The first tuberculosis (TB) vaccine to be tested for efficacy in infants in more than 40 years has proved ineffective as a TB booster shot, but it may have laid the groundwork for the next phase in TB vaccine research.
The world has relied on the Bacille Calmette-Guerin (BCG) vaccine against TB for over 90 years, despite recent controversy over its efficacy. In clinical trials, effectiveness estimates have ranged from 80 percent protection to none at all; the reasons for these differences are not yet understood.
Researchers from the South Africa TB Vaccine Initiative (SATVI), Oxford University and Aeras, a non-profit organization working on TB vaccines, were hoping a recent trial in South Africa’s Western Cape Province would change all that. They tested a new TB vaccine booster, known as MVA85A, in almost 2,800 BCG-vaccinated infants between the ages of four and six months.
While the two-year trial confirmed the vaccine was safe for use in infants, MVA85A was shown to be ineffective, meaning that it provided no additional protection to the babies who received it, according to results published online in The Lancet on 4 February.
May still hold promise
While dozens of TB vaccine candidates are in the pipeline, MVA85A was the furthest along in clinical trials, having been previously tested in adults, according to Ann Ginsberg, vice president of scientific affairs and acting chief medical officer for Aeras, which provided funding for the trial. In the adult trials, MVA85A showed positive results in protecting participants from TB.
While the vaccine was unsuccessful in HIV-negative babies, it may still hold some promise for other populations, according to Oxford University's Helen McShane, who added that researchers are still unsure why the trial failed.
The vaccine continues to be tested in HIV-positive adults and may be tested as a possible substitute for the BCG vaccine in HIV-positive babies. Made from a weakened strain of bovine TB, BCG cannot be given to babies living with HIV; the infants’ weakened immune systems make them susceptible to blood infections following BCG-vaccination.
“I have been working on TB for 15 years, and I am not going to stop now,” said McShane, who originally developed the vaccine. “The need for a new TB vaccine is more urgent than ever, and it’s crucial we maintain the momentum and keep the field moving forward.”
TB kills 1.4 million people a year globally, according to the World Health Organisation.
Study dispels myths, feeds future research
While McShane admitted the results from the MVA85A trial were disappointing, she and others involved stressed the trial had served to dispel myths about vaccine research, provide new data and pave the way for future studies.
“Ten years ago it wasn’t clear that this kind of study could be done,” McShane told IRIN. “This study represents a huge step forward… It's important to understand that only by doing trials like this can we find out what does and doesn’t work.”
The field of TB vaccine research has been complicated by the fact that scientists still aren’t sure why, with so many contracting a latent form of the disease, only 10 percent of patients will develop active TB. McShane added that scientists don’t know whether an intervention that protects against latent infection will also protect against active TB.
Because some babies in the South African trial were followed for as long as three years, McShane said the study offers valuable, previously unavailable data. This has already provided researchers with some clues about how to improve future trials involving MVA85A by, for instance, doubling doses, coupling it with another TB vaccine candidate, or working on delivery mechanisms that could introduce the vaccine directly into patients’ lungs, where BCG’s protective effect is weakest.
SATVI director Willem Hanekom added that, while the study failed to deliver positive results, it had helped develop lasting infrastructure and expertise in one of the world’s worst-affected countries; in South Africa, one in 20 people will die from the disease.
“It’s important to understand that these kinds of trials can only be done in areas with very high incidence, otherwise we can’t reach the end points necessary to see if vaccines work,” he told IRIN. “We know that the communities we work with could potentially benefit from this.”
South Africa is currently home to 1,544 clinical trials, 37 of which are related to TB, according to the South African National Clinical Trials Registrar. SATVI itself has conducted 15 TB vaccine trials.