A new recombinant BCG vaccine induces specific Th17 and Th1 effector cells with higher protective efficacy against tuberculosis
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2014-11-14
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Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that is a major public health problem.
The vaccine used for TB prevention is Mycobacterium bovis bacillus Calmette-Gue´rin (BCG), which provides variable efficacy
in protecting against pulmonary TB among adults. Consequently, several groups have pursued the development of a new
vaccine with a superior protective capacity to that of BCG. Here we constructed a new recombinant BCG (rBCG) vaccine
expressing a fusion protein (CMX) composed of immune dominant epitopes from Ag85C, MPT51, and HspX and evaluated
its immunogenicity and protection in a murine model of infection. The stability of the vaccine in vivo was maintained for up
to 20 days post-vaccination. rBCG-CMX was efficiently phagocytized by peritoneal macrophages and induced nitric oxide
(NO) production. Following mouse immunization, this vaccine induced a specific immune response in cells from lungs and
spleen to the fusion protein and to each of the component recombinant proteins by themselves. Vaccinated mice
presented higher amounts of Th1, Th17, and polyfunctional specific T cells. rBCG-CMX vaccination reduced the extension of
lung lesions caused by challenge with Mtb as well as the lung bacterial load. In addition, when this vaccine was used in a
prime-boost strategy together with rCMX, the lung bacterial load was lower than the result observed by BCG vaccination.
This study describes the creation of a new promising vaccine for TB that we hope will be used in further studies to address
its safety before proceeding to clinical trials.
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COSTA, Adeliane Castro da et al. A new recombinant BCG vaccine induces specific Th17 and Th1 effector cells with higher protective efficacy against tuberculosis. Plos One, San Francisco, v. 9, n. 11, p. e112848, 2014.