Article: article from journal or magazin.
Host genetic determinants of T cell responses to the MRKAd5 HIV-1 gag/pol/nef vaccine in the step trial.
Journal of Infectious Diseases
National Institute of Allergy
Publication types: Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Understanding how human genetic variation impacts individual response to immunogens is fundamental for rational vaccine development. To explore host mechanisms involved in cellular immune responses to the MRKAd5 human immunodeficiency virus type 1 (HIV-1) gag/pol/nef vaccine tested in the Step trial, we performed a genome-wide association study of determinants of HIV-specific T cell responses, measured by interferon γ enzyme-linked immunospot assays. No human genetic variant reached genome-wide significance, but polymorphisms located in the major histocompatibility complex (MHC) region showed the strongest association with response to the HIV-1 Gag protein: HLA-B alleles known to be associated with differences in HIV-1 control were responsible for these associations. The implication of the same HLA alleles in vaccine-induced cellular immunity and in natural immune control is of relevance for vaccine design. Furthermore, our results demonstrate the importance of considering the host immunogenetic background in the analysis of immune responses to T cell vaccines.
AIDS Vaccines/genetics, AIDS Vaccines/immunology, Adult, CD8-Positive T-Lymphocytes, Enzyme-Linked Immunosorbent Assay, Gene Products, gag, Genes, gag, Genes, nef, Genes, pol, Genotype, HIV Infections/genetics, HIV Infections/immunology, HIV-1/genetics, HIV-1/immunology, Humans, Male, Middle Aged, Polymorphism, Genetic, Regression Analysis, T-Lymphocytes/immunology, Young Adult
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