title: Antibodies to reticulocyte binding protein-like homologue 4 inhibit invasion of Plasmodium falciparum into human erythrocytes.
abstract: Plasmodium falciparum invasion into human erythrocytes relies on the interaction between multiple parasite ligands and their respective erythrocyte receptors. The sialic acid-independent invasion pathway is dependent on the expression of P. falciparum reticulocyte binding protein-like homologue 4 (PfRh4), as disruption of the gene abolishes the ability of parasites to switch to this pathway. We show that PfRh4 is present as an invasion ligand in culture supernatants as a 160-kDa proteolytic fragment. We confirm that PfRh4 binds to the surfaces of erythrocytes through recognition of an erythrocyte receptor that is neuraminidase resistant but trypsin and chymotrypsin sensitive. Serum antibodies from malaria-exposed individuals show reactivity against the binding domain of PfRh4. Purified immunoglobulin G raised in rabbits against the binding domain of PfRh4 blocked the binding of native PfRh4 to the surfaces of erythrocytes and inhibited erythrocyte invasion of parasites using sialic acid-independent invasion pathways and grown in neuraminidase-treated erythrocytes. Our results suggest PfRh4 is a potential vaccine candidate.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
authors.forename: Wai-Hong
authors.initials: WH
authors.lastname: Tham
authors.forename: Danny W
authors.initials: DW
authors.lastname: Wilson
authors.forename: Linda
authors.initials: L
authors.lastname: Reiling
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: James G
authors.initials: JG
authors.lastname: Beeson
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology*; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000378:metabolism; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D008565:Membrane Proteins; D015800:Protozoan Proteins; C464927:RH4 protein, Plasmodium falciparum; D011956:Receptors, Cell Surface