期刊
JOURNAL OF INFECTIOUS DISEASES
卷 210, 期 12, 页码 1928-1937出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiu347
关键词
BCG; Delta ureC::hly; VPM1002; vaccine; Mycobacterium tuberculosis; memory T cells
资金
- European Community NEWTBVAC [HEALTH-F3-2009-241745]
- European Community ADITEC [HEALTH-F4-2011-280873]
Bacillus Calmette-Gu,rin (BCG) has been used for vaccination against tuberculosis for nearly a century. Here, we analyze immunity induced by a live tuberculosis vaccine candidate, recombinant BCG Delta ureC::hly vaccine (rBCG), with proven preclinical and clinical safety and immunogenicity. We pursue in-depth analysis of the endogenous mycobacteria-specific CD4(+) T-cell population, comparing the more efficacious rBCG with canonical BCG to determine which T-cell memory responses are prerequisites for superior protection against tuberculosis. rBCG induced higher numbers and proportions of antigen-specific memory CD4(+) T cells than BCG, with a CXCR5(+)CCR7(+) phenotype and low expression of the effector transcription factors T-bet and Bcl-6. We found that the superior protection of rBCG, compared with BCG, correlated with higher proportions and numbers of these central memory T cells and of T follicular helper cells associated with specific antibody responses. Adoptive transfer of mycobacteria-specific central memory T cells validated their critical role in protection against pulmonary tuberculosis.
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