In this study, we showed that anti-M2e antibodies are not neutralizing antibodies; however they are capable of binding to the M2 proteins that are abundantly presented on the surface of the infected cells (data not shown). These can describe an efficient delayed clearance of the virus in M2e vaccinated chickens based on the previously described NK cell involvement in ADCC [35] . Significant improvement of virus clearance in vaccinated chickens with tetrameric M2e may be considered in a new vaccination strategy by vaccinating chickens with both a killed vaccine and a nanoparticle vaccine in order to provide robust protection, cross-reactive immunity, and clearance in case of emerging new strains of the virus.