Recombinant bacille Calmette–Guerin coexpressing Ag85b, CFP10, and interleukin-12 elicits effective protection against Mycobacterium tuberculosis

摘要

[[abstract]]Background The tuberculosis (TB) pandemic continues to be a leading cause of human morbidity and mortality despite widespread use of the only licensed anti-TB vaccine, BCG. The protective efficacy of BCG in preventing pulmonary TB remains highly variable, so that an effective new vaccine is urgently required. Methods In the present study, we assessed the ability of novel recombinant BCG vaccine (rBCG) against Mycobacterium tuberculosis (MTB) by using modern immunological methods. Results ELISPOT assays demonstrated that rBCG vaccine co-expressing two mycobacterial antigens (Ag85B and CFP10) and human interleukin (IL)-12 (rBCG2) elicits greater interferon-γ (IFN-γ) release in mouse lung and spleen, compared to parental BCG. Also, rBCG2 is able to trigger a Th1-polarized response. Our results also showed that rBCG2 vaccination significantly limits M. tuberculosis H37Rv multiplication in macrophages. Surprisingly, rBCG2 was able to induce significantly higher tumor necrosis factor-α (TNF-α) production by peripheral blood mononuclear cells exposed to a non-mycobacterial stimulus, compared to parental BCG. Conclusion In this study, we demonstrated that the novel rBCG2 vaccine might be a promising candidate vaccine against MTB infection.