Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques |
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Authors: | 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 |
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Affiliation: | aDivision of Virology, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, 21702;;bMapp Biopharmaceutical, Inc., San Diego, CA, 92121; and;cKentucky BioProcessing, LLC, Owensboro, KY, 42301 |
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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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Keywords: | passive immunization therapy |
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