Tuberculosis vaccine hopes dashed

A major trial of a new booster vaccine has ended in failure, marking a major setback in the fight against tuberculosis (TB).

It was the first big study in infants since the Bacillus Calmette-Guerin (BCG) vaccine was introduced in 1921.

BCG is only partially effective against the bacterium that causes TB, which is why several international teams are working on new vaccines.

The latest, known as MVA85A, failed to protect babies who had already had BCG.

The trial, in South Africa, involved 2,794 healthy children aged four to six months, half of whom received MVA85A and the rest a placebo.

They were followed up for an average of two years.

The researchers, reporting in the Lancet medical journal, found 32 cases of TB in those who had received the vaccine compared with 39 in the placebo group.

This gave an effectiveness of 17%, which is so low as to be statistically non-significant.

'Disappointing'

Designed to boost the immune responses that have been primed by the BCG vaccine, MVA85A has been undergoing human trials for more than a decade, showing it to be safe and to stimulate a high level of immune response in adults.

Prof Helen McShane, from the University of Oxford, who developed the vaccine, said: "[It] 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, a significant step in itself, and there is much that we and others can learn from the study and the data it has produced."

In an accompanying editorial Christopher Dye, of the World Health Organization (WHO), and Paul Fine, from the London School of Hygiene and Tropical Medicine, said although the results were disappointing they were "not a terminal prognosis for MVA85A, or for any of the other tuberculosis vaccines in development".

They added: "Now is a key moment in tuberculosis vaccine research.

"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."

The MVA85A study was funded by AERAS, the Wellcome Trust and Oxford-Emergent Tuberculosis Consortium.

AERAS, a not-for-profit organisation, was set up to develop new TB vaccines. MVA85A was the most advanced of six vaccine candidates it is helping develop.

Dr Tom Evans, interim CEO of AERAS said: "Because of the urgency to control the global TB epidemic, and despite these trial results, we remain steadfast in our belief that an improved TB vaccine will be developed and represents the best hope for eliminating the disease."

TB is a major global health problem with an estimated 8.7 million cases and 1.4 million deaths a year, according to the WHO.

The disease is the leading cause of death among people with HIV in South Africa.

Historic

Dr Richard White, an epidemiologist at the London School of Hygiene & Tropical Medicine and Director of the TB Modelling and Analysis Consortium, said:

"This is a very disappointing result, but this was just the first of around 12 new tuberculosis vaccines currently being tested in humans and around 50 vaccine candidates currently being tested in the lab. It was a historic trial, the first of a new TB vaccine for nearly a century. It will lead to much valuable knowledge to help us design effective vaccines in the future. "