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Infection and Immunity, April 2004, p. 2014-2021, Vol. 72, No. 4
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.4.2014-2021.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Induction of Protective Cellular Immunity against Mycobacterium tuberculosis by Recombinant Attenuated Self-Destructing Listeria monocytogenes Strains Harboring Eukaryotic Expression Plasmids for Antigen 85 Complex and MPB/MPT51

Department of Microbiology and Immunology,¹ Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu,² Clinical Research Center, National Kinki-Chuo Hospital for Chest Diseases, Osaka,³ Department of Developmental and Reconstructive Medicine, Division of Microbiology and Oral Infection, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan⁴

Received 29 October 2003/ Returned for modification 16 December 2003/ Accepted 7 January 2004

We report here the induction of specific protective cellular immunity against Mycobacterium tuberculosis by the employment of vaccination with recombinant attenuated Listeria monocytogenes strains. We constructed self-destructing attenuated L. monocytogenes 2 strains carrying eukaryotic expression plasmids for the antigen 85 complex (Ag85A and Ag85B) and for MPB/MPT51 (mycobacterial protein secreted by M. bovis BCG/mycobacterial protein secreted by M. tuberculosis) molecules. Infection of these recombinant bacteria allowed expression of the genes in the J774A.1 murine macrophage cell line. Intraperitoneal vaccination of C57BL/6 mice with these recombinant bacteria was capable of inducing purified protein derivative-specific cellular immune responses, such as foot pad reactions, proliferative responses of splenocytes, and gamma interferon production from splenocytes, suggesting the efficacy of vaccination against mycobacterial infection by use of these recombinant L. monocytogenes strains. Furthermore, intravenous vaccination with recombinant bacteria carrying expression plasmids for Ag85A, Ag85B, or MPB/MPT51 in BALB/c mice elicited significant protective responses, comparable to those evoked by a live Mycobacterium bovis BCG vaccine. Notably, this is the first report to show that MPB/MPT51 is a major protective antigen in addition to Ag85A and Ag85B, which have been reported to be major mycobacterial protective antigens.

Editor: S. H. E. Kaufmann

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