Published Apr 10, 2026 | 7:10 PM ⚊ Updated Apr 10, 2026 | 7:11 PM
Tuberculosis. (iStock)
Synopsis: The only currently licensed TB vaccine is BCG, developed more than a century ago. While effective against severe forms of TB in young children, it offers little protection to adolescents and adults, the groups most exposed to pulmonary TB. VPM1002, a recombinant version of BCG developed by Vakzine Projekt Management and licensed to the Serum Institute of India, was designed to address precisely this gap.
A large-scale clinical trial in India has found that a next-generation tuberculosis vaccine, VPM1002, reduces the risk of extrapulmonary tuberculosis by half, offering renewed hope in the global fight against a disease that continues to infect millions every year.
The phase 3 trial, published in The BMJ on 9 April 2026, is one of the largest TB vaccine trials ever conducted, enrolling 12,717 people across 18 sites in six Indian states.
While neither VPM1002 nor the second vaccine tested, Immuvac, offered broad protection against all forms of TB, both demonstrated meaningful protection against extrapulmonary TB, the form of the disease that affects organs beyond the lungs and is associated with higher rates of mortality and delayed diagnosis.
TB remains one of the world’s most pressing public health crises. In 2023, an estimated 10.8 million people were diagnosed with the disease globally, with India alone reporting 2.55 million cases in 2024. The rate of new infections rose by 4.6 percent between 2020 and 2023, underscoring the urgency of finding better preventive tools.
The only currently licensed TB vaccine is BCG, developed more than a century ago. While effective against severe forms of TB in young children, it offers little protection to adolescents and adults, the groups most exposed to pulmonary TB.
VPM1002, a recombinant version of BCG developed by Vakzine Projekt Management and licensed to the Serum Institute of India, was designed to address precisely this gap.
Participants, all household contacts of newly diagnosed smear-positive TB patients and therefore at high risk of infection, were randomly assigned to receive VPM1002, Immuvac, or a placebo. They were followed for 38 months after their first dose.
The primary goal of preventing all confirmed TB, pulmonary and extrapulmonary combined, was not met by either vaccine. VPM1002 showed an overall efficacy of 21.4 percent against all TB and 19.5 percent against pulmonary TB, neither of which was statistically significant.
However, VPM1002 showed a statistically significant efficacy of 50.4 percent against extrapulmonary TB across all age groups, cutting incidence from 2.06 to 1.02 cases per 1,000 person-years. In adults aged 36 to 60, that protection rose to 79.5 percent. Immuvac showed a 33.2 percent efficacy against extrapulmonary TB overall, though this did not reach statistical significance.
Extrapulmonary TB, which affects the lymph nodes, bones, brain, kidneys, and other organs, accounts for roughly a third of all TB diagnoses and can carry mortality rates of up to 40 percent in some countries, partly because it is harder to detect and diagnose than pulmonary TB.
Some of the most striking findings came from younger age groups. In a post hoc analysis of children aged 6 to under 14, VPM1002 showed an efficacy of 64.6 percent against all forms of TB, 62.1 percent against pulmonary TB, and 77.6 percent against extrapulmonary TB. In children aged 6 to under 10, Immuvac showed a 74.2 percent efficacy against extrapulmonary TB.
Both results are particularly significant because BCG, the current standard, provides no meaningful protection beyond the age of five. The trial’s inclusion of children as young as six, alongside adults with pre-existing conditions such as diabetes, gives the findings added real-world relevance.
“Because no licensed vaccine currently protects people over five years old, this study included vulnerable household contacts aged six years and older irrespective of comorbidities, reflecting a real world scenario,” the authors noted.
Neither vaccine offered any protection to underweight participants, whether children or adults. In children under 18 of normal weight, VPM1002 showed 45.1 percent efficacy against all TB and 56.9 percent against pulmonary TB. In those who were underweight, the protection disappeared entirely.
The authors say this finding has direct implications for how any future vaccination programme should be designed, particularly in low- and middle-income countries where undernutrition and TB often coincide.
“The data emphasise the need for nutritional support along with vaccination, particularly for children over five years old,” the authors wrote.
A further notable finding was that both vaccines appeared to prevent progression from latent TB infection to active disease. Among participants who tested negative for TB infection at the start of the trial but converted to positive by six months, VPM1002 showed a 68.4 percent efficacy against all TB and 78.9 percent against extrapulmonary TB. Immuvac showed a 50.7% efficacy against all TB in the same group.
This suggests the vaccines may have utility not just as a preventive tool but also in slowing disease progression in those already exposed, a finding the authors describe as clinically important.
Neither vaccine, however, prevented initial infection with the TB bacterium, as measured by tuberculin skin test conversion rates at six months.
Both vaccines were well tolerated. Mild, self-healing reactions at the injection site were observed in roughly one third of participants in each vaccine group, significantly more than in the placebo group, as expected.
Serious adverse events occurred in fewer than 10 percent of participants across all three groups and none were linked to the vaccines. There were 109 deaths across the trial, distributed evenly across the three groups, and none were attributed to vaccination.
The PreVenTB trial was conducted across Delhi, Maharashtra, Odisha, Karnataka, Tamil Nadu, and Telangana, and funded by the Indian Council of Medical Research. It was registered with Clinical Trials Registry India. Enrolment began in July 2019 and was completed in December 2020, with follow-up concluding in July 2024.
The trial was double-blind, meaning neither participants nor clinical staff knew which vaccine or placebo had been administered. Participants received two doses administered one month apart. A second dose was given to 11,829 of the 12,717 enrolled participants.
Despite the disruption caused by the Covid-19 pandemic, 96.7 percent of participants completed the full 38-month follow-up, a retention rate the authors describe as a significant strength.
The pandemic did, however, prevent some participants from receiving their second dose within the required window, excluding them from the most rigorous per protocol analysis.
The authors suggest that VPM1002 could be considered as a booster vaccine at ages 5 to 8, 12 to 14, and 18 to 35 years, complementing the BCG vaccine already given at birth in many countries. They argue that eliminating TB will only be possible if booster doses are introduced at younger ages.
They also call for future trials to test whether combining vaccination with nutritional supplementation can extend protection to underweight children and adults with a body mass index below 18, a group currently left unprotected.
The findings place VPM1002 among a small number of TB vaccine candidates showing statistically significant protection in a large-scale phase 3 trial. The researchers acknowledge that the results may not translate directly to other countries or ethnic groups, and that further studies in specific high-risk populations are warranted.
Nevertheless, the scale, design, and real-world inclusivity of the PreVenTB trial give its findings considerable weight. For India, which carries the world’s highest TB burden, and for global health authorities working towards TB elimination, the evidence that a next-generation vaccine can halve the risk of extrapulmonary TB and offer strong protection to children represents a meaningful step forward.
