Two doses cut the disease rate in half for people with a latent TB infection
A new tuberculosis vaccine shows promise in preventing the bacteria from causing disease in people who are infected, but aren’t sick. If approved, it could help control the spread of a disease considered one of the world’s top killers, responsible for 1.6 million deaths in 2017, according to the World Health Organization.
In a clinical trial, the new vaccine halved the number of people who developed active TB from latent infections of Mycobacterium tuberculosis, compared with those who received a placebo. Of 1,623 participants treated with two doses of the vaccine and followed for just over two years, 10 went on to develop tuberculosis, an incidence of 0.3 cases per 100 people per year. That’s compared with 22 participants out of 1,660 who received two placebo shots, or 0.6 cases per 100 people per year.
The results were reported online September 25 in the New England Journal of Medicine, a day before the United Nations General Assembly’s first high-level meeting on ending tuberculosis.
“The results are extremely encouraging,” says Richard Chaisson, an infectious disease physician and director of the Johns Hopkins Center for Tuberculosis Research, who was not involved in the research. “This is the first study of new tuberculosis vaccines that has had such dramatic results.”
The only currently available tuberculosis vaccine, bacille Calmette-Guérin, or BCG, was developed nearly a century ago in 1921. It is used to protect against the disease in childhood in many parts of the world, but it isn’t effective for adults. “A new vaccine that works in adults and children is essential” to ending the TB epidemic, Chaisson says.
In a latent tuberculosis infection, the immune system keeps the bacteria in check, preventing the development of symptoms and the spread of the bacteria to others. About one quarter of the world’s population is estimated to have a latent infection. But around 10 to 15 percent will go on to develop tuberculosis, which usually targets the lungs, causing a persistent, sometimes bloody cough, fever, chills and night sweats. The bacteria spreads via coughs and sneezes from a sick person to close contacts.
The new vaccine, M72/AS01E — one of 12 TB vaccines currently in clinical trials — is made of two proteins from the bacteria that provoke an immune response in people, plus a substance that enhances that response. Nearly 3,300 participants aged 18 to 50 years from Kenya, South Africa and Zambia were randomly assigned a treatment in the Phase II trial designed to test the drug’s efficacy. About half got two injections of the vaccine a month apart, and the other half got two placebo shots. There were more reports of headache and pain or swelling at the injection site in the vaccinated group compared with the placebo group, but no serious safety issues emerged.
Those with latent tuberculosis infections are more likely to get sick if they are also infected with HIV, have diabetes, smoke or suffer from malnutrition. TB is also more common in the first year of infection. Identifying people at higher risk and treating them with antibiotics is a viable strategy, Chaisson says, but doing so for all of the infected people is “simply not feasible.”
“A vaccine for the larger population could be an effective way to further reduce the incidence of the disease,” he says. “Focusing on people already infected is a novel approach that could have a key role in tuberculosis control.”
O. Van Der Meeren et al. Phase 2b controlled trial of M72/AS01E vaccine to prevent tuberculosis. New England Journal of Medicine. Published online September 25, 2018. doi: 10.1056/NEJMoa1803484.