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

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PloS one, ISSN: 1932-6203, Vol: 9, Issue: 2, Page: e88420

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10.1371/journal.pone.0088420; 10.1371/journal.pone.0088420.g001; 10.1371/journal.pone.0088420.g004; 10.1371/journal.pone.0088420.g002; 10.1371/journal.pone.0088420.g003
PMC3917906; 3917906
Manuel E. Patarroyo; Martha Patricia Alba; Hernando Curtidor; Magnolia Vanegas; Hannia Almonacid; Manuel A. Patarroyo; Leonardo Mariño-Ramírez
Public Library of Science (PLoS); Universidad del Rosario; Figshare
Agricultural and Biological Sciences; Biochemistry, Genetics and Molecular Biology; Medicine; 616.9362; ERYTHROCYTE-MEMBRANE PROTEIN-1; CHONDROITIN-SULFATE-A; PLASMODIUM-FALCIPARUM; ANTIMALARIAL VACCINE; PLACENTAL MALARIA; ALPHA-DOMAINS; EXPRESSION; ANTIBODIES; PARASITES; PEPTIDES; Plasmodium; Malaria; Inmunología; Biological Sciences; Chemistry; Biochemistry; immunology; microbiology; Protozoology; Parastic protozoans; Plasmodium falciparum; Virology; Animal models of infection; Model organisms; Animal models; Synthetic chemistry; Clinical immunology; immunity; vaccination; vaccines; Vaccine development; Infectious diseases; Parasitic diseases; malaria; Tropical diseases (non-neglected); Public health; habps; variability; characterization; crystallized; duffy; binding; domains; motif; trials; modified; efficacy; induced; derived; peptides; biochemistry; protozoology; parastic protozoans; plasmodium falciparum; virology; animal models of infection; model organisms; animal models; synthetic chemistry; clinical immunology; vaccine development; infectious diseases; parasitic diseases; tropical diseases (non-neglected); public health
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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.