Plant-based expression of a partially humanized neutralizing monoclonal IgG directed against an immunodominant epitope on the ricin toxin A subunit

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• 作者：Joanne M. O&rsquo ; Hara^a ; ^b ; Kevin Whaley^c ; Michael Pauly^c ; Larry Zeitlin^c ; Nicholas J. Mantis^a ; ^b ; ^{nmantis@wadsworth.org}
• 关键词：Antibody ; Toxin ; Biodefense ; Therapeutics
• 刊名：Vaccine
• 出版年：2012
• 出版时间：8 February 2012
• 年：2012
• 卷：30
• 期：7
• 页码：1239-1243
• 全文大小：433 K

文摘

GD12 is a murine monoclonal IgGb>1b> (mAb) that recognizes an immunodominant linear neutralizing epitope (163-TLARSFIICIQM-174) on the A subunit (RTA) of ricin toxin. With the long-term goal of using GD12 as a potential countermeasure against ricin intoxication, we have produced a chimeric derivative of GD12 (cGD12) in which the murine heavy and light chain variable regions were fused to a human IgGb>1b> framework. The chimeric mAb, expressed and purified using a Nicotiana-based system demonstrated epitope specificity and ricin neutralizing activity similar to the parental murine mAb. Passive administration of cGD12 (10 ¦Ìg) to mice by intraperitoneal injection protected the animals against a systemic ricin challenge. In a post-exposure setting, the murine and chimeric mAbs administered as much as 6 h after toxin challenge were each capable of rescuing mice from toxin-induced death, revealing the potential of GD12 to serve as both a prophylactic and therapeutic for ricin intoxication.