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Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak.

作者信息

Bornholdt Zachary A, Turner Hannah L, Murin Charles D, Li Wen, Sok Devin, Souders Colby A, Piper Ashley E, Goff Arthur, Shamblin Joshua D, Wollen Suzanne E, Sprague Thomas R, Fusco Marnie L, Pommert Kathleen B J, Cavacini Lisa A, Smith Heidi L, Klempner Mark, Reimann Keith A, Krauland Eric, Gerngross Tillman U, Wittrup Karl D, Saphire Erica Ollmann, Burton Dennis R, Glass Pamela J, Ward Andrew B, Walker Laura M

机构信息

Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

出版信息

Science. 2016 Mar 4;351(6277):1078-83. doi: 10.1126/science.aad5788. Epub 2016 Feb 18.

DOI:10.1126/science.aad5788
PMID:26912366
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4900763/
Abstract

Antibodies targeting the Ebola virus surface glycoprotein (EBOV GP) are implicated in protection against lethal disease, but the characteristics of the human antibody response to EBOV GP remain poorly understood. We isolated and characterized 349 GP-specific monoclonal antibodies (mAbs) from the peripheral B cells of a convalescent donor who survived the 2014 EBOV Zaire outbreak. Remarkably, 77% of the mAbs neutralize live EBOV, and several mAbs exhibit unprecedented potency. Structures of selected mAbs in complex with GP reveal a site of vulnerability located in the GP stalk region proximal to the viral membrane. Neutralizing antibodies targeting this site show potent therapeutic efficacy against lethal EBOV challenge in mice. The results provide a framework for the design of new EBOV vaccine candidates and immunotherapies.

摘要

相似文献

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本文引用的文献

[1]
Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection.

Cell. 2016-1-28

[2]
Improved PEP-FOLD Approach for Peptide and Miniprotein Structure Prediction.

J Chem Theory Comput. 2014-10-14

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Emergence of Ebola Virus Escape Variants in Infected Nonhuman Primates Treated with the MB-003 Antibody Cocktail.

Cell Rep. 2015-9-29

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Science. 2015-8-14

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Structural basis for Marburg virus neutralization by a cross-reactive human antibody.

Cell. 2015-2-26

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Structures of protective antibodies reveal sites of vulnerability on Ebola virus.

Proc Natl Acad Sci U S A. 2014-12-2

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Molecular characterization of the monoclonal antibodies composing ZMAb: a protective cocktail against Ebola virus.

Sci Rep. 2014-11-6

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A call to action to enhance filovirus disease outbreak preparedness and response.

Viruses. 2014-9-30

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Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak.

Science. 2014-8-28

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Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp.

Nature. 2014-8-29

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