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

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.

Keywords: antitoxin; intramuscular; intratracheal; neutralizing units; ricin; swine.

Figure 1

Kaplan–Meier curves of ricin-intoxicated swine that were subjected to treatment with anti-ricin equine-derived F(ab’)₂ at 18 h post-exposure. Swine exposed to a lethal dose of ricin were treated intravenously (i.v.) or not with anti-ricin F(ab’)₂ at a dose of 3.5 mL/kg body weight 18 h later and then monitored for survival up to 14 days. (a) intramuscular (i.m.)-exposed swine: solid line, no Ab treatment (0/5 live/total), dashed line, Ab-treated (10/12 live/total, 83% survival). (b) intratracheal (i.t.)-exposed swine: solid line, no Ab treatment (0/11 live/total), dashed line, Ab-treated (11/13 live/total, 85% survival).

Figure 2

Kaplan–Meier curves of ricin-intoxicated swine that were subjected to treatment with anti-ricin equine-derived F(ab’)₂ at 24 h post-exposure. Swine exposed to a lethal dose of ricin were treated i.v. with anti-ricin F(ab’)₂ at a dose of ~5000 NU/ kg body weight 24 h later and then monitored for survival up to 14 days. Solid line, i.m.-intoxicated swine (7/12 live/total = 58% survival), dashed line, i.t.-intoxicated swine (5/19 live/total = 26% survival).