Recombinant BCG expressing the LTAK63 adjuvant induces increased early and long-term immune responses against Mycobacteria

The development of more effective vaccines against Mycobacterium tuberculosis has become a world priority. Previously, we have shown that a recombinant BCG expressing the LTAK63 adjuvant (rBCG-LTAK63) displayed higher protection than BCG against tuberculosis challenge in mice. In order to elucidate the immune effector mechanisms induced by rBCG-LTAK63, we evaluated the immune response before and after challenge. The potential to induce an innate immune response was investigated by intraperitoneal immunization with BCG or rBCG-LTAK63: both displayed increased cellular infiltration in the peritoneum with high numbers of neutrophils at 24 h and macrophages at 7 d. The rBCG-LTAK63-immunized mice displayed increased production of Nitric Oxide at 24 h and Hydrogen Peroxide at 7 d. The number of lymphocytes was higher in the rBCG-LTAK63 group when compared to BCG. Immunophenotyping of lymphocytes showed that rBCG-LTAK63 immunization increased CD4+ and CD8+ T cells. An increased long-term Th1/Th17 cytokine profile was observed 90 d after subcutaneous immunization with rBCG-LTAK63. The evaluation of immune responses at 15 d after challenge showed that rBCG-LTAK63-immunized mice displayed increased TNF-a-secreting CD4+ T cells and multifunctional IL-2+ TNF-a+ CD4+ T cells as compared to BCG-immunized mice. Our results suggest that immunization with rBCG-LTAK63 induces enhanced innate and long-term immune responses as compared to BCG. These results can be correlated with the superior protection induced against TB
Keywords
Tuberculosis;  vaccine;  recombinant BCG;  innate immunity;  long-term immunity

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Santos CCD, Rodríguez D, Kanno AI, Leite LCC, Nascimento IP. Recombinant BCG expressing the LTAK63 adjuvant induces increased early and long-term immune responses against Mycobacteria. Hum. Vaccin. Immunother.. 2020;16(3):673-683. doi:10.1080/21645515.2019.1669414.
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