In a promising development that seems to put the world a step closer to a better vaccine against tuberculosis (TB), researchers today published final results from a phase 2b trial, which showed nearly 50% protection against progression to active TB.
The findings confirm earlier results first reported in 2018 for the adjuvanted subunit vaccine (M72/AS01E) developed by GlaxoSmithKline (GSK) and the International AIDS Vaccine Initiative (IAVI). Researchers published their findings today in the New England Journal of Medicine and presented them at the 50th Union World Congress on Lung Health in Hyderabad, India.
Currently, the only TB vaccine, bacilli Calmette-Guerin (BCG), has been in use since 1921. Though it is fairly effective for infants and young children, its protection varies widely in adults. Demand for a better vaccine has been rising, especially in the face of rising levels of multidrug-resistant TB.
Studies suggest that a vaccine targeted to adolescents and adults would be the strongest tool to cut levels of TB.
In September 2018, an international group of researchers published their initial findings, including that the vaccine was 54% effective in preventing latent Mycobacterium tuberculosis from progressing to the active form of the disease in young and middle-aged adults.
Solid protection, no safety signals
The study took place in three countries in which TB is endemic: Kenya, South Africa, and Zambia. It involved 3,573 HIV-negative adults ages 18 to 50. Participants received either two doses of M72/AS01E or placebo 30 days apart. Investigators followed them for 3 years.
According to the final analysis, 13 people in the vaccine group progressed to active TB, compared with 26 in the placebo group, for a 49.7% effectiveness level. Those who received vaccine doses sustained their M72-specific immune response through 3 years.
The investigators noted that the final findings did not confirm initial findings that suggested the vaccine might be more effective in those age 25 or younger.
The final results also confirm the vaccine's safety profile. The team saw no increase in adverse events, fatal events, or immune-mediated diseases over the extended follow-up period.
The researchers concluded that the results support further evaluation of the vaccine as a tool for global TB control and mark progress toward a TB vaccine for adolescents and adults that meets the World Health Organization recommended profile. They added that the results need to be confirmed in larger, longer studies and broader populations, such as people of different ages and those from different ethnic backgrounds and geographic locations.
Cautious step closer to new vaccine
Thomas Breuer, MD, MSc, chief medical officer of GSK Vaccines, said today in a news release, "These results demonstrate that for the first time in almost a century, the global community potentially has a new tool to help provide protection against TB."
He also thanked the scientists for their work in developing the vaccine with IAVI and other key groups.
Another expert said the world is one more cautious and exciting step closer to a vaccine for TB. Paula Fujiwara, MD, MPH, scientific director for the International Union Against Tuberculosis and Lung Disease (The Union), the group hosting this week's meeting in India, said in a press release today, "A vaccine is the ultimate prevention tool and the announcement today is welcome news, but as researchers discuss how to move the trial into its final phase, we simultaneously need to be doing all we can to prevent tuberculosis with medications that we already have at our disposal."
She pointed out that last year, TB killed 1.5 million people. "We cannot end the TB emergency unless we dramatically scale up prevention in those parts of the world where we are treating it. The cost of inaction is more unnecessary suffering and death," Fujiwara said.
Oct 29 N Engl J Med abstract
Sep 25, 2018, CIDRAP News scan "Adjuvanted TB vaccine shows promise in curbing active infections"
Oct 29 GSK press release
Oct 29 The Union press release