Antibodies from a Human Survivor Define Sites of Vulnerability for Broad Protection against Ebolaviruses
Copyright © 2017 Elsevier Inc. All rights reserved..
Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GPCL) generated in host cell endosomes. Only a few somatic hypermutations are required for broad antiviral activity, and germline-approximating variants display enhanced GPCL recognition, suggesting that such antibodies could be elicited more efficiently with suitably optimized GP immunogens. Our findings inform the development of both broadly effective immunotherapeutics and vaccines against filoviruses.
| Errataetall: |
CommentIn: Cell. 2017 May 18;169(5):773-775. - PMID 28525748 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:169 |
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| Enthalten in: |
Cell - 169(2017), 5 vom: 18. Mai, Seite 878-890.e15 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wec, Anna Z [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.07.2017 Date Revised 10.12.2019 published: Print CommentIn: Cell. 2017 May 18;169(5):773-775. - PMID 28525748 Citation Status MEDLINE |
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| doi: |
10.1016/j.cell.2017.04.037 |
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| Förderinstitution / Projekttitel: |
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| 500 | |a CommentIn: Cell. 2017 May 18;169(5):773-775. - PMID 28525748 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2017 Elsevier Inc. All rights reserved. | ||
| 520 | |a Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GPCL) generated in host cell endosomes. Only a few somatic hypermutations are required for broad antiviral activity, and germline-approximating variants display enhanced GPCL recognition, suggesting that such antibodies could be elicited more efficiently with suitably optimized GP immunogens. Our findings inform the development of both broadly effective immunotherapeutics and vaccines against filoviruses | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a EBOV | |
| 650 | 4 | |a Ebola virus | |
| 650 | 4 | |a ebolavirus | |
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| 650 | 4 | |a human broadly neutralizing antibodies | |
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| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
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| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a Ebola Vaccines |2 NLM | |
| 700 | 1 | |a Herbert, Andrew S |e verfasserin |4 aut | |
| 700 | 1 | |a Murin, Charles D |e verfasserin |4 aut | |
| 700 | 1 | |a Nyakatura, Elisabeth K |e verfasserin |4 aut | |
| 700 | 1 | |a Abelson, Dafna M |e verfasserin |4 aut | |
| 700 | 1 | |a Fels, J Maximilian |e verfasserin |4 aut | |
| 700 | 1 | |a He, Shihua |e verfasserin |4 aut | |
| 700 | 1 | |a James, Rebekah M |e verfasserin |4 aut | |
| 700 | 1 | |a de La Vega, Marc-Antoine |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Wenjun |e verfasserin |4 aut | |
| 700 | 1 | |a Bakken, Russell R |e verfasserin |4 aut | |
| 700 | 1 | |a Goodwin, Eileen |e verfasserin |4 aut | |
| 700 | 1 | |a Turner, Hannah L |e verfasserin |4 aut | |
| 700 | 1 | |a Jangra, Rohit K |e verfasserin |4 aut | |
| 700 | 1 | |a Zeitlin, Larry |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, Xiangguo |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Jonathan R |e verfasserin |4 aut | |
| 700 | 1 | |a Walker, Laura M |e verfasserin |4 aut | |
| 700 | 1 | |a Ward, Andrew B |e verfasserin |4 aut | |
| 700 | 1 | |a Dye, John M |e verfasserin |4 aut | |
| 700 | 1 | |a Chandran, Kartik |e verfasserin |4 aut | |
| 700 | 1 | |a Bornholdt, Zachary A |e verfasserin |4 aut | |
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