HIV-1 Subtype C Mosaic Gag Expressed by BCG and MVA Elicits Persistent Effector T Cell Responses in a Prime-Boost Regimen in Mice

PLoS One. 2016 Jul 18;11(7):e0159141. doi: 10.1371/journal.pone.0159141. eCollection 2016.

Abstract

Over 90% of HIV/AIDS positive individuals in sub-Saharan Africa are infected with highly heterogeneous HIV-1 subtype C (HIV-1C) viruses. One of the best ways to reduce the burden of this disease is the development of an affordable and effective prophylactic vaccine. Mosaic immunogens are computationally designed to overcome the hurdle of HIV diversity by maximizing the expression of potential T cell epitopes. Mycobacterium bovis BCG ΔpanCD auxotroph and modified vaccinia Ankara (MVA) vaccines expressing HIV-1C mosaic Gag (GagM) were tested in a prime-boost regimen to demonstrate immunogenicity in a mouse study. The BCG-GagM vaccine was stable and persisted 11.5 weeks post vaccination in BALB/c mice. Priming with BCG-GagM and boosting with MVA-GagM elicited higher Gag-specific IFN-γ ELISPOT responses than the BCG-GagM only and MVA-GagM only homologous vaccination regimens. The heterologous vaccination also generated a more balanced and persistent CD4+ and CD8+ T cell Gag-specific IFN-γ ELISPOT response with a predominant effector memory phenotype. A Th1 bias was induced by the vaccines as determined by the predominant secretion of IFN-γ, TNF-α, and IL-2. This study shows that a low dose of MVA (104 pfu) can effectively boost a BCG prime expressing the same mosaic immunogen, generating strong, cellular immune responses against Gag in mice. Our data warrants further evaluation in non-human primates. A low dose vaccine would be an advantage in the resource limited countries of sub-Saharan Africa and India (where the predominating virus is HIV-1 subtype C).

MeSH terms

  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology
  • AIDS Vaccines / therapeutic use*
  • Animals
  • BCG Vaccine / genetics
  • BCG Vaccine / immunology
  • BCG Vaccine / therapeutic use*
  • Female
  • HIV Infections / immunology
  • HIV Infections / prevention & control*
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Humans
  • Interferon-gamma / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mycobacterium bovis / genetics
  • Mycobacterium bovis / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / virology
  • Vaccination
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Vaccines, Synthetic / therapeutic use
  • Vaccinia virus / genetics
  • Vaccinia virus / immunology
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology
  • Viral Vaccines / therapeutic use*
  • gag Gene Products, Human Immunodeficiency Virus / genetics
  • gag Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • AIDS Vaccines
  • BCG Vaccine
  • Vaccines, Synthetic
  • Viral Vaccines
  • gag Gene Products, Human Immunodeficiency Virus
  • Interferon-gamma

Grants and funding

This work is also based upon research supported by the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation. Tsungai Jongwe received bursaries from the Schlumberger Foundation, the Oppenheimer Memorial Trust and the Poliomyelitis Research Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.