COMPARISON OF MUCOSAL AND SYSTEMIC HUMORAL IMMUNE-RESPONSES AND SUBSEQUENT PROTECTION IN MICE ORALLY INOCULATED WITH A HOMOLOGOUS OR A HETEROLOGOUS ROTAVIRUS

Rotaviruses are the single most important cause of severe diarrhea in young children worldwide, and vaccination is probably the most effecti ve way to control the disease, Most current live virus vaccine candida tes are based on the host range-restricted attenuation of heterologous animal rotaviruses in humans. The protective efficacy of these vaccin e candidates has been variable. To better understand the nature of the heterologous rotavirus-induced active immune response, we compared th e differences in the mucosal and systemic immune responses generated b y heterologous (nonmurine) and homologous (murine) rotaviruses as well as the ability of these infections to produce subsequent protective i mmunity in a mouse model. Sucking mice were orally inoculated with a h eterologous simian or bovine rotavirus (strain RRV or NCDV) or a homol ogous murine rotavirus (wild-type or tissue culture-adapted) strain EH P at various doses. Six weeks later, mice were challenged with a virul ent murine rotavirus (wild-type strain EC(W)) and the shedding of vira l antigen in feces was quantitated. Levels of rotavirus-specific serum immunoglobulin G (IgG) and fecal IgA prior to challenge were measured and correlated with subsequent viral shedding or protection. Heterolo gous rotavirus-induced active protection was highly dependent on the s train and dose of the virus tested. Mice inoculated with a high dose ( 10(7) PFU per mouse) of RRV were completely protected, while the prote ction was diminished in animals inoculated with NCDV or lower doses of RRV. The ability of a heterologous rotavirus to stimulate a detectabl e intestinal IgA response correlated with the ability of the virus to generate protective immunity. Serum IgG titer did not correlate with p rotection. Homologous rotavirus infection, on the other hand, was much more efficient at inducing both mucosal and systemic immune responses as well as protection regardless of the virulence of the virus strain or the size of the immunizing dose.