Plasmodium vivax, P-cynomolgi, and P-knowlesi: Identification of homologueproteins associated with the surface of merozoites

We have identified a Plasmodium vivax merozoite surface protein (MSP) that migrates on SDS-polyacrylamide gels at a M-r of about 185 kDa. This protein was recognized by a P. vivax monoclonal antibody (mAb) that localizes the, protein by immunofluorescence to the surface of merozoites and also immuno precipitates this protein from NP-40 detergent extracts of [S-35]methionine metabolically radiolabeled P. vivax schizonts. The P. vivax MSP does not b ecome biosynthetically radiolabeled with [H-3]glucoamine, [H-3]myristate, [ H-3]palmitate, or [H-3]mannose, indicating that this P. vivax MSP is hot po sttranslationally modified and bound to the merozoite membrane by a glycosy lphosphatidylinositol (GPT) lipid anchor. Thus, in this respect, this prote in is different from members of the MSP-1 protein family and from MSP-2 and MSP-4 of P. falciparum. The mAb cross-reacts with and outlines the surface of P. cynomolgi merozoites and immunoprecipitates a 150-kDa P. cynomolgi h omologue. The mAb was used as an affinity reagent to purify the native homo logous MSP ham NP-40 extracts of P. cynomolgi mature schizonts in order to develop a specific polyclonal antiserum. The resulting anti-PcyMSP rabbit a ntiserum cross-reacts strongly with the P. vivax 185-kDa MSP and also recog nizes an analogous 110-kDa protein from P. knowlesi. We have determined via an immunodepletion experiment that the 110-kDa P. knowlesi NSP corresponds to the PK 110 protein partially characterized earlier (Perler et al. 1987) . The potential of P, vivax MSP as a vaccine candidate was addressed by con ducting in vitro inhibition of erythrocyte invasion assays, and the IgG fra ction of both the P. vivax MSP mAb and the P. cynomolgi MSP rabbit antiseru m significantly inhibited entry of P. vivax merozoites. We denote, on a pre liminary basis, these antigenically related merozite surface proteins PvMSP -185, PcyMSP-150, and PkMSP-110. (C) 1999 Academic Press.