The newest tuberculosis (TB) vaccine choice, that had previously shown success in increasing levels of immune response in adults, has now demonstrated that it does not have this effect in babies.

The authors of this study, which was published in The Lancet, suggest that the findings are ‘disappointing’ and imply a critical roadblock in furthering the study of tuberculosis.

Helen McShane from the University of Oxford who developed the vaccine explained:

“Despite reaffirming the promising safety profile, the vaccine candidate MVA85A did not offer extra protection against TB in South African infants who had already received the BCG vaccine. The vaccine induced modest immune responses against TB in the infants, but these were much lower than those previously seen in adults, and were insufficient to protect against the disease.

This is the first efficacy trial of a new TB vaccine since Bacille Calmette-Guérin (BCG), a significant step in itself, and there is much that we and others can learn from the study and the data it has produced.”

BCG was the only existing vaccine to date, created 90 years ago. However, BCG does not guard against pulmonary TB, the most common variety of the disease in adults and youths.

TB causes death in nearly 1.4 million people around the globe every year.

The MVA85A vaccine was created to improve on the immune responses of the previous BCG vaccine, creating a more powerful immune response against TB.

Previous trials have shown the vaccine to be safe and consistently successful in adults, and believed to be a powerful protector against TB.

The aim of the Phase II randomized trial was to assess more closely how the human immune system responded, as well as examining the safety and efficacy of MVA85A in preventing TB in infants.

The trial, which took place in South Africa, consisted of 2,794 healthy babies who had been vaccinated with BCG, between four and six months of age. The infants were randomized to receive MVA85A (1,399 babies), or placebo (1,395) – they were followed for up to three years.

The investigators found 39 cases of TB in the placebo group and 32 in the MVA85A group, revealing an efficacy of 17.3 percent for this vaccine, which the researchers described as not-statistically significant.

MVA85A was generally well accepted. Serious side effects were documented in both groups (18 percent in vaccine group and 18 percent in placebo group), however none were accredited to the vaccine.

The most common side effects reported were gastrointestinal infections and respiratory infections.

The authors concluded, “Whether a substantially greater magnitude of response, a response that is qualitatively different, or a completely new immunological response would be necessary for protection is unclear.”

Christopher Dye, Director of Health Information in the Office of HIV/AIDS, Tuberculosis, Malaria and Neglected Tropical Diseases at WHO, and Paul Fine from London School of Hygiene and Tropical Medicine, UK, in an associated Comment in the same journal, suggest that this is not a ”terminal prognosis” for the current vaccine.

Questions that remain unanswered include:

  • If used independently of BCG, might the MVA85A vaccine be effective against infant and childhood TB?

  • In view of the variable performance of BCG in different populations, can we assume that the same results will be obtained with MVA85A in other populations?

  • Could MVA85A, working as a booster to BCG, protect teenagers and adults against pulmonary tuberculosis in a way that it cannot protect infants?

  • How effective is this vaccine for HIV-positive patients?

The authors add, “Now is a key moment in tuberculosis vaccine research. Trials such as that of Tameris and colleagues are at last generating hard evidence about protection against tuberculosis in human beings, the most important goal of immunisation. If the history of tuberculosis vaccine research teaches us anything, it is to expect surprises. We need to go on playing the high-stakes game.”

Written by Kelly Fitzgerald