Intranasal inactivated influenza vaccines have the advantage over parenteral vaccines in that they are not associated with the pain of an injection. However, they would be most useful if they were available for all age groups, including high-risk groups, and also would provide cross-protection against variant virus strains. Supporting the latter objective is our observation that intranasal inactivated vaccines provide cross-protection against variants within a subtype of the A virus (or variants within the B virus), together with inducing highly cross-reactive secretory-IgA antibodies to viral HA and the weakly cross-reactive IgG antibodies in the respiratory tract. This review summarizes the most important observations of our studies on intranasal inactivated influenza vaccines, which have been ongoing since 1987. These studies center on a mouse model of influenza in which mice are immunized intranasally with inactivated vaccines mixed with a cholera toxin B subunit adjuvant and then infected with mouse-adapted influenza viruses.
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