Influenza virus is one of the major sources of
respiratory tract infection. Due to antigenic drift in
surface glycoproteins the virus causes annual epidemics with severe morbidity and mortality. Although
hemagglutinin (HA) is one of the highly variable
surface glycoproteins of the influenza virus, it remains the most attractive target for
vaccine development against seasonal
influenza infection because
antibodies generated against HA provide virus neutralization and subsequent protection against the
virus infection. Combination of recombinant adenovirus (rAd) vector-based
vaccine and
mucosal administration is a promising regimen for safe and effective vaccination against
influenza. In this study, we constructed rAd encoding the globular head region of HA from A/Puerto Rico/8/34 virus as
vaccine candidate. The rAd
vaccine was engineered to express high level of the
protein in secreted form. Intranasal or sublingual immunization of mice with the rAd-based
vaccine candidates induced significant levels of sustained HA-specific mucosal
IgA and
IgG. When challenged with lethal dose of homologous virus, the vaccinated mice were completely protected from the
infection. The results demonstrate that intranasal or sublingual vaccination with HA-encoding rAd elicits protective immunity against
infection with homologous influenza virus. This finding underlines the potential of our recombinant adenovirus-based
influenza vaccine candidate for both efficacy and rapid production.