A Two-Antibody Pan-Ebolavirus Cocktail Confers Broad Therapeutic Protection in Ferrets and Nonhuman Primates

被引：72

作者：

Bornholdt, Zachary A. ^{[1
]}

Herbert, Andrew S. ^{[2
]}

Mire, Chad E. ^{[3
]}

He, Shihua ^{[4
]}

Cross, Robert W. ^{[3
]}

Wec, Anna Z. ^{[5
,8
]}

Abelson, Dafna M. ^{[1
]}

Geisbert, Joan B. ^{[3
]}

James, Rebekah M. ^{[2
]}

Rahim, Niaz ^{[4
,7
]}

Zhu, Wenjun ^{[4
]}

Borisevich, Viktoriya ^{[3
]}

Banadyga, Logan ^{[4
]}

Gunn, Bronwyn M. ^{[6
]}

Agans, Krystle N. ^{[3
]}

Wirchnianski, Ariel S. ^{[5
]}

Goodwin, Eileen ^{[8
]}

Tierney, Kevin ^{[4
]}

Shestowsky, William S. ^{[1
]}

Bohorov, Ognian ^{[1
]}

Bohorova, Natasha ^{[1
]}

Velasco, Jesus ^{[1
]}

Ailor, Eric ^{[1
]}

Kim, Do ^{[1
]}

Pauly, Michael H. ^{[1
]}

Whaley, Kevin J. ^{[1
]}

Alter, Galit ^{[6
]}

Walker, Laura M. ^{[8
]}

Chandran, Kartik ^{[5
]}

Zeitlin, Larry ^{[1
]}

Qiu, Xiangguo ^{[4
,7
]}

Geisbert, Thomas W. ^{[3
]}

Dye, John M. ^{[2
]}

机构：

[1] Mapp Biopharmaceut Inc, San Diego, CA 92121 USA

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

[3] Univ Texas Med Branch, Galveston Natl Lab, Dept Microbiol & Immunol, Galveston, TX 77555 USA

[4] Publ Hlth Agcy Canada, Natl Microbiol Lab, Special Pathogens Program, Winnipeg, MB, Canada

[5] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA

[6] Ragon Inst, Cambridge, MA USA

[7] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada

[8] Adimab LLC, Lebanon, NH USA

来源：

CELL HOST & MICROBE | 2019年 / 25卷 / 01期

关键词：

MONOCLONAL-ANTIBODY; VIRUS INFECTION; SURVIVOR;

D O I：

10.1016/j.chom.2018.12.005

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Recent and ongoing outbreaks of Ebola virus disease (EVD) underscore the unpredictable nature of ebolavirus reemergence and the urgent need for antiviral treatments. Unfortunately, available experimental vaccines and immunotherapeutics are specific for a single member of the Ebolavirus genus, Ebola virus (EBOV), and ineffective against other ebolaviruses associated with EVD, including Sudan virus (SUDV) and Bundibugyo virus (BDBV). Here we show that MBP134(AF), a pan-ebolavirus therapeutic comprising two broadly neutralizing human antibodies (bNAbs), affords unprecedented effectiveness and potency as a therapeutic countermeasure to antigenically diverse ebolaviruses. MBP134(AF) could fully protect ferrets against lethal EBOV, SUDV, and BDBV infection, and a single 25-mg/kg dose was sufficient to protect NHPs against all three viruses. The development of MBP134(AF) provides a successful model for the rapid discovery and translational advancement of immunotherapeutics targeting emerging infectious diseases.

引用

页码：49 / +

页数：15

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