In malaria caused by Plasmodium falciparum, the PfEMP1 family of variant surface antigens encoded by var genes are adhesion molecules that play a pivotal role in malaria pathogenesis and clinical disease. These data show that parasites with a virulence-associated adhesion phenotype share infected erythrocytes surface epitopes that can be targeted by strain-transcending antibodies to PfEMP1. The existence of shared surface epitopes amongst functionally similar disease-associated P. falciparum parasite isolates suggests that development of therapeutic interventions to prevent severe malaria is a realistic goal.
Researchers have identified a key protein that is common to many potentially fatal forms of the condition. They found that antibodies that targeted this protein were effective against these severe malaria strains. "We hope this discovery will inform new treatments or vaccines to block the formation of rosettes and so prevent many life-threatening cases of malaria", said Alexander Rowe.
The protein has sticky properties that enable it to bind to red blood cells and form dangerous clumps that can block blood vessels. These clumps, or rosettes, can cause severe illness, including coma and brain damage. Presently, between 10 and 20 per cent of people with severe malaria die from it, and the disease - which is spread by blood-sucking mosquitoes - claims about one million lives per year.
Malaria parasites, once in the bloodstream, are able to alter the protein molecules on their surfaces to evade attack by the immune system. These surface proteins are usually poor targets for treatments or vaccines because they are highly variable between different malaria parasite strains.
Now, researchers have found that the surface proteins of rosette-forming parasites share similarities that may allow them to act as a target for treatments to block progress of the disease.
Scientists from the University of Edinburgh worked with collaborators from Cameroon, Mali, Kenya and The Gambia to test their antibodies against parasites collected from patients. The study, published in PLoS Pathogens, was supported by the Wellcome Trust.
Induction of Strain-Transcending Antibodies Against Group A PfEMP1 Surface Antigens from Virulent Malaria Parasites Ashfaq Ghumra, Jean-Philippe Semblat, Ricardo Ataide, Carolyne Kifude, Yvonne Adams, Antoine Claessens, Damian N. Anong, Peter C. Bull, Clare Fennell, Monica Arman, Alfred Amambua-Ngwa, Michael Walther, David J. Conway, Lalla Kassambara, Ogobara K. Doumbo, Ahmed Raza, J. Alexandra Rowe J Alexandra Rowe. PLoS Pathogens: 19 Apr 2012 doi:10.1371/journal.ppat.1002665
University of Edinburgh