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


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Abstract
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
Reference
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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https://repositorio.butantan.gov.br/handle/butantan/3033
Issue Date
2020


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