Defence Research and Development Canada-Suffield, Box 4000, Station Main, Medicine Hat, AB T1A 8K6, Canada.
Toxins (Basel). 2014 Jan 21;6(1):380-93. doi: 10.3390/toxins6010380.
Therapeutic antibodies can confer an instant protection against biothreat agents when administered. In this study, intact IgG and F(ab')2 from goat anti-ricin hyperimmune sera were compared for the protection against lethal ricin mediated intoxication. Similar ricin-binding affinities and neutralizing activities in vitro were observed between IgG and F(ab')2 when compared at the same molar concentration. In a murine ricin intoxication model, both IgG and F(ab')2 could rescue 100% of the mice by one dose (3 nmol) administration of antibodies 1 hour after 5 × LD50 ricin challenge. Nine days later, when the rescued mice received a second ricin challenge (5 × LD50), only the IgG-treated mice survived; the F(ab')2-treated mice did not. The experimental design excluded the possibility of residual goat IgG responsible for the protection against the second ricin challenge. Results confirmed that the active immunity against ricin in mice was induced quickly following the passive delivery of a single dose of goat IgG post-exposure. Furthermore, it was demonstrated that the induced active immunity against ricin in mice lasted at least 5 months. Therefore, passive IgG therapy not only provides immediate protection to the victim after ricin exposure, but also elicits an active immunity against ricin that subsequently results in long term protection.
治疗性抗体在给药时可以立即提供针对生物威胁剂的保护。在这项研究中，比较了来自抗蓖麻毒素高免山羊血清的完整 IgG 和 F(ab')2 ，以比较它们对致死性蓖麻毒素介导的中毒的保护作用。当以相同的摩尔浓度比较时，观察到 IgG 和 F(ab')2 之间具有相似的蓖麻毒素结合亲和力和体外中和活性。在小鼠蓖麻毒素中毒模型中，两种 IgG 和 F(ab')2 都可以通过在 5×LD50 蓖麻毒素攻击后 1 小时给予 1 剂量（3 nmol）抗体来挽救 100%的小鼠。9 天后，当获救的小鼠接受第二次蓖麻毒素挑战（5×LD50）时，只有 IgG 治疗的小鼠存活；F(ab')2 治疗的小鼠没有。实验设计排除了剩余的山羊 IgG 对抗第二次蓖麻毒素挑战的保护作用的可能性。结果证实，在暴露后单次给予山羊 IgG 进行被动给药后，小鼠体内迅速产生针对蓖麻毒素的主动免疫。此外，还证明了小鼠体内针对蓖麻毒素的诱导性主动免疫至少持续 5 个月。因此，被动 IgG 治疗不仅在蓖麻毒素暴露后立即为受害者提供保护，而且还引发针对蓖麻毒素的主动免疫，从而导致长期保护。
