AIDSWEEKLY Plus, Monday, 23 June 1997
Daniel J. DeNoon, Senior Editor
A new research tool has led to the discovery of seven new HIV epitopes likely to induce anti-HIV cytotoxic lymphocyte (CTL) responses.
The finding is a first step in the development of a vaccine capable of inducing anti-HIV CTL responses to nearly all types of HIV-1 in nearly all types of people.
Evidence from long-term non-progressors and from individuals resistant to HIV suggests that cellular immune responses to HIV - particularly HIV specific CD8(+) CTLs - are the most important correlates of immunity to the virus.
The new tool, EpiMatrix/HIV, is a computer-driven algorithm that went online in November 1996. Given a number of primary HIV protein sequences, it predicts the sequences most likely to bind to major histocompatibility complex (MHC) molecules.
Brown University researcher James Schafer and colleagues used EpiMatrix to predict which HIV-1 ligands are most likely to bind to the human leukocyte antigen (HLA) alleles HLA-A2 and HLA-B27. Those ligands predicted by EpiMatrix to be more than 50 percent likely to bind were screened against the Los Alamos National Laboratory HIV-1 Sequence Database for conservation among HIV strains.
Schafer et al. then used in vitro binding assays to evaluate those ligands with predicted binding and high-level conservation (10 putative HLA-A2 ligands and 19 putative HLA- B27 ligands).
They reported their findings in a poster presentation to the 9th Annual Meeting of the National Cooperative Vaccine Development Groups for AIDS (NCVDG), held May 4-7, 1997, in Bethesda, Maryland.
"Two previously unknown putative A2 ligands, as well as a published A2 ligand (30 percent of the A2 ligands tested), were able to increase the stabilization of HLA-A2 by greater than 50 percent over zero peptide controls," Schafer et al. wrote in their poster abstract. "Five previously unknown putative B27 ligands, as well as a published B27 ligand (32 percent of the B27 ligands tested), were able to increase the stabilization of HLA-A2 by greater than 50 percent over zero peptide controls."
The researchers proposed that the newly discovered ligands be included as candidate antigens in the design of a new international HIV-1 vaccine.
EpiMatrix was developed at Brown University and implemented for the Internet by AVX Design Inc., Providence, Rhode Island. Located on the Internet at http://www.epimatrix.com/hiv, it is both an Internet website and an online tool.
The site is linked to the Los Alamos database of HIV sequences and can thus access all HIV sequences in the public domain. These sequences include more than 400 separate HIV-1 proteins from all of the viral clades.
The EpiMatrix algorithm yields a score for each HIV-1 peptide. The peptides are scored in a 10-mer frame. Scoring is a quantitative estimate of the likelihood (relative to other sequences) that a peptide will bind to a given human leukocyte antigen (HLA) molecule. Matrices for all major (more than 10 percent population prevalence) MHC alleles representing world populations are included in the algorithm.
There are two scoring methods: single-allele predictions score for specific HLA alleles and clustered predictions score peptides by the prevalence of MHC alleles in selected populations.
EpiMatrix/HIV is available at no charge thanks to funding from the National Institute of Allergy and Infectious Diseases Division of AIDS.
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