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Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein.

Gilchuk P, Kuzmina N, Ilinykh PA, Huang K, Gunn BM, Bryan A, Davidson E, Doranz BJ, Turner HL, Fusco ML, Bramble MS, Hoff NA, Binshtein E, Kose N, Flyak AI, Flinko R, Orlandi C, Carnahan R, Parrish EH, Sevy AM, Bombardi RG, Singh PK, Mukadi P, Muyembe-Tamfum JJ, Ohi MD, Saphire EO, Lewis GK, Alter G, Ward AB, Rimoin AW, Bukreyev A, Crowe JE
Immunity. 2018 49 (2): 363-374.e10

PMID: 30029854 · PMCID: PMC6104738 · DOI:10.1016/j.immuni.2018.06.018

Ebolaviruses cause severe disease in humans, and identification of monoclonal antibodies (mAbs) that are effective against multiple ebolaviruses are important for therapeutics development. Here we describe a distinct class of broadly neutralizing human mAbs with protective capacity against three ebolaviruses infectious for humans: Ebola (EBOV), Sudan (SUDV), and Bundibugyo (BDBV) viruses. We isolated mAbs from human survivors of ebolavirus disease and identified a potent mAb, EBOV-520, which bound to an epitope in the glycoprotein (GP) base region. EBOV-520 efficiently neutralized EBOV, BDBV, and SUDV and also showed protective capacity in relevant animal models of these infections. EBOV-520 mediated protection principally by direct virus neutralization and exhibited multifunctional properties. This study identified a potent naturally occurring mAb and defined key features of the human antibody response that may contribute to broad protection. This multifunctional mAb and related clones are promising candidates for development as broadly protective pan-ebolavirus therapeutic molecules.

Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

MeSH Terms (27)

3T3 Cells Adult Animals Antibodies, Monoclonal Antibodies, Neutralizing Antibodies, Viral Cell Line Chlorocebus aethiops CHO Cells Cricetulus Disease Models, Animal Drosophila Ebolavirus Female Ferrets Glycoproteins Guinea Pigs Hemorrhagic Fever, Ebola Humans Immunoglobulin G Jurkat Cells Male Mice Mice, Inbred BALB C Mice, Knockout THP-1 Cells Vero Cells

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