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Potent antibody lineage against malaria transmission elicited by human vaccination with Pfs25

Author

Listed:
  • Brandon McLeod

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

  • Kazutoyo Miura

    (National Institutes of Health)

  • Stephen W. Scally

    (The Hospital for Sick Children Research Institute)

  • Alexandre Bosch

    (The Hospital for Sick Children Research Institute)

  • Ngan Nguyen

    (Atreca)

  • Hanjun Shin

    (Atreca)

  • Dongkyoon Kim

    (Atreca)

  • Wayne Volkmuth

    (Atreca)

  • Sebastian Rämisch

    (The Scripps Research Institute)

  • Jessica A. Chichester

    (The University of Pennsylvania)

  • Stephen Streatfield

    (Fraunhofer USA Center for Molecular Biotechnology CMB)

  • Colleen Woods

    (PATH’s Malaria Vaccine Initiative)

  • William R. Schief

    (The Scripps Research Institute)

  • Daniel Emerling

    (Atreca)

  • 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

Transmission-blocking vaccines have the potential to be key contributors to malaria elimination. Such vaccines elicit antibodies that inhibit parasites during their development in Anopheles mosquitoes, thus breaking the cycle of transmission. To date, characterization of humoral responses to Plasmodium falciparum transmission-blocking vaccine candidate Pfs25 has largely been conducted in pre-clinical models. Here, we present molecular analyses of human antibody responses generated in a clinical trial evaluating Pfs25 vaccination. From a collection of monoclonal antibodies with transmission-blocking activity, we identify the most potent transmission-blocking antibody yet described against Pfs25; 2544. The interactions of 2544 and three other antibodies with Pfs25 are analyzed by crystallography to understand structural requirements for elicitation of human transmission-blocking responses. Our analyses provide insights into Pfs25 immunogenicity and epitope potency, and detail an affinity maturation pathway for a potent transmission-blocking antibody in humans. Our findings can be employed to guide the design of improved malaria transmission-blocking vaccines.

Suggested Citation

  • Brandon McLeod & Kazutoyo Miura & Stephen W. Scally & Alexandre Bosch & Ngan Nguyen & Hanjun Shin & Dongkyoon Kim & Wayne Volkmuth & Sebastian Rämisch & Jessica A. Chichester & Stephen Streatfield & C, 2019. "Potent antibody lineage against malaria transmission elicited by human vaccination with Pfs25," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11980-6
    DOI: 10.1038/s41467-019-11980-6
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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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