Evaluation of Immunogenicity and Protective Efficacy Elicited by Mycobacterium bovis BCG Overexpressing Ag85A Protein against Mycobacterium tuberculosis Aerosol Infection

Front Cell Infect Microbiol. 2016 Jan 28:6:3. doi: 10.3389/fcimb.2016.00003. eCollection 2016.

Abstract

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is currently the only vaccine available for preventing tuberculosis (TB), however, BCG has varying success in preventing pulmonary TB. In this study, a recombinant BCG (rBCG::Ag85A) strain overexpressing the immunodominant Ag85A antigen was constructed, and its immunogenicity and protective efficacy were evaluated. Our results indicated that the Ag85A protein was successfully overexpressed in rBCG::Ag85A, and the Ag85A peptide-MHC complexes on draining lymph node dendritic cells of C57BL/6 mice infected with rBCG::Ag85A were detectable 4 h post-infection. The C57BL/6 mice infected with this strain had stronger antigen-specific interferon-gamma (IFN-γ) responses and higher antibody titers than those immunized with BCG, and the protective experiments showed that rBCG::Ag85A can enhance protection against Mycobacterium tuberculosis (M. tuberculosis) H37Rv infection compared to the BCG vaccine alone. Our results demonstrate the potential of rBCG::Ag85A as a candidate vaccine against TB.

Keywords: Ag85A; Mycobacterium tuberculosis; immunogenicity; protective efficacy; recombinant BCG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / genetics
  • Acyltransferases / immunology*
  • Animals
  • Antibodies, Bacterial / immunology*
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology*
  • BCG Vaccine / immunology*
  • Bacterial Load / immunology
  • Dendritic Cells / immunology
  • Female
  • Interferon-gamma / immunology
  • Lung / microbiology
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium bovis / immunology*
  • Mycobacterium tuberculosis / immunology*
  • Recombinant Proteins / immunology
  • Spleen / microbiology
  • Th1 Cells / immunology
  • Tuberculosis / immunology*
  • Tuberculosis / prevention & control
  • Vaccination
  • Vaccines, Synthetic / immunology

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • BCG Vaccine
  • Recombinant Proteins
  • Vaccines, Synthetic
  • Interferon-gamma
  • Acyltransferases
  • antigen 85A, Mycobacterium tuberculosis