The candidate is moving to long-awaited phase III trials — if successful, it would be the first new jab against the disease in more than 100 years.
A promising vaccine candidate for tuberculosis is getting a new lease of life after two major funders have decided to pour US$550 million into its final phase of clinical trials. If successful, it would be the first new tuberculosis vaccine on the market in more than a century.
“TB has been chronically underresourced, underfunded and underappreciated for a very long time,” says Thomas Scriba, the deputy director of the South African Tuberculosis Vaccine Initiative, who will be involved in the trials.
The Bill & Melinda Gates Foundation and Wellcome announced the funding on 28 June. The vaccine candidate was developed by drug firm GSK, which has licensed it to the Gates Medical Research Institute.
Tuberculosis, caused by Mycobacterium tuberculosis, is one of the world’s biggest epidemics, claiming 1.6 million lives each year. The burden is particularly high in low- and middle-income countries. This disparity was dramatically showcased during the COVID-19 pandemic, when disruptions to health services led to increased infections.
A major challenge in fighting tuberculosis is that the bacterium can hide in the body for years before becoming an active infection that shows symptoms. Estimates suggest that one in four people globally carry this latent infection. And although the BCG vaccine (short for Bacillus Calmette-Guerin) — which was developed in 1921 and remains the only available jab against tuberculosis — protects children effectively, it offers limited help in adults.
The vaccine candidate, called M72/AS01E, aims to tackle the latent infections. And it showed promise in data published from phase II trials in 2019, demonstrating a 54% efficacy in adults who hosted the bacterium. But GSK abandoned it owing to a lack of commercial potential.
Moving to phase III trials is long overdue, says Scriba. “It’s entirely appropriate that there’s substantial investment in this field so that we can actually appropriately respond to the magnitude of the TB problem,” he adds. The trial will recruit 26,000 participants in several countries across Asia and Africa.
M72/AS01E consists of a fused protein called M72 — comprised of two M. tuberculosis antigens — and an adjuvant, AS01E. Researchers chose the antigens on the basis of their high immunogenicity — a strong ability to provoke the immune system, which stimulates the crucial T-cell response needed to fight the bacteria and to create memory cells for future attacks.
Although active tuberculosis is treatable with a six-to-nine-month course of antibodies, the lengthy process has led to high incompletion rates and antibiotic resistance. The lack of access to treatment for those in poverty also remains a barrier.
The investment in the vaccine candidate is an acknowledgement of the gap that needs to be addressed in preventing tuberculosis, says Alexander Pym, Wellcome’s director of Infectious Disease. A new vaccine would be a gamechanger, he adds.
And a handful of other tuberculosis vaccine candidates in phase III trials offer hope that a new method of prevention will reach people soon. But M72/AS01E so far surpasses the rest in the quantity and quality of data, says Ajit Lalvani, the director of the Tuberculosis Research Unit at Imperial College London.
“I’m confident that by the end of this decade, we will have a new TB vaccine on the shelves, and hopefully more than one,” says Scriba.