Rotavirus-specific cytotoxic T lymphocyte response of mice after oral inoculation with candidate rotavirus vaccine strains RRV or WC3.

The immunologic basis of homotypic and heterotypic protection by immunization with two candidate rotavirus vaccine strains (simian strain RRV and bovine strain WC3, respectively) was investigated. Mice were orally inoculated with RRV, and 6 d later splenic lymphocytes lysed target cells infected with RRV (serotype 3) but not with human rotavirus serotypes 1 or 2; 4 w after inoculation, cytotoxic T lymphocytes (CTLs) generated in vitro from CTL precursors were also strain-specific. Also, the frequency of RRV-specific CTLs from CTLp after RRV immunization was 20-fold greater than that of cross-reactive CTLs. Inoculation of mice with WC3 (serotype 6), on the other hand, produced cross-reactive CTLs from CTLp at 4 w; CTLs lysed target cells infected with WC3 or human serotypes 1, 2, or 3 to the same extent. The frequency of cross-reactive CTLs after WC3 immunization was greater than or equal to 20-fold greater than that of WC3-specific CTLs. Cross-reactive, rotavirus-specific CTLs induced after WC3 immunization may in part explain the immunologic basis of protection against heterotypic challenge.