Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak

Zachary A Bornholdt; Hannah L Turner; Charles D Murin; Wen Li; Devin Sok; Colby A Souders; Ashley E Piper; Arthur Goff; Joshua D Shamblin; Suzanne E Wollen; Thomas R Sprague; Marnie L Fusco; Kathleen B J Pommert; Lisa A Cavacini; Heidi L Smith; Mark Klempner; Keith A Reimann; Eric Krauland; Tillman U Gerngross; Karl D Wittrup; Erica Ollmann Saphire; Dennis R Burton; Pamela J Glass; Andrew B Ward; Laura M Walker

doi:10.1126/science.aad5788

Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak

Science. 2016 Mar 4;351(6277):1078-83. doi: 10.1126/science.aad5788. Epub 2016 Feb 18.

Authors

Zachary A Bornholdt¹, Hannah L Turner², Charles D Murin³, Wen Li⁴, Devin Sok¹, Colby A Souders⁵, Ashley E Piper⁶, Arthur Goff⁶, Joshua D Shamblin⁶, Suzanne E Wollen⁶, Thomas R Sprague⁶, Marnie L Fusco¹, Kathleen B J Pommert¹, Lisa A Cavacini⁵, Heidi L Smith⁵, Mark Klempner⁵, Keith A Reimann⁵, Eric Krauland⁴, Tillman U Gerngross⁴, Karl D Wittrup⁴, Erica Ollmann Saphire¹, Dennis R Burton⁷, Pamela J Glass⁶, Andrew B Ward², Laura M Walker⁴

Affiliations

¹ Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
² Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
³ 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.
⁴ Adimab, Lebanon, NH 03766, USA.
⁵ MassBiologics, University of Massachusetts Medical School, Boston, MA 02126, USA.
⁶ U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
⁷ 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.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Antibodies, Monoclonal / chemistry
Antibodies, Monoclonal / isolation & purification*
Antibodies, Monoclonal / therapeutic use
Antibodies, Neutralizing / chemistry
Antibodies, Neutralizing / isolation & purification*
Antibodies, Neutralizing / therapeutic use
Antibodies, Viral / chemistry
Antibodies, Viral / isolation & purification*
Antibodies, Viral / therapeutic use
Antibody Formation
Antigen-Antibody Complex / chemistry
Democratic Republic of the Congo / epidemiology
Disease Outbreaks
Ebola Vaccines / immunology
Ebola Vaccines / therapeutic use
Ebolavirus / immunology*
Hemorrhagic Fever, Ebola / epidemiology
Hemorrhagic Fever, Ebola / immunology*
Hemorrhagic Fever, Ebola / therapy
Humans
Immunization, Passive
Mice
Survivors
Tissue Donors
Viral Envelope Proteins / chemistry
Viral Envelope Proteins / immunology*
Virion / immunology

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Antigen-Antibody Complex
Ebola Vaccines
Viral Envelope Proteins
envelope glycoprotein, Ebola virus

Abstract

Publication types

MeSH terms

Substances

Grants and funding