Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, NY 12208, United States.
Vaccine. 2012 Feb 8;30(7):1239-43. doi: 10.1016/j.vaccine.2011.12.058. Epub 2011 Dec 22.
GD12 is a murine monoclonal IgG(1) (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 IgG(1) 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 (10μg) 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 6h 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.
GD12 是一种鼠源单克隆 IgG1（mAb），它识别蓖麻毒素 A 亚基（RTA）上的一个免疫显性线性中和表位（163-TLARSFIICIQM-174）。为了长期将 GD12 用作抗蓖麻毒素中毒的潜在对策，我们已经制备了 GD12 的嵌合衍生物（cGD12），其中鼠源重链和轻链可变区融合到人 IgG1 框架中。该嵌合 mAb 使用基于烟草原生质体的系统表达和纯化，表现出与亲本鼠源 mAb 相似的表位特异性和蓖麻毒素中和活性。通过腹腔注射将 cGD12（10μg）被动给予小鼠，可保护动物免受全身性蓖麻毒素攻击。在暴露后环境中，在毒素攻击后 6 小时内给予鼠源和嵌合 mAb 均可使小鼠免于毒素诱导的死亡，这表明 GD12 有可能作为预防性和治疗性药物用于蓖麻毒素中毒。
