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

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)