title: Plasmodium falciparum merozoite invasion is inhibited by antibodies that target the PfRh2a and b binding domains.
abstract: Plasmodium falciparum, the causative agent of the most severe form of malaria in humans invades erythrocytes using multiple ligand-receptor interactions. The P. falciparum reticulocyte binding-like homologue proteins (PfRh or PfRBL) are important for entry of the invasive merozoite form of the parasite into red blood cells. We have analysed two members of this protein family, PfRh2a and PfRh2b, and show they undergo a complex series of proteolytic cleavage events before and during merozoite invasion. We show that PfRh2a undergoes a cleavage event in the transmembrane region during invasion consistent with activity of the membrane associated PfROM4 protease that would result in release of the ectodomain into the supernatant. We also show that PfRh2a and PfRh2b bind to red blood cells and have defined the erythrocyte-binding domain to a 15 kDa region at the N-terminus of each protein. Antibodies to this receptor-binding region block merozoite invasion demonstrating the important function of this domain. This region of PfRh2a and PfRh2b has potential in a combination vaccine with other erythrocyte binding ligands for induction of antibodies that would block a broad range of invasion pathways for P. falciparum into human erythrocytes.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
authors.forename: Tony
authors.initials: T
authors.lastname: Triglia
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Sash
authors.initials: S
authors.lastname: Lopaticki
authors.forename: Chaitali
authors.initials: C
authors.lastname: Dekiwadia
authors.forename: David T
authors.initials: DT
authors.lastname: Riglar
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Hodder
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Ralph
authors.forename: Jake
authors.initials: J
authors.lastname: Baum
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology / Q000494:pharmacology*; D002478:Cells, Cultured; D004705:Endocytosis / Q000187:drug effects; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D006801:Humans; D052940:Merozoites / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D011485:Protein Binding / Q000187:drug effects; D054730:Protein Interaction Domains and Motifs / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011817:Rabbits
chemical_list: D000913:Antibodies, Protozoan; D015800:Protozoan Proteins; C551090:Rh2a protein, Plasmodium falciparum; C545352:Rh2b protein, Plasmodium falciparum