Cell-mediated immunity induced by recombinant Mycobacterium bovis Bacille Calmette-Guérin strains against an intracellular bacterial pathogen: importance of antigen secretion or membrane-targeted antigen display as lipoprotein for vaccine efficacy

J Immunol. 2002 Feb 15;168(4):1869-76. doi: 10.4049/jimmunol.168.4.1869.

Abstract

Live recombinant vaccines expressing defined pathogen-derived Ags represent powerful candidates for future vaccination strategies. In this study, we report on the differential induction of protective cell-mediated immunity elicited by different recombinant Mycobacterium bovis Bacille Calmette-Guérin (BCG) strains displaying p60 Ag of Listeria monocytogenes in secreted, cytosolic, or membrane-attached form for T cell recognition. Anti-listerial protection evoked by the membrane-linked p60 lipoprotein of rBCG Mp60 and that of the p60 derivative secreted by rBCG Sp60-40 were nearly equal, whereas cytosolic p60 displayed by rBCG Np60 failed to protect mice from listeriosis. In vivo depletion of CD4 or CD8 T cell subpopulations in rBCG Mp60-vaccinated mice before listerial challenge revealed interactions of both T cell subsets in anti-listerial protection. In rBCG Sp60-40-vaccinated animals, CD4 T cells predominantly contributed to anti-listerial control as shown by the failure of anti-CD8 mAb treatment to impair the outcome of listeriosis in rBCG Sp60-40-vaccinated mice after L. monocytogenes challenge. Hence, differential Ag display by rBCG influences cell-mediated immunity, which in turn may impact vaccine efficacy due to the different requirements of CD4 or CD8 T cells for pathogen elimination.

MeSH terms

  • Animals
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology
  • Antigens, Bacterial / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • Bacterial Proteins / metabolism
  • Bacterial Vaccines / immunology*
  • DNA, Bacterial / genetics
  • Genetic Vectors
  • Kinetics
  • Lipoproteins / genetics
  • Lipoproteins / immunology
  • Lipoproteins / metabolism
  • Listeria monocytogenes / immunology*
  • Listeriosis / immunology
  • Listeriosis / prevention & control
  • Lymphocyte Depletion
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mycobacterium bovis / genetics*
  • Survival Analysis
  • T-Lymphocytes / immunology*
  • Vaccines, DNA / immunology

Substances

  • 60 kDa protein, Listeria monocytogenes
  • Antigens, Bacterial
  • Bacterial Proteins
  • Bacterial Vaccines
  • DNA, Bacterial
  • Lipoproteins
  • Membrane Proteins
  • Vaccines, DNA