ROTAVIRUS-2 6 VIRUS-LIKE PARTICLES ADMINISTERED INTRANASALLY WITH CHOLERA-TOXIN, ESCHERICHIA-COLI HEAT-LABILE TOXIN (LT), AND LT-R192G INDUCE PROTECTION FROM ROTAVIRUS CHALLENGE/

We have shown that rotavirus 2/6 viruslike particles composed of prote ins VP2 and VP6 (2/6-VLPs) administered to mice intranasally with chol era toxin (CT) induced protection from rotavirus challenge, as measure d by virus shedding. Since it is unclear if CT will be approved for hu man use, we evaluated the adjuvanticity of Escherichia coli heat-labil e toxin (LT) and LT-R192G, Mice were inoculated intranasally with 10 m u g of 2/6-VLPs combined with CT, LT, or LT-R192G. All three adjuvants induced equivalent geometric mean titers of rotavirus-specific serum antibody and intestinal immunoglobulin G (IgG). Mice inoculated with 2 /6-VLPs with LT produced significantly higher titers of intestinal IgA than mice given CT as the adjuvant. All mice inoculated with 2/6-VLPs mixed with LT and LT-R192G were totally protected (100%) from rotavir us challenge, while mice inoculated with 2/6-VLPs mixed with CT showed a mean 91% protection from challenge. The availability of a safe, eff ective mucosal adjuvant such as LT-R192G will increase the practicalit y of administering recombinant vaccines mucosally.