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

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, Nicolai C. Jung, Olivia S. McLaine, Yelenna Skomorovska-Prokvolit, Agnes Orban, D. Herbert Opi, Payton Kirtley, Kiersey Nielson, Maya Aleshnick, Gigliola Zanghi, Nastaran Rezakhani, Ashley M. Vaughan, Brandon K. Wilder, Jetsumon Sattabongkot, Wai-Hong Tham, Jean Popovici, James G. Beeson, Jürgen Bosch () and Christopher L. King ()
Additional contact information
Anna C. Winnicki: Case Western Reserve University School of Medicine
Melanie H. Dietrich: Walter and Eliza Hall Institute of Medical Research
Lee M. Yeoh: Burnet Institute
Lenore L. Carias: Case Western Reserve University School of Medicine
Wanlapa Roobsoong: Mahidol University
Chiara L. Drago: Burnet Institute
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
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
Brandon K. Wilder: Oregon Health & Science University
Jetsumon Sattabongkot: Mahidol University
Wai-Hong Tham: Walter and Eliza Hall Institute of Medical Research
Jean Popovici: Institut Pasteur du Cambodge
James G. Beeson: Burnet Institute
Jürgen Bosch: Case Western Reserve University School of Medicine
Christopher L. King: Case Western Reserve University School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-53848-4

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