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

使用植物源单克隆抗体延迟治疗埃博拉病毒感染可为恒河猴提供保护

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作者:Gene Garrard Olinger Jr, James Pettitt, Do Kim, Cara Working, Ognian Bohorov, Barry Bratcher, Ernie Hiatt, Steven D Hume, Ashley K Johnson, Josh Morton, Michael Pauly, Kevin J Whaley, Calli M Lear, Julia E Biggins, Corinne Scully, Lisa Hensley, Larry Zeitlin

Abstract

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.

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