New insight into malaria could boost the search for a vaccine

Malaria mosquito
Sanger Institute scientists have discovered a protein that's pivotal to malaria infection and may be a good target for vaccine discovery.

The effort to develop an effective vaccine against malaria has been long and frustrating, largely because scientists have been unable to figure out precisely how the parasite that causes the disease, Plasmodium, infects red blood cells. Now researchers at the Wellcome Trust Sanger Institute in the U.K. believe they’ve solved a piece of that puzzle in a way that could be used to make an effective vaccine against malaria.

The key is a protein on the surface of Plasmodium called P113. By anchoring itself to another protein called RH5, P113 builds a bridge of sorts between the parasite and the cell it wants to infect, according to a press release from the institute.

Sanger Institute scientists already knew that Plasmodium parasites use RH5 to bind to a receptor on blood cells. What they didn’t know was how RH5 was able to attach itself to Plasmodium. Turns out P113 acts like Velcro, capturing RH5 on the parasite’s surface.

"We knew both proteins were essential for invasion but this is the first time anyone has seen the interaction between RH5 and P113 and showed that they work together,” said Sanger Institute author Julian Rayner in the release. P113, he added, could be a vaccine target, because if an antibody were able to block the protein, the malaria parasite would be unable to invade red blood cells.

Malaria is spread by mosquitoes and affects more than 200 million people a year. The disease caused about 500,000 deaths in 2015, according to Sanger, and 70% of its victims were children younger than 5.

Anything that disrupts RH5 would be a viable vaccine candidate, the Sanger Institute scientists suggest, because the protein is essential for infection by all of the Plasmodium strains known to cause the most severe forms of malaria. "There is a great need for an effective malaria vaccine, and the RH5 complex is the most important link between parasite and host that we yet know of,” said lead author Gavin Wright.

Many of the efforts aimed at combating malaria are focused on finding new ways to cripple Plasmodium. Scientists at Seattle BioMed, for example, have developed a weakened version of the parasite by removing some of its genes, in the hopes that it will create immunity against malaria without causing infection. Others are looking at different proteins on the surface of Plasmodium, including the National Institute of Allergy and Infectious Diseases, which has been developing a vaccine that targets the proteins AMA1 and RON2.

The Sanger Institute scientists say one advantage of RH5 is that only a small corner of the protein is needed to bind to P113. That could make it more feasible to create a vaccine that blocks P113 while simultaneously targeting other proteins. Indeed, it may take a multi-pronged approach to topple the bridge to malaria infection.