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

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. © 2001 Wiley‐Liss, Inc.

Direct Ex Vivo Analyses of HLA-DR1 Transgenic Mice Reveal an Exceptionally Broad Pattern of Immunodominance in the Primary HLA-DR1-Restricted CD4 T-Cell Response to Influenza Virus Hemagglutinin

“…The identification of immunodominant influenza virus-derived peptides presented by a common human MHC class II molecule as we describe in this report will be extremely valuable at several levels for present efforts in vaccine design and in the study of the natural infection of humans with influenza virus. First, there is a great deal of interest in peptide-based vaccines as stable reagents to induce protection against pathogenic organisms such as influenza virus (10,17,33,39,40,76,83). One of the main challenges in the design of peptide-based vaccines is the extent of polymorphism in the human MHC, which in turn influences the degree of coverage that any set of peptides will have in the targeted population.…”

Favorable and Unfavorable HLA Class I Alleles and Haplotypes in Zambians Predominantly Infected with Clade C Human Immunodeficiency Virus Type 1

“…Such evolution may gradually alter the genetic composition and responsiveness of populations in greatest need of effective HIV-AIDS vaccines. Consensus through continuous monitoring of disease progression in diverse ethnic groups carefully characterized for their HLA profiles should improve the design of epitope-rich vaccine constructs (9,37,48) and help predict their relative population coverage (58,60). Tables 4 and 5.…”

“…The same favorable HLA alleles were overrepresented in canarypox-HIV vaccine recipients with repeatedly detected CTL responses to certain viral proteins (32). These findings imply that HLA typing data may be useful in predicting the relative population coverage (58,60) of epitoperich HIV vaccine constructs (9,37,47).…”

Effective antigen cross-presentation by prostate cancer patients' dendritic cells: implications for prostate cancer immunotherapy

“…This is particularly in issue in prostate cancer, where African Americans are over-represented, but in whom there is a o20% incidence of the HLA A2.1 allele. 38 We have shown that we are able to cross-present apoptotic material derived from whole prostate tumor cells to DCs for the activation of autologous T cells. This offers the possibility of activating a broad spectrum of potentially tumor reactive T cells, allowing immunization without prior knowledge of specific tumor antigens, yet while presenting any one antigen on multiple HLA molecules.…”