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Open AccessArticle

Post-Exposure Anti-Ricin Treatment Protects Swine against Lethal Systemic and Pulmonary Exposures

1
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 76100, Israel
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Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona 76100, Israel
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Department of Pharmacology, Israel Institute for Biological Research, Ness-Ziona 76100, Israel
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Veterinary Center for Preclinical Research, Israel Institute for Biological Research, Ness-Ziona 76100, Israel
*
Authors to whom correspondence should be addressed.
Toxins 2020, 12(6), 354; https://doi.org/10.3390/toxins12060354
Received: 23 April 2020 / Revised: 21 May 2020 / Accepted: 25 May 2020 / Published: 28 May 2020
(This article belongs to the Section Plant Toxins)
Ricin, a plant-derived toxin originating from the seeds of Ricinus communis (castor bean plant), is one of the most lethal toxins known. To date, there is no approved post-exposure therapy for ricin exposures. This work demonstrates for the first time the therapeutic efficacy of equine-derived anti-ricin F(ab’)2 antibodies against lethal pulmonary and systemic ricin exposures in swine. While administration of the antitoxin at 18 h post-exposure protected more than 80% of both intratracheally and intramuscularly ricin-intoxicated swine, treatment at 24 h post-exposure protected 58% of the intramuscular-exposed swine, as opposed to 26% of the intratracheally exposed animals. Quantitation of the anti-ricin neutralizing units in the anti-toxin preparations confirmed that the disparate protection conferred to swine subjected to the two routes of exposure stems from variance between the two models. Furthermore, dose response experiments showed that approximately 3 times lesser amounts of antibody are needed for high-level protection of the intramuscularly compared to the intratracheally intoxicated swine. This study, which demonstrates the high-level post-exposure efficacy of anti-ricin antitoxin at clinically relevant time-points in a large animal model, can serve as the basis for the formulation of post-exposure countermeasures against ricin poisoning in humans. View Full-Text
Keywords: ricin; antitoxin; swine; neutralizing units; intratracheal; intramuscular ricin; antitoxin; swine; neutralizing units; intratracheal; intramuscular
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Falach, R.; Sapoznikov, A.; Evgy, Y.; Aftalion, M.; Makovitzki, A.; Agami, A.; Mimran, A.; Lerer, E.; Ben David, A.; Zichel, R.; Katalan, S.; Rosner, A.; Sabo, T.; Kronman, C.; Gal, Y. Post-Exposure Anti-Ricin Treatment Protects Swine against Lethal Systemic and Pulmonary Exposures. Toxins 2020, 12, 354.

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