Format

Send to

Choose Destination
Mol Ther. 2016 Feb;24(2):398-405. doi: 10.1038/mt.2015.216. Epub 2015 Dec 8.

Variable Virulence and Efficacy of BCG Vaccine Strains in Mice and Correlation With Genome Polymorphisms.

Author information

1
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.
2
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China.
3
Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
4
Center for Animal Experiment/Animal Biosafety Level III Laboratory, State Key Laboratory of Virology, Wuhan University, Wuhan, China.
5
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
6
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.

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.

PMID:
26643797
PMCID:
PMC4817822
DOI:
10.1038/mt.2015.216
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center