Host genetic determinants of T cell responses to the MRKAd5 HIV-1 gag/pol/nef vaccine in the step trial.

Journal Article (Journal Article;Multicenter Study)

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.

Full Text

Duke Authors

Cited Authors

  • Fellay, J; Frahm, N; Shianna, KV; Cirulli, ET; Casimiro, DR; Robertson, MN; Haynes, BF; Geraghty, DE; McElrath, MJ; Goldstein, DB; National Institute of Allergy and Infectious Diseases Center for HIV/AIDS Vaccine Immunology, ; NIAID HIV Vaccine Trials Network,

Published Date

  • March 15, 2011

Published In

Volume / Issue

  • 203 / 6

Start / End Page

  • 773 - 779

PubMed ID

  • 21278214

Pubmed Central ID

  • PMC3071133

Electronic International Standard Serial Number (EISSN)

  • 1537-6613

Digital Object Identifier (DOI)

  • 10.1093/infdis/jiq125


  • eng

Conference Location

  • United States