Antibody-independent protection against rotavirus infection of mice stimulated by intranasal immunization with chimeric VP4 or VP6 protein

This study was to determine whether individual rotavirus capsid proteins co uld stimulate protection against rotavirus shedding in an adult mouse model . BALB/c mice were intranasally or intramuscularly administered purified Es cherichia coli-expressed murine rotavirus strain EDIM VP4, VP6, or truncate d VP7 (TrVP7) protein fused to the 42.7-kDa maltose-binding protein (MBP). One month after the last immunization, mice were challenged with EDIM and s hedding of rotavirus antigen was measured. When three 9-mu g doses of one o f the three rotavirus proteins fused to MBP were administered intramuscular ly with the saponin adjuvant QS-21, serum. rotavirus immunoglobulin G (IgG) was induced by each protein. Following EDIM challenge, shedding was signif icantly (P = 0.02) reduced (i.e., 38%) in MBP::VP6-immunized mice only. Thr ee 9-mu g doses of chimeric MBP::VP6 or MBP::TrVP7 administered intranasall y with attenuated E. coli heat-labile toxin LT(R192G) also induced serum ro tavirus IgG, but MBP::VP4 immunization stimulated no detectable rotavirus a ntibody. No protection against EDIM shedding was observed in the MBP::TrVP7 -immunized mice, However, shedding was reduced 93 to 100% following MBP::VP 6 inoculation and 56% following MBP::VP4 immunization relative to that of c ontrols (P = <0.001). Substitution of cholera toxin for LT(R192G) as the ad juvant, reduction of the number of doses to 1, and challenge of the mice 3 months after the last immunization did not reduce the level of protection s timulated by intranasal administration of MBP::VPG. When MBP::VP6 was admin istered intranasally to B-cell-deficient mu Mt mice that made no rotavirus antibody, shedding was still reduced to <1% of that of controls. These resu lts show that mice can be protected against rotavirus shedding by intranasa l administration of individual rotavirus proteins and that this protection can occur independently of rotavirus antibody.