title: 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.
abstract: 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 Delta 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.
authors.affiliation: Department of Microbiology and Immunology, Hamamatsu University School of Medicine, Handayama, Hamamatsu, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Miki
authors.forename: Toshi
authors.initials: T
authors.lastname: Nagata
authors.forename: Takao
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yeung-Hyen
authors.initials: YH
authors.lastname: Kim
authors.forename: Masato
authors.initials: M
authors.lastname: Uchijima
authors.forename: Naoya
authors.initials: N
authors.lastname: Ohara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakamura
authors.forename: Masaji
authors.initials: M
authors.lastname: Okada
authors.forename: Yukio
authors.initials: Y
authors.lastname: Koide
mesh_terms: D000217:Acyltransferases / Q000235:genetics; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D002417:Cattle; D002460:Cell Line; D007111:Immunity, Cellular; D007114:Immunization; D008089:Listeria monocytogenes / Q000235:genetics*; D008264:Macrophages; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010957:Plasmids / Q000235:genetics; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000517:prevention & control; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C082911:MPT51 protein, Mycobacterium; D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis; C121433:antigen 85B, Mycobacterium tuberculosis