Advances in development of tuberculosis vaccines and preventive drug therapies: current pipeline, evidence, and access.
The paper highlights that while there are promising developments in tuberculosis vaccines and preventive treatments, effective implementation and sustained financing are crucial for achieving meaningful public health impact.
Where it sits
this study against the rest of the semax corpusSummary and findings
This paper reviews the current pipeline of tuberculosis vaccines and preventive drug therapies, highlighting 18 vaccine candidates in active clinical development as of June 4, 2026. It also discusses various short-course rifamycin-containing tuberculosis preventive treatment regimens. The findings indicate a need for effective implementation and sustained financing to achieve population-level impact.
Abstract
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.
Background
This paper addresses the ongoing challenge of tuberculosis, which is the leading cause of death from a single infectious agent worldwide. Previous literature indicates that despite some progress, the targets set by the WHO End TB Strategy are not being met. This study is significant as it provides an updated overview of the vaccine candidates and preventive treatments that could potentially alter the trajectory of tuberculosis incidence and mortality.
Methods
The review encompasses evidence published between January 6, 2020, and January 6, 2026, focusing on tuberculosis vaccines and preventive treatment. It discusses various vaccine platforms and short-course rifamycin-containing treatment regimens. Specific details on study design, population, and primary versus secondary outcomes are not reported in abstract.
Results
As of June 4, 2026, there are 18 active clinical vaccine candidates, with six in phase 3. The paper notes that short-course rifamycin-containing regimens show non-inferior efficacy compared to longer isoniazid monotherapy. Specific numeric findings regarding efficacy and completion rates are not reported in abstract.
Interpretation
The findings suggest a promising pipeline for tuberculosis vaccines and preventive treatments, but the clinical significance of these candidates remains to be fully established. While some regimens show statistical significance, the clinical relevance and long-term impact on tuberculosis incidence are uncertain. Limitations such as reliance on pooled analyses and the lack of definitive phase 3 data for some treatments may confound the conclusions.
Key findings
- 10·7 million people developed tuberculosis in 2024.
- 1·23 million people died from tuberculosis in 2024.
- 18 tuberculosis vaccine candidates are in active clinical development as of June 4, 2026.
- 5·3 million people at high risk of tuberculosis initiated preventive treatment globally in 2024.
- 6 months of daily levofloxacin is supported by randomized trials to reduce incident multidrug-resistant tuberculosis.
Limitations
- The efficacy of many vaccine candidates remains unverified in late-stage trials.
- The study relies on data from various sources and may not reflect the most current clinical outcomes.
- Short follow-up periods limit the assessment of long-term effectiveness.