Live-attenuated Mycobacterium tuberculosis vaccine, MTBVAC, in adults with or without M tuberculosis sensitisation: a single-centre, phase 1b–2a, double-blind, dose-escalation, randomised controlled trial

BACKGROUND: An effective adult vaccine is needed to control tuberculosis. We evaluated the safety and immunogenicity of a live-attenuated Mycobacterium tuberculosis vaccine (MTBVAC). METHODS: CFU dose). The primary outcomes were the occurrence of systemic solicited adverse events within 7 days and unsolicited adverse events within 28 days after vaccination, the occurrence of solicited and unsolicited injection-site reactions within 84 days after vaccination, and the occurrence of serious adverse events (SAEs) until the end of study, 365 days after vaccination. Data were analysed per modified intention to treat. The trial is now complete and closed. FINDINGS: CFU doses induced T-helper-cell-1 cytokine-expressing CD4 T-cell responses that exceeded BCG-induced responses in participants who were QFT negative and QFT positive. INTERPRETATION: dose of MTBVAC could be selected for a subsequent efficacy evaluation. FUNDING: Congressionally Directed Medical Research Programmes and US National Institutes of Health.