The only tuberculosis vaccine in use today was first given to humans in 1921. Little has moved in this field since, while the disease kills roughly 1.5 million people worldwide each year. A new vaccine candidate, M72/AS01E, could change that. Its phase 3 trial has now completed enrollment and is testing in roughly 20,000 participants whether the protection seen in earlier studies can be confirmed.
Where the Research Stands
The BCG vaccine, named after the bacteriologists Calmette and Guerin, reliably protects infants against severe TB but fails in adults with latent infection. That is exactly the global problem: an estimated quarter of the world's population carries Mycobacterium tuberculosis without being ill. If the immune system is weakened, for example by HIV or malnutrition, the disease breaks out.
M72/AS01E targets this group. The candidate combines a fusion protein made of two TB antigens with the adjuvant system AS01E, also used in the approved malaria vaccine RTS,S, which amplifies the immune response. In a phase 2b trial, whose final results appeared in the New England Journal of Medicine, the vaccine showed 54 percent protection against active pulmonary tuberculosis over three years. That sounds modest, but in TB research it is a historic result. No other candidate for adults had previously shown any measurable effect.
The Phase 3 Trial
The Bill and Melinda Gates Medical Research Institute, a nonprofit arm of the Gates Foundation, sponsors the phase 3 trial. It is funded jointly by the Gates Foundation and the Wellcome Trust, with a total investment estimated at around 550 million US dollars.
The trial runs at 54 sites across five countries: South Africa, Kenya, Malawi, Zambia and Indonesia. Participants include people with and without HIV, because TB is especially dangerous for HIV-positive people and an effective vaccine is urgently needed in precisely these populations. Enrollment of roughly 20,000 volunteers was completed faster than expected, the Gates Medical Research Institute announced.
What Is at Stake
Tuberculosis is the infectious disease that kills the most people worldwide, having recently returned to first place after COVID-19. In low-income countries it mostly strikes people of working age, and the economic follow-on costs are enormous. At the same time, multi-drug-resistant strains are spreading, against which even the newest antibiotics are only of limited use.
Protection of 54 percent, if deployed at scale, would prevent millions of cases per year. WHO modelling suggests a TB vaccine at this effectiveness could save more than 75 million lives by 2050. The vaccine is being developed by GlaxoSmithKline and licensed to the Gates Medical Research Institute.
What Comes Next
Phase 3 results are expected in the coming years. If the candidate confirms its efficacy, approval by the WHO, the FDA and the EMA would be the next step, followed by negotiations over pricing and distribution for low-income countries, where the disease burden is greatest. Gavi, the vaccine alliance, has already signalled interest in adding the vaccine to its portfolio.