Recombinant BCG coexpressing Ag85B, CFP10, and interleukin-12 induces multifunctional Th1 and memory T cells in mice

APMIS. 2012 Jan;120(1):72-82. doi: 10.1111/j.1600-0463.2011.02815.x. Epub 2011 Oct 6.

Abstract

Mycobacterium tuberculosis (MTB) continues to be a leading cause of human deaths due to an infectious agent. Current efforts are focused on making better TB vaccines. We describe the generation and immunological characterization of recombinant BCG (rBCG). This rBCG was generated by incorporating an expression plasmid encoding two mycobacterial antigens (Ag85B and CFP10) and human interleukin (IL)-12 into a BCG strain. Immunogenicity studies in mice showed that rBCG coexpressing Ag85B, CFP10, and IL-12 (rBCG::Ag85B-CFP10-IL-12) induces a robust immune response in mice. The rBCG vaccine promotes a T-cell response against MTB that is characterized by a high proportion of polyfunctional and memory T cells in spleen and lung. Our results showed strong immunogenicity and mycobacterial growth inhibition of rBCG::Ag85B-CFP10 plus IL-12 than that of BCG vaccine.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / genetics
  • Acyltransferases / immunology
  • Animals
  • Antibodies, Bacterial / blood
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology
  • BCG Vaccine / genetics*
  • BCG Vaccine / immunology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology
  • Base Sequence
  • Cytokines / biosynthesis
  • DNA Primers / genetics
  • Female
  • Humans
  • Immunologic Memory*
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mycobacterium bovis / genetics*
  • Mycobacterium bovis / immunology*
  • Spleen / immunology
  • T-Lymphocyte Subsets / immunology
  • Th1 Cells / immunology*
  • Tuberculosis / immunology
  • Tuberculosis / microbiology
  • Tuberculosis / prevention & control
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • BCG Vaccine
  • Bacterial Proteins
  • CFP-10 protein, Mycobacterium tuberculosis
  • Cytokines
  • DNA Primers
  • Vaccines, Synthetic
  • Interleukin-12
  • Acyltransferases
  • antigen 85B, Mycobacterium tuberculosis