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.
Dawson
D V
DV
Department of Epidemiology and Biostatistics, Case Western Reserve University, MetroHealth Medical Center, Cleveland, Ohio 44109-1998, USA. dvd2@po.cwru.edu
Ozgur
M
M
Sari
K
K
Ghanayem
M
M
Kostyu
D D
DD
D000465:Algorithms; D000483:Alleles; D015195:Drug Design; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005455:Fluorescent Antibody Technique; D005787:Gene Frequency; D005805:Genes, MHC Class I / Q000235:genetics*; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D006801:Humans; D010641:Phenotype; D011110:Polymorphism, Genetic; D011485:Protein Binding; D044469:Racial Groups / Q000235:genetics*; D014614:Vaccines, Synthetic
D000939:Epitopes; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D014614:Vaccines, Synthetic