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Investigation of immune response mechanisms effective of a BCG vaccine recombinant against tuberculosis by systems biology

Grant number: 19/02305-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): April 01, 2019
Effective date (End): March 31, 2021
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Luciana Cezar de Cerqueira Leite
Grantee:Lázaro Moreira Marques Neto
Home 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.