Advances in development of tuberculosis vaccines and preventive drug therapies: current pipeline, evidence, and access.

Tuberculosis remains the leading cause of death from a single infectious agent globally. The WHO Global Tuberculosis Report 2025 indicates that progress towards the WHO End TB Strategy targets remains off track despite modest declines in incidence and mortality. In 2024, an estimated 10·7 million people developed tuberculosis and 1·23 million died from the disease. In this Series paper, we examine evidence published between Jan 6, 2020, and Jan 6, 2026, to provide an updated overview of tuberculosis vaccines and tuberculosis preventive treatment (TPT). As of June 4, 2026, 18 tuberculosis vaccine candidates are in active clinical development, including six in phase 3 (M72/AS01E, MTBVAC, VPM1002, GamTBvac, Immuvac [MIP], and BCG revaccination trials), representing the most diverse and advanced pipeline since the introduction of BCG in 1921. Platforms include live-attenuated mycobacterial vaccines (eg, MTBVAC), recombinant BCG-derived approaches (eg, VPM1002), protein-adjuvant subunit vaccines (eg, M72/AS01E), viral-vectored candidates (eg, AdHu5Ag85A, ChAdOx1.85A, and TB/FLU-04L), and inactivated whole-cell strategies (eg, DAR-901, RUTI, and Immuvac [MIP]). However, only a few candidates have progressed to late-stage efficacy evaluation. Short-course rifamycin-containing TPT regimens-1 month of daily isoniazid plus rifapentine, 3 months of once-weekly isoniazid plus rifapentine, 3 months of daily isoniazid plus rifampicin, and 4 months of daily rifampicin-show non-inferior efficacy and higher completion rates than 6-9 months of daily isoniazid monotherapy and are WHO-preferred options for drug-susceptible tuberculosis. In 2024, 5·3 million people at high risk of tuberculosis initiated TPT globally, including 3·5 million household contacts and 1·8 million people with HIV. For contacts of multidrug-resistant or rifampicin-resistant tuberculosis, randomised trials and pooled analyses support 6 months of daily levofloxacin to reduce incident multidrug-resistant tuberculosis. Bedaquiline-containing preventive regimens and shorter fluoroquinolone-based combinations are under clinical evaluation, but definitive phase 3 efficacy data are not yet available. The expansion of the vaccine pipeline alongside improved short-course preventive regimens offers a credible opportunity to accelerate tuberculosis incidence decline, although translation into population-level impact will depend on shown efficacy, sustained financing, reliable drug and vaccine supply, and effective implementation in high-burden settings.