Intradermal Administration of RiVax, a Ricin Vaccine

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Title: Intradermal Administration of RiVax, a Ricin Vaccine
Author: Selvaduray, Praveena
Abstract: 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 .
URI: http : / /hdl .handle .net /2152 .5 /812
Date: 2010-11-02

Citation

Intradermal Administration of RiVax, a Ricin Vaccine. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /812 .

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