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Structural basis for recognition of the malaria vaccine candidate Pfs48/45 by a transmission blocking antibody

Author

Listed:
  • Frank Lennartz

    (University of Oxford)

  • Florian Brod

    (University of Oxford)

  • Rebecca Dabbs

    (University of Oxford)

  • Kazutoyo Miura

    (NIH)

  • David Mekhaiel

    (University of Oxford)

  • Arianna Marini

    (University of Oxford)

  • Matthijs M. Jore

    (Radboud University Medical Centre)

  • Max M. Søgaard

    (ExpreS2ion Biotechnologies)

  • Thomas Jørgensen

    (ExpreS2ion Biotechnologies)

  • Willem A. Jongh

    (ExpreS2ion Biotechnologies)

  • Robert W. Sauerwein

    (Radboud University Medical Centre)

  • Carole A. Long

    (NIH)

  • Sumi Biswas

    (University of Oxford)

  • Matthew K. Higgins

    (University of Oxford)

Abstract

The quest to develop an effective malaria vaccine remains a major priority in the fight against global infectious disease. An approach with great potential is a transmission-blocking vaccine which induces antibodies that prevent establishment of a productive infection in mosquitos that feed on infected humans, thereby stopping the transmission cycle. One of the most promising targets for such a vaccine is the gamete surface protein, Pfs48/45. Here we establish a system for production of full-length Pfs48/45 and use this to raise a panel of monoclonal antibodies. We map the binding regions of these antibodies on Pfs48/45 and correlate the location of their epitopes with their transmission-blocking activity. Finally, we present the structure of the C-terminal domain of Pfs48/45 bound to the most potent transmission-blocking antibody, and provide key molecular information for future structure-guided immunogen design.

Suggested Citation

  • Frank Lennartz & Florian Brod & Rebecca Dabbs & Kazutoyo Miura & David Mekhaiel & Arianna Marini & Matthijs M. Jore & Max M. Søgaard & Thomas Jørgensen & Willem A. Jongh & Robert W. Sauerwein & Carole, 2018. "Structural basis for recognition of the malaria vaccine candidate Pfs48/45 by a transmission blocking antibody," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06340-9
    DOI: 10.1038/s41467-018-06340-9
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    Cited by:

    1. Kuang-Ting Ko & Frank Lennartz & David Mekhaiel & Bora Guloglu & Arianna Marini & Danielle J. Deuker & Carole A. Long & Matthijs M. Jore & Kazutoyo Miura & Sumi Biswas & Matthew K. Higgins, 2022. "Structure of the malaria vaccine candidate Pfs48/45 and its recognition by transmission blocking antibodies," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

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