Tuberculosis presents a puzzling paradox. Since 1921 there has been a vaccine for it, yet the disease kills over 1.25 million people annually. The reason is simple: the BCG vaccine protects children from severe TB, but offers almost no protection against the pulmonary form that causes most adult deaths. In February 2026, a potential breakthrough arrived when the Phase 3 trial for M72/AS01E, the first serious candidate for a fundamentally new TB vaccine, hit an unexpected milestone: full enrollment of 20,000 subjects, eleven months ahead of schedule.
How M72/AS01E Differs from BCG
BCG (Bacille Calmette-Guérin) is the world's most widely administered vaccine. Since 1921, roughly four billion doses have been given. It protects children against disseminated TB and TB meningitis. Against pulmonary TB, the airborne form responsible for most infections, BCG provides almost no adult protection. That is why TB continues killing over one million people yearly despite a century of vaccination.
M72/AS01E works differently. The vaccine contains a synthetic fusion protein from two TB antigens and pairs with adjuvant AS01E, which activates two immune receptors and triggers a far stronger T-cell response than BCG. The AS01 system is not new: a similar formulation (AS01B) is used in the approved malaria vaccine Mosquirix in sub-Saharan Africa. Originally developed by GSK, M72/AS01E is now advanced by the Gates Medical Research Institute, funded by the Bill and Melinda Gates Foundation and the Wellcome Trust.
What Phase 2b Data Showed
Early efficacy data came from a placebo-controlled Phase 2b trial of 3,556 HIV-negative adults with latent TB in Kenya, Zambia, and South Africa. The New England Journal of Medicine published 2018 primary results: 54.0 percent efficacy after 24 months. The final 36-month analysis (NEJM 2019) found 49.7 percent.
Compared to COVID or measles vaccines exceeding 90 percent efficacy, this looks modest. Context matters. Some 1.7 billion people are latently infected with Mycobacterium tuberculosis globally, roughly one quarter of humanity. In high-TB burden countries, a 50 percent reduction in active disease could save hundreds of thousands of lives yearly. For the 1.25 million who died in 2023, it comes too late. For generations ahead, it could be decisive.
Phase 3: 54 Sites, Five Countries, 20,000 Volunteers
The ongoing Phase 3 trial (NCT06062238) is far larger. Twenty thousand adolescents and adults enrolled across 54 sites in Indonesia, Kenya, Malawi, South Africa, and Zambia. The selection is deliberate: these are countries where TB is endemic and vaccine efficacy can be measured in real epidemiological conditions.
In February 2026 the Gates Medical Research Institute announced full enrollment, eleven months ahead of the original schedule. This is unusual in clinical research, where recruitment normally falters due to infrastructure gaps and protocol changes. Eleven months early suggests that local networks in these five countries are robust. Critics including Doctors Without Borders note that even positive Phase 3 results will depend on pricing to determine whether high-TB countries actually gain access. That question remains entirely open.
In Comparison: How Long Other Vaccine Breakthroughs Took
From Phase 3 data to market approval, vaccines typically require years. The malaria vaccine RTS,S/AS01 (Mosquirix): Phase 3 data 2011, WHO recommendation October 2021. Ten years. The oral polio vaccine, approved in 1961, took three decades to reveal that attenuated viruses occasionally revert to virulent forms. Today, thanks to successor vaccines, polio has declined 99.9 percent and is endemic in only two countries (WHO 2024).
TB is harder than polio. Mycobacterium tuberculosis persists for decades in latent infection, resists immune responses more stubbornly than poliovirus, and spreads by respiratory droplet rather than fecal-oral route. The goal is a vaccine that does not prevent latent infection but significantly reduces progression to active disease. Not perfect protection, but substantial.
April 2028: The Pivotal Date
The Phase 3 trial primary analysis is scheduled for April 2028. If M72/AS01E meets the necessary efficacy threshold and confirms a safe profile, regulatory submissions to the WHO, FDA, and possibly EMA follow. In parallel, negotiations over procurement and pricing with Gavi and the Global Fund, two international financing mechanisms through which vaccines reach low-income countries, will occur.
A key risk remains: the 49.7 percent efficacy from Phase 2b is no guarantee for Phase 3. If the larger trial shows lower efficacy, regulatory hurdles could rise. April 2028 will determine more than just M72/AS01E's fate. It will show whether science has finally achieved what a century could not: a vaccine that effectively protects adults against history's deadliest bacterial infection.