Danish researchers one step closer to developing a cerebral malaria vaccine – University of Copenhagen

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14 March 2017

Danish researchers one step closer to developing a cerebral malaria vaccine

Malaria

Cerebral malaria is one of the most serious forms of malaria, which can cause both death and severe neurological damage. Most deaths are among children. Researchers from the Faculty of Health and Medical Sciences at the University of Copenhagen have made a discovery which is the first step towards developing a vaccine against cerebral malaria.

Every year, more than 200 million people are affected by malaria, and more than 500,000 die from malaria infection. Most deaths occur in children under the age of five, many of whom live in Africa. There are three serious sub-strains of malaria, one of them being cerebral malaria, which can cause severe neurological complications and result in death. A research team from the Faculty of Health and Medical Sciences at the University of Copenhagen has now identified a group of malaria proteins, bringing them one step closer to the goal of developing a vaccine that can protect children against cerebral malaria.

There are two carriers of the malaria parasite: mosquitoes and people. When a malaria-infected mosquito sucks blood from a human being, it simultaneously passes on the malaria parasite. Inside the human organism, the parasite takes up residence in the red blood cells and is in this way transported around the body through the blood stream. As they circulate, the infected blood cells adhere to the inner wall of the arteries. When a concentration of malaria parasites builds up in the brain, it causes increased pressure, which in many cases results in neurological injury – and in the worst case – death.

The figure illustrates how the protein (PfEMP1) on the surface of the malaria-infected red blood cell binds to the ICAM-1 Receptors

“In order for the blood cells to become entrenched in the blood stream, the malaria protein in the blood cell must be able to bind to the receptors located on the inside of the arteries. There is a particular receptor, ICAM-1, which is especially associated with cerebral malaria. We have identified the proteins that bind ICAM-1, and have – in collaboration with researchers at the University of Oxford – mapped the binding structure. This means that we now know what part of the malaria protein to target with a vaccine to prevent the parasite from attaching itself and thus prevent the development of cerebral malaria,” explains Professor Anja T.R. Jensen from the Centre for Medical Parasitology, Department of Immunology and Microbiology (ISIM).

Cerebral malaria affects both patient and society
For many of the children infected with cerebral malaria, the future prospects are not particularly bright. Even though the children are treated, the mortality rate is between 15 and 20%, and many of the survivors are left with severe neurological damage.  Cerebral malaria may, among other things, negatively impact learning, language and inhibit motor skills.

“Finding a vaccine to protect children against malaria is about saving lives as well as improving living conditions. This applies equally to the individual child and society as a whole. The neurological damage may have a major impact on the children’s ability to learn, cause them to become incapacitated, and generally have a negative impact on the economies of the countries affected,” says postdoc Yvonne Adam from the Centre for Medical Parasitology, ISIM.

The study “Structure-Guided Identification of a family of Dual Receptor-Binding PfEMP1 that Is Associated with Cerebral Malaria” has just been published in the scientific journal Cell Host & Microbe. The most important contributors are the Novo Nordisk Foundation, the Lundbeck Foundation and the Danish Medical Research Council. The research is carried out in cooperation with the University of Oxford.


Contact:
Professor Anja T. R. Jensen, email: atrj@sund.ku.dk, Tel.: +45 35 32 76 82 
Postdoc Yvonne Adams, email: yadams@sund.ku.dk, Tel.: +45 35 33 76 75