Optimizing HIV-1-specific CD8+ T-cell Induction by Recombinant BCG in Prime-Boost Regimens With Heterologous Viral Vectors

Eur J Immunol. 2011 Dec;41(12):3542-52. doi: 10.1002/eji.201141962. Epub 2011 Oct 26.

Abstract

The desire to induce HIV-1-specific responses soon after birth to prevent breast milk transmission of HIV-1 led us to propose a vaccine regimen which primes HIV-1-specific T cells using a recombinant Mycobacterium bovis bacillus Calmette-Guérin (rBCG) vaccine. Because attenuated live bacterial vaccines are typically not sufficiently immunogenic as stand-alone vaccines, rBCG-primed T cells will likely require boost immunization(s). Here, we compared modified Danish (AERAS-401) and Pasteur lysine auxotroph (222) strains of BCG expressing the immunogen HIVA for their potency to prime HIV-1-specific responses in adult BALB/c mice and examined four heterologous boosting HIVA vaccines for their immunogenic synergy. We found that both BCG.HIVA(401) and BCG.HIVA(222) primed HIV-1-specific CD8(+) T-cell-mediated responses. The strongest boosts were delivered by human adenovirus-vectored HAdV5.HIVA and sheep atadenovirus-vectored OAdV7.HIVA vaccines, followed by poxvirus MVA.HIVA; the weakest was plasmid pTH.HIVA DNA. The prime-boost regimens induced T cells capable of efficient in vivo killing of sensitized target cells. We also observed that the BCG.HIVA(401) and BCG.HIVA(222) vaccines have broadly similar immunologic properties, but display a number of differences mainly detected through distinct profiles of soluble intercellular signaling molecules produced by immune splenocytes in response to both HIV-1- and BCG-specific stimuli. These results encourage further development of the rBCG prime-boost regimen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / immunology*
  • Adenoviridae / immunology
  • Animals
  • Atadenovirus / immunology
  • BCG Vaccine / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Genetic Vectors / immunology
  • HIV Infections / immunology
  • HIV-1 / immunology*
  • Immunization / methods
  • Immunization, Secondary / methods
  • Mice
  • Mice, Inbred BALB C
  • Sheep
  • Signal Transduction / immunology
  • Vaccination / methods
  • Vaccines, Synthetic / immunology
  • Viral Vaccines / immunology*

Substances

  • AIDS Vaccines
  • BCG Vaccine
  • Epitopes, T-Lymphocyte
  • Vaccines, Synthetic
  • Viral Vaccines