PMID- 26912366 OWN - NLM STAT- MEDLINE DCOM- 20160325 LR - 20181113 IS - 1095-9203 (Electronic) IS - 0036-8075 (Print) IS - 0036-8075 (Linking) VI - 351 IP - 6277 DP - 2016 Mar 4 TI - Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak. PG - 1078-83 LID - 10.1126/science.aad5788 [doi] AB - 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. CI - Copyright (c) 2016, American Association for the Advancement of Science. FAU - Bornholdt, Zachary A AU - Bornholdt ZA AD - Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. FAU - Turner, Hannah L AU - Turner HL AD - Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. FAU - Murin, Charles D AU - Murin CD AD - 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. FAU - Li, Wen AU - Li W AD - Adimab, Lebanon, NH 03766, USA. FAU - Sok, Devin AU - Sok D AD - Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. FAU - Souders, Colby A AU - Souders CA AD - MassBiologics, University of Massachusetts Medical School, Boston, MA 02126, USA. FAU - Piper, Ashley E AU - Piper AE AD - U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA. FAU - Goff, Arthur AU - Goff A AD - U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA. FAU - Shamblin, Joshua D AU - Shamblin JD AD - U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA. FAU - Wollen, Suzanne E AU - Wollen SE AD - U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA. FAU - Sprague, Thomas R AU - Sprague TR AD - U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA. FAU - Fusco, Marnie L AU - Fusco ML AD - Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. FAU - Pommert, Kathleen B J AU - Pommert KB AD - Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. FAU - Cavacini, Lisa A AU - Cavacini LA AD - MassBiologics, University of Massachusetts Medical School, Boston, MA 02126, USA. FAU - Smith, Heidi L AU - Smith HL AD - MassBiologics, University of Massachusetts Medical School, Boston, MA 02126, USA. FAU - Klempner, Mark AU - Klempner M AD - MassBiologics, University of Massachusetts Medical School, Boston, MA 02126, USA. FAU - Reimann, Keith A AU - Reimann KA AD - MassBiologics, University of Massachusetts Medical School, Boston, MA 02126, USA. FAU - Krauland, Eric AU - Krauland E AD - Adimab, Lebanon, NH 03766, USA. FAU - Gerngross, Tillman U AU - Gerngross TU AD - Adimab, Lebanon, NH 03766, USA. FAU - Wittrup, Karl D AU - Wittrup KD AD - Adimab, Lebanon, NH 03766, USA. FAU - Saphire, Erica Ollmann AU - Saphire EO AD - Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. FAU - Burton, Dennis R AU - Burton DR AD - 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. FAU - Glass, Pamela J AU - Glass PJ AD - U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA. FAU - Ward, Andrew B AU - Ward AB AD - Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. FAU - Walker, Laura M AU - Walker LM AD - Adimab, Lebanon, NH 03766, USA. LA - eng GR - UM1 AI100663/AI/NIAID NIH HHS/United States GR - U19AI109762/AI/NIAID NIH HHS/United States GR - R01 AI067927/AI/NIAID NIH HHS/United States GR - R01AI067927/AI/NIAID NIH HHS/United States GR - U19 AI109762/AI/NIAID NIH HHS/United States GR - T32 AI007244/AI/NIAID NIH HHS/United States GR - UM1AI100663/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20160218 PL - United States TA - Science JT - Science (New York, N.Y.) JID - 0404511 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Neutralizing) RN - 0 (Antibodies, Viral) RN - 0 (Antigen-Antibody Complex) RN - 0 (Ebola Vaccines) RN - 0 (Viral Envelope Proteins) RN - 0 (envelope glycoprotein, Ebola virus) SB - IM MH - Animals MH - Antibodies, Monoclonal/chemistry/*isolation & purification/therapeutic use MH - Antibodies, Neutralizing/chemistry/*isolation & purification/therapeutic use MH - Antibodies, Viral/chemistry/*isolation & purification/therapeutic use MH - Antibody Formation MH - Antigen-Antibody Complex/chemistry MH - Democratic Republic of the Congo/epidemiology MH - Disease Outbreaks MH - Ebola Vaccines/immunology/therapeutic use MH - Ebolavirus/*immunology MH - Hemorrhagic Fever, Ebola/epidemiology/*immunology/therapy MH - Humans MH - Immunization, Passive MH - Mice MH - Survivors MH - Tissue Donors MH - Viral Envelope Proteins/chemistry/*immunology MH - Virion/immunology PMC - PMC4900763 MID - NIHMS788347 EDAT- 2016/02/26 06:00 MHDA- 2016/03/26 06:00 PMCR- 2016/09/04 CRDT- 2016/02/26 06:00 PHST- 2015/10/07 00:00 [received] PHST- 2016/02/08 00:00 [accepted] PHST- 2016/02/26 06:00 [entrez] PHST- 2016/02/26 06:00 [pubmed] PHST- 2016/03/26 06:00 [medline] PHST- 2016/09/04 00:00 [pmc-release] AID - science.aad5788 [pii] AID - 10.1126/science.aad5788 [doi] PST - ppublish SO - Science. 2016 Mar 4;351(6277):1078-83. doi: 10.1126/science.aad5788. Epub 2016 Feb 18.