Largest TB Vaccine Trial in Decades Finds VPM1002 Halves Extrapulmonary Risk but Falls Short of Broad Protection
Phase 3 PreVenTB trial of 12,717 people across India shows VPM1002 cuts extrapulmonary tuberculosis by 50%, but neither candidate prevents pulmonary TB or latent infection.
Overview
Results from the PreVenTB trial, one of the largest tuberculosis vaccine trials conducted in decades, were published in The BMJ on April 9, 2026. The Phase 3 trial enrolled 12,717 household contacts of recently diagnosed TB patients across 18 sites in six Indian states and followed them for 38 months. Two vaccine candidates — VPM1002 and Immuvac — were tested against placebo in a randomized, double-blind design funded by the Indian Council of Medical Research.
Neither vaccine achieved statistically significant protection against all forms of tuberculosis or against pulmonary TB specifically. However, VPM1002 demonstrated 50.4 percent efficacy against extrapulmonary TB across all age groups — a finding that carries clinical weight because extrapulmonary disease is associated with higher mortality than its pulmonary counterpart.
What We Know
The trial randomized participants equally into three groups of roughly 4,239 each, with a second dose administered one month after the first. Retention was exceptionally high: 96.7 percent of participants completed the full follow-up, a figure the authors describe as a significant strength of the study.
VPM1002, a recombinant variant of the century-old BCG vaccine developed by Vakzine Projekt Management and manufactured by the Serum Institute of India, showed the more promising results of the two candidates:
- 50.4 percent efficacy against extrapulmonary TB across all ages
- 79.5 percent efficacy against extrapulmonary TB in adults aged 36 to 60
- 64.6 percent efficacy against all TB forms in children aged 6 to 13, and 77.6 percent against extrapulmonary TB in the same age group
- Among participants who converted from tuberculin skin-test positive, 68.4 percent efficacy against all TB and 78.9 percent against extrapulmonary TB
Immuvac showed more limited results, with 33.2 percent efficacy against extrapulmonary TB that was not statistically significant. Protection was observed only in children aged 6 to 9 against extrapulmonary TB.
Overall, VPM1002 achieved just 21.4 percent efficacy against all forms of TB and 19.5 percent against pulmonary TB — neither figure reaching statistical significance.
Both vaccines were safe. Mild injection-site reactions occurred in approximately 33 percent of vaccine recipients, and serious adverse events were below 10 percent across all groups with none attributed to vaccination. A total of 109 deaths occurred during the trial, evenly distributed among the three arms, and none were linked to the vaccines.
What We Don’t Know
Several uncertainties remain. The trial enrolled only household contacts of TB patients in India, and the findings may not generalize to other countries or ethnicities. COVID-19 disrupted portions of the follow-up period, which may have affected data completeness.
Perhaps the most striking gap is the failure of both vaccines to protect underweight individuals. In normal-weight children under 18, VPM1002 showed 45.1 percent efficacy against all TB, but this protection disappeared entirely in underweight participants. The researchers emphasized that nutritional support may be necessary alongside vaccination, particularly for children over five years old — a finding with significant implications for TB-endemic regions where malnutrition is prevalent.
The confidence intervals for several age-specific subgroup analyses were wide, indicating considerable uncertainty about the precision of those efficacy estimates. Neither vaccine prevented initial latent TB infection, only progression from latent to active disease in certain subgroups.
Analysis
Tuberculosis kills approximately 1.25 million people annually, making it the world’s deadliest infectious disease. The existing BCG vaccine, developed over a century ago, protects young children against severe TB but does not offer meaningful protection for adolescents and adults. The PreVenTB trial represents one of the most ambitious attempts to find a successor.
The results are a mixed outcome for global TB control efforts. VPM1002’s failure to provide broad protection against pulmonary TB — the form responsible for most transmission — means it cannot serve as a general replacement for BCG. Yet the 50 percent reduction in extrapulmonary TB, and the stronger signals in specific age groups and among those with latent infection, suggest the vaccine may have a role in targeted public health strategies.
The nutrition finding may prove as consequential as the vaccine data itself. If vaccine efficacy depends on adequate nutritional status, TB control programs in high-burden countries will need to integrate nutritional interventions alongside immunization campaigns — a logistically complex but potentially transformative approach.
The trial’s scale and rigor set a benchmark for future TB vaccine research. With multiple other candidates in various stages of development, including the M72/AS01E vaccine that showed 50 percent efficacy against active TB disease in a separate trial, the field continues to advance incrementally toward the goal of a broadly protective TB vaccine.