Evaluation of live and inactivated influenza A virus vaccines in a mouse model

Induction of cross-protective immunity against serologically distinct subtypes of influenza A virus in mice was examined in an attempt to correlate cross-protection with heterotypic lymphocyte responses. Live and inactivated virus vaccines protected against the homologous subtype, but only whole virus protected against heterologous subtypes. Live virus vaccines provided better cross-protection than inactivated virus vaccines. A weak defense against heterotypic challenge generated by live H0N1 virus could be boosted by cross-stimulation with whole H3N2 virus and by restimulation with pathogenic H0N1 virus. Heterotypic protection persisted for at least five months. Live viruses induced cross-reactive cytotoxic T cells in normal mice. However, cross-stimulation with heterologous virus was required to generate secondary cytotoxicity. Cross-reactive B lymphocytes were evident after inoculation with whole virus.