Purified immunoglobulin F(ab')2 could protect mice and rhesus monkeys from lethal ricin intoxication
Abstract
Objective: Ricin is a highly toxic ribosome-inactivation lectin derived from castor beans. So far, there has been no antidote to treat ricin-poisoned patients, and the development of a safe and effective antidote is urgently needed.
Methods: Firstly, the ricin was prepared and used to construct the ricin intoxication mouse and rhesus monkey model. Secondly, the pepsin-digested F(ab')2 fragments of serum IgGs from horses inoculated with Freund’s-adjuvanted purified ricin were prepared. Thirdly, the protective efficacy was evaluated in a lethal ricin intoxication mouse and rhesus monkey model.
Results: The purity quotient of the prepared ricin and F(ab')2 fragments were more than 90% and 85%, respectively. The LD50 of ricin in mice and rhesus monkeys was 2.7 and 9 μg/kg, respectively. 6.25 and 1.85 mg/kg F(ab')2 could treat the lethal ricin intoxication mice and rhesus monkeys models, respectively. Finally, the effect of this therapeutic antibody on peripheral blood immune cells was examined by analyzing peripheral blood immune cells through single cell sequencing technique, and its associated mechanism was elucidated, by restraining neutrophil activation, proliferation and differentiation.
Conclusion: Purified F(ab')2 fragments using needle-free devices can completely protect mice and rhesus monkeys from a lethal dose of ricin intoxication.