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

Authors
  • Falach, Reut1
  • Sapoznikov, Anita1
  • Evgy, Yentl1
  • Aftalion, Moshe1
  • Makovitzki, Arik2
  • Agami, Avi2
  • Mimran, Avishai2
  • Lerer, Elad2
  • Ben David, Alon2
  • Zichel, Ran2
  • Katalan, Shahaf
  • Rosner, Amir
  • Sabo, Tamar1
  • Kronman, Chanoch1
  • Gal, Yoav1
  • 1 (T.S.)
  • 2 (R.Z.)
Type
Published Article
Journal
Toxins
Publisher
MDPI AG
Publication Date
May 28, 2020
Volume
12
Issue
6
Identifiers
DOI: 10.3390/toxins12060354
PMID: 32481526
PMCID: PMC7354453
Source
PubMed Central
Keywords
License
Green

Abstract

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.

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