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Potent AMA1-specific human monoclonal antibody against Plasmodium vivax Pre-erythrocytic and Blood Stages

Author

Listed:
  • Anna C. Winnicki

    (Case Western Reserve University School of Medicine)

  • Melanie H. Dietrich

    (Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Lee M. Yeoh

    (Burnet Institute
    The University of Melbourne)

  • Lenore L. Carias

    (Case Western Reserve University School of Medicine)

  • Wanlapa Roobsoong

    (Mahidol University)

  • Chiara L. Drago

    (Burnet Institute
    Monash University)

  • Alyssa N. Malachin

    (Case Western Reserve University School of Medicine)

  • Karli R. Redinger

    (Case Western Reserve University School of Medicine)

  • Lionel Brice Feufack-Donfack

    (Institut Pasteur du Cambodge)

  • Lea Baldor

    (Institut Pasteur du Cambodge)

  • Nicolai C. Jung

    (Walter and Eliza Hall Institute of Medical Research)

  • Olivia S. McLaine

    (Case Western Reserve University School of Medicine)

  • Yelenna Skomorovska-Prokvolit

    (Case Western Reserve University School of Medicine)

  • Agnes Orban

    (Institut Pasteur du Cambodge)

  • D. Herbert Opi

    (Burnet Institute
    The University of Melbourne
    Monash University)

  • Payton Kirtley

    (Oregon Health & Science University)

  • Kiersey Nielson

    (Oregon Health & Science University)

  • Maya Aleshnick

    (Oregon Health & Science University)

  • Gigliola Zanghi

    (Seattle Children’s Research Institute)

  • Nastaran Rezakhani

    (Seattle Children’s Research Institute)

  • Ashley M. Vaughan

    (Seattle Children’s Research Institute
    University of Washington)

  • Brandon K. Wilder

    (Oregon Health & Science University)

  • Jetsumon Sattabongkot

    (Mahidol University)

  • Wai-Hong Tham

    (Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Jean Popovici

    (Institut Pasteur du Cambodge)

  • James G. Beeson

    (Burnet Institute
    The University of Melbourne
    Monash University)

  • Jürgen Bosch

    (Case Western Reserve University School of Medicine
    InterRayBio LLC)

  • Christopher L. King

    (Case Western Reserve University School of Medicine
    Veterans Affairs Medical Center)

Abstract

New therapeutics are necessary for preventing Plasmodium vivax malaria due to easy transmissibility and dormancy in the liver that increases the clinical burden due to recurrent relapse. In this manuscript we characterize 12 Pv Apical Membrane Antigen 1 (PvAMA1) specific human monoclonal antibodies from Peripheral Blood Mononuclear Cells of a Pv-exposed individual. PvAMA1 is essential for sporozoite and merozoite invasion, making it a unique therapeutic target. We show that humAb 826827 blocks the invasion of human reticulocytes using Pv clinical isolates and inhibits sporozoite invasion of human hepatocytes in vitro (IC50 of 0.3 – 3.7 µg/mL). Inoculation of human liver transgenic (FRG-humHep) female mice with humAb 826827 significantly reduces liver infection in vivo. The crystal structure of rPvAMA1 bound to 826827 shows that 826827 partially occupies the highly conserved hydrophobic groove in PvAMA1 that binds its known receptor, RON2. We have isolated a potent humAb that is isolate-transcendent, blocks both pre-erythrocytic and blood stage infection, and could be a potential therapy for Pv.

Suggested Citation

  • Anna C. Winnicki & Melanie H. Dietrich & Lee M. Yeoh & Lenore L. Carias & Wanlapa Roobsoong & Chiara L. Drago & Alyssa N. Malachin & Karli R. Redinger & Lionel Brice Feufack-Donfack & Lea Baldor & Nic, 2024. "Potent AMA1-specific human monoclonal antibody against Plasmodium vivax Pre-erythrocytic and Blood Stages," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53848-4
    DOI: 10.1038/s41467-024-53848-4
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    References listed on IDEAS

    as
    1. Prakash Srinivasan & Adam Yasgar & Diane K. Luci & Wandy L. Beatty & Xin Hu & John Andersen & David L. Narum & J. Kathleen Moch & Hongmao Sun & J. David Haynes & David J. Maloney & Ajit Jadhav & Anton, 2013. "Disrupting malaria parasite AMA1–RON2 interaction with a small molecule prevents erythrocyte invasion," Nature Communications, Nature, vol. 4(1), pages 1-9, October.
    2. Palak N. Patel & Thayne H. Dickey & Ababacar Diouf & Nichole D. Salinas & Holly McAleese & Tarik Ouahes & Carole A. Long & Kazutoyo Miura & Lynn E. Lambert & Niraj H. Tolia, 2023. "Structure-based design of a strain transcending AMA1-RON2L malaria vaccine," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Christian Ritz & Florent Baty & Jens C Streibig & Daniel Gerhard, 2015. "Dose-Response Analysis Using R," PLOS ONE, Public Library of Science, vol. 10(12), pages 1-13, December.
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