Five years after the global TB vaccine roadmap launched, progress is real but painfully thin

Summary This narrative review updates the 2021 Global Roadmap for tuberculosis (TB) vaccine research and development, assessing progress across three themes (pipeline diversification, preclinical/clinical acceleration, public health impact) over the preceding five years. As of early 2026, only seven candidates remain in phase 2b/3 trials (three actively recruiting) and three in phase 1, while M72/AS01E has reached full enrollment in a multicountry phase 3 efficacy trial. Alternative “prevention of infection” and “prevention of recurrence” endpoint trials (BCG revaccination, DAR-901, H56:IC31, VPM1002) largely failed to demonstrate efficacy, with H56:IC31 even associated with increased relapse. No correlate of protection has been identified, and 2025 funding cuts severely disrupted vaccine-readiness programs in low- and middle-income countries. Comment This roadmap update is candid about a stalling pipeline: too few active candidates, no correlate of protection, and alternative trial endpoints proving unreliable shortcuts. A core scientific truth underlies this struggle: M tuberculosis is a necessary but not sufficient...