Induction of circulating T follicular helper cells and regulatory T cells correlating with HIV-1 gp120 variable loop antibodies by a subtype C prophylactic vaccine tested in a Phase I trial in India

PLoS One. 2018 Aug 29;13(8):e0203037. doi: 10.1371/journal.pone.0203037. eCollection 2018.

Abstract

A Phase I HIV-1 vaccine trial sponsored by the International AIDS Vaccine Initiative (IAVI) was conducted in India in 2009 to test a subtype C prophylactic vaccine in a prime-boost regimen comprising of a DNA prime (ADVAX) and MVA (TBC-M4) boost. The trial demonstrated that the regimen was safe and well tolerated and resulted in enhancement of HIV-specific immune responses. Preliminary observations on vaccine-induced immune responses were limited to analysis of neutralizing antibodies and IFN-γ ELISPOT response. The present study involves a more detailed analysis of the nature of the vaccine-induced humoral immune response using specimens that were archived from the volunteers at the time of the trial. Interestingly, we found vaccine induced production of V1/V2 and V3 region-specific antibodies in a significant proportion of vaccinees. Variable region antibody levels correlated directly with the frequency of circulating T follicular helper cells (Tfh) and regulatory T cells (Treg). Our findings provide encouraging evidence to demonstrate the immunogenicity of the tested vaccine. Better insights into vaccine-induced immune responses can aid in informing future design of a successfulHIV-1 vaccine.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • 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*
  • B-Lymphocytes / immunology
  • Female
  • HIV Antibodies / blood*
  • HIV Envelope Protein gp120 / immunology*
  • HIV-1
  • Humans
  • Immunity, Humoral
  • India
  • Male
  • Peptide Fragments / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Vaccination

Substances

  • AIDS Vaccines
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • HIV envelope protein gp120 (135-148)
  • HIV envelope protein gp120 (305-321)
  • Peptide Fragments
  • gp120 protein, Human immunodeficiency virus 1