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

Author

Listed:
  • Li-Jin Chan

    (The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Anugraha Gandhirajan

    (Case Western Reserve University)

  • Lenore L. Carias

    (Case Western Reserve University)

  • Melanie H. Dietrich

    (The Walter and Eliza Hall Institute of Medical Research)

  • Oscar Vadas

    (University of Geneva
    University of Geneva)

  • Remy Visentin

    (University of Geneva
    University of Geneva)

  • Camila T. França

    (The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Sebastien Menant

    (The Walter and Eliza Hall Institute of Medical Research)

  • Dominique Soldati-Favre

    (University of Geneva)

  • Ivo Mueller

    (The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Christopher L. King

    (Case Western Reserve University
    Veteran Affairs Research Service, VA Medical Center)

  • Wai-Hong Tham

    (The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

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.

Suggested Citation

  • Li-Jin Chan & Anugraha Gandhirajan & Lenore L. Carias & Melanie H. Dietrich & Oscar Vadas & Remy Visentin & Camila T. França & Sebastien Menant & Dominique Soldati-Favre & Ivo Mueller & Christopher L., 2021. "Naturally acquired blocking human monoclonal antibodies to Plasmodium vivax reticulocyte binding protein 2b," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21811-2
    DOI: 10.1038/s41467-021-21811-2
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