Mouse challenge studies with death as an endpoint remain the gold standard in assessing the potency of ricin toxin, a Category B biothreat agent derived from the castor bean (Ricinus communis). However, animal studies are expensive, time consuming and ethically concerning. In an effort to reduce reliance on animals in vaccine development, we developed a monoclonal antibody (MAb)-based ricin competition ELISA (RiCoE) that indicates conformation integrity of ricin toxin. In forced degradation (heat-denaturation) experiments with native ricin holotoxin, we demonstrate a correlation between the decline in MAb reactivity in RiCoE and a corresponding loss of toxin potency in Vero cells (IC₅₀) and mice (LD₅₀). The RiCoE assay was applied to differentially sourced commercial lots of ricin toxin derived from R. communis blends and compared to toxin potency in mice. There was near perfect congruence between RiCoE values with two different MAbs (PB10, SyH7) and ricin potency in the mouse model using morbidity as an endpoint. In conclusion, we propose that RiCoE can serve as a rapid and sensitive substitute to mouse lethal dose challenge studies as a means to determine ricin toxin potency and will be valuable at various stages of vaccine development.

以死亡为终点的小鼠攻击研究仍然是评估蓖麻毒素（一种来自蓖麻子（Ricinus communis）的B类生物威胁剂）效力的金标准。然而，动物研究是昂贵，费时且在伦理上令人关注的。在努力减少对疫苗开发的动物的依赖，我们开发了一种单克隆抗体（mAb）基里CIN合作mpetition Ë表示蓖麻毒素的结构完整性LISA（RiCoE）。在使用天然蓖麻毒素全毒素的强制降解（热变性）实验中，我们证明了RiCoE中的单克隆抗体反应性下降与Vero细胞（IC ₅₀）和小鼠（LD₅₀）。所述RiCoE测定施加于差动来源市售批次衍生自蓖麻毒素的蓖麻共混物，并与在小鼠中毒素的效力。以发病率为终点，在小鼠模型中，RiCoE值与两种不同的单克隆抗体（PB10，SyH7）和蓖麻毒素效价之间几乎完全一致。总之，我们建议RiCoE可以作为小鼠致死剂量挑战研究的一种快速而敏感的替代品，作为确定蓖麻毒素毒素效价的一种手段，在疫苗开发的各个阶段都将是有价值的。