title: The glutamate-rich protein (GLURP) of Plasmodium falciparum is a target for antibody-dependent monocyte-mediated inhibition of parasite growth in vitro.
abstract: Monocyte-dependent as well as direct inhibitory effects of antimalarial antibodies point toward antigens accessible at the time of merozoite release as targets for biologically active antibodies capable of mediating protection against Plasmodium falciparum. The glutamate-rich protein (GLURP), being an antigen associated with mature schizont-infected erythrocytes, was therefore the object of the present investigation, in which we analyzed whether anti-GLURP antibodies can either interfere directly with merozoite invasion or act indirectly by promoting a monocyte-dependent growth inhibition, antibody-dependent cellular inhibition. GLURP-specific human immunoglobulin G (IgG) antibodies, from pooled IgG of healthy Liberian adults who were clinically immune to malaria, were purified by affinity chromatography on columns containing R0 (N-terminal nonrepetitive region of GLURP) or R2 (C-terminal repetitive region of GLURP) recombinant protein or synthetic peptides as ligands. Analysis of the pattern of reactivity of highly purified anti-GLURP antibodies led to the definition of at least four B-cell epitopes. One epitope was specific for R0, two were specific for R2, and the fourth displayed cross-reactivity between R0 and R2. None of the purified IgG antibodies had direct invasion-inhibitory effects, even at high concentrations. In contrast, when allowed to cooperate with monocytes, all anti-GLURP IgG preparations mediated a strong monocyte-dependent parasite growth inhibition in a dose-dependent manner.
authors.affiliation: Department of Clinical Biochemistry, Statens Seruminstitut, Copenhagen S, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Theisen
authors.forename: S
authors.initials: S
authors.lastname: Soe
authors.forename: C
authors.initials: C
authors.lastname: Oeuvray
authors.forename: A W
authors.initials: AW
authors.lastname: Thomas
authors.forename: J
authors.initials: J
authors.lastname: Vuust
authors.forename: S
authors.initials: S
authors.lastname: Danielsen
authors.forename: S
authors.initials: S
authors.lastname: Jepsen
authors.forename: P
authors.initials: P
authors.lastname: Druilhe
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D000913:Antibodies, Protozoan / Q000276:immunology* / Q000302:isolation & purification; D000953:Antigens, Protozoan / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D003429:Cross Reactions / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes / Q000276:immunology; D004912:Erythrocytes; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000302:isolation & purification; D016778:Malaria, Falciparum / Q000276:immunology*; D009000:Monocytes; D010455:Peptides / Q000276:immunology; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D019138:Antibodies, Blocking; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000939:Epitopes; D007074:Immunoglobulin G; D010455:Peptides; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C072492:glutamate-rich protein, Plasmodium