Cross‐protection and cross‐reactive cytotoxic T cells induced by influenza virus vaccines in mice

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Abstract
Subunit and intact influenza A virus vaccines have been compared with infectious virus in a mouse model for their ability to induce memory for cross‐reactive cytotoxic T cell responses and to protect mice from challenge with different subtypes of influenza A virus. There is an overall correlation between secondary cytotoxic T cell responses and cross‐protection. The most long‐lasting and successful cross‐protection was observed after intranasal infection with influenza virus A/X31 (H3N2) that replicates efficiently in mice and induces high levels of memory for cross‐reactive cytotoxic T cell responses. Short‐lasting cross‐protection and low levels of T cell‐mediated cytotoxicity were associated with infection by A/USSR (H 1N1) virus, that replicates to lower titers in mice, or after multiple injections of inactivated whole virus vaccine. No cross‐protection to challenge with heterologous influenza virus was detectable after 1‐2 injections of HANA influenza subunit vaccine which failed to prime hosts for cytotoxic T cell responses. These findings may have important implications for vaccination strategy. If cytotoxic T cells play a role in the protection of humans from influenza, live attenuated vaccines should be considered instead of the currently recommended inactivated virus or subunit vaccines.