Intrarectal immunization of mice with VP6 and either LT(R192G) or CTA1-DD as adjuvant protects against fecal rotavirus shedding after EDIM challenge.

ABSTRACT

Intranasal or oral delivery of the chimeric rotavirus VP6 protein MBPVP6 to mice elicited >90% reductions in fecal rotavirus shedding after murine rotavirus challenge. Protection depended on co-administration of adjuvants, the most effective being bacterial toxins. Because of safety and efficacy concerns following intranasal or oral toxin delivery, protective efficacy of MBPVP6 after intrarectal delivery with toxin adjuvants was determined and compared to that induced after intranasal and oral immunization. Adult BALB/c mice were orally challenged with the murine rotavirus strain EDIM 4 weeks after their second immunization with MBPVP6 and either LT(R192G), an attenuated Escherichia coli heat-labile toxin, or CTA1-DD, a cholera toxin derivative. Reductions in fecal rotavirus shedding were then determined relative to mock-immunized mice. Immunization with MBPVP6 and either adjuvant by any route (except oral immunization with CTA1-DD) significantly (P<0.0001) reduced rotavirus shedding. As was previously found after oral and intranasal immunization, intrarectal immunization with MBPVP6 and adjuvant was associated with T cell responses (IFNgamma and IL-17) but not B cell (antibody) responses.