Potent AMA1-specific human monoclonal antibody against Plasmodium vivax Pre-erythrocytic and Blood Stages - Archive ouverte HAL
Article Dans Une Revue Nature Communications Année : 2024

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

Melanie H Dietrich
Lee M Yeoh
Lenore L Carias
  • Fonction : Auteur
Wanlapa Roobsoong
Chiara L Drago
  • Fonction : Auteur
Alyssa N Malachin
  • Fonction : Auteur
Karli R Redinger
Nicolai C Jung
  • Fonction : Auteur
Olivia S Mclaine
  • Fonction : Auteur
Yelenna Skomorovska-Prokvolit
  • Fonction : Auteur
D. Herbert Opi
Payton Kirtley
  • Fonction : Auteur
Kiersey Nielson
Maya Aleshnick
  • Fonction : Auteur
Gigliola Zanghi
  • Fonction : Auteur
Nastaran Rezakhani
  • Fonction : Auteur
Ashley M Vaughan
Brandon K Wilder
Jetsumon Sattabongkot
  • Fonction : Auteur
Wai-Hong Tham
Jean Popovici
James G Beeson
  • Fonction : Auteur

Résumé

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 (IC 50 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.
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hal-04844576 , version 1 (18-12-2024)

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Anna C Winnicki, Melanie H Dietrich, Lee M Yeoh, Lenore L Carias, Wanlapa Roobsoong, et al.. Potent AMA1-specific human monoclonal antibody against Plasmodium vivax Pre-erythrocytic and Blood Stages. Nature Communications, 2024, 15 (1), pp.10556. ⟨10.1038/s41467-024-53848-4⟩. ⟨hal-04844576⟩

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