A protective immune response in mice to viral components other than hemagglutinin in a live influenza A virus vaccine model.

Previously, we generated influenza A viruses that possess chimeric type (A/B) hemagglutinins (HA), in which immunogenic regions of type A HA were replaced with those of type B HA, and showed that these viruses were attenuated in mice (J. Virol. 77 (2003) 8031). Here, we intranasally immunized mice with these viruses and then challenged them with a wild-type A virus to assess a protective immune response to viral components other than HA in the form of a live virus. All immunized mice survived challenge with a lethal dose of wild-type virus; none or a limited amount of virus, if any, was recovered from nasal turbinates or lungs of the mice 3 days post-challenge. These results provide direct evidence that immune responses to viral components other than HA confer protection against influenza A virus infection in a mouse model, suggesting the usefulness of live vaccines for viruses that have undergone antigenic drift with respect to HA, or for viruses with heterosubtypic HAs.