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

Autor(es)

Dos Santos, Carina Carvalho ^{[1, 2]} ; Rodriguez, Dunia ^[2] ; Issamu, Alex Kanno ^[2] ; De Cerqueira Leite, Luciana Cezar ^{[1, 2]} ; Nascimento, Ivan Pereira ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Programa Posgrad Interunidades Biotecnol, Sao Paulo, SP - Brazil

^[2] Inst Butantan, Lab Desenvolvimento Vacinas, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: HUMAN VACCINES & IMMUNOTHERAPEUTICS; v. 16, n. 3, p. 673-683, 2020.
• Citações Web of Science: 0

Resumo

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-alpha-secreting CD4(+) T cells and multifunctional IL-2(+) TNF-alpha(+) 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. (AU)

• Processo FAPESP: 17/24832-6 - Desenvolvimento de vacinas baseadas em BCG recombinante: Tuberculose, Pertussis, Pneumococo e Schistosoma
• Beneficiário: Luciana Cezar de Cerqueira Leite
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/01271-0 - Identificação de biomarcadores de proteção e caracterização de um novo candidato vacinal contra tuberculose baseado em BCG recombinante
• Beneficiário: Carina Carvalho dos Santos
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto