Broad HIV epitope specificity and viral inhibition induced by multigenic HIV-1 adenovirus subtype 35 vector vaccine in healthy uninfected adults

PLoS One. 2014 Mar 7;9(3):e90378. doi: 10.1371/journal.pone.0090378. eCollection 2014.

Abstract

A correlation between in vivo and in vitro virus control mediated by CD8+ T-cell populations has been demonstrated by CD8 T-cell-mediated inhibition of HIV-1 and SIV replication in vitro in peripheral blood mononuclear cells (PBMCs) from infected humans and non-human primates (NHPs), respectively. Here, the breadth and specificity of T-cell responses induced following vaccination with replication-defective adenovirus serotype 35 (Ad35) vectors containing a fusion protein of Gag, reverse transcriptase (RT), Integrase (Int) and Nef (Ad35-GRIN) and Env (Ad35-ENV), derived from HIV-1 subtype A isolates, was assessed in 25 individuals. The vaccine induced responses to a median of 4 epitopes per vaccinee. We correlated the CD8 responses to conserved vs. variable regions with the ability to inhibit a panel of 7 HIV-1 isolates representing multiple clades in a virus inhibition assay (VIA). The results indicate that targeting immunodominant responses to highly conserved regions of the HIV-1 proteome may result in an increased ability to inhibit multiple clades of HIV-1 in vitro. The data further validate the use of the VIA to screen and select future HIV vaccine candidates. Moreover, our data suggest that future T cell-focused vaccine design should aim to induce immunodominant responses to highly conserved regions of the virus.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • AIDS Vaccines / immunology*
  • AIDS Vaccines / therapeutic use
  • Adenoviridae / immunology*
  • Adolescent
  • Adult
  • Double-Blind Method
  • Epitopes / immunology*
  • Female
  • HIV Infections / immunology
  • HIV Infections / prevention & control
  • HIV-1 / immunology*
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Young Adult

Substances

  • AIDS Vaccines
  • Epitopes

Grants and funding

This study was funded by the International AIDS Vaccine Initiative and its donors, including the generous support of the American people through the United States Agency for International Development (USAID; USAID Cooperative Agreement Number GPO-A-00-06-00006-00). The contents of this manuscript are the responsibility of IAVI and do not necessarily reflect the views of USAID or the US government. The following organizations/institutions played a direct role in study design, data collection and analysis, decision to publish, and preparation of this manuscript: International AIDS Vaccine Initiative (IAVI), IAVI Human Immunology Laboratory, Imperial College and the University of Rochester School of Medicine & Dentistry, Rochester.