Potent AMA1-specific human monoclonal antibody against Plasmodium vivax Pre-erythrocytic and Blood Stages
Issued Date
2024-12-01
Resource Type
eISSN
20411723
Scopus ID
2-s2.0-85211104298
Journal Title
Nature Communications
Volume
15
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Communications Vol.15 No.1 (2024)
Suggested Citation
Winnicki A.C., Dietrich M.H., Yeoh L.M., Carias L.L., Roobsoong W., Drago C.L., Malachin A.N., Redinger K.R., Feufack-Donfack L.B., Baldor L., Jung N.C., McLaine O.S., Skomorovska-Prokvolit Y., Orban A., Opi D.H., Kirtley P., Nielson K., Aleshnick M., Zanghi G., Rezakhani N., Vaughan A.M., Wilder B.K., Sattabongkot J., Tham W.H., Popovici J., Beeson J.G., Bosch J., King C.L. Potent AMA1-specific human monoclonal antibody against Plasmodium vivax Pre-erythrocytic and Blood Stages. Nature Communications Vol.15 No.1 (2024). doi:10.1038/s41467-024-53848-4 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/102376
Title
Potent AMA1-specific human monoclonal antibody against Plasmodium vivax Pre-erythrocytic and Blood Stages
Author(s)
Winnicki A.C.
Dietrich M.H.
Yeoh L.M.
Carias L.L.
Roobsoong W.
Drago C.L.
Malachin A.N.
Redinger K.R.
Feufack-Donfack L.B.
Baldor L.
Jung N.C.
McLaine O.S.
Skomorovska-Prokvolit Y.
Orban A.
Opi D.H.
Kirtley P.
Nielson K.
Aleshnick M.
Zanghi G.
Rezakhani N.
Vaughan A.M.
Wilder B.K.
Sattabongkot J.
Tham W.H.
Popovici J.
Beeson J.G.
Bosch J.
King C.L.
Dietrich M.H.
Yeoh L.M.
Carias L.L.
Roobsoong W.
Drago C.L.
Malachin A.N.
Redinger K.R.
Feufack-Donfack L.B.
Baldor L.
Jung N.C.
McLaine O.S.
Skomorovska-Prokvolit Y.
Orban A.
Opi D.H.
Kirtley P.
Nielson K.
Aleshnick M.
Zanghi G.
Rezakhani N.
Vaughan A.M.
Wilder B.K.
Sattabongkot J.
Tham W.H.
Popovici J.
Beeson J.G.
Bosch J.
King C.L.
Author's Affiliation
Faculty of Tropical Medicine, Mahidol University
Institut Pasteur du Cambodge
University of Washington School of Medicine
Walter and Eliza Hall Institute of Medical Research
University of Melbourne
Monash University
Louis Stokes Cleveland VA Medical Center
Oregon Health & Science University
Seattle Biomedical Research Institute
CASE School of Medicine
Burnet Institute
InterRayBio LLC
Institut Pasteur du Cambodge
University of Washington School of Medicine
Walter and Eliza Hall Institute of Medical Research
University of Melbourne
Monash University
Louis Stokes Cleveland VA Medical Center
Oregon Health & Science University
Seattle Biomedical Research Institute
CASE School of Medicine
Burnet Institute
InterRayBio LLC
Corresponding Author(s)
Other Contributor(s)
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.
