A LARGE phase 3 study of a tuberculosis vaccine strategy has found limited overall protection against microbiologically confirmed tuberculosis, but suggests meaningful efficacy against extrapulmonary disease in specific patient groups.
Tuberculosis Vaccine Shows Targeted Protection Against Severe Disease
Tuberculosis remains a major global infectious disease, with pulmonary and extrapulmonary forms contributing significantly to morbidity and mortality, particularly in high-burden settings.
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.
Limited Overall Protection Against Tuberculosis
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.
Stronger Signal for Extrapulmonary Tuberculosis
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.
Implications for Clinical and Public Health Practice
For clinicians and TB control programmes, these findings suggest that while current tuberculosis vaccine candidates may not provide broad protection against all forms of tuberculosis, they could offer targeted benefit in reducing extrapulmonary disease, particularly in high-risk or immunologically primed populations.
Both vaccines also demonstrated favourable immunogenicity, inducing Mycobacterium tuberculosis-specific CD4+ T-cell responses, supporting biological activity despite modest clinical efficacy.
Overall, the study highlights the ongoing challenge of developing a broadly effective tuberculosis vaccine, while suggesting potential value in stratified vaccination approaches targeting specific patient groups and disease phenotypes.
Reference
Singh M et al; PreVenTB Trial Team. PreVenTB trial: protocol for evaluation of efficacy and safety of two vaccines VPM1002 and Immuvac (Mw) in preventing tuberculosis (TB) in healthy household contacts of newly diagnosed sputum smear-positive pulmonary TB patients: phase III, randomised, double-blind, three-arm placebo-controlled trial. BMJ Open. 2024;14(8):e082916.
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