Cell-Mediated Immunity Induced by RecombinantMycobacterium bovisBacille Calmette-Guérin Strains Against an Intracellular Bacterial Pathogen: Importance of Antigen Secretion or Membrane-Targeted Antigen Display as Lipoprotein for Vaccine Efficacy | Zendy

Leander Grode | Zendy; Mischo Kursar | Zendy; Joachim Fensterle | Zendy; Stefan H. E. Kaufmann | Zendy; Jürgen Hess | Zendy

Open Access

Cell-Mediated Immunity Induced by RecombinantMycobacterium bovisBacille Calmette-Guérin Strains Against an Intracellular Bacterial Pathogen: Importance of Antigen Secretion or Membrane-Targeted Antigen Display as Lipoprotein for Vaccine Efficacy

Author(s) -

Leander Grode,

Mischo Kursar,

Joachim Fensterle,

Stefan H. E. Kaufmann,

Jürgen Hess

Publication year - 2002

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.168.4.1869

Subject(s) - microbiology and biotechnology , listeria monocytogenes , biology , mycobacterium bovis , antigen , immunity , pathogen , secretion , t cell , mycobacterium tuberculosis , intracellular parasite , cd8 , vaccination , virology , immunology , tuberculosis , immune system , bacteria , biochemistry , medicine , genetics , pathology

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.

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