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A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes

Author

Listed:
  • Camila H. Coelho

    (National Institutes of Health)

  • Wai Kwan Tang

    (National Institutes of Health)

  • Martin Burkhardt

    (National Institutes of Health)

  • Jacob D. Galson

    (Division of Immunology and Children’s Research Center, University Children’s Hospital Zurich, University of Zurich (UZH)
    Alchemab Therapeutics Ltd, 55-56 Russell Square)

  • Olga Muratova

    (National Institutes of Health)

  • Nichole D. Salinas

    (National Institutes of Health)

  • Thiago Luiz Alves e Silva

    (National Institutes of Health)

  • Karine Reiter

    (National Institutes of Health)

  • Nicholas J. MacDonald

    (National Institutes of Health)

  • Vu Nguyen

    (National Institutes of Health)

  • Raul Herrera

    (National Institutes of Health)

  • Richard Shimp

    (National Institutes of Health)

  • David L. Narum

    (National Institutes of Health)

  • Miranda Byrne-Steele

    (iRepertoire Inc.)

  • Wenjing Pan

    (iRepertoire Inc.)

  • Xiaohong Hou

    (iRepertoire Inc.)

  • Brittany Brown

    (iRepertoire Inc.)

  • Mary Eisenhower

    (iRepertoire Inc.)

  • Jian Han

    (iRepertoire Inc.)

  • Bethany J. Jenkins

    (National Institutes of Health)

  • Justin Y. A. Doritchamou

    (National Institutes of Health)

  • Margery G. Smelkinson

    (National Institutes of Health)

  • Joel Vega-Rodríguez

    (National Institutes of Health)

  • Johannes Trück

    (Division of Immunology and Children’s Research Center, University Children’s Hospital Zurich, University of Zurich (UZH))

  • Justin J. Taylor

    (Fred Hutchinson Cancer Research Center)

  • Issaka Sagara

    (University of Sciences, Techniques, and Technology)

  • Sara A. Healy

    (National Institutes of Health)

  • Jonathan P. Renn

    (National Institutes of Health)

  • Niraj H. Tolia

    (National Institutes of Health)

  • Patrick E. Duffy

    (National Institutes of Health
    National Institutes of Health)

Abstract

Malaria elimination requires tools that interrupt parasite transmission. Here, we characterize B cell receptor responses among Malian adults vaccinated against the first domain of the cysteine-rich 230 kDa gamete surface protein Pfs230, a key protein in sexual stage development of P. falciparum parasites. Among nine Pfs230 human monoclonal antibodies (mAbs) that we generated, one potently blocks transmission to mosquitoes in a complement-dependent manner and reacts to the gamete surface; the other eight show only low or no blocking activity. The structure of the transmission-blocking mAb in complex with vaccine antigen reveals a large discontinuous conformational epitope, specific to domain 1 of Pfs230 and comprising six structural elements in the protein. The epitope is conserved, suggesting the transmission-blocking mAb is broadly functional. This study provides a rational basis to improve malaria vaccines and develop therapeutic antibodies for malaria elimination.

Suggested Citation

  • Camila H. Coelho & Wai Kwan Tang & Martin Burkhardt & Jacob D. Galson & Olga Muratova & Nichole D. Salinas & Thiago Luiz Alves e Silva & Karine Reiter & Nicholas J. MacDonald & Vu Nguyen & Raul Herrer, 2021. "A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21955-1
    DOI: 10.1038/s41467-021-21955-1
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    Cited by:

    1. Wai Kwan Tang & Nichole D. Salinas & Surendra Kumar Kolli & Shulin Xu & Darya V. Urusova & Hirdesh Kumar & John R. Jimah & Pradeep Annamalai Subramani & Madison M. Ogbondah & Samantha J. Barnes & John, 2024. "Multistage protective anti-CelTOS monoclonal antibodies with cross-species sterile protection against malaria," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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