title: Virulence, immunogenicity, and protective efficacy of two recombinant Mycobacterium bovis bacillus Calmette-Guérin strains expressing the antigen ESAT-6 from Mycobacterium tuberculosis.
abstract: We constructed two recombinant Mycobacterium bovis BCG (rBCG) strains expressing ESAT-6 of Mycobacterium tuberculosis, named rBCG-1 and rBCG-2. rBCG-1 contained the ESAT-6 gene linked to BCG hsp60 and expressed a fusion protein, while rBCG-2, with a secretory sequence, could secret ESAT-6 into the culture medium. There was no evidence for increased virulence of the two rBCG strains when we made a comparison between them and BCG with regard to organ bacterial loads, lung histology, and survival time. rBCG-1 induced significantly higher specific antibody titers and stronger cellular immune response than BCG, whereas rBCG-2 had immunogenicity similar to that of the parental BCG strain. Both rBCG-1 and rBCG-2 conferred marked protection against M. tuberculosis infection, yet in terms of protective efficacy, they showed no significant improvements upon conventional BCG vaccine.
authors.affiliation: Research Unit of Infection and Immunity, West China Medical Center, Sichuan University, No. 17, 3rd Section, Ren Min Nan Road, Chengdu, Sichuan 610041, People's Republic of China. baolang@wcums.edu.cn
authors.forename: Lang
authors.initials: L
authors.lastname: Bao
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Huidong
authors.initials: H
authors.lastname: Zhang
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001500:BCG Vaccine / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins; D002417:Cattle; D018834:Chaperonin 60 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000276:immunology*; D014774:Virulence
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D018834:Chaperonin 60; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D007371:Interferon-gamma