A mouse model for ricin poisoning and for evaluating protective effects of antiricin antibodies

Abstract

Background. Ricin is a potential bioterrorism agent and no specific antidote or treatment exists for ricin poisoning. For this reason, we developed ricin-specific antibodies that were tested in a murine model of ricin poisoning for use as antidotes against symptoms of ricin poisoning. Methods. Mice were poisoned with a lethal dose of ricin (5 μg) and their temperature and general condition were monitored for determination of a surrogate and humane end point. Mice were then treated with injections of ricin and different combinations of polyclonal anti-ricin antibodies. Antibody effect was evaluated for various doses and using various time points from ricin to antibody injection. Also, the effect of adjuvant symptomatic treatment was examined. Brain, heart, intestines, kidney, liver, lung, pancreas, spleen, and stomach tissues were sampled for histopathological analysis. Results. The mouse model was reproducible and easy to use. A clear protective effect of both anti-ricin A-chain and anti-ricin B-chain antibodies–but not of irrelevant antibodies–was demonstrated with no added effect of symptomatic treatment. Conclusions. These data suggest that specific polyclonal antibodies against ricin A- and B-chain may reproducibly protect mice against ricin poisoning, even when the antibodies are administered up to 1.5 h after poisoning.

Keywords :

• Acute poisoning
• Antidote
• Toxic plants
• Poisoning management
• Toxins
• Ricin toxin

Acknowledgments

Thanks to Associate Professor Ricardo Feinstein for pathological expertise and to John-Erik Stig Hansen for valuable inputs and discussion. Also, thanks to expert technical assistance from Søren T. G. Andersen, Anisette Ammentorp Lander, and Lena Enig that made this project possible.