Modulation of immune responses induced by recombinant BCG expressing LTAK63 adjuvant in an immunotherapeutic model...

Tuberculosis (TB) remains a major global health issue, with current treatments relying on prolonged multidrug regimens that can reduce patient compliance, and lead to drug resistance. Immunotherapeutic vaccines against Mycobacterium tuberculosis (Mtb) offer a novel approach. We have previously shown that the recombinant BCG expressing LTAK63 adjuvant (rBCG-LTAK63) decreases bacillary load and lung inflammation in Mtb-infected mice. In this work, we further investigated specific immune mechanism induced in mice infected with Mtb and treated with rBCG-LTAK63 in combination with conventional chemotherapy; different routes of administration of rBCG-LTAK63 were evaluated, such as SC, IN, and IV. Immunotherapy with rBCG-LTAK63 induces early innate immune cells migration (predominantly NK cells and monocytes/macrophages) to distinct sites; increased IFN-γ, TNF-α, and IL-17 T cells, FoxP3 expressing regulatory T cells correlating with reduced bacillary load, particularly with IN administration. The findings highlight the potential of rBCG-LTAK63 to complement TB treatment.