More than a century after the first tuberculosis vaccine was introduced, the world is struggling to control one of its oldest diseases. Tuberculosis (TB) continues to kill more people annually than any other infectious disease, surpassing even the COVID-19 pandemic at its peak. Yet, there is still no effective vaccine for adolescents and adults.
Once exposed to Mycobacterium tuberculosis, individuals may get infected and remain asymptomatic for years. Others develop subclinical disease, showing minimal or no symptoms while harbouring infection. A subset progresses to active TB, which may manifest as pulmonary TB (PTB) — the infectious form that drives transmission — or as extrapulmonary TB (EPTB), which affects organs beyond the lungs and is harder to diagnose, more debilitating, and sometimes fatal.
No one-size-fits-all vaccine
With such diversity in disease pathways, expecting a single “one-shot” vaccine to prevent all forms of TB may be unrealistic. This expectation has shaped global disappointment in TB vaccine development especially since most previous trials have focused primarily on preventing pulmonary TB.
Meanwhile, the burden remains immense. In many low- and middle-income countries, TB incidence ranges between 200 and 300 per 100,000 population. Reducing this to 10-20 per 100,000 — the threshold for elimination — will require sustained effort and enormous public health investment. For India, which carries one of the world’s highest TB burdens, the challenge is systemic.
India’s goal of eliminating TB is ambitious and necessary. But achieving it will require a holistic approach towards all forms of disease and all age groups moving beyond the search for a perfect solution and embracing a layered, pragmatic approach. As tools are discovered and tested, decisions will need to be made on their deployment.
The first layer is better detection. Advances in diagnostics, including tools for identifying subclinical TB, can help identify individuals at risk earlier. The second is preventive therapy, ensuring that those with latent infection receive treatment before progressing to active disease. The third — arguably the most complex — is vaccination. However, access to diagnostics and preventive therapy remains uneven, making vaccination an especially critical pillar.
Recent findings from the BMJ-published PreVenTB trial conducted by the Indian Council of Medical Research (ICMR) provide such an opportunity. Conducted across 18 sites in India and involving more than 12,700 household contacts of TB patients, the trial evaluated VPM1002 developed by SIIPL and Immuvac developed by Cadila, in a real-world, high-risk population aged six years and above, including individuals with comorbidities and varying infection status closely reflecting real life conditions.
The trial reported efficacy of VPM1002 and Immuvac as: 50.4% efficacy of VPM1002 against extrapulmonary TB (statistically significant); 64.6% efficacy of VPM1002 in children aged 6-14 years against all TB (PTB and EPTB); More than 60% efficacy of Immuvac against EPTB in children aged 6-10 years; more than 60% efficacy against progression to disease among those developing latent infection during follow-up and overall 21.4% efficacy of VPM1002 against all TB (Reference: Subho Sarkar, Consultant Intervention Pulmonologist; from LinkedIn). These are not trivial findings.
Extrapulmonary TB is the hidden burden of the epidemic, harder to diagnose, frequently missed, and associated with significant morbidity and mortality. A reduction of over 50% in such cases represents a meaningful clinical and public health impact, including reduced health-care costs and patient suffering.
The data also highlight a strong signal in school-age children and adolescents, where efficacy exceeded 60% which is an add-on benefit of vaccination in this age group. This is particularly relevant because India currently has no structured TB vaccination strategy beyond infancy. If confirmed, this could open the door to a booster-dose TB prevention strategy.
Need for nutritional support
Another important piece of evidence generated from study is the role of nutrition. Reduced efficacy was observed in individuals with low body mass index (BMI), underscoring the need for nutritional support for vaccines to work optimally in undernourished in context of broader health determinants.
From a programmatic standpoint, VPM1002 offers additional advantages. It is a single-dose vaccine based on a modified BCG platform, making it operationally simpler than multi-dose, adjuvanted vaccines in development. In a country of India’s scale, logistical simplicity is a decisive advantage. The vaccine can be manufactured at large scale and cost effectively.
TB is largely a disease of low and middle income countries (LMIC) and their governments must act proactively. Waiting for expansive solutions developed elsewhere is neither practical nor sustainable. LMICs cannot afford to wait for a silver bullet, because there is no one-stop solution for TB, especially when there are results from a Phase III trial conducted in an Indian population across all age groups (six years and above) and against all forms of TB, including PTB and EPTB. It is to be noted that no other TB vaccine trial till date has studied efficacy against EPTB and none of the currently ongoing trials worldwide has included EPTB as the efficacy end-point.
India has navigated similar public health decisions before. TrueNat was the first ‘make in India’ Molecular test approved and adopted by the National TB Elimination Programme before its World Health Organization pre-qualification study.
During the COVID-19 pandemic, Bharat Biotech’s Covaxin was initially approved in “clinical trial mode” to enable early access while additional data continued to accumulate. That decision was driven not by perfection, but by urgency and it helped accelerate protection at a critical time.
India has also demonstrated this approach with indigenous rotavirus vaccines, which were introduced despite modest efficacy and wide confidence intervals. Since then, they have helped reduce severe disease and child mortality and have been incorporated into the national immunisation programme (Bhandari et al., The Lancet, 2014).
A smarter TB strategy
TB is, in many ways, a slow-moving pandemic. Yet, it has not always been met with the same urgency in policy action. The policy question, therefore, is how innovations, including moderately effective vaccines such as VPM1002 and Immuvac, can be intelligently integrated into the TB elimination programme. Targeted use among household contacts, deployment in school-age children, and alignment with nutrition and preventive therapy programmes could together lead to a form a more effective TB control framework. A combination of vaccines effective across different indications and age groups may be needed to have an impact.
India’s TB challenge is unlikely to be solved by a single breakthrough. It will require a combination of early detection, preventive treatment, targeted vaccination against both pulmonary and extrapulmonary TB, case-based clinical management, nutritional supplementation, and sustained public health investment.
Waiting for a perfect vaccine may delay progress indefinitely, especially when no trial other than the PreVenTB trial has evaluated vaccine efficacy against both pulmonary and extrapulmonary TB in individuals aged six years and above. In contrast, deploying tools that reduce severe disease, particularly EPTB, can deliver immediate and tangible benefits.
The PreVenTB trial trial is comprehensive, well-designed and well conducted, offering a meaningful signal — perhaps a light at the end of the tunnel in TB vaccine development. Given the urgency of the challenge and the limited time to act, we must focus on solutions that are available today and supported by robust evidence of efficacy against both PTB and EPTB in individuals aged six years and above under real-world conditions, rather than wait indefinitely in the hope that better options may emerge in the future — an outcome that is far from certain.
Dr. Balram Bhargava is former Director-General, Indian Council of Medical Research (ICMR). Dr. Soumya Swaminathan is former Chief Scientist of the World Health Organization
Published – June 06, 2026 12:16 am IST