期刊
MOLECULAR IMMUNOLOGY
卷 66, 期 2, 页码 392-401出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2015.04.017
关键词
Tuberculosis; Vaccine; Recombinant BCG; Mycobacterium tuberculosis; Ag85 complex; HspX
资金
- National High Technology Research and Development of China (863 program) [2012AA02A401]
- National Mega-projects of Science Research for the 12th Five-year Program of China [2012ZX10003008-005]
Although Bacillus Calmette-Guerin (BCG) vaccine confers protection from Mycobacterium tuberculosis infection in children, its immune protection gradually wanes over time, and consequently leads to an inability to prevent the reactivation of latent infection of M. tuberculosis. Therefore, improving BCG for better control of tuberculosis (TB) is urgently needed. We thus hypothesized that recombinant BCG overexpressing immunodominant antigens expressed at different growth stages of M. tuberculosis could provide a more comprehensive protection against primary and latent M. tuberculosis infection. Here, a novel cocktail of recombinant BCG (rBCG) strains, namely ABX, was produced by combining rECG::85A, rBCG::85B, and rBCG::X, which overexpressed respective multistage antigens Ag85A, Ag85B, and HspX of M. tuberculosis. Our results showed that ABX was able to induce a stronger immune protection than individual rBCGs or BCG against primary TB infection in C57BL/6 mice. Mechanistically, the immune protection was attributed to stronger antigen-specific CD4(+) Thl responses, higher numbers of IFN-gamma(+) CD4(+) T-EM and IL-2(+) CD8(+) T-CM cells elicited by ABX. These findings thus provide a novel strategy for the improvement of BCG efficacy and potentially a promising prophylactic TB vaccine candidate, warranting further investigation. (C) 2015 Elsevier Ltd. All rights reserved.
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