reducing the activity and secretion of microbial antioxidants enhances the immunogenicity of bcg降低微生物的活性和分泌抗氧化剂增强bcg的免疫原性.pdfVIP

Reducing the Activity and Secretion of Microbial Antioxidants Enhances the Immunogenicity of BCG 1 2 1 1 1 Shanmugalakshmi Sadagopal , Miriam Braunstein , Cynthia C. Hager , Jie Wei , Alexandria K. Daniel , 1¤ 1 1 1 1 3 Markian R. Bochan , Ian Crozier , Nathaniel E. Smith , Hiriam O. Gates , Louise Barnett , Luc Van Kaer , James O. Price4, Timothy S. Blackwell1,4, Spyros A. Kalams 1,3, Douglas S. Kernodle1,3,4* 1 Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America, 2 Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, United States of America, 3 Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America, 4 Department of Veterans Affairs Medical Center, Nashville, Tennessee, United States of America Abstract Background: In early clinical studies, the live tuberculosis vaccine Mycobacterium bovis BCG exhibited 80% protective efficacy against pulmonary tuberculosis (TB). Although BCG still exhibits reliable protection against TB meningitis and miliary TB in early childhood it has become less reliable in protecting against pulmonary TB. During decades of in vitro cultivation BCG not only lost some genes due to deletions of regions of the chromosome but also underwent gene duplication and other mutations resulting in increased antioxidant production. Methodology/Principal Findings: To determine whether microbial antioxidants in