title: 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.
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.
authors.affiliation: Department of Immunology, Max-Planck-Institute for Infection Biology, Berlin, Germany.
authors.forename: Leander
authors.initials: L
authors.lastname: Grode
authors.forename: Mischo
authors.initials: M
authors.lastname: Kursar
authors.forename: Joachim
authors.initials: J
authors.lastname: Fensterle
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hess
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001428:Bacterial Vaccines / Q000276:immunology*; D004269:DNA, Bacterial / Q000235:genetics; D005822:Genetic Vectors; D007700:Kinetics; D008074:Lipoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology / Q000517:prevention & control; D008212:Lymphocyte Depletion; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000235:genetics*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: C078516:60 kDa protein, Listeria monocytogenes; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D004269:DNA, Bacterial; D008074:Lipoproteins; D008565:Membrane Proteins; D019444:Vaccines, DNA