| Literature DB >> 26912366 |
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.
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.Entities:
Mesh:
Substances:
Year: 2016 PMID: 26912366 PMCID: PMC4900763 DOI: 10.1126/science.aad5788
Source DB: PubMed Journal: Science ISSN: 0036-8075 Impact factor: 47.728