Intradermal Administration of RiVax, a Ricin Vaccine
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Ricin toxin is a CDC Level B Biothreat due to its extreme toxicity and ease of production. The most effective method for minimizing ricin toxicity in humans is prophylactic vaccination. We have previously described the efficacy and safety of RiVax, a recombinant mutant of ricin A chain (RTA). RiVax has no residual toxicity from either its ribotoxic site or its vascular leak-inducing site. When administered by intramuscular (IM) injection, it was safe and immunogenic in mice, rabbits, and humans. A three dose regimen of IM administered RiVax also protected mice from an LD50dose of ricin delivered by injection, gastric gavage or aerosol. In this study we have attempted to increase the utility and immunogenicity of RiVax. To this end, we have compared intradermal (ID) vs. IM administration of RiVax by evaluating the following parameters of vaccine efficacy: (1) short-term antibody responses and protection of mice from a 10X LD50of ricin following a three dose vaccine regimen; (2) long-term antibody responses and protection of mice from a 10X LD50of ricin following a three dose vaccine regimen; (3) protective effect of a single high dose of RiVax from a 10X LD50dose of ricin; (4) the minimum dose of ricin at which fully vaccinated animals are no longer protected; (5) the rate of antigen trafficking to draining lymph nodes (DLN) following administration of RiVax. In the short term, when RiVax was delivered with alum, very low doses of vaccine administered ID were superior to the same low doses administered IM, with regard to both antibody production and protection against ricin delivered by injection, gavage, or aerosol. Low doses of ID vaccine were also superior in maintaining lung function in mice exposed to aerosolized ricin. Comparing the same parameters in the long term or after a single dose of RiVax, ID and IM vaccinations were equally effective. Both ID and IM vaccination were also similar in their ability to protect mice from a supra-lethal challenge with injected ricin. One possible explanation for the improved efficacy of low doses of RiVax administered ID was that the vaccine trafficked more effectively to the DLNs. This appeared to be the trend, albeit not a statistically significant one. Given the increased efficacy of low doses of ID vaccine in protecting mice against ricin delivered to the lung and gut, we suggest that it should be considered for testing in humans.