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Host Genetic Determinants of T Cell Responses to the MRKAd5 HIV-1 gag/pol/nef Vaccine in the Step Trial.

Fellay, Jacques and Frahm, Nicole and Shianna, Kevin V and Cirulli, Elizabeth T and Casimiro, Danilo R and Robertson, Michael N and Haynes, Barton F and Geraghty, Daniel E and McElrath, M Juliana and Goldstein, David B (2011) Host Genetic Determinants of T Cell Responses to the MRKAd5 HIV-1 gag/pol/nef Vaccine in the Step Trial. The Journal of infectious diseases, 203 (6). pp. 773-779. ISSN 1537-6613

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Article URL: http://jid.oxfordjournals.org/content/203/6/773.lo...

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.

Item Type: Article
Additional Information: This is a pre-copy-editing, author-produced PDF of an article accepted for publication in The Journal of Infectious Diseases following peer review. The definitive publisher-authenticated version "Host Genetic Determinants of T Cell Responses to the MRKAd5 HIV-1 gag/pol/nef Vaccine in the Step Trial" is available online at:http://jid.oxfordjournals.org/content/203/6/773.long
DOI: 10.1093/infdis/jiq125
PubMed ID: 21278214
NIHMSID: NIHMS278547
PMCID: PMC3071133
Grant Numbers: U19 AI067854-05
Keywords or MeSH Headings: 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 Infections/prevention & control HIV-1/genetics* HIV-1/immunology Humans Male Middle Aged Polymorphism, Genetic Regression Analysis T-Lymphocytes/immunology* Young Adult
Subjects: Cellular and Organismal Processes > Immune Response > Cellular immunity
Cellular and Organismal Processes > Immune Response > Immunogenetics
Depositing User: Library Staff
Date Deposited: 07 Mar 2011 23:06
Last Modified: 16 Sep 2015 07:17
URI: http://authors.fhcrc.org/id/eprint/484

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