THE GLUTAMATE-RICH PROTEIN (GLURP) OF PLASMODIUM-FALCIPARUM IS A TARGET FOR ANTIBODY-DEPENDENT MONOCYTE-MEDIATED INHIBITION OF PARASITE GROWTH IN-VITRO

Monocyte-dependent as well as direct inhibitory effects of antimalaria l antibodies point toward antigens accessible at the time of merozoite release as targets for biologically active antibodies capable of medi ating protection against Plasmodium falciparum. The glutamate-rich pro tein (GLURP), being an antigen associated with mature schizont-infecte d erythrocytes, was therefore the object of the present investigation, in which we analyzed whether anti-GLURP antibodies can either interfe re directly with merozoite invasion or act indirectly by promoting a m onocyte-dependent growth inhibition, antibody-dependent cellular inhib ition. GLURP-specfic human immunoglobulin G (IgG) antibodies, from poo led IgG of healthy Liberian adults who were clinically immune to malar ia, were purified by affinity chromatography on columns containing R0 (N-terminal nonrepetitive region of GLURP) or R2 (C-terminal repetitiv e region of GLURP) recombinant protein or synthetic peptides as ligand s. Analysis of the pattern of reactivity of highly purified anti GLURP antibodies led to the definition of at least four B-cell epitopes, On e epitope was specific for R0, two were specific for R2, and the fourt h displayed cross-reactivity between R0 and R2, None of the purified I gG antibodies had direct invasion-inhibitory effects, even at high con centrations. In contrast, when allowed to cooperate with monocytes, al l anti-GLURP IgG preparations mediated a strong monocyte-dependent par asite growth inhibition in a dose-dependent manner.