Important note: Information in this article was accurate in March 1999. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, March 1, 1999
Daniel J. DeNoon, Senior Editor
It is widely believed that the most effective AIDS vaccine should capable of eliciting HIV specific cytotoxic lymphocyte (CTL) responses. Unfortunately, the genetic diversity of human leukocyte antigen (HLA) alleles means that an epitope that turns on CTL for one person does nothing in another.
Thus researchers are faced with the tedious task of finding the HIV CTL epitopes for each MHC type.
"HIV is a language. It's a lexicon of words, and there are many dialects," said Ann De Groot of Brown University, Providence, Rhode Island. "We are looking for the words that turn on the immune system."
To this end, three teams of scientists are combing HIV for CTL epitopes. Their method is laborious: first they select HLA alleles and HIV protein sequences, and then they use the EpiMatrix algorithm to evaluate and select possible CTL epitopes. The identified epitopes are then tested in major histocompatibility complex (MHC) binding assays. The final steps in the process would be evaluation of the epitopes for immunogenicity and inclusion in a candidate vaccine.
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.
The program 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:
EpiMatrix/HIV is available at no charge thanks to funding from the National Institute of Allergy and Infectious Diseases Division of AIDS.
"The algorithm was highly effective in finding conserved epitopes that bind MHC," De Groot said. "We think it could be used to improve existing vaccines."
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