Malaria vaccine trial shows lower efficacy in younger than in older infantsBMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e7665 (Published 13 November 2012) Cite this as: BMJ 2012;345:e7665
A candidate malaria vaccine has produced disappointing results, showing lower efficacy in young babies than it does in older infants, the latest trial data show.
The efficacy of the vaccine RTS,S/AS01 in infants aged 6-12 weeks against clinical and severe malaria was 31% and 37%, respectively, found the study, published in the New England Journal of Medicine.1 Last year phase 1 clinical trials of the same vaccine in infants aged 5-17 months showed an efficacy rate of 56% for clinical malaria and 47% for severe malaria.2
Salim Abdulla, principal investigator in the trial, which is being conducted by a partnership between the drug firm GlaxoSmithKline, the Malaria Vaccine Initiative, and 11 African research centres, said that the study showed the vaccine to be safe to use in young babies and that it worked.
He added, “The efficacy is lower than what we saw last year with the older 5-17 month age category, which surprised some of us scientists at the African trial sites. It makes us even more eager to gather and analyse more data from the trial to determine what factors might influence efficacy against malaria and better understand the potential of RTS,S.”
Around 60 malaria vaccines are currently in development, with RTS,S being in the most advanced stages and, after last year’s data were published, the one which experts were most optimistic about.
Andrew Witty, chief executive of GSK, admitted that he would like to have seen higher efficacy rates in this trial.
“But we always knew this group [of children] would be more challenging,” he said. He said that the results were still encouraging and could lead to the development of customised vaccines.
“The vaccine works despite the fact that it does not achieve the level we would have hoped for. The benefit we have seen is above that of bed nets,” he said.
More than 6000 babies in seven African countries took part in the trial. At least one episode of severe malaria occurred in 58 of 3995 infants in the vaccine group and in 46 of 2008 infants in the control group, giving a vaccine efficacy of 36.6%. Vaccine efficacy against clinical malaria episodes was 31.3%. Insecticide treated bed nets were used by 86% of the trial participants, showing that the vaccine gave protection beyond the use of bed nets.
Researchers cited several possible reasons for the lower efficacy in the younger age group. The co-administration of the malaria vaccine with the pentavalent vaccine and oral poliovirus vaccine may have resulted in immune interference, while the presence of higher levels of maternal antibodies in both the control and the vaccine group in the younger babies may have lessened the differences between the groups.
By the end of 2014 more data will be available on the longer term efficacy of the vaccine during 30 months of follow up after the third dose and on the effect of a booster dose.
Eleanor Riley, professor of immunology at the London School of Hygiene and Tropical Medicine, said, “We have known for a long time that the vaccine is partially but not completely effective and that it would need to be deployed alongside a range of other malaria prevention measures (such as insecticide treated bed nets, for example). These data confirm that the vaccine is potentially useful in significantly reducing the risk of malaria but that it is not the complete solution.”
She cited a previous smaller study of the same vaccine that showed an efficacy rate of between 25% and 70%.3
“So this much larger trial tells us that the true efficacy is closer to the lower end of that range—that is, 30%,” she said.
Cite this as: BMJ 2012;345:e7665