Naturally acquired blocking human monoclonal antibodies to Plasmodiumvivax reticulocyte binding protein 2b
Li-Jin Chan, Anugraha Gandhirajan, Lenore L Carias, Melanie H Dietrich, Oscar Vadas, Remy Visentin, Camila T Franca, Sebastien Menant, Dominique Soldati-Favre, Ivo Mueller, Christopher L King, Wai-Hong Tham
NATURE COMMUNICATIONS | NATURE RESEARCH | Published : 2021
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 fo..View full abstract
Awarded by European Research Council under the European Union's Horizon 2020 Research and Innovation program
Awarded by Howard Hughes Medical Institute-Wellcome Trust International Research
Awarded by National Health and Medical Research Council of Australia
We thank Sokunthea Sreng, Seila Suon, Chanaki Amaratunga, and Rick M. Fairhurst who identified P. vivax immune subjects acquired necessary approval and helped with the PBMC collection. We thank Janet Newman and Bevan Marshall from the CSIRO Collaborative Crystallization Centre (www.csiro.au/C3) (CSIRO; Parkville, Australia) for assistance with setting up the crystallization screens. We thank Mike Lawrence for his invaluable advice and assistance in the improvement of the structure refinement for antibody complex PvRBP2b-253245. This research was undertaken in part using the MX2 beamline at the Australian Synchrotron, part of ANSTO, and made use of the Australian Cancer Research Foundation (ACRF) detector. We also thank the MX2 beamline staff at the Australian Synchrotron for their assistance during data collection. We thank Alexandre Hainard, from the Proteomics Platforms at the University of Geneva, for assistance with HDX-MS data acquisition. O.V. was funded by Carigest SA (to D.S.-F.) R.V. was funded by the European Research Council under the European Union's Horizon 2020 Research and Innovation program under grant agreement no. 695596 (to D.S.-F.). W.-H.T. is a Howard Hughes Medical Institute-Wellcome Trust International Research Scholar (208693/Z/17/Z) and supported by the National Health and Medical Research Council of Australia (GNT1143187, GNT1160042, GNT1160042, GNT1154937).