Advances in TB treatment: identification of biomarkers that predict treatment outcome and the molecular characterization of innate immune responses induced by rBCG-LTAK63

• Grant number: 17/03332-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: June 20, 2017
• End date: June 19, 2018
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Luciana Cezar de Cerqueira Leite
• Grantee: Carina Carvalho dos Santos
• Supervisor: Thomas Henricus Maria Ottenhoff
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: Leiden University Medical Center (LUMC) , Netherlands
• Associated to the scholarship: 14/01271-0 - Identification of biomarkers of protection and immunological characterization of a novel vaccine candidate against tuberculosis based on Recombinant BCG, BP.DD

Abstract

Tuberculosis (TB) was responsible for more than 10.4 million cases and 1.8 million deaths in 2015. This is primarily because the only available vaccine, BCG, fails to reduce TB incidence sufficiently, there is a lack of biomarkers of protection and of biomarkers predicting treatment outcome, and there is a rising frequency of multi drug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains. So far, we have been investigating the immune responses induced by a novel vaccine candidate, rBCG-LTAK63, to identify correlates of protection against TB using flow cytometry and real-time PCR. Additional approaches like dcRT-MLPA, a focused gene expression profiling technique recently developed at Leiden University Medical Center could complement this study. In this project, we propose to use dcRT-MLPA to molecularly characterize the innate immune response following infection of primary human cells with rBCG-LTAK63, and to evaluate the treatment response kinetics for TB in slow versus fast responders over a 6-month period to identify biomarker signatures that predict treatment outcome before or early after treatment initiation. (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)

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)

HEEMSKERK, M. T.; KORBEE, C. J.; ESSELINK, J. J.; DOS SANTOS, C. CARVALHO; VAN VEEN, S.; GORDIJN, I. F.; VRIELING, F.; WALBURG, K. V.; ENGELE, C. G.; DIJKMAN, K.; et al. Repurposing diphenylbutylpiperidine-class antipsychotic drugs for host-directed therapy of Mycobacterium tuberculosis and Salmonella enterica infections. SCIENTIFIC REPORTS, v. 11, n. 1, OCT 4 2021. (17/03332-5)

BOLAND, RALF; HEEMSKERK, MATTHIAS T.; FORN-CUNI, GABRIEL; KORBEE, CORNELIS J.; WALBURG, KIMBERLEY V.; ESSELINK, JEROEN J.; CARVALHO DOS SANTOS, CARINA; DE WAAL, AMY M.; VAN DER HOEVEN, DANIEL C. M.; VAN DER SAR, ELISA; et al. Repurposing Tamoxifen as Potential Host-Directed Therapeutic for Tuberculosis. MBIO, v. N/A, p. 23-pg., 2022-12-07. (17/03332-5)