Identification of biomarkers of protection and immunological characterization of a novel vaccine candidate against tuberculosis based on Recombinant BCG

• Grant number: 14/01271-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: May 01, 2014
• End date: April 30, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Luciana Cezar de Cerqueira Leite
• Grantee: Carina Carvalho dos Santos
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated scholarship(s): 17/03332-5 - Advances in TB treatment: identification of biomarkers that predict treatment outcome and the molecular characterization of innate immune responses induced by rBCG-LTAK63, BE.EP.DD

Abstract

Tuberculosis (TB) continues to generate an overwhelming effect on the lives of many people, leading to an alarming number of 1.4 million deaths per year and the only available vaccine currently, Mycobacterium bovis bacille Calmette-Guérin (BCG), have shown disagreements about its protective effect. For several decades vaccines candidates have been developed against TB, some even reaching clinical trials. Although numerous approaches have been used to develop new vaccines against TB, improving the bacillus Calmette - Guérin (BCG) has received more attention, since it is the only vaccine in use until now. The development of new and more effective vaccines against TB is a challenge that requires a better understanding of the pathological and protective immune response in tuberculosis, once the immune response against Mycobacterium tuberculosis must be further elucidated and data clear correlation of protective immunity are scarce. The availability of biomarkers of protection will allow the selection of best candidates and vaccine strategies faster and more rational in an earlier stage of the development process. To get these biomarkers, peripheral blood is the ideal source, although they can be studied in any tissue or body fluid. One approach that has been applied in the search for biomarkers of protection in TB is a systemic approach, since it allows to evaluate changes in gene expression profiles in a cell, tissue, organ or whole organism providing a dynamic link between the genome and proteome. In this work we characterize the kinetics of the immune response elicited by rBCG-LTAK63, a vaccine candidate against TB based on recombinant BCG, before and after challenge by characterization of the humoral and cellular response using ELISA and flow cytometry respectively and evaluating the transcriptional profile of genes associated with immune response. By correlating the immune parameters and protective efficacy of this vaccine candidate, we hope to identify biomarkers of protection in the lung and blood, seeking a true understanding of what constitutes protection in TB. (AU)

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)

LARISSA V NASCIMENTO; CARINA C SANTOS; LUCIANA CC LEITE; IVAN P NASCIMENTO. Characterisation of alternative expression vectors for recombinant Bacillus Calmette-Guérin as live bacterial delivery systems. Memórias do Instituto Oswaldo Cruz, v. 115, 2020-05-15. (14/01271-0, 17/24832-6)

DOS SANTOS, CARINA C.; WALBURG, KIMBERLEY, V; VAN VEEN, SUZANNE; WILSON, LOUIS G.; TRUFEN, CARLOS E. M.; NASCIMENTO, IVAN P.; OTTENHOFF, TOM H. M.; LEITE, LUCIANA C. C.; HAKS, MARIELLE C.. Recombinant BCG-LTAK63 Vaccine Candidate for Tuberculosis Induces an Inflammatory Profile in Human Macrophages. VACCINES, v. 10, n. 6, p. 14-pg., 2022-06-01. (17/24832-6, 14/01271-0, 17/03332-5)

DOS SANTOS, CARINA CARVALHO; RODRIGUEZ, DUNIA; ISSAMU, ALEX KANNO; DE CERQUEIRA LEITE, LUCIANA CEZAR; NASCIMENTO, IVAN PEREIRA. Recombinant BCG expressing the LTAK63 adjuvant induces increased early and long-term immune responses against Mycobacteria. HUMAN VACCINES & IMMUNOTHERAPEUTICS, v. 16, n. 3, p. 673-683, 2020. (17/24832-6, 14/01271-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SANTOS, Carina Carvalho dos. The relationship between developmental kinetics and metabolic response in bovine embryos submitted to stress during in vitro culture.. 2019. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.