Preclinical toxicity and efficacy testing of RiVax, a recombinant protein vaccine against ricin

Abstract

Ricin toxin is a plant-derived ribosome inactivating protein (RIP) of extraordinary toxicity. Vaccination using ricin toxoid or its A chain (RTA) is protective in animals but both vaccines have two potential toxicities, RIP and vascular leak syndrome (VLS). Previously we described three recombinant RTA constructs from which both toxicities were eliminated by site-specific mutations. One mutant, V76M/Y80A, RiVax, has now been further characterized for immunogenicity and toxicity in animals. We have found that RiVax is safe at doses of at least 8 mg in mice, 800-fold higher than the protective dose, and induces neutralizing antibodies in both mice and rabbits.