"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", explains Helen McShane from the University of Oxford who developed the 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."*
The only existing vaccine, BCG, was created 90 years ago and does not prevent pulmonary TB, the most common form of the disease in adolescents and adults. TB still kills around 1.4 million people worldwide each year.
The MVA85A candidate is designed to boost immune responses that have already been primed by the BCG vaccine, so eliciting a stronger immune response against TB. Earlier trials have shown the vaccine to be safe and to produce consistently powerful immune responses in adults, thought to be important for protection against TB.
This new randomised phase 2 trial was designed to further assess the safety, immune response, and efficacy of MVA85A in preventing tuberculosis disease in children.
The trial took place in South Africa and involved 2794 healthy, BCG-vaccinated infants aged 4 months, who were randomised to receive MVA85A (1399 infants) or placebo (1395), and followed for up to 37 months.
The researchers found 39 cases of TB in the placebo group and 32 in the MVA85A group, demonstrating a non-significant vaccine efficacy of 17.3%.
MVA85A was generally well tolerated. Similar numbers of serious adverse events were reported in both groups (18% placebo vs 18% vaccine), but none were deemed to be vaccine related. Respiratory and gastrointestinal infections were the most commonly reported serious adverse events.
Discussing the disappointing results, the study authors say that "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."
Writing in a linked Comment, 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 say that the findings are not a "terminal prognosis" for MVA85A and several questions have yet to be answered including: "could MVA85A be effective against infant and childhood tuberculosis when used independently of BCG?...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 adolescents and adults against pulmonary tuberculosis in a way that it cannot protect infants?...might this vaccine work if administered to people infected with HIV?"
They 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."
Notes to Editors:
*Quote direct from author and cannot be found in text of Article.
Journal
The Lancet