B21 DNA vaccine expressing ag85b, rv2029c, and rv1738 confers a robust therapeutic effect against latent <i>Mycobacterium tuberculosis</i> infection

Latent tuberculosis infection (LTBI) treatment is known to accelerate the decline in TB incidence, especially in high-risk populations. Mycobacterium tuberculosis ( M. tb ) 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 ( A39 , B37 , B31 , and B21 ) 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 B21 vaccine stimulated the strongest cellular immune responses, namely Th1/Th17 and CD8 + cytotoxic T lymphocyte responses. It also induced the generation of strengthened effector memory and central memory T cells. In latently infected mice, the B21 vaccine significantly reduced bacterial loads in the spleens and lungs and decreased lung pathology. In conclusion, the B21 DNA vaccine can enhance T cell responses and control the reactivation of LTBI.