title: Immunogenicity and protective efficacy of a novel recombinant BCG strain overexpressing antigens Ag85A and Ag85B.
abstract: Recombinant Bacillus Calmette-Guérin (rBCG) strain is the promising vaccine candidate for tuberculosis (TB) prevention, which aims at providing more enduring and enhanced protection than the parental BCG vaccine. In this study, three rBCG strains overexpressing immunodominant antigens Ag85B (rBCG::85B), Ag85A (rBCG::85A), or both (rBCG::AB) of Mycobacterium tuberculosis were constructed, respectively. rBCG strains showed higher level of overexpression of Ag85A and/or Ag85B proteins than BCG containing empty vector pMV261(rBCG::261), which had low levels of endogenous expression of both proteins as expected. rBCG::AB strain could provide the strongest short-term and long-term protection in the lung against intravenous infection with virulent M. tuberculosis than rBCG::261 control and other two rBCG strains overexpressing single antigen. The stronger and longer-lasting protection provided by rBCG::AB than rBCG::261 was correlated with systemic in vitro antigen-specific IFN-γ responses. Therefore, our results indicate that rBCG::AB could be a very promising TB vaccine candidate and should be further evaluated for the preclinical test.
authors.affiliation: Laboratory of Biosafety, Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.forename: Ruiling
authors.initials: R
authors.lastname: Fu
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Chen
authors.forename: Kun
authors.initials: K
authors.lastname: Tan
authors.forename: Lingxia
authors.initials: L
authors.lastname: Chen
authors.forename: Xindong
authors.initials: X
authors.lastname: Teng
authors.forename: Jia
authors.initials: J
authors.lastname: Lu
authors.forename: Chunwei
authors.initials: C
authors.lastname: Shi
authors.forename: Xionglin
authors.initials: X
authors.lastname: Fan
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001500:BCG Vaccine / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007110:Immunity, Active; D016056:Immunodominant Epitopes / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control; D014611:Vaccination / Q000639:trends
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D016056:Immunodominant Epitopes; D007371:Interferon-gamma; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis; C121433:antigen 85B, Mycobacterium tuberculosis