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

Bornholdt ZA; Turner HL; Murin CD; Li W; Sok D; Souders CA; Piper AE; Goff A; Shamblin JD; Wollen SE; Sprague TR; Fusco ML; Pommert KBJ; Cavacini LA; Smith HL; Klempner M; Reimann KA; Krauland E; Gerngross TU; Wittrup KD; Saphire EO; Burton DR; Glass PJ; Ward AB; Walker LM

Science, Vol.351, No.6277, 1078-1083, 2016

DOI10.1126/science.aad5788 Export Citation

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

Bornholdt ZA, Turner HL, Murin CD, Li W, Sok D, Souders CA, Piper AE, Goff A, Shamblin JD, Wollen SE, Sprague TR, Fusco ML, Pommert KBJ, Cavacini LA, Smith HL, Klempner M, Reimann KA, Krauland E, Gerngross TU, Wittrup KD, Saphire EO, Burton DR, Glass PJ, Ward AB, Walker LM

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.