A large-scale efficacy trial of a promising tuberculosis (TB) vaccine will soon launch with $550 million in pledged funding from two major philanthropies, giving an enormous boost to a moribund field.
The placebo-controlled trial will begin early next year and will enroll 26,000 adults to test the vaccine, dubbed M72, at some 50 sites in Africa and Southeast Asia. The study will mostly enlist people who are free of TB symptoms but have latent infections with Mycobacterium tuberculosis, which causes the respiratory disease. The trial will primarily assess whether M72 can prevent them from developing pulmonary TB—a form of the disease that can be deadly if untreated. A currently available TB vaccine developed more than a century ago offers adults little protection against this form of the illness.
The trial will also recruit 4000 uninfected participants to assess the vaccine’s safety in the general population and test whether it can prevent infection. Trevor Mundel, who heads the global health program at the Bill & Melinda Gates Foundation, one of the trial’s funders, said at a press conference this morning that he expects the trial to take 4 to 6 years to complete.
“This is a superbly designed phase 3 trial of a very promising TB vaccine,” says Barry Bloom, an emeritus professor at the Harvard T.H. Chan School of Public Health who long has studied TB. “If it is even 50% protective in the vaccinated population, it could save millions of lives, especially in developing countries.”
So far, M72 has crawled through clinical trials. It contains an engineered protein made from two different pieces of M. tuberculosis, mixed with a potent oil-and-water emulsion called an adjuvant that revs up the recipient’s immune response.
A trial with 3300 people completed in 2015 and published in 2018 found that a group of adults with latent infections who received the vaccine had half as many cases of pulmonary TB as a group that got a placebo. In 2020, a research branch of the Gates foundation acquired the license from the vaccine’s initial developer, GSK, to further develop the candidate and—if it proves its worth in the efficacy trial—to sell it to poor countries hit hardest by TB. The Gates foundation will provide $400 million of the estimated $550 million needed to complete the trial, with the Wellcome Trust footing the rest of the bill.
Mundel said it has taken so long to launch this study in part because it’s “an enormous enterprise for both of our organizations” that required extensive negotiations. Researchers also had to conduct epidemiological studies to identify sites around the world that had the highest burden of latent TB, and thus the highest risk of pulmonary disease—a step that will streamline the process of evaluating the vaccine.
In 2021, TB sickened 10.6 million people, and 1.6 million people died from the disease, according to World Health Organization estimates. A widely used TB vaccine known as bacille Calmette-Guérin (BCG) contains a weakened version of Mycobacterium bovis, which causes TB in cattle. It offers some protection to young children, but does little to prevent pulmonary disease in adolescents and adults. BCG also offers little protection in some areas of the world, such as tropical regions of India and Africa. Research suggests that in these regions, people have widespread immunity to mycobacteria in their environments that are close to the one that causes TB—lowering their susceptibility to TB infection and obscuring the impact of the vaccine.
The foundations backing the study have yet to select a manufacturer to produce low-cost versions of the vaccine if it proves safe and effective—GSK retains the rights for high-income countries. But they insist the vaccine ultimately will reach low- and middle-income countries, which have the world’s greatest TB burden. “Central to our mission is making sure that whatever we invest in is ultimately, where it’s in our power, to make it accessible and affordable,” said Wellcome’s Alexander Pym, a commitment that Mundel echoed.
Mundel says he hopes the clinical trial sites the research teams establish for this trial can also help evaluate the 17 other TB vaccines in development. “There is a rich portfolio of TB vaccines coming behind [M72],” he said. Keeping the sites active to test them “will best justify this very large investment,” he says, creating “an evergreen, viable network for the future vaccine work.”
