The new tuberculosis vaccine MVA85A has been found to be less effective than initially thought, prompting widespread consternation in the press. The Daily Mail reported that the vaccine "does little to protect children", while BBC News and The Guardian said hopes for the vaccine had been "dashed". Although the stories are based on solid science, the news is actually less worrying than the headlines suggest.
The reports are based on an early trial of a booster vaccine that researchers hope might help improve the effectiveness of the existing BCG vaccine. Although the BCG is effective in the UK, new vaccines and boosters are needed as it is less effective in countries with a high burden of tuberculosis (TB).
The research focused on the safety and effectiveness of the vaccine, which had previously shown much promise. Despite the disappointing results, researchers hope to test the vaccine further on different populations, which may be more successful.
Progress in medical knowledge is not just based on success stories – failures also add to a greater scientific understanding. Although the results of this trial of MVA85A may be disappointing, they will feed back into the development of new vaccines against tuberculosis.
The study was carried out by researchers from South Africa, the US and the UK. It was funded by Aeras, the Wellcome Trust and the Oxford-Emergent Tuberculosis Consortium (OETC) Ltd. Aeras is a non-profit product development organisation dedicated to the development of products to prevent tuberculosis. The Oxford-Emergent Tuberculosis Consortium is a joint venture between the University of Oxford and Emergent BioSolutions Inc.
It was published in the peer-reviewed medical journal The Lancet.
The research was covered well by BBC News, The Guardian and The Independent.
A randomised controlled trial was performed to assess the safety and efficacy of a new tuberculosis vaccine, comparing the vaccine with a placebo.
This is the ideal type of study design to address this question.
The researchers enrolled 2,797 healthy infants aged between four and six months from a rural region near Cape Town, South Africa.
All of the infants had previously received the BCG vaccine. They were randomised to receive either the new tuberculosis vaccine MVA85A (1,399 children) or a placebo that consisted of a candida skin test antigen (1,398 children).
The researchers wanted to see if the vaccine was safe by monitoring the incidence of adverse and serious adverse events in all vaccinated infants. They also looked at whether the vaccine could prevent tuberculosis in children who had received at least one dose of either the placebo or the MVA85A vaccine who had not deviated from the study protocol.
The infants were followed for 24.6 months on average. In that time, more infants who had the MVA85A tuberculosis vaccine had adverse events than infants who received the placebo (89% had at least one adverse event in the vaccine group, compared with 45% in the placebo group).
However, the number of children who had adverse events that affected their whole body (systemic) or who had serious adverse events was similar for the two groups, and none of the serious adverse events was related to MVA85A.
Thirty-two infants in the MVA85A tuberculosis vaccine group developed tuberculosis, compared with 39 infants in the placebo group. The efficacy of MVA85A against tuberculosis was not statistically different to the placebo as the slightly lower rate of tuberculosis in the vaccine group could have been the result of chance.
The researchers wanted to see how many children were infected with M. tuberculosis, the bacteria responsible for most cases of tuberculosis, even if they did not have any symptoms.
They found that 178 children (13%) who received the MVA85A vaccine were infected with the bacteria, compared with 171 (12%) children who received the placebo. Again, this was not a statistically different result.
The researchers found that the MVA85A vaccine was safe and there was some evidence that it stimulated an immune response. However, they could not explain why the MVA85A vaccine did not provide protection against the M. tuberculosis infection or tuberculosis.
They state that the reasons for this need to be explored and that, "Information gained from the successful execution of this study will aid the planning of future trials and vaccination strategies. Substantial global efforts to develop an improved vaccine against tuberculosis must continue".
The effectiveness of the BCG against tuberculosis is variable and has been found to be less effective in countries such as South Africa, where as many as 1% of the population has TB. An effective booster vaccine would therefore be useful.
Although this study found the new vaccine is safe, it does not appear to have performed better than the placebo in children who had already had the BCG vaccine when the researchers looked at:
Despite this setback, several further lines of investigation are being pursued by researchers. They now want to look at whether the MVA85A vaccine might work better in other sub-populations, and whether it might improve protection against pulmonary tuberculosis (a type of lung infection caused by the M. tuberculosis bacteria) in people who have HIV, for example.
Other TB vaccines are in development, and the knowledge gained during this study will be useful. The researchers also collected samples assessing immune response to the vaccine, and these may be useful to determine what sort of response is required for protection against TB.
Although the results of the effectiveness of MVA85A in this trial may be disappointing, the findings are sure to help the future development of vaccines against tuberculosis.