Publication Date:
2016-02-26
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- R01AI067927/AI/NIAID NIH HHS/ -- U19AI109762/AI/NIAID NIH HHS/ -- UM1AI100663/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2016 Mar 4;351(6277):1078-83. doi: 10.1126/science.aad5788. Epub 2016 Feb 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉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. ; 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. ; Adimab, Lebanon, NH 03766, USA. ; MassBiologics, University of Massachusetts Medical School, Boston, MA 02126, USA. ; U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912366" target="_blank"〉PubMed〈/a〉
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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