The only vaccine against Tuberculosis today in use, BCG (a live-attenuated strain of Mycobacterium bovis) offers variable protection against the respiratory forms of TB. MTBVAC is a new TB vaccine candidate, based on a rational attenuation of an M. tuberculosis clinical isolate by inactivation of transcriptional factor phoP and fadD26 genes, both essential for M. tuberculosis virulence. MTBVAC conserves all the genomic regions absent in BCG, and therefore it expresses the whole repertoire of T cell epitopes described for TB, including the major immunodominant antigens of the RD1 region: ESAT6 and CFP10, absent in BCG.
After almost 20 years of discovery and preclinical development, MTBVAC is the only live attenuated vaccine based on the human pathogen that has successfully entered clinical trials as a preventive vaccine. Our studies are focused to decipher the molecular mechanisms of attenuation and protection of MTBVAC in order to support the acceleration of efficacy clinical trials. Preclinical studies have demonstrated that MTBVAC-induced immunity to ESAT6 and CFP10 correlate with improved efficacy relative to BCG. This finding encourages exploration of inmune responses against these antigens as potential biomarkers and possible correlates of vaccine-induced protection in human clinical trials. We have identified possible correlates of vaccine-induced protection. Such data would be extremely valuable as they would greatly accelerate clinical development to efficacy trials. MTBVAC, currently starting two advanced Phase 2a dose-defining clinical trials in newborns and adolescents at SATVI in South Africa (NCT02933281 and NCT02729571).