Therapeutic Intervention of Ebola Virus Infection in Rhesus Macaques with the MB-003 Monoclonal Antibody Cocktail

被引:170
作者
Pettitt, James [1 ]
Zeitlin, Larry [2 ]
Kim, Do H. [2 ]
Working, Cara [3 ]
Johnson, Joshua C. [1 ]
Bohorov, Ognian [2 ]
Bratcher, Barry [3 ]
Hiatt, Ernie [3 ]
Hume, Steven D. [3 ]
Johnson, Ashley K. [3 ]
Morton, Josh [3 ]
Pauly, Michael H. [2 ]
Whaley, Kevin J. [2 ]
Ingram, Michael F. [1 ]
Zovanyi, Ashley [1 ]
Heinrich, Megan [1 ]
Piper, Ashley [1 ]
Zelko, Justine [1 ]
Olinger, Gene G. [1 ]
机构
[1] US Army Med Res Inst Infect Dis, Div Virol, Frederick, MD 21702 USA
[2] Mapp Biopharmaceut Inc, San Diego, CA 92121 USA
[3] Kentucky BioProc LLC, Owensboro 42301, KY USA
关键词
POSTEXPOSURE PROTECTION; NONHUMAN-PRIMATES;
D O I
10.1126/scitranslmed.3006608
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Ebola virus (EBOV) remains one of the most lethal transmissible infections and is responsible for high fatality rates and substantial morbidity during sporadic outbreaks. With increasing human incursions into endemic regions and the reported possibility of airborne transmission, EBOV is a high-priority public health threat for which no preventive or therapeutic options are currently available. Recent studies have demonstrated that cocktails of monoclonal antibodies are effective at preventing morbidity and mortality in nonhuman primates (NHPs) when administered as a post-exposure prophylactic within 1 or 2 days of challenge. To test whether one of these cocktails (MB-003) demonstrates efficacy as a therapeutic (after the onset of symptoms), we challenged NHPs with EBOV and initiated treatment upon confirmation of infection according to a diagnostic protocol for U.S. Food and Drug Administration Emergency Use Authorization and observation of a documented fever. Of the treated animals, 43% survived challenge, whereas both the controls and all historical controls with the same challenge stock succumbed to infection. These results represent successful therapy of EBOV infection in NHPs.
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页数:6
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