By humanizing the M2e-binding scFv, we generated human-like FLU BiTE<sup>®</sup> antibody constructs, with increased in vitro cytotoxic activity and in vivo protective capacity against influenza A virus infection.
We conclude that local cellular immune responses are important for protection against influenza A virus infection, that these can be most efficiently induced by aerosol immunization targeting the lower respiratory tract, and that S-FLU is a promising universal influenza vaccine candidate.