Increased B and T Cell Responses in M. bovis Bacille Calmette-Guérin Vaccinated Pigs Co-Immunized with Plasmid DNA Encoding a Prototype Tuberculosis Antigen

PLoS One. 2015 Jul 14;10(7):e0132288. doi: 10.1371/journal.pone.0132288. eCollection 2015.

Abstract

The only tuberculosis vaccine currently available, bacille Calmette-Guérin (BCG) is a poor inducer of CD8(+) T cells, which are particularly important for the control of latent tuberculosis and protection against reactivation. As the induction of strong CD8(+) T cell responses is a hallmark of DNA vaccines, a combination of BCG with plasmid DNA encoding a prototype TB antigen (Ag85A) was tested. As an alternative animal model, pigs were primed with BCG mixed with empty vector or codon-optimized pAg85A by the intradermal route and boosted with plasmid delivered by intramuscular electroporation. Control pigs received unformulated BCG. The BCG-pAg85A combination stimulated robust and sustained Ag85A specific antibody, lymphoproliferative, IL-6, IL-10 and IFN-γ responses. IgG1/IgG2 antibody isotype ratio reflected the Th1 helper type biased response. T lymphocyte responses against purified protein derivative of tuberculin (PPD) were induced in all (BCG) vaccinated animals, but responses were much stronger in BCG-pAg85A vaccinated pigs. Finally, Ag85A-specific IFN-γ producing CD8(+) T cells were detected by intracellular cytokine staining and a synthetic peptide, spanning Ag85A131-150 and encompassing two regions with strong predicted SLA-1*0401/SLA-1*0801 binding affinity, was promiscuously recognized by 6/6 animals vaccinated with the BCG-pAg85A combination. Our study provides a proof of concept in a large mammalian species, for a new Th1 and CD8(+) targeting tuberculosis vaccine, based on BCG-plasmid DNA co-administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Antibodies, Bacterial / immunology
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology*
  • B-Lymphocytes / immunology*
  • BCG Vaccine / genetics
  • BCG Vaccine / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Epitopes, T-Lymphocyte / immunology
  • Immunity, Cellular
  • Immunity, Humoral
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / metabolism
  • Mycobacterium bovis / immunology*
  • Plasmids / genetics
  • Species Specificity
  • Swine
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Time Factors
  • Vaccination*
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • BCG Vaccine
  • Epitopes, T-Lymphocyte
  • Vaccines, DNA
  • Interferon-gamma

Grants and funding

Gaëlle Vandermeulen is a postdoctoral researcher of the Fonds de la Recherche Scientifique-FNRS. This work was partially supported by FWO-Vlaanderen, EDCTP (MVA85A IP.2007.32080.002), EU (FP7 NEWTBVAC) and TRANSVAC –TNA1204-6.