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

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.