Taking a new, large-scale approach, researchers tested a library of proteins from the Plasmodium falciparum parasite with antibodies produced by the immune systems of a group of infected children.
The tests measured which proteins the children's immune systems responded to, revealing antigens that had not previously been identified as possible vaccine targets and new insights into the ways antigens could be used in combination to increase protection.
"Resistance to malaria drugs is an increasing problem so vaccines are desperately needed to battle the Plasmodium falciparum parasite before it has a chance to make people sick," said Dr Faith Osier, first author of the study from the Kenya Medical Research Institute.
A group of children infected with malaria was followed over a six-month period by scientists at the Kenya Medical Research Institute (KEMRI).
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While some patients became sick, others were protected by naturally occurring antibodies that stopped the malaria parasite from penetrating their red blood cells during the blood stage of the disease, which produces severe symptoms such as fever and anaemia.
Researchers used samples taken from these children to identify combinations of antibodies that provided up to 100 per cent protection against clinical episodes of malaria.
They had previously developed a new approach to express large panels of correctly folded, full-length proteins from the Plasmodium falciparum parasite, targeting proteins involved in the invasion of human red blood cells.
In this study, Sanger Institute scientists collaborated with colleagues in Kenya to see which of them the children's immune systems had developed antibodies against.
"The use of these proteins by the Sanger Institute's Malaria Programme is helping to zero in on and exploit the weakest point in the malaria parasite's life cycle," said Rayner.
The findings of this research add further weight to the theory that a successful blood-stage vaccine needs to target multiple antigens, researchers said.