Abstract
Current seasonal influenza vaccines offer strain-specific protection and, thus, are less effective against mismatched strains. A broadly protective influenza vaccine is desirable to provide comprehensive protection against a wide range of influenza viruses for seasonal and pandemic influenza preparedness. Here, we evaluated the vaccine candidates based on bovine adenoviral (BAd) vectors expressing nucleoprotein (NP) of influenza A (BAd-C5-NP/A) and B (BAd-C5-NP/B) viruses linked to the autophagy-inducing peptide C5 (AIP-C5 or C5) to develop a predominantly T-cell-based vaccine. Robust cellular immune responses and humoral responses were elicited in mice with a single intranasal inoculation. Mice immunized with the BAd Bivalent (BAd-C5-NP/A + BAd-C5-NP/B) vaccine formulation exhibited protective immunity, providing protection against a broad panel of homosubtypic and heterosubtypic influenza A and B viruses, as evidenced by the absence of morbidity and mortality, along with significant reductions in lung viral titers. Protective immunity against seasonal influenza viruses was observed in ferrets following the BAd Bivalent vaccine immunization. These findings support further investigation of the potential of a unique Ad vaccine platform for mucosal immunization expressing NP linked to AIP-C5 as a broadly protective influenza vaccine.