Poster Presentation First Malaria World Congress 2018

Plasmodium vivax Reticulocyte Binding Protein 2p1: Functional activity and host immune response (#253)

Anongruk Chim-ong 1 , Thitiporn Surit 2 , Sittinont Chainarin 1 , Jetsumon Sattabongkot 3 , Liwang Cui 4 , Wanlapa Roobsoong 3 , Wang Nguitragool 1
  1. Molecular Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
  2. Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
  3. Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
  4. Entomology, Pennsylvania State University, University Park, PA 16802, USA

Understanding the interaction between parasite ligands and erythrocyte receptors is important for development of new intervention against malaria. Plasmodium vivax preferentially invades reticulocytes (young red blood cells). It is believed that this restricted ability to invade specific host cells is mediated by the reticulocyte binding protein family. RNA sequencing of clinical P. vivax isolates confirmed the presence of six transcriptionally active genes that likely encodes proteins (PvRBP1a, PvRBP1b, PvRBP2a, PvRBP2b, PvRBP2c, and PvRBP2p1) Of these, PvRBP2p1 is most similar to PfRH5, a promising candidate for P. falciparum vaccine development.

This study aims to evaluate the functional roles of PvRBP2p1 in P. vivax invasion. We expressed full-length PvRBP2p1 in E. coli.  Using the conventional erythrocyte binding assay, we found that the recombinant protein binds both mature erythrocytes and reticulocytes. We further found that treatment of erythrocyte with trypsin and chymotrypsin led to reduced binding. To examine the subcellular localization of the protein, antibody against recombinant PvRBP2p1 was produced and used in indirect immune-fluorescence assays. The protein was found only in mature schizonts and localized at the apical end of the merozoite. Antibody levels to PvRBP2p1 were determined in both malaria patients and asymptomatic parasite carriers using ELISA. Interestingly, a significant negative correlation between parasitemia and the PvRBP2p1 antibody level was detected. The level of anti-PvRBP2p1 antibody was also higher in carriers than in patients, suggesting a protective role of these antibodies, perhaps by blocking parasite invasion.

This study provides, for the first time, evidence supporting PvRBP2p1’s potential as a candidate for vaccine development against P. vivax blood stage infection.