The eagerly awaited results from the world's first large-scale trial of a malaria vaccine are in, and they confirm what other, smaller studies had shown: The vaccine, called RTS,S, offers partial protection, cutting episodes of malaria in babies and toddlers in half. Although not nearly as impressive as most vaccines currently in use, experts say the vaccine could help curtail malaria's massive death toll significantly.
RTS,S was developed by GlaxoSmithKline (GSK) Biologicals in Rixensart, Belgium, in partnership with the PATH Malaria Vaccine Initiative (MVI). It contains an engineered protein that combines a protein fragment from the malaria parasite, Plasmodium falciparum, and a protein from the Hepatitis B virus that helps trigger a strong immune response. The first field trial, in 2000 children in Mozambique, showed that RTS,S lowered the risk of developing malaria symptoms by 30%, with no severe side effects. Phase II trials in Mozambique, Kenya, and Tanzania have consistently shown that the vaccine can cut the number of malaria episodes by between 35% and 53%.
The phase III trial—the final test—enrolled more than 15,000 babies aged 6 to 12 weeks and toddlers between 5 and 17 months across sub-Saharan Africa. All were scheduled to receive three doses, each 1 month apart; a subgroup will receive a booster dose 18 months later. Today, the partnership presented the first data at a meeting at the Bill & Melinda Gates Foundation, which supported the trial; the results were also published online today by The New England Journal of Medicine.
The data show that in 6000 children aged 5 to 17 months, three doses of the vaccine cut the risk of any episode of malaria by 56% and the risk of severe disease by 47%. The vaccine also looks fairly safe. Children who received the vaccine had a slightly higher rate of seizures than those who received the control injection, a rabies vaccine. But the independent safety board that keeps watch over the trial has not raised any concerns, says MVI Director Christian Loucq.
"I am thrilled," says Joe Cohen, who leads the malaria vaccine project at GSK Biologicals. The fact that the huge trial confirms results from smaller predecessors is "fabulous," he says. Robert Newman, head of the World Health Organization's (WHO's) malaria program, agrees. "The results are in line with what we expected. But one fears they won't hold up, so 'in line' is very encouraging."
Vaccines against viruses and bacteria usually have protection rates of up to 90%, but P. falciparum, a parasite with a complex lifecycle, has proven a much more difficult target, which is why the vaccine should be combined with other strategies, such as bed nets, says Cohen. "This vaccine will not be a magic bullet against what is a very, very difficult disease," says Cohen. "It is one weapon to be added to an arsenal of other interventions."
The trial will continue for 3 more years, and more work will be needed to determine where and how RTS,S might have the most impact. GSK, which has invested more than $300 million in RTS,S to date, has pledged to keep the price as low as possible—just manufacturing costs plus a small return to be reinvested in development of second-generation malaria vaccines or vaccines against other neglected tropical diseases.
Even so, the complex vaccine will be expensive by developing world standards, and its cost-effectiveness is a major issue for vaccine developers and public health experts, says Scott Filler of the Global Fund to Fight AIDS, Tuberculosis and Malaria. "The key question is going to be cost," he says, given the limited funds available for fighting malaria. "These are going to be incredibly challenging questions for which we—the community as a whole—don't have answers yet."