Investigation of immune response mechanisms effective of a BCG Vaccine Recombinant against Tuberculosis by Systems Biology

• Grant number: 19/02305-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): April 01, 2019
• Effective date (End): May 31, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Luciana Cezar de Cerqueira Leite
• Grantee: Lázaro Moreira Marques Neto
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 17/24832-6 - Development of vaccines based on recombinant BCG: Tuberculosis, Pertussis, Pneumococcus and Schistosoma, AP.TEM

Abstract

The development of an effective vaccine for tuberculosis and its progression towards clinical trials will require greater knowledge about the effector mechanisms of induction of immune response. Currently, there are several strategies under development for TB, but the lack of protective biomarkers has been a limiting factor. An enormous effort has been devoted to the study of the immunological mechanisms of TB infection in order to establish biomarkers to be used in diagnosis, treatment and prevention. High-performance techniques such as transcriptomics allow you to analyze thousands of variables at the same time. Systems vaccinology combines the measurement of multiple parameters with the analysis in networks of interaction and predictive modeling to identify gene signatures for correlates of protection .In the area of tuberculosis, studies in systems biology have focused on host factors induced during infection with latent and active TB capable of controlling infection with M. tuberculosis to subsidize the development of new vaccines, since the only vaccine in current use, BCG, offers partial protection. In addition, the vast majority of developing vaccines have offered some enhancement of protection in animal models, but there is still no evidence of human protection. The only vaccine that has reached phase III clinical trials has shown no protective effect in humans.Since we obtained a recombinant BCG strain expressing a nontoxic derivative of heat labile toxin from E. coli, LTK63, or the A subunit of this toxin as adjuvant, with higher levels of protection than BCG in animal challenge models, we believe that these strains can serve as a model for the definition of correlates of protection and identification of gene signatures as biomarkers through systems biology.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TRENTINI, MONALISA MARTINS; KANNO, ALEX ISSAMU; RODRIGUEZ, DUNIA; MARQUES-NETO, LAZARO MOREIRA; ETO, SILAS FERNANDES; CHUDZINKI-TAVASSI, ANA MARISA; LEITE, LUCIANA CEZAR DE CERQUEIRA. Recombinant BCG expressing the LTAK63 adjuvant improves a short-term chemotherapy schedule in the control of tuberculosis in mice. FRONTIERS IN IMMUNOLOGY, v. 13, p. 12-pg., 2022-08-31. (17/24832-6, 19/02305-0, 19/06454-0)

MARQUES-NETO, LAZARO MOREIRA; TRENTINI, MONALISA MARTINS; KANNO, ALEX ISSAMU; RODRIGUEZ, DUNIA; LEITE, LUCIANA CEZAR DE CERQUEIRA. Recombinant BCG expressing the LTAK63 adjuvant increased memory T cells and induced long-lasting protection against Mycobacterium tuberculosis challenge in mice. FRONTIERS IN IMMUNOLOGY, v. 14, p. 11-pg., 2023-07-13. (19/06454-0, 19/02305-0, 17/24832-6)