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Molecular definition of multiple sites of antibody inhibition of malaria transmission-blocking vaccine antigen Pfs25

Author

Listed:
  • Stephen W. Scally

    (The Hospital for Sick Children Research Institute)

  • Brandon McLeod

    (The Hospital for Sick Children Research Institute
    University of Toronto)

  • Alexandre Bosch

    (The Hospital for Sick Children Research Institute)

  • Kazutoyo Miura

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Qi Liang

    (Kymab Ltd.)

  • Sean Carroll

    (Atreca)

  • Sini Reponen

    (Atreca)

  • Ngan Nguyen

    (Atreca)

  • Eldar Giladi

    (Atreca)

  • Sebastian Rämisch

    (The Scripps Research Institute)

  • Vidadi Yusibov

    (Fraunhofer USA Center for Molecular Biotechnology CMB)

  • Allan Bradley

    (Kymab Ltd.
    Wellcome Trust Sanger Institute)

  • Franck Lemiale

    (PATH’s Malaria Vaccine Initiative)

  • William R. Schief

    (The Scripps Research Institute)

  • Daniel Emerling

    (Atreca)

  • Paul Kellam

    (Kymab Ltd.
    Imperial College London)

  • C. Richter King

    (PATH’s Malaria Vaccine Initiative)

  • Jean-Philippe Julien

    (The Hospital for Sick Children Research Institute
    University of Toronto
    University of Toronto)

Abstract

The Plasmodium falciparum Pfs25 protein (Pfs25) is a leading malaria transmission-blocking vaccine antigen. Pfs25 vaccination is intended to elicit antibodies that inhibit parasite development when ingested by Anopheles mosquitoes during blood meals. The Pfs25 three-dimensional structure has remained elusive, hampering a molecular understanding of its function and limiting immunogen design. We report six crystal structures of Pfs25 in complex with antibodies elicited by immunization via Pfs25 virus-like particles in human immunoglobulin loci transgenic mice. Our structural findings reveal the fine specificities associated with two distinct immunogenic sites on Pfs25. Importantly, one of these sites broadly overlaps with the epitope of the well-known 4B7 mouse antibody, which can be targeted simultaneously by antibodies that target a non-overlapping site to additively increase parasite inhibition. Our molecular characterization of inhibitory antibodies informs on the natural disposition of Pfs25 on the surface of ookinetes and provides the structural blueprints to design next-generation immunogens.

Suggested Citation

  • Stephen W. Scally & Brandon McLeod & Alexandre Bosch & Kazutoyo Miura & Qi Liang & Sean Carroll & Sini Reponen & Ngan Nguyen & Eldar Giladi & Sebastian Rämisch & Vidadi Yusibov & Allan Bradley & Franc, 2017. "Molecular definition of multiple sites of antibody inhibition of malaria transmission-blocking vaccine antigen Pfs25," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01924-3
    DOI: 10.1038/s41467-017-01924-3
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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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