title: Host genetic determinants of T cell responses to the MRKAd5 HIV-1 gag/pol/nef vaccine in the step trial.
abstract: 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.
authors.affiliation: Center for Human Genome Variation, Duke University School of Medicine, Durham, NC 27708, USA. jcf20@duke.edu
authors.forename: Jacques
authors.initials: J
authors.lastname: Fellay
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Shianna
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Cirulli
authors.forename: Danilo R
authors.initials: DR
authors.lastname: Casimiro
authors.forename: Michael N
authors.initials: MN
authors.lastname: Robertson
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Geraghty
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.forename: David B
authors.initials: DB
authors.lastname: Goldstein
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics* / Q000276:immunology; D000328:Adult; D018414:CD8-Positive T-Lymphocytes; D004797:Enzyme-Linked Immunosorbent Assay; D015683:Gene Products, gag; D015750:Genes, gag; D015754:Genes, nef; D015751:Genes, pol; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D015683:Gene Products, gag