After decades of frustration for scientists trying to create a useful vaccine against the malaria parasite Plasmodium falciparum, a public-private partnership said on Friday (October 15) it has produced a promising candidate.

GlaxoSmithKline's RTS,S/AS02A, a fusion of immunogenic components of the circumsporozoite protein with hepatitis B surface antigen, plus a proprietary adjuvant, achieved a 58% efficacy against severe disease in 1- to 5-year-olds in a phase IIb trial in Mozambique, with signs of better efficacy among the younger end of the range. Nearly 40% of malaria mortality is believed to occur in children under 1 year old.

Pedro Alonso of the University of Barcelona, who led the clinical trial design and implementation, told The Scientist, "The importance of this result is that it's the first conclusive evidence that we can produce a malaria vaccine. Up to now, it's just been controversy in the international research community… after this paper, that discussion is over."

"It's the first conclusive evidence that a vaccine that prevents infection and disease in children living in endemic areas of Africa is possible," Alonso said. There must be trials of safety and efficacy in children under 12 months, but "I think we should be hopeful." Details of the results of this proof of concept study appear this week in The Lancet.

Joe Cohen, co-developer of the vaccine at GlaxoSmithKline Biologicals, where he is director of Research and Development for Emerging Diseases, told The Scientist: "We're extremely happy. We're elated." He pointed out in a statement that there was skepticism in the scientific community about the approach being taken. "But we were highly committed and kept at it for over 15 years."

However, Alan Schapira, coordinator of the strategy and policy team of the Roll Back Malaria Department at the World Health Organization (WHO), sounded a note of caution over the new results. Speaking to The Scientist on Friday (October 15), he stressed some statistical uncertainties.

There were 1605 children in the trial, but many fewer cases of severe malaria, Schapira pointed out. Taking two standard deviations above and below the result would give a range of around 20 to 80% efficacy against severe disease, he said. And the protective efficacy against infection was only 30%.

The vaccine is designed to protect against infection rather than disease, preparing the immune system to attack the sporozoite—the malaria stage that first enters the bloodstream from the mosquito bite and within 30 minutes is sequestered in the liver to begin the transformations and multiplications that cause disease.

"So, it comes almost as a good surprise that it protects so well against severe malaria," said Schapira. "One could think of some explanatory hypothesis… but we still need to be very cautious. It's really encouraging, but let's see what larger scale trials are going to show us." The central value of 58% efficacy against severe disease "would make it a fine adjunct to our malaria control strategies," said Schapira. "But we'd still need vector control and effective treatment."

Nevertheless, this remains the best candidate malaria vaccine result obtained to date. "This is has been a very rich collaboration," said Alonso, "which tells us how the international community can tackle the very complex health problems of the world and of developing countries."

The research was conducted by a cooperative including, among others, GlaxoSmithKline Biologicals, University of Barcelona, University of Maputo in Mozambique, the government of Mozambique, and local communities in Mozambique, with the Malaria Vaccine Initiative, and supported in part by funding from the Bill and Melinda Gates Foundation.