title: rBCG30-induced immunity and cross-protection against Mycobacterium leprae challenge are enhanced by boosting with the Mycobacterium tuberculosis 30-kilodalton antigen 85B.
abstract: Leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. Vaccines are needed that protect against both infections and do so better than the suboptimal Mycobacterium bovis BCG vaccine. Here, we evaluated rBCG30, a vaccine previously demonstrated to induce protection superior to that of BCG against Mycobacterium tuberculosis and Mycobacterium bovis challenge in animal models, for efficacy against Mycobacterium leprae challenge in a murine model of leprosy. rBCG30 overexpresses the M. tuberculosis 30-kDa major secretory protein antigen 85B, which is 85% homologous with the M. leprae homolog (r30ML). Mice were sham immunized or immunized intradermally with BCG or rBCG30 and challenged 2.5 months later by injection of viable M. leprae into each hind footpad. After 7 months, vaccine efficacy was assessed by enumerating the M. leprae bacteria per footpad. Both BCG and rBCG30 induced significant protection against M. leprae challenge. In the one experiment in which a comparison between BCG and rBCG30 was feasible, rBCG30 induced significantly greater protection than did BCG. Immunization of mice with purified M. tuberculosis or M. leprae antigen 85B also induced protection against M. leprae challenge but less so than BCG or rBCG30. Notably, boosting rBCG30 with M. tuberculosis antigen 85B significantly enhanced r30ML-specific immune responses, substantially more so than boosting BCG, and significantly augmented protection against M. leprae challenge. Thus, rBCG30, a vaccine that induces improved protection against M. tuberculosis, induces cross-protection against M. leprae that is comparable or potentially superior to that induced by BCG, and boosting rBCG30 with antigen 85B further enhances immune responses and protective efficacy.
authors.affiliation: Laboratory Research Branch, National Hansen's Disease Programs, LSU School of Veterinary Medicine, Baton Rouge, Louisiana, USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Gillis
authors.affiliation: Division of Infectious Diseases, Department of Medicine, School of Medicine, University of California-Los Angeles, Los Angeles, California, USA.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Tullius
authors.affiliation: Division of Infectious Diseases, Department of Medicine, School of Medicine, University of California-Los Angeles, Los Angeles, California, USA mhorwitz@mednet.ucla.edu.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Horwitz
mesh_terms: D000217:Acyltransferases / Q000276:immunology*; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D056738:Cross Protection / Q000276:immunology*; D005260:Female; D007114:Immunization / Q000379:methods; D007918:Leprosy / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000276:immunology; D009166:Mycobacterium leprae / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014611:Vaccination / Q000379:methods
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D032581:Tuberculosis Vaccines; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis