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

<p>Latent tuberculosis infection (LTBI) treatment is known to accelerate the decline in TB incidence, especially in high-risk populations. <em>Mycobacterium tuberculosis</em> (<em>M. tb</em>) 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 (<em>A39</em>, <em>B37</em>, <em>B31</em>, and <em>B21</em>) 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 <em>B21</em> 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 <em>B21</em> vaccine significantly reduced bacterial loads in the spleens and lungs and decreased lung pathology. In conclusion, the <em>B21</em> DNA vaccine can enhance T cell responses and control the reactivation of LTBI.</p>