TB Vaccine Trial Shows Limited Overall Protection but Targets Extrapulmonary Disease

A phase 3 trial of two tuberculosis vaccines has found limited overall protection against microbiologically confirmed tuberculosis, but suggests meaningful efficacy against extrapulmonary disease in specific patient groups. Meanwhile, a mathematical modeling study indicates that the population-level success of new TB vaccines could hinge on their ability to block infectious asymptomatic TB, where people transmit the bacteria without symptoms.

The PreVenTB trial, conducted across 18 sites in India, enrolled 12,717 healthy household contacts of individuals with smear-positive tuberculosis. Participants were randomly assigned to receive either VPM1002, Immuvac, or placebo, with follow-up over 38 months to assess prevention of active tuberculosis, development of latent infection, and immunogenicity. In the per-protocol analysis, tuberculosis occurred in 1.68% of participants receiving VPM1002, compared with 2.13% in the placebo group. Immuvac showed similar rates at 2.09%. These findings translated into modest vaccine efficacy estimates against all forms of TB, with confidence intervals crossing zero for most comparisons, indicating uncertainty in overall protection. No significant protection was observed against pulmonary tuberculosis, which represents the most common and transmissible form of the disease. Both vaccines were, however, well tolerated, with mild local reactions reported in approximately one-third of participants.

A more notable finding was observed for extrapulmonary tuberculosis, where VPM1002 showed higher efficacy, including up to 50.4% protection in the per-protocol analysis. Immuvac also demonstrated some protection in this subgroup. The effect appeared stronger among participants with a positive tuberculin skin test, where both vaccines showed efficacy exceeding 60%. Post hoc analyses further suggested enhanced protection in children aged 6–14 years, particularly for VPM1002, where efficacy estimates were higher across all tuberculosis forms, although these findings require cautious interpretation. Both vaccines also demonstrated favourable immunogenicity, inducing Mycobacterium tuberculosis-specific CD4+ T-cell responses, supporting biological activity despite modest clinical efficacy.

According to a mathematical modeling study published in PLOS Medicine on February 12, 2026, the population-level success of new TB vaccines could hinge on their ability to block infectious asymptomatic TB. Using models based on high-burden settings, researchers compared three vaccine scenarios: preventing progression to infectious symptomatic TB only; preventing progression to any infectious disease, including asymptomatic disease; and preventing progression to any disease. Across all short-term (3-year) scenarios, symptomatic TB cases were reduced by a similar amount (≈1.6–2.3%). Over longer periods (20 years), vaccines that block infectious asymptomatic disease averted far more cases—19.4% and 23.3% vs. just 7.3% in the symptomatic-only scenario—mainly by curbing silent transmission. The study highlights that overlooking efficacy against asymptomatic infection could underestimate the long-term benefits of new TB vaccines in ending the global epidemic.

In other tuberculosis prevention efforts, the STEP-TB study aims to generate real-world evidence on the safety of tuberculosis preventive treatment (TPT) among individuals at high risk of developing active tuberculosis disease in the Republic of Korea. STEP-TB is a multicenter, prospective observational cohort study conducted at four university-affiliated hospitals in the Republic of Korea. Adults aged ≥19 years who are eligible for latent tuberculosis infection (LTBI) testing or TPT according to national guidelines will be enrolled, including individuals with chronic kidney disease, chronic lung disease, diabetes mellitus, immunosuppressive conditions, malignancy, or occupational risk. The primary outcome is the occurrence of adverse events during TPT. Secondary outcomes include TPT completion rates, predictors of non-initiation and discontinuation, and progression to active TB. The study is registered under CRIS Registration Number KCT0011063. According to national TB surveillance data, a total of 19,540 TB cases were notified in Korea in 2023, corresponding to an incidence rate of 38.2 per 100,000 population, a 9.2% decrease compared with 2022.

The Centers for Disease Control and Prevention (CDC) has announced a funding opportunity to strengthen tuberculosis prevention, diagnosis, treatment, and surveillance across Asia, with a particular focus on India, the Philippines, and Vietnam. With an expected first-year funding pool of $3 million, the program aims to support organizations that can advance TB control efforts. The funding opportunity will be awarded through a cooperative agreement mechanism, with 1 to 3 awards expected, average annual funding up to $1 million per award, and project duration up to five years. The deadline is 22-Jun-2026.

Tuberculosis remains the leading infectious disease to cause deaths globally. Annual TB incidence is falling but slowly; the highest number of cases ever reported was in 2023. Less than half of children with TB disease are treated compared to over two-thirds of adults with TB, and less than a third of children exposed to TB in a household receive TB preventive therapy. In 2022, the WHO published a new recommendation that ‘decentralized TB services may be used in children and adolescents with signs and symptoms of TB and/or in those exposed to TB.’ An example from Uganda showed that the introduction and support of TB services for children at primary and secondary care levels increased TB detection (by more than double in children and in adults), improved TB treatment outcomes, and initiated contact investigation and preventive treatment by community healthcare workers. This model was subsequently adopted nationally. In 2024, the WHO updated recommendations for preventive therapy for household contacts of people with drug-resistant TB.