James Crowe
Faculty Member
Last active: 3/31/2019

Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection.

Flyak AI, Shen X, Murin CD, Turner HL, David JA, Fusco ML, Lampley R, Kose N, Ilinykh PA, Kuzmina N, Branchizio A, King H, Brown L, Bryan C, Davidson E, Doranz BJ, Slaughter JC, Sapparapu G, Klages C, Ksiazek TG, Saphire EO, Ward AB, Bukreyev A, Crowe JE
Cell. 2016 164 (3): 392-405

PMID: 26806128 · PMCID: PMC4733404 · DOI:10.1016/j.cell.2015.12.022

Recent studies have suggested that antibody-mediated protection against the Ebolaviruses may be achievable, but little is known about whether or not antibodies can confer cross-reactive protection against viruses belonging to diverse Ebolavirus species, such as Ebola virus (EBOV), Sudan virus (SUDV), and Bundibugyo virus (BDBV). We isolated a large panel of human monoclonal antibodies (mAbs) against BDBV glycoprotein (GP) using peripheral blood B cells from survivors of the 2007 BDBV outbreak in Uganda. We determined that a large proportion of mAbs with potent neutralizing activity against BDBV bind to the glycan cap and recognize diverse epitopes within this major antigenic site. We identified several glycan cap-specific mAbs that neutralized multiple ebolaviruses, including SUDV, and a cross-reactive mAb that completely protected guinea pigs from the lethal challenge with heterologous EBOV. Our results provide a roadmap to develop a single antibody-based treatment effective against multiple Ebolavirus infections.

Copyright © 2016 Elsevier Inc. All rights reserved.

MeSH Terms (17)

Animals Antibodies, Monoclonal Antibodies, Neutralizing Cross Reactions Disease Models, Animal Ebolavirus Epitope Mapping Guinea Pigs Hemorrhagic Fever, Ebola Humans Mice Mice, Inbred BALB C Microscopy, Electron Models, Molecular Mutagenesis Survivors Uganda

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