Trial results are promising, but marred by poor efficacy against severe forms of the disease.
The world's leading candidate for a malaria vaccine has cleared another hoop on the way to widespread use, proponents say. But the vaccine's low efficacy against severe forms of the disease has disappointed some experts. The latest findings from a phase III clinical trial in thousands of African children appear today in The New England Journal of Medicine1.
This vaccine against the Plasmodium falciparum parasite — called RTS,S/AS01 and funded by GlaxoSmithKline and the PATH Malaria Vaccine Initiative — has carried the hopes of many since rising to the fore in the race to develop a malaria vaccine. If approved by regulators, it would be the first vaccine against malaria, and the first against a parasitic disease, notes Vasee Moorthy, who studies malaria at the Initiative for Vaccine Research, run by the World Health Organization (WHO).
Beginning in March 2009, 15,460 children split into two age groups — 6–12 weeks or 5–17 months — were given either the vaccine or a control. In the first 6,000 children aged 5–17 months, the vaccine had an efficacy against clinical malaria of around 50%. The efficacy of the vaccine against severe malaria in this same group was around 45%.
"The results of this study represent a major scientific achievement, for which the WHO congratulates the vaccine development partnership," says Moorthy. "These promising results are in line with the earlier results seen in phase II studies. Malaria has never had a vaccine get this far."
Half-full, or half-empty?
Not all experts are quite as optimistic. The vaccine's overall efficacy against severe malaria in all age groups was around 31%. This was disappointing to researchers — previous, smaller trials had suggested that the vaccine would prove to be more effective against the severe form of the disease than against the clinical manifestation, which is defined as a temperature of 37.5 °C or higher and significant amounts of P. falciparium in the blood.
Adrian Hill, director of the Jenner Institute in Oxford, UK, which develops vaccines against global diseases, says it is a great step that the trial has been done in a large number of children. But "overall, it's really disappointing in terms of what we had hoped", he says, adding that the low efficacy for severe malaria "really is a problem".
Kim Mulholland, a professor of child health and vaccinology at the London School of Hygiene and Tropical Medicine, says that although the low numbers are surprising and "quite disappointing", researchers should not necessarily rule out RTS,S. The vaccine's higher efficacy in older children is much more promising, he says. "Forty-five per cent of a pretty common condition is something that's really worth going for."
And Tsiri Agbenyega, head of the Malaria Research Unit at Komfo Anokye Hospital in Kumasi, Ghana and chairman of the RTS,S Clinical Trials Partnership Committee, remains optimistic. "Obviously one would want to have a higher efficacy when it comes to severe disease, but we're still hoping we can improve on the vaccine as we go along with the trials."
Thomas Smith, who studies the epidemiology of malaria at the Swiss Tropical Institute in Basel, says it may be premature to say exactly what the efficacy is based on the early data from the trial, which is still ongoing.
"For me, the main question is how long the efficacy is going to last," he says. "The duration of efficacy is something we're uncertain about. We should see this as a very positive step in that it's the first time a malaria vaccine has made it so far. But we shouldn't assume this is going to be widely deployed."
In a year, the study team will have finished collecting and processing the vaccine efficacy data for clinical and severe malaria in the younger group.
The WHO will assess the potential for the vaccine to prevent the spread of malaria when the full trial results come out in 2014. "Depending on the results, the WHO may be able to issue a recommendation for use of RTS,S as early as 2015," says Moorthy.
The RTS,S Clinical Trials Partnership et al. N. Engl. J. Med. http://dx.doi.org/10.1056/NEJMoa1102287 (2011).
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Cressey, D. Malaria vaccine one step closer to approval. Nature (2011). https://doi.org/10.1038/news.2011.601