Naturally acquired blocking human monoclonal antibodies to Plasmodium vivax reticulocyte binding protein 2b

Abstract

Plasmodium vivax preferentially invades reticulocytes and recognition of these cells is mediated by P. vivax Reticulocyte Binding Protein 2b (PvRBP2b) binding to human Transferrin receptor 1 (TfR1) and Transferrin (Tf). Longitudinal cohort studies in Papua New Guinea, Thailand and Brazil show that PvRBP2b antibodies are correlated with protection against P. vivax infection and disease. Here, we isolate and characterize anti-PvRBP2b human monoclonal antibodies from two individuals in Cambodia with natural P. vivax infection. These antibodies bind with high affinities and map to different regions of PvRBP2b. Several human antibodies block PvRBP2b binding to reticulocytes and inhibit complex formation with human TfR1-Tf. We describe different structural mechanisms for functional inhibition, including either steric hindrance with TfR1-Tf or the reticulocyte membrane. These results show that naturally acquired human antibodies against PvRBP2b can inhibit its function which is important for P. vivax invasion.

Longitudinal IgG antibody responses to Plasmodium vivax blood-stage antigens during and after acute vivax malaria in individuals living in the Brazilian Amazon

“…The concentration was measured in a NanoDrop (Thermo Fisher Scientific), and purified proteins were frozen at -80ºC until further use. The PvRBP recombinant proteins were expressed with relevant tags as previously described [6, 22, 23] ( Table S1 ). The sequences of all P. vivax recombinant proteins were based on the genome of the P. vivax Sal-1 strain, a monkey-adapted parasite line originally isolated from a P. vivax patient in El Salvador [24].…”

“…The ideal malaria blood-stage vaccine is capable of inducing a specific and durable immune response against antigens that are essential for parasite survival. Parasite-specific antibodies can play a critical role in naturally acquired protective immunity against blood-stage malaria by disrupting the interactions between parasite ligands and cognate host receptors required for RBC invasion [4][5][6]. Screens of IgG antibody responses against P. vivax antigens with potential roles in erythrocyte binding and/or invasion in Papua New Guinea children living in areas highly endemic for P. vivax identified or confirmed several antigens as vaccine candidates, including erythrocyte binding protein (EBP), Duffy binding protein region II (DBPII), RBP1a, RBP2b, PVX_081550, Pv12, and Pv41 [7,8].…”

Longitudinal IgG antibody responses to Plasmodium vivax blood-stage antigens during and after acute vivax malaria in individuals living in the Brazilian Amazon

“…The concentration was measured in a NanoDrop (Thermo Fisher Scientific), and purified proteins were frozen at −80˚C until further use. The PvRBP recombinant proteins were expressed with relevant tags as previously described [6,23,24] (S1 Table ). The sequences of all P. vivax recombinant proteins were based on the genome of the P. vivax Sal-1 strain, a monkey-adapted parasite line originally isolated from a P. vivax patient in El Salvador [25].…”

“…The ideal malaria blood-stage vaccine is capable of inducing a specific and durable immune response against antigens that are essential for parasite survival. Parasite-specific antibodies can play a critical role in naturally acquired protective immunity against blood-stage malaria by disrupting the interactions between parasite ligands and cognate host receptors required for RBC invasion [4][5][6]. Screens of IgG antibody responses against P. vivax antigens with potential roles in erythrocyte binding and/or invasion in Papua New Guinea children living in areas highly endemic for P. vivax identified or confirmed several antigens as vaccine candidates, including erythrocyte binding protein (EBP), Duffy binding protein region II (DBPII), K08AI125682.…”

“…The ideal malaria blood-stage vaccine is capable of inducing a specific and durable immune response against antigens that are essential for parasite survival. Parasite-specific antibodies can play a critical role in naturally acquired protective immunity against blood-stage malaria by disrupting the interactions between parasite ligands and cognate host receptors required for RBC invasion [ 4 – 6 ]. Screens of IgG antibody responses against P .…”