PHASE 1 STUDY OF SAFETY & IMMUNOGENICITY OF AN ALUM-FORMULATED RECOMBINANT RICIN

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DESCRIPTION (provided by applicant): Ricin is a highly potent toxin, easily produced from abundantly available castor beans, for which there is no vaccine to protect against intoxication or effective post-exposure treatment beyond supportive care. This has led the Centers for Disease Control and Prevention to classify ricin as a level B biothreat. Indeed, evidence has been found suggesting that terrorist groups have attempted to develop it as a weapon, and there have been instances of domestic attacks. The investigators have developed a non-toxic ricin vaccine, RiVax, from the A-chain subunit of ricin, by introducing two site-specific mutations that eliminate both its ribotoxic and vascular leak syndrome-inducing activities. Once preclinical testing demonstrated that this vaccine, as a frozen sucrose/Tween formulation, was safe and immunogenic in mice and rabbits, the investigators conducted a Phase 1 study in 15 human volunteers and showed that it was safe and able to elicit ricin neutralizing immune responses. In order to improve the efficacy of this vaccine, by increasing the degree and duration of the response, the investigators have developed an aluminum hydroxide (Alhydrogel) formulation and have shown that it greatly improves immunogenicity in mice. The investigators now propose to conduct a dose-escalating Phase 1 trial, involving 3 groups of 10 healthy volunteers to determine if this new formulation is safe in humans and increases and prolongs the response. Doses of 1, 10 and 100 micrograms - each with 0.5 mg Alhydrogel, will be given at weeks 0, 6, and 26 and serum will be assessed for anti-vaccine and neutralizing titers.