Experience With Entry of the First-ever Live MTB Vaccine in Clinical Trials
MTBVAC is the first live-attenuated vaccine based on MTB to enter clinical trials. The construction and preclinical characterization of MTBVAC fulfils the Geneva consensus safety requirements for progressing live mycobacterial vaccines to Phase I clinical evaluation.[116,117] Two stable deletion mutations and safety that is at least comparable with BCG in the relevant animal models are the safety criteria for live TB vaccines. The Spanish biopharmaceutical company Biofabri produced and characterized MTBVAC as a freeze-dried preparation in compliance with cGMP following European Pharmacopoeia monograph and the WHO recommendations to assure the quality, safety and efficacy of BCG vaccines.
To date, the development of MTBVAC, which is based on the stage-gating approach described in the blueprint, has been accomplished with the help of external expert advisors appointed by and facilitated through the TBVI Product Development Team (TBVI PDT) and Clinical Development Team (TBVI CDT). Early contacts with relevant regulatory authorities were imperative for establishing a cGMP production process and design preclinical characterization studies to support conduct of first-in-human evaluation with the final product. Biofabri is currently optimizing a scale-up industrial process to support large-scale clinical trials of MTBVAC as a BCG-replacement strategy, given once at birth by the intradermal route. The next steps of MTBVAC development require safe age de-escalation in healthy newborns in high-incidence countries. This challenging and complex task requires effective resource mobilization and a robust package to convince relevant regulatory bodies for safety, immunogenicity and promising efficacy profile.
Expert Rev Vaccines. 2013;12(12):1431-1448. © 2013 Expert Reviews Ltd.