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Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak
Science 18 Feb 2016:
pp.
DOI: 10.1126/science.aad5788
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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 (NAbs) 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.
http://science.sciencemag.org/conten...cience.aad5788
Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak
- Zachary A. Bornholdt[SUP]1[/SUP],
- Hannah L. Turner[SUP]2[/SUP],
- Charles D. Murin[SUP]1[/SUP],[SUP]2[/SUP],
- Wen Li[SUP]3[/SUP],
- Devin Sok[SUP]1[/SUP],
- Colby A. Souders[SUP]4[/SUP],
- Ashley E. Piper[SUP]5[/SUP],
- Arthur Goff[SUP]5[/SUP],
- Joshua D. Shamblin[SUP]5[/SUP],
- Suzanne E. Wollen[SUP]5[/SUP],
- Thomas R. Sprague[SUP]5[/SUP],
- Marnie L. Fusco[SUP]1[/SUP],
- Kathleen B. J. Pommert[SUP]1[/SUP],
- Lisa A. Cavacini[SUP]4[/SUP],
- Heidi L. Smith[SUP]4[/SUP],
- Mark Klempner[SUP]4[/SUP],
- Keith A. Reimann[SUP]4[/SUP],
- Eric Krauland[SUP]3[/SUP],
- Tillman U. Gerngross[SUP]3[/SUP],
- Dane K. Wittrup[SUP]3[/SUP],
- Erica Ollmann Saphire[SUP]1[/SUP],
- Dennis R. Burton[SUP]1[/SUP],[SUP]6[/SUP],
- Pamela J. Glass[SUP]5[/SUP],
- Andrew B. Ward[SUP]2[/SUP],
- Laura M. Walker[SUP]3[/SUP],*
- [SUP]1[/SUP]Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
- [SUP]2[/SUP]Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
- [SUP]3[/SUP]Adimab LLC, Lebanon, NH 03766, USA.
- [SUP]4[/SUP]MassBiologics, University of Massachusetts Medical School, Boston, MA 02126, USA.
- [SUP]5[/SUP]U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
- [SUP]6[/SUP]Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02142, USA.
- ↵*Corresponding author. E-mail: laura.walker{at}adimab.com
Science 18 Feb 2016:
pp.
DOI: 10.1126/science.aad5788
You are currently viewing the abstract.
View Full Text
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 (NAbs) 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.
http://science.sciencemag.org/conten...cience.aad5788