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Structure of the malaria vaccine candidate Pfs48/45 and its recognition by transmission blocking antibodies

Author

Listed:
  • Kuang-Ting Ko

    (South Parks Road, University of Oxford
    Dorothy Crowfoot Hodgkin Building, University of Oxford)

  • Frank Lennartz

    (South Parks Road, University of Oxford)

  • David Mekhaiel

    (University of Oxford)

  • Bora Guloglu

    (South Parks Road, University of Oxford
    Dorothy Crowfoot Hodgkin Building, University of Oxford)

  • Arianna Marini

    (University of Oxford)

  • Danielle J. Deuker

    (University of Oxford)

  • Carole A. Long

    (NIH)

  • Matthijs M. Jore

    (Radboud University Medical Centre)

  • Kazutoyo Miura

    (NIH)

  • Sumi Biswas

    (University of Oxford)

  • Matthew K. Higgins

    (South Parks Road, University of Oxford
    Dorothy Crowfoot Hodgkin Building, University of Oxford)

Abstract

An effective malaria vaccine remains a global health priority and vaccine immunogens which prevent transmission of the parasite will have important roles in multi-component vaccines. One of the most promising candidates for inclusion in a transmission-blocking malaria vaccine is the gamete surface protein Pfs48/45, which is essential for development of the parasite in the mosquito midgut. Indeed, antibodies which bind Pfs48/45 can prevent transmission if ingested with the parasite as part of the mosquito bloodmeal. Here we present the structure of full-length Pfs48/45, showing its three domains to form a dynamic, planar, triangular arrangement. We reveal where transmission-blocking and non-blocking antibodies bind on Pfs48/45. Finally, we demonstrate that antibodies which bind across this molecule can be transmission-blocking. These studies will guide the development of future Pfs48/45-based vaccine immunogens.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33379-6
    DOI: 10.1038/s41467-022-33379-6
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    References listed on IDEAS

    as
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