AUTHOR=Weng Shufeng , Zhang Jinyi , Ma Huixia , Zhou Jingyu , Jia Liqiu , Wan Yanmin , Cui Peng , Ruan Qiaoling , Shao Lingyun , Wu Jing , Wang Honghai , Zhang Wenhong , Xu Ying 

TITLE=B21 DNA vaccine expressing ag85b, rv2029c, and rv1738 confers a robust therapeutic effect against latent Mycobacterium tuberculosis infection

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1025931

DOI=10.3389/fimmu.2022.1025931

ISSN=1664-3224

ABSTRACT=<p>Latent tuberculosis infection (LTBI) treatment is known to accelerate the decline in TB incidence, especially in high-risk populations. <italic>Mycobacterium tuberculosis</italic> (<italic>M. tb</italic>) expression profiles differ at different growth periods, and vaccines protective and therapeutic effects may increase when they include antigenic compositions from different periods. To develop a post-exposure vaccine that targets LTBI, we constructed four therapeutic DNA vaccines (<italic>A39</italic>, <italic>B37</italic>, <italic>B31</italic>, and <italic>B21</italic>) using different combinations of antigens from the proliferation phase (Ag85A, Ag85B), PE/PPE family (Rv3425), and latent phase (Rv2029c, Rv1813c, Rv1738). We compared the immunogenicity of the four DNA vaccines in C57BL/6j mice. The <italic>B21</italic> vaccine stimulated the strongest cellular immune responses, namely Th1/Th17 and CD8<sup>+</sup> cytotoxic T lymphocyte responses. It also induced the generation of strengthened effector memory and central memory T cells. In latently infected mice, the <italic>B21</italic> vaccine significantly reduced bacterial loads in the spleens and lungs and decreased lung pathology. In conclusion, the <italic>B21</italic> DNA vaccine can enhance T cell responses and control the reactivation of LTBI.</p>