1101, HLA A*0301, and HLA B*07 ligands conserved in many isolates of HIV-1 were synthesized. Seventy-five HLA A*0201, HLA A*1101 and HLA B*07 peptides were incubated with transport associated protein (TAP)-deficient T2 cells transfected with the gene for the corresponding human HLA molecule (HLA A*0201, HLA A*1101, and HLA B*07). Binding and stabilization of peptide-HLA complexes on the surface of the T2 cells was measured by FACS. T cell responses to the entire set of 100 peptides (HLA A*0201, HLA A*1101, HLA A*0301, and HLA B*07) were measured in ELIspot assays using PBMC from healthy HIV-1 infected subjects who possessed a matching HLA allele. RESULTS: Fifty-seven (76%) of the 75 peptides tested in binding studies, including all (three of three) of the control (published) ligands bound to the T2 cells expressing the corresponding MHC molecule. Forty-three of the 100 peptides (43%) including all (four of four) of the control (published) epitopes tested in ELIspot assays stimulated gamma-interferon release. Thirty-one of these 43 epitopes are novel, highly conserved HIV-1 epitopes. EpiMatrix predicted and assays confirmed MHC-restriction by more than one HLA allele for nine of the 43 novel epitopes; of these epitopes five were recognized in the context of MHC "supertypes" and four were promiscuous epitopes. CONCLUSION: Epitopes identified using this approach were conserved in a broad range of HIV-1 sequences derived from isolates obtained in Latin America, Africa, Asia, the Pacific Islands, Europe and the US. The successful identification of cross-clade epitopes by this bioinformatics approach may accelerate the development of a globally relevant HIV-1 vaccine.
    [Abstract] [Full Text] [Related] [New Search]