title: Vaccine-induced gag-specific T cells are associated with reduced viremia after HIV-1 infection.
abstract: The contribution of host T-cell immunity and HLA class I alleles to the control of human immunodeficiency virus (HIV-1) replication in natural infection is widely recognized. We assessed whether vaccine-induced T-cell immunity, or expression of certain HLA alleles, impacted HIV-1 control after infection in the Step MRKAd5/HIV-1 gag/pol/nef study. Vaccine-induced T cells were associated with reduced plasma viremia, with subjects targeting ≥3 gag peptides presenting with half-log lower mean viral loads than subjects without Gag responses. This effect was stronger in participants infected proximal to vaccination and was independent of our observed association of HLA-B*27, -B*57 and -B*58:01 alleles with lower HIV-1 viremia. These findings support the ability of vaccine-induced T-cell responses to influence postinfection outcome and provide a rationale for the generation of T-cell responses by vaccination to reduce viremia if protection from acquisition is not achieved. Clinical trials identifier: NCT00095576.
authors.affiliation: Vaccine and Infectious Disease Division and the HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center.
authors.forename: Holly
authors.initials: H
authors.lastname: Janes
authors.forename: David P
authors.initials: DP
authors.lastname: Friedrich
authors.forename: Amy
authors.initials: A
authors.lastname: Krambrink
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Smith
authors.forename: Esper G
authors.initials: EG
authors.lastname: Kallas
authors.forename: Helen
authors.initials: H
authors.lastname: Horton
authors.forename: Danilo R
authors.initials: DR
authors.lastname: Casimiro
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Geraghty
authors.forename: Peter B
authors.initials: PB
authors.lastname: Gilbert
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000328:Adult; D000483:Alleles; D004311:Double-Blind Method; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load / Q000276:immunology; D014766:Viremia / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D012367:RNA, Viral; D054301:gag Gene Products, Human Immunodeficiency Virus
keywords: Gag-specific T cells; HIV-1 vaccine; HLA class I alleles; Step study