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

Vaccine. 2021 Dec 8;39(50):7277-7285. doi: 10.1016/j.vaccine.2021.06.049. Epub 2021 Jul 6.


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.

Keywords: BCG; MTBVAC; Newborns; Protection; Trained immunity.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • BCG Vaccine
  • Humans
  • Infant, Newborn
  • Mycobacterium tuberculosis*
  • Tuberculosis Vaccines*
  • Tuberculosis* / prevention & control
  • Vaccines, Attenuated


  • BCG Vaccine
  • Tuberculosis Vaccines
  • Vaccines, Attenuated