The first test of a new tuberculosis vaccine in decades has found it to be useless in preventing new infections in infants as well as in stopping the progression of existing ones.
The study, reported online by the Lancet on Monday, was conducted in about 2,800 South African infants. Although the vaccine did not protect them, it might benefit adolescents or adults.
“We’re disappointed that the trial did not have a positive outcome,” said Tom Evans, a physician who heads Aeras, the nonprofit biotechnology company in Rockville that developed the vaccine. He added, “We can’t necessarily say this kind of vaccine is not going to be efficacious in another population.”
About a third of the dozen tuberculosis vaccines in human testing bear some biological resemblance to Aeras’s product, MVA85A. The study results are unlikely to stop work on the other “candidate” vaccines, at least immediately.
Evans and others sought to put the best spin on the results.
In a Lancet commentary, two experts said the study “presents the tuberculosis vaccine community with a serious challenge” but is “at last generating hard evidence about protection against tuberculosis.”
The experiment, run in the rural outskirts of Cape Town, produced data that were both detailed and unambiguous. That is an achievement in itself, Evans said.
“We got a very clean answer that will help us move forward,” he said.
Aeras has six TB vaccines in clinical trials and a larger number in laboratory development.
About 8.7 million people became ill with tuberculosis in 2011, the latest year for which there are complete statistics, and 1.4 million died. The bacterium Mycobacterium tuberculosis is carried by about one-third of the world’s population, according to some estimates. Transmission is usually through the air, with the organism infecting the lungs. In most people the infection is “latent,” controlled by the body’s immune defenses.
A vaccine with limited effectiveness, BCG, was developed in France in the 1920s and is still given to infants in many countries, but not in the United States.
BCG does not protect against infection, but it does reduce the chance that infection will spread from the lungs to other organs such as the brain. It offers no protection to adolescents or adults, which are the groups responsible for nearly all transmission and in which the most deaths occur.
Aeras’s vaccine was designed to build upon the limited immunity BCG produces. Specifically, it was supposed to stimulate lymphocytes to produce gamma-interferon, an antimicrobial substance.
The researchers, who were South African, British and American, immunized 2,797 4-month-old infants. Half received MVA85A and half a placebo injection. All had received BCG. The children were then followed for two years.
Thirteen percent in the vaccine group became infected with the TB bacterium, and 2 percent developed active disease. In the placebo group, 12 percent became infected and 3 percent developed disease. The differences were not statistically significant.
Among the things the study demonstrated was the importance of having a placebo group in vaccine studies. It helps prevent the conclusion that anything bad that happens after immunization must be the result of the vaccine.
In the vaccine group, 80 percent of children had at least one “systemic” (body-wide) side effect. But so did 76 percent of children getting a placebo. A “serious adverse event” was reported in 18 percent of children in each group. Seven children who got the vaccine and four in the placebo group died during the study.
None of the problems were judged to come from the vaccine.
Aeras was created in 1998 under another name. It has 160 employees and an annual budget of about $50 million, but has no products for sale. The money for its work comes mainly from three sources: the Bill and Melinda Gates Foundation, and the development agencies of the British and Dutch governments.