title: Variable Virulence and Efficacy of BCG Vaccine Strains in Mice and Correlation With Genome Polymorphisms.
abstract: Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the only vaccine available for tuberculosis (TB) control. However, BCG is not an ideal vaccine and has two major limitations: BCG exhibits highly variable effectiveness against the development of TB both in pediatric and adult populations and can cause disseminated BCG disease in immunocompromised individuals. BCG comprises a number of substrains that are genetically distinct. Whether and how these genetic differences affect BCG efficacy remains largely unknown. In this study, we performed comparative analyses of the virulence and efficacy of 13 BCG strains, representing different genetic lineages, in SCID and BALB/c mice. Our results show that BCG strains of the DU2 group IV (BCG-Phipps, BCG-Frappier, BCG-Pasteur, and BCG-Tice) exhibit the highest levels of virulence, and BCG strains of the DU2 group II (BCG-Sweden, BCG-Birkhaug) are among the least virulent group. These distinct levels of virulence may be explained by strain-specific duplications and deletions of genomic DNA. There appears to be a general trend that more virulent BCG strains are also more effective in protection against Mycobacterium tuberculosis challenge. Our findings have important implications for current BCG vaccine programs and for future TB vaccine development.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China; Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Fudan University, Shanghai, China; Shanghai Engineering Research Center of Industrial Microorganisms, Shanghai, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China.
authors.forename: Huan-Wei
authors.initials: HW
authors.lastname: Ru
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China.
authors.forename: Fu-Zeng
authors.initials: FZ
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China.
authors.forename: Rui-Feng
authors.initials: RF
authors.lastname: Sun
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Fan
authors.affiliation: Center for Animal Experiment/Animal Biosafety Level III Laboratory, State Key Laboratory of Virology, Wuhan University, Wuhan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Guo
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jun-Tao
authors.initials: JT
authors.lastname: Mai
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Wen-Xi
authors.initials: WX
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China.
authors.forename: Qing-Xia
authors.initials: QX
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. Electronic address: jun.liu@utoronto.ca.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000627:therapeutic use; D058674:Chromosome Duplication; D014644:Genetic Variation; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009163:Mycobacterium bovis / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity*; D017384:Sequence Deletion; D016019:Survival Analysis; D014376:Tuberculosis / Q000662:veterinary*; D014774:Virulence
chemical_list: D001500:BCG Vaccine