title: Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak.
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.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Bornholdt
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Hannah L
authors.initials: HL
authors.lastname: Turner
authors.affiliation: 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.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Murin
authors.affiliation: Adimab, Lebanon, NH 03766, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Devin
authors.initials: D
authors.lastname: Sok
authors.affiliation: MassBiologics, University of Massachusetts Medical School, Boston, MA 02126, USA.
authors.forename: Colby A
authors.initials: CA
authors.lastname: Souders
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Piper
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Goff
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Shamblin
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Wollen
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Sprague
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Marnie L
authors.initials: ML
authors.lastname: Fusco
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Kathleen B J
authors.initials: KB
authors.lastname: Pommert
authors.affiliation: MassBiologics, University of Massachusetts Medical School, Boston, MA 02126, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cavacini
authors.affiliation: MassBiologics, University of Massachusetts Medical School, Boston, MA 02126, USA.
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Smith
authors.affiliation: MassBiologics, University of Massachusetts Medical School, Boston, MA 02126, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Klempner
authors.affiliation: MassBiologics, University of Massachusetts Medical School, Boston, MA 02126, USA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Reimann
authors.affiliation: Adimab, Lebanon, NH 03766, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Krauland
authors.affiliation: Adimab, Lebanon, NH 03766, USA.
authors.forename: Tillman U
authors.initials: TU
authors.lastname: Gerngross
authors.affiliation: Adimab, Lebanon, NH 03766, USA.
authors.forename: Karl D
authors.initials: KD
authors.lastname: Wittrup
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Erica Ollmann
authors.initials: EO
authors.lastname: Saphire
authors.affiliation: 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.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Glass
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Ward
authors.affiliation: Adimab, Lebanon, NH 03766, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Walker
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000302:isolation & purification* / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000302:isolation & purification* / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000737:chemistry / Q000302:isolation & purification* / Q000627:therapeutic use; D000917:Antibody Formation; D000936:Antigen-Antibody Complex / Q000737:chemistry; D015023:Democratic Republic of the Congo / Q000453:epidemiology; D004196:Disease Outbreaks; D046129:Ebola Vaccines / Q000276:immunology / Q000627:therapeutic use; D029043:Ebolavirus / Q000276:immunology*; D019142:Hemorrhagic Fever, Ebola / Q000453:epidemiology / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007116:Immunization, Passive; D051379:Mice; D017741:Survivors; D014019:Tissue Donors; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology*; D014771:Virion / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000936:Antigen-Antibody Complex; D046129:Ebola Vaccines; D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus