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Post-Exposure Anti-Ricin Treatment Protects Swine Against Lethal Systemic and Pulmonary Exposures.
Falach, Reut; Sapoznikov, Anita; Evgy, Yentl; Aftalion, Moshe; Makovitzki, Arik; Agami, Avi; Mimran, Avishai; Lerer, Elad; Ben David, Alon; Zichel, Ran; Katalan, Shahaf; Rosner, Amir; Sabo, Tamar; Kronman, Chanoch; Gal, Yoav.
Afiliación
  • Falach R; Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 76100, Israel.
  • Sapoznikov A; Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 76100, Israel.
  • Evgy Y; Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 76100, Israel.
  • Aftalion M; Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 76100, Israel.
  • Makovitzki A; Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona 76100, Israel.
  • Agami A; Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona 76100, Israel.
  • Mimran A; Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona 76100, Israel.
  • Lerer E; Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona 76100, Israel.
  • Ben David A; Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona 76100, Israel.
  • Zichel R; Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona 76100, Israel.
  • Katalan S; Department of Pharmacology, Israel Institute for Biological Research, Ness-Ziona 76100, Israel.
  • Rosner A; Veterinary Center for Preclinical Research, Israel Institute for Biological Research, Ness-Ziona 76100, Israel.
  • Sabo T; Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 76100, Israel.
  • Kronman C; Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 76100, Israel.
  • Gal Y; Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 76100, Israel.
Toxins (Basel) ; 12(6)2020 05 28.
Article en En | MEDLINE | ID: mdl-32481526
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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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Ricina / Fragmentos Fab de Inmunoglobulinas / Antitoxinas / Anticuerpos Neutralizantes Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Año: 2020 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Ricina / Fragmentos Fab de Inmunoglobulinas / Antitoxinas / Anticuerpos Neutralizantes Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Año: 2020 Tipo del documento: Article