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

GD12 is a murine monoclonal IgG1 (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 IgG1 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 μg) 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.

► GD12 is a murine monoclonal antibody that protects mice from ricin toxin. ► A partially humanized version of GD12 was produced in plants. ► Chimeric GD12 neutralizes ricin toxin in vitro and in vivo. ► Chimeric GD12 protected mice when administered 6 h post ricin challenge.