Construction and development of new vaccines against tuberculosis and evolution of the M. tuberculosis
IPS: Carlos Martín, Jesús Gonzalo-Asensio y Nacho Aguiló
After nearly 20 years of discovery, characterization and preclinical development, MTBVAC is the only live attenuated vaccine based on the human pathogen (M. tuberculosis) that has entered clinical trials as a preventive vaccine against tuberculosis (TB). Our studies are focused on deciphering the molecular mechanisms of MTBVAC attenuation and protection, trying to identify possible protective biomarkers that can help speed up efficacy trials. Following the good results on safety in adults in Switzerland (Clinical Phase 1 a) (Spertini et al. 2015), it has been shown that MTBVAC is also a safe and more immunogenic vaccine than BCG in newborns in a TB endemic country such as South Africa (Phase 1 b) (Tameris et al. 2019). In 2019, MTBVAC have started two clinical Phase 2a in newborns and adolescents in South Africa. In Oct 2022, MTBVAC entered a Phase 3 efficacy evaluation in newborns in Sub-Saharan Africa.
Since TB affects humans but also several species of mammals, we studied the evolution of the M. tuberculosis complex. (MTBC). The MTBC comprises 8 lineages with a homology greater than 99.95% at the genomic level. This, together with the absence of “classical” virulence factors or the lack of horizontal gene transfer events, makes understanding pathogen-host adaptation mechanisms challenging.