HLA ALLELE SELECTION FOR DESIGNING PEPTIDE VACCINES

A central problem in developing vaccines against rapidly evolving viru ses such as HIV and Influenza is the mutability of their antigens. In principle; the problem can be mitigated by using peptides from conserv ed portions of viral proteins. However, because cytotoxic T lymphocyte s (CTLs), which such vaccines would stimulate, recognize pathogenic pe ptides only in association with class I products of the Major Histocom patibility Complex (MHC), and because human leukocyte antigen genes (H LA; the human MHC) are highly polymorphic, a peptide vaccine would hav e to bind a number of different HLA products. A natural question then, which is pertinent to the safety of the vaccine is, which HLA molecul es should be targeted to achieve a prespecified coverage (say 90%) of a population. Taking account of disequilibrium between linked HLA loci , we identify 3-6 class I HLA alleles, depending on ethnic group, whic h cover about 90% of the population. While this leaves large numbers o f individuals uncovered, a high level of herd immunity, and hence erad ication of the virus, can be achieved through such a vaccine.