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

Author(s)

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

Affiliation

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

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

• Document type: Journal article
• Source: HUMAN VACCINES & IMMUNOTHERAPEUTICS; v. 16, n. 3, p. 673-683, 2020.
• Web of Science Citations: 0

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-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)

• FAPESP's process: 17/24832-6 - Development of vaccines based on recombinant BCG: Tuberculosis, Pertussis, Pneumococcus and Schistosoma
• Grantee: Luciana Cezar de Cerqueira Leite
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/01271-0 - Identification of biomarkers of protection and immunological characterization of a novel vaccine candidate against tuberculosis based on Recombinant BCG
• Grantee: Carina Carvalho dos Santos
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)