Production, Characterisation and Testing of an Ovine Antitoxin against Ricin; Efficacy, Potency and Mechanisms of Action.

Autor: Whitfield SJC; Chemical, Biological and Radiological Division, Dstl, Porton Down, Salisbury SP4 0JQ, UK. SJWHITFIELD@dstl.gov.uk., Griffiths GD; Chemical, Biological and Radiological Division, Dstl, Porton Down, Salisbury SP4 0JQ, UK. dcjenner@dstl.gov.uk., Jenner DC; Chemical, Biological and Radiological Division, Dstl, Porton Down, Salisbury SP4 0JQ, UK. RJGWYTHER@dstl.gov.uk., Gwyther RJ; Chemical, Biological and Radiological Division, Dstl, Porton Down, Salisbury SP4 0JQ, UK. fmstahl@dstl.gov.uk., Stahl FM; Chemical, Biological and Radiological Division, Dstl, Porton Down, Salisbury SP4 0JQ, UK. ljcork@dstl.gov.uk., Cork LJ; Chemical, Biological and Radiological Division, Dstl, Porton Down, Salisbury SP4 0JQ, UK. jlholley@dstl.gov.uk., Holley JL; Chemical, Biological and Radiological Division, Dstl, Porton Down, Salisbury SP4 0JQ, UK., Green AC; Chemical, Biological and Radiological Division, Dstl, Porton Down, Salisbury SP4 0JQ, UK. acgreen@dstl.gov.uk., Clark GC; Chemical, Biological and Radiological Division, Dstl, Porton Down, Salisbury SP4 0JQ, UK. gcclark@dstl.gov.uk.
Jazyk: angličtina
Zdroj: Toxins [Toxins (Basel)] 2017 Oct 18; Vol. 9 (10). Date of Electronic Publication: 2017 Oct 18.
DOI: 10.3390/toxins9100329
Abstrakt: Ricin is a type II ribosome-inactivating toxin that catalytically inactivates ribosomes ultimately leading to cell death. The toxicity of ricin along with the prevalence of castor beans (its natural source) has led to its increased notoriety and incidences of nefarious use. Despite these concerns, there are no licensed therapies available for treating ricin intoxication. Here, we describe the development of a F(ab')₂ polyclonal ovine antitoxin against ricin and demonstrate the efficacy of a single, post-exposure, administration in an in vivo murine model of intoxication against aerosolised ricin. We found that a single dose of antitoxin afforded a wide window of opportunity for effective treatment with 100% protection observed in mice challenged with aerosolised ricin when given 24 h after exposure to the toxin and 75% protection when given at 30 h. Treated mice had reduced weight loss and clinical signs of intoxication compared to the untreated control group. Finally, using imaging flow cytometry, it was found that both cellular uptake and intracellular trafficking of ricin toxin to the Golgi apparatus was reduced in the presence of the antitoxin suggesting both actions can contribute to the therapeutic mechanism of a polyclonal antitoxin. Collectively, the research highlights the significant potential of the ovine F(ab')₂ antitoxin as a treatment for ricin intoxication.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
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