Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques

被引:280
作者
Olinger, Gene Garrard, Jr. [1 ]
Pettitt, James [1 ]
Kim, Do [2 ]
Working, Cara [3 ]
Bohorov, Ognian [2 ]
Bratcher, Barry [3 ]
Hiatt, Ernie [3 ]
Hume, Steven D. [3 ]
Johnson, Ashley K. [3 ]
Morton, Josh [3 ]
Pauly, Michael [2 ]
Whaley, Kevin J. [2 ]
Lear, Calli M. [1 ]
Biggins, Julia E. [1 ]
Scully, Corinne [1 ]
Hensley, Lisa [1 ]
Zeitlin, Larry [2 ]
机构
[1] USA, 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, KY 42301 USA
关键词
passive immunization; therapy; HEMORRHAGIC-FEVER; NONHUMAN-PRIMATES; PROPHYLAXIS; VACCINATION; EXPRESSION; DISEASE; IGG;
D O I
10.1073/pnas.1213709109
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
Filovirus infections can cause a severe and often fatal disease in humans and nonhuman primates, including great apes. Here, three anti-Ebola virus mouse/human chimeric mAbs (c13C6, h-13F6, and c6D8) were produced in Chinese hamster ovary and in whole plant (Nicotiana benthamiana) cells. In pilot experiments testing a mixture of the three mAbs (MB-003), we found that MB-003 produced in both manufacturing systems protected rhesus macaques from lethal challenge when administered 1 h postinfection. In a pivotal follow-up experiment, we found significant protection (P < 0.05) when MB-003 treatment began 24 or 48 h postinfection (four of six survived vs. zero of two controls). In all experiments, surviving animals that received MB-003 experienced little to no viremia and had few, if any, of the clinical symptoms observed in the controls. The results represent successful postexposure in vivo efficacy by a mAb mixture and suggest that this immunoprotectant should be further pursued as a postexposure and potential therapeutic for Ebola virus exposure.
引用
收藏
页码:18030 / 18035
页数:6
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