Ramifications of HLA class I polymorphism and population genetics for vaccine development

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Abstract
HLA polymorphism can complicate the design and development of vaccines, especially those that contain a selected number of epitopes and are directed at pathogens prevalent worldwide. Because of HLA class I restricted antigen recognition and ethnic variation in HLA distribution, such vaccines may not be uniformly effective across populations. We, therefore, considered whether it is possible to assemble a panel of HLA‐A and/or HLA‐B alleles that would allow the formulation of a single vaccine for a set of Caucasian, Black, or Asian populations. In applying an algorithm to predict levels of favorable response, we identified predominant alleles in 15 representative populations. Approximately 80% of the individuals in one African Black population and five Asian populations were positive for at least one of three HLA‐A alleles. Eighty percent coverage was also theoretically possible in five Caucasian populations with only five HLA‐A alleles. Four of five Black populations analyzed also required five alleles, but the allelic combinations differed. Our findings suggest that HLA‐A alleles may be preferred targets because of the increased heterogeneity at HLA‐B, although addition of a single HLA‐B allele to a set of HLA‐A alleles improved coverage. This approach provides for the identification of combinations of alleles that represent a desired percentage of a population and that could be targeted in designing vaccines. For vaccines with known HLA‐restricted epitopes, it allows a prediction of theoretical levels of “responder” and “non‐responder” status. Finally, these results might be used in the analysis of protein sequences to identify potential CD8+ T‐cell epitopes in populations of interest. Biologic variables that may have further relevance are discussed. Genet. Epidemiol. 20:87–106, 2001.