MTBVAC, a live TB vaccine poised to initiate efficacy trials 100 years after BCG.

• MTBVAC construction and characterization has abided by Pasteur principles, similar to BCG. • BCG has served as gold standard for safety and efficacy in MTBVAC development. • MTBVAC shows superior efficacy in mice, guinea pigs, NHP, and similar safety to BCG. • MTBVAC is safe and immunogenic in clinical trials in adults and newborns. • MTBVAC is ready to initiate efficacy trials 100 years after BCG. At its 100th birthday of its first administration to a newborn, BCG has been (and continues being) an inspiration for the construction and development of hundreds of new TB vaccine candidates in the last two and a half decades. Today, 14 candidates are in clinical development inside the global TB vaccine pipeline. MTBVAC is one of these candidates. Based on a live-attenuated Mycobacterium tuberculosis clinical isolate, MTBVAC's 25 years of vaccine discovery, construction and characterisation have followed Pasteur principles, and in the process, BCG has served as a reference gold standard for establishing the safety and protective efficacy of new TB vaccine candidates. MTBVAC, which contains the antigen repertoire of M. tuberculosis , is now poised to initiate Phase 3 efficacy trials in newborns in TB-endemic countries. BCG's efficacy extends beyond that against TB, shown to confer heterologous non-specific immunity to other diseases and reduce all-cause mortality in the first months of life. Today, WHO recognises the importance that any new TB vaccine designed for administration at birth, should show similar non-specific benefits as BCG vía mechanisms of trained immunity and/or cross-reactivity of adaptive immune responses to other pathogens. Key recent studies provide strong support for MTBVAC's ability of inducing trained immunity and conferring non-specific heterologous protection similar to BCG. Research on alternative delivery routes of MTBVAC, such as a clinically feasible aerosol route, could facilitate vaccine administration for long-term TB eradication programmes in the future. [ABSTRACT FROM AUTHOR]