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- 02/14/2017

Malaria vaccine target’s invasion partner uncovered

Pharma Horizon

A molecular bridge attaches the plasmodium parasite to the red blood cell. Credit Sanger Institute: Genome Research Ltd

A team at the Wellcome Trust Sanger Institute has discovered how a promising malarial vaccine target – the protein RH5 – helps parasites to invade human red blood cells.  Published today in Nature Communications, the study reveals that a previously mysterious protein on the surface of the parasite called P113 anchors the RH5 protein, and provides a molecular bridge between the parasite and a red blood cell.

The discovery could be used to make a more effective malaria vaccine.

More than 200 million people a year are infected with malaria and the disease caused the deaths of nearly half a million people worldwide in 2015. Children under the age of five made up 70 percent of these deaths. Malaria is caused by Plasmodium parasites which are spread by infected mosquitos and an effective vaccine would vastly improve the lives of millions of people.

Previous research by teams at the Sanger Institute discovered that to invade human red blood cells, Plasmodium parasites need RH5 to bind to a receptor called basigin on the surface of the blood cells. However, it was not known how RH5 was attached to the surface of the parasite.

In this latest study the researchers discovered that when the Plasmodium RH5 protein is released, it is immediately caught by another parasite protein called P113. Thousands of P113 molecules on the surface of each parasite act like a Velcro chain, capturing RH5 at the surface of the parasite. The tethered RH5 then binds to the basigin receptor on the human red blood cell, bridging the gap just long enough to let the parasite invade the blood cell.

Two more proteins – CyRPA and RIPR – were already known to be essential to the parasite and to form a complex with RH5.  The researchers uncovered the details of how these three proteins bound to each other* and that only one small part of the RH5 protein was needed to bind P113. This small region could become an easy-to-produce and cost-effective part of a multi-component malaria vaccine.