Using an adult mouse model to study active immunity against
rotavirus infection, it was previously shown that oral immunization with some, but not all, animal rotavirus strains induced protection against subsequent
infection following oral challenge with the murine rotavirus strain
EDIM. To determine if a specific rotavirus
protein could be associated with protection in this model, mice were immunized with a series of 18 reassortants between the fully protective
EDIM strain and a partially protective heterologous rotavirus strain (RRV-G). Reassortants that contained genes for
EDIM proteins responsible for protection were anticipated to provide complete protection; however, no
EDIM proteins were found to be both necessary and sufficient for full protection. Instead, protection was found to be highly correlated with viral shedding (P = 0.005) and with serum rotavirus
IgA titers stimulated by the different reassortants (P < 0.001). This indicated that protection was related to the intestinal replication properties of the different reassortants rather than to specific immunogenic properties of
EDIM proteins. This conclusion was supported by the finding that the titers of serum rotavirus
IgA, but not
IgG, stimulated in mice following oral immunization with a series of animal rotaviruses was directly related to protection against
EDIM. If these findings can be extended to humans, they suggest that the efficiency of intestinal replication following oral inoculation with a live
rotavirus vaccine candidate may be the primary determinant of successful immunization.