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

被引：173

作者：

Bornholdt, Zachary A. ^{[1
]}

Turner, Hannah L. ^{[2
]}

Murin, Charles D. ^{[1
,2
]}

Li, Wen ^{[3
]}

Sok, Devin ^{[1
]}

Souders, Colby A. ^{[4
]}

Piper, Ashley E. ^{[5
]}

Goff, Arthur ^{[5
]}

Shamblin, Joshua D. ^{[5
]}

Wollen, Suzanne E. ^{[5
]}

Sprague, Thomas R. ^{[5
]}

Fusco, Marnie L. ^{[1
]}

Pommert, Kathleen B. J. ^{[1
]}

Cavacini, Lisa A. ^{[4
]}

Smith, Heidi L. ^{[4
]}

Klempner, Mark ^{[4
]}

Reimann, Keith A. ^{[4
]}

Krauland, Eric ^{[3
]}

Gerngross, Tillman U. ^{[3
]}

Wittrup, Karl D. ^{[3
]}

Saphire, Erica Ollmann ^{[1
]}

Burton, Dennis R. ^{[1
,6
,7
]}

Glass, Pamela J. ^{[5
]}

Ward, Andrew B. ^{[2
]}

Walker, Laura M. ^{[3
]}

机构：

[1] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA

[3] Adimab, Lebanon, NH 03766 USA

[4] Univ Massachusetts, Sch Med, MassBiol, Boston, MA 02126 USA

[5] US Army, Med Res Inst Infect Dis, Frederick, MD 21702 USA

[6] MIT, Ragon Inst, Massachusetts Gen Hosp, Cambridge, MA 02142 USA

[7] Harvard Univ, Cambridge, MA 02142 USA

来源：

SCIENCE | 2016年 / 351卷 / 6277期

关键词：

MONOCLONAL-ANTIBODIES; NONHUMAN-PRIMATES; B-CELLS; INFECTION; REARRANGEMENTS; SELECTION; MACAQUES; COCKTAIL; DISEASE;

D O I：

10.1126/science.aad5788

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1078 / 1083

页数：6

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