MTBVAC, a live TB vaccine poised 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.
Competing Interests: Declaration of Competing Interest C.M., D.M., N.A. and J. G. are co-inventors on a patent on Tuberculosis Vaccine held by the University of Zaragoza and Biofabri. Biofabri is industrial partner of University of Zaragoza and the exclusive licensee and industrial and clinical developer of MTBVAC. The authors declare that they have no other known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)