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.g001, 10.1371/journal.pone.0088420.g003, 10.1371/journal.pone.0088420.g002, 10.1371/journal.pone.0088420, 10.1371/journal.pone.0088420.g004
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.

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