Using the PfEMP1 head structure binding motif to deal a blow at severe malaria.

Abstract

Plasmodium falciparum (Pf) malaria causes 200 million cases worldwide, 8 million being severe and complicated leading to ∼1 million deaths and ∼100,000 abortions annually. Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) has been implicated in cytoadherence and infected erythrocyte rosette formation, associated with cerebral malaria; chondroitin sulphate-A attachment and infected erythrocyte sequestration related to pregnancy-associated malaria and other severe forms of disease. An endothelial cell high activity binding peptide is described in several of this ∼300 kDa hypervariable protein's domains displaying a conserved motif (GACxPxRRxxLC); it established H-bonds with other binding peptides to mediate red blood cell group A and chondroitin sulphate attachment. This motif (when properly modified) induced PfEMP1-specific strain-transcending, fully-protective immunity for the first time in experimental challenge in Aotus monkeys, opening the way forward for a long sought-after vaccine against severe malaria.

• Authors: Manuel E Patarroyo, Martha Patricia Alba, Hernando Curtidor, Magnolia Vanegas, Hannia Almonacid, Manuel A Patarroyo
• Journal: PloS one (PLoS One) Vol. 9 Issue 2 Pg. e88420 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24516657 (Publication Type: Journal Article)

Chemical References

• Malaria Vaccines
• Protozoan Proteins
• erythrocyte membrane protein 1, Plasmodium falciparum
• Chondroitin Sulfates

Topics

• Animals
• Aotidae
• Chondroitin Sulfates (metabolism)
• Erythrocytes (immunology, metabolism)
• Humans
• Malaria Vaccines (immunology)
• Malaria, Falciparum (immunology, metabolism, prevention & control)
• Protein Binding (immunology)
• Protozoan Proteins (metabolism)