PLoS ONE (Jan 2014)

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

  • Manuel E Patarroyo,
  • Martha Patricia Alba,
  • Hernando Curtidor,
  • Magnolia Vanegas,
  • Hannia Almonacid,
  • Manuel A Patarroyo

DOI
https://doi.org/10.1371/journal.pone.0088420
Journal volume & issue
Vol. 9, no. 2
p. e88420

Abstract

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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.