Vaccination focusing immunity on conserved antigens protects mice and ferrets against virulent H1N1 and H5N1 influenza A viruses

Immunization against conserved virus components induces broad, heterosubtypic protection against diverse influenza A viruses, providing a strategy for controlling unexpected outbreaks or pandemics until strain-matched vaccines become available. This study characterized immunization to nucleoprotein (NP) and matrix 2 (M2) by DNA priming followed by parenteral or mucosal boosting in mice and ferrets. DNA vaccination followed by boosting with antigen-matched recombinant adenovirus (rAd) or cold-adapted (ca) influenza virus provided robust protection against virulent H1N1 and H5N1 challenges. Compared to other boosts, mucosal rAd induced stronger IgA responses, more virus-specific activated T-cells in the lung, and better protection against morbidity following challenge even eight months post-boost. In ferrets, both mucosal and parenteral rAd boosting protected from lethal H5N1 challenge. These findings demonstrate potent protection by vaccination highly focused on conserved antigens and identify immune response measures in mice that differed among vaccinations and correlated with outcome.