Characterization of domains of the phosphoriboprotein P0 of Plasmodium falciparum

Antibodies against the amino-terminal domain of the Plasmodium falciparum P 0 phosphoriboprotein were detected extensively in immune people living in m alaria endemic areas of India. It has been shown earlier that specific anti bodies raised against the PfP0N domain (17-61 amino acid) of the PfP0 prote in inhibit P. falciparum growth in vitro. To study the properties of the re st of the protein, the remaining 61-316 amino acids on the carboxy-side of the PfP0 protein were expressed as a glutathione-S-transferase fusion prote in (PfP0C). Antibodies raised against PfP0C identified the 38 kDa PO protei n on a parasite Western blot analysis. An ELISA assay using both the PfP0N and PfP0C fusion proteins showed no reactivity with malaria patient sera sa mples, but showed extensive reactions with the immune sera. Antibodies agai nst both the PfP0C and PfP0N domains were raised in rabbits and different i nbred strains of mice. T-cells from immunized mice showed lymphoproliferati on when presented with PfP0 protein domains. IgG from both anti-PfP0N and a nti-PfP0C sera inhibited the growth of P. falciparum in vitro in a concentr ation dependent manner. The IgG did not show ally significant effect on the growth of intraerythrocytic stages, but specifically inhibited re-invasion of red cells. Merozoites and sexual stages showed surface reactivity to bo th anti-PfP0N and anti-PfP0C antibodies in immunofluorescence assays. These properties strongly indicate PfP0 as a possible target for invasion-blocki ng antibodies. (C) 2000 Elsevier Science B.V. All rights reserved.