The binding mechanism that allows red blood cells infected with aggressive strains of malaria to stick to blood vessels has been discovered in a new study on children in Tanzania.
Researchers from the University of Copenhagen, in collaboration with Seattle Biomedical Research Institute, the University of Oxford and the National Institute for Medical Research, Tanzania, found that malaria parasites grow in red blood cells and stick to a protein found in blood vessel walls, known as the endothelial protein C receptor (EPCR).
The research builds on a study conducted in 2012, which showed that a family of parasite proteins, called PfEMP1, were responsible for cerebral binding and other severe forms of malaria infection, but the EPCR to which it binds remained unknown.
In the study, published in the journal Nature, a full-length PfEMP1 was generated in the lab. Next, the scientists used human cell microarray technology developed by UK company Retrogenix to examine which of over 2,500 human proteins this PfEMP1 protein could bind to.
University of Copenhagen assistant professor Louis Turner said; "A lot of work then went into confirming this binding in the lab and not least to show that parasites from non-immune children with severe malaria symptoms in Tanzania often bound EPCR."
The new discovery that malaria parasites bind with the EPCR may advance vaccine and drug interventions to treat malaria, says Dr Matthew Higgins from the University of Oxford.
"Now that we know the pair of proteins involved, we can begin zooming further in to reveal the molecular details of how malaria parasites grab onto the sides of blood vessels," says Higgins. "We want to know exactly which bits of the parasite protein are needed to bind to the receptor in the blood vessel wall. Then, we can aim to design vaccines or drugs to prevent this binding."
The University of Copenhagen, together with the National Institute of Medical Research, Tanzania, is now preparing Phase I trials for a vaccine to prevent parasite binding in the placenta and malaria during pregnancy.
Image: Severe malaria symptoms such as cerebral malaria often result in minor blood clots in the brain.
