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

ZA Bornholdt, HL Turner, CD Murin, W Li, D Sok… - Science, 2016 - science.org
ZA Bornholdt, HL Turner, CD Murin, W Li, D Sok, CA Souders, AE Piper, A Goff, JD Shamblin…
Science, 2016science.org
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 …
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.
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