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Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak.
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.
Afiliação
  • Bornholdt ZA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Turner HL; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Murin CD; 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.
  • Li W; Adimab, Lebanon, NH 03766, USA.
  • Sok D; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Souders CA; MassBiologics, University of Massachusetts Medical School, Boston, MA 02126, USA.
  • Piper AE; U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
  • Goff A; U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
  • Shamblin JD; U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
  • Wollen SE; U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
  • Sprague TR; U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
  • Fusco ML; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Pommert KB; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Cavacini LA; MassBiologics, University of Massachusetts Medical School, Boston, MA 02126, USA.
  • Smith HL; MassBiologics, University of Massachusetts Medical School, Boston, MA 02126, USA.
  • Klempner M; MassBiologics, University of Massachusetts Medical School, Boston, MA 02126, USA.
  • Reimann KA; MassBiologics, University of Massachusetts Medical School, Boston, MA 02126, USA.
  • Krauland E; Adimab, Lebanon, NH 03766, USA.
  • Gerngross TU; Adimab, Lebanon, NH 03766, USA.
  • Wittrup KD; Adimab, Lebanon, NH 03766, USA.
  • Saphire EO; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Burton DR; 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.
  • Glass PJ; U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
  • Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Walker LM; Adimab, Lebanon, NH 03766, USA.
Science ; 351(6277): 1078-83, 2016 Mar 04.
Article em En | MEDLINE | ID: mdl-26912366
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas do Envelope Viral / Doença pelo Vírus Ebola / Ebolavirus / Anticorpos Neutralizantes / Anticorpos Monoclonais / Anticorpos Antivirais Limite: Animals / Humans País/Região como assunto: Africa Idioma: En Revista: Science Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas do Envelope Viral / Doença pelo Vírus Ebola / Ebolavirus / Anticorpos Neutralizantes / Anticorpos Monoclonais / Anticorpos Antivirais Limite: Animals / Humans País/Região como assunto: Africa Idioma: En Revista: Science Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos