Recombinant Mycobacterium smegmatis expressing antigen 85B for immunotherapy of Mycobacterium tuberculosis-infected mice

表达抗原85B的重组耻垢分枝杆菌用于结核分枝杆菌感染小鼠的免疫治疗

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Abstract

Tuberculosis is a serious, chronic infectious disease worldwide, primarily caused by Mycobacterium tuberculosis (Mtb). Antigen 85B is a potential vaccine candidate for Mtb. In this study, we constructed a recombinant strain expressing Antigen 85B (rMs-Ag85B) in the Mycobacterium smegmatis (Ms). The immunological characteristics and the therapeutic efficacy of the vaccine were evaluated in mice. The results showed that rMs-Ag85B exhibited slow growth under static culture conditions, with a significant reduction in biofilm formation compared to the Ms strain. Immunologically, subcutaneous immunization with rMs-Ag85B induced stronger humoral and cellular immune responses. As a therapeutic vaccine, rMs-Ag85B modulated the aggregation of CD4(+) and CD8(+) T cells in spleen and lung, promoted Th1/Th2-type cytokines secretions, and increased inflammatory cytokines releases and alleviated pathological damages in the lung of Mtb infected mice. Moreover, rMs-Ag85B significantly reduced the Mtb loads in the spleen of mice. In conclusion, rMs-Ag85B vaccine provided an immunotherapeutic effect against Mtb infection and could be used as a candidate vaccine for the immunotherapy of tuberculosis.

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