Induction and maintenance of bi-functional (IFN-γ + IL-2+ and IL-2+ TNF-α+) T cell responses by DNA prime MVA boosted subtype C prophylactic vaccine tested in a Phase I trial in India

PLoS One. 2019 Mar 28;14(3):e0213911. doi: 10.1371/journal.pone.0213911. eCollection 2019.

Abstract

Effective vaccine design relies on accurate knowledge of protection against a pathogen, so as to be able to induce relevant and effective protective responses against it. An ideal Human Immunodeficiency virus (HIV) vaccine should induce humoral as well as cellular immune responses to prevent initial infection of host cells or limit early events of viral dissemination. A Phase I HIV-1 prophylactic vaccine trial sponsored by the International AIDS Vaccine Initiative (IAVI) was conducted in India in 2009.The trial tested a HIV-1 subtype C vaccine in a prime-boost regimen, comprising of a DNA prime (ADVAX) and Modified Vaccine Ankara (MVA) (TBC-M4) boost. The trial reported that the vaccine regimen was safe, well tolerated, and resulted in enhancement of HIV-specific immune responses. However, preliminary immunological studies were limited to vaccine-induced IFN-γ responses against the Env and Gag peptides. The present study is a retrospective study to characterize in detail the nature of the vaccine-induced cell mediated immune responses among volunteers, using Peripheral Blood Mononuclear Cells (PBMC) that were archived during the trial. ELISpot was used to measure IFN-γ responses and polyfunctional T cells were analyzed by intracellular multicolor flow cytometry. It was observed that DNA priming and MVA boosting induced Env and Gag specific bi-functional and multi-functional CD4+ and CD8+ T cells expressing IFN-γ, TNF-α and IL-2. The heterologous prime-boost regimen appeared to be slightly superior to the homologous prime-boost regimen in inducing favorable cell mediated immune responses. These results suggest that an in-depth analysis of vaccine-induced cellular immune response can aid in the identification of correlates of an effective immunogenic response, and inform future design of HIV vaccines.

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 / administration & dosage*
  • AIDS Vaccines / immunology
  • Female
  • HIV Infections / immunology
  • HIV Infections / prevention & control
  • HIV-1* / immunology
  • Healthy Volunteers
  • Humans
  • Immunity, Cellular
  • Immunization, Secondary
  • India
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Male
  • T-Lymphocytes / immunology*
  • Tumor Necrosis Factor-alpha / metabolism
  • Vaccines, DNA / administration & dosage
  • Viral Vaccines / administration & dosage

Substances

  • AIDS Vaccines
  • IL2 protein, human
  • Interleukin-2
  • MVA vaccine
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Vaccines, DNA
  • Viral Vaccines
  • Interferon-gamma

Grants and funding

The vaccine trial and the present study were supported and coordinated by the International AIDS Vaccine Initiative (IAVI). IAVI’s work is made possible by generous support from many donors including the Bill & Melinda Gates Foundation, the Ministry of Foreign Affairs of Denmark, Irish Aid, the Ministry of Finance of Japan in partnership with The World Bank, the Ministry of Foreign Affairs of the Netherlands, the Norwegian Agency for Development Cooperation (NORAD), the United Kingdom Department for International Development (DFID), and the USAID. The full list of IAVI donors is available at www.iavi.org. This study was made possible by the generous support of the American people through funding from United States Agency for International Development (USAID; Grant ID: 2233). The contents are the responsibility of the authors does not necessarily reflect the views of USAID or the United States Government.