Recombinant adenoviruses displaying matrix 2 ectodomain epitopes on their fiber proteins as universal influenza vaccines

Influenza is a zoonotic disease that poses severe threats to public health and the 26 global economy. Re-emerging influenza pandemics highlight the demand for 27 universal influenza vaccines. We developed a novel virus platform, AdC68-F3M2e, by 28 introducing three conserved M2e epitopes into the HI loop of the chimpanzee 29 adenovirus (AdV) fiber protein. The M2e epitopes were expressed sufficiently on the 30 AdV virion surface without affecting fiber trimerization. Additionally, one 31 recombinant adenovirus, AdC68-F3M2e(H1-H5-H7), induced robust M2e-specific 32 antibody responses in BALB/c mice after two sequential vaccinations and conferred 33 efficient protection against homologous and heterologous IV challenges. We find that 34 AdV with tandem M2e epitopes in fiber is a potential strategy for IV prevention.