In this study, we evaluated a new approach to immunizing chickens against AI that uses a nanoparticle platform to carry an antigenic epitope. Further designing and testing of new nanoparticle vaccines should demonstrate that they are effective tools for stimulation of an immune response against M2e and other B-or T-cell epitopes. Therefore, application of the nanoparticle platform facilitates the development of a new generation of vaccines that harbor conserved epitopes of avian influenza viruses and would not be rendered ineffective by viral mutations such as antigenic shifts and drifts. The nanotechnology described here offers the opportunity to rapidly produce new vaccines according to the emergence of new strains of influenza virus without going through the time-consuming steps of production currently used in manufacturing commercial influenza vaccines. For future studies, the chicken's LPAI infection model needs to be improved to evaluate clinical signs and higher virus shedding. This may help to better evaluate virus shedding, specifically cloacal virus shedding. Also, vaccination and HPAI challenge may be used to evaluate the vaccine efficiency in protection against high-pathogenicity AI viruses.