Andrew Joseph , 2025-04-28 10:00:00
A closely watched clinical trial testing what could be the world’s first new tuberculosis vaccine in a century has hit its enrollment target, ahead of expectations.
The Phase 3 study of the M72/AS01E vaccine, which is taking place at 54 sites across five countries, started delivering shots to volunteers last March. While its sponsors had originally said it may take up to two years to complete enrollment, they announced Monday that the sites in South Africa, Kenya, Malawi, Zambia, and Indonesia have successfully recruited the 20,000 participants needed for the study.
“People have generally been really enthusiastic about participating,” said Lee Fairlie, a researcher at Johannesburg’s University of the Witwatersrand and one of the principal investigators for the South Africa trial sites.
The two-dose M72 vaccine has generated high hopes among experts that they could in the coming years have a new tool to reduce deaths from and cut transmission of one of the world’s leading killers. But its clinical trial is advancing at a time when the TB field is grappling with dramatic U.S. global health funding cuts, which are already threatening treatment and surveillance programs. The U.S. has also moved to pull support for Gavi, which helps low-income countries — including those with the highest TB burdens — purchase vaccines.
“We don’t know yet what the full impacts are of the cuts, but almost certainly it will have a huge impact on TB screening, diagnosis, and probably treatment,” Fairlie said.
The vaccine trial is being funded by the Gates Foundation and the Wellcome Trust, and has not been affected by the U.S. withdrawal from the global health stage. The Gates Medical Research Institute, which is a subsidiary of the foundation, is leading the development of the vaccine, which includes an adjuvant — an ingredient that can supercharge the immune response a vaccine elicits — provided by GSK.
Tuberculosis, which is a bacterial infection, still kills more than a million people a year. It’s estimated that perhaps a quarter of the global population has a latent case, meaning cases in which individuals are not sick despite harboring the bacteria, but some percentage of them will eventually get seriously ill from their infections. When people develop this full-blown, pulmonary form of TB, it’s also when they’re likely to spread the bacterium.
The vaccine is designed to prevent adolescents and adults from advancing to the dangerous stage of an infection. An existing TB vaccine, which is known as BCG and dates back to 1921, can protect babies and young children against severe TB, but isn’t particularly effective in older people.
Those involved in the trial said it completed enrollment so quickly because it was designed to focus on sites in areas that previous epidemiological studies had identified as TB hotspots. TB is so pervasive in these communities that many people were eager to volunteer for a study, having a personal understanding of the potential impact of being able to prevent cases. Sponsors also credited the trial sites for working in their communities over time to build trust with people.
“Community engagement was something that was built in at a very early stage at all the clinical trial sites,” said Alex Pym, the director of infectious disease at Wellcome, who earlier in his career worked on TB control in South Africa.
Initially, the trial was set to enroll 26,000 people, but the researchers refined the protocol over time, and found that they could get an answer about the safety and efficacy of the vaccine with 20,000 volunteers.
The study is powered to measure a vaccine efficacy of about 50%, which the shot reached in an earlier Phase 2 study. Though researchers hope for even better results, they emphasize that having a tool that is 50% effective at reducing pulmonary TB could still have dramatic effects, given that there are millions of cases each year.
The trial is expected to take three to five years, though it will depend on how quickly cases of pulmonary TB develop among participants, some of whom will receive the vaccine and some of whom will receive placebo doses.
Even so, the vaccine’s backers are already starting to make plans to move toward potential regulatory approval, manufacturing efforts, and an eventual rollout — including decisions on which groups to target and where to launch it first.
“In the long term, we have to make the vaccine available, accessible, and affordable,” said Alemnew Dagnew, who leads M72’s clinical development at Gates MRI.
