Recurrence of distinct strains of seasonal influenza viruses requires the development of universal vaccines. Previous studies have demonstrated the cross-protection effects of influenza virus A-derived extracellular domain of ion channel matrix protein 2 (M2e) vaccines in an adult mouse model. However, M2e vaccine efficacy of wide-range protection against influenza remains largely unknown in aged mice. I hypothesized that co-immunization with M2e virus-like particle (M2e-VLP) vaccine and hemagglutinin-based VLP vaccine (HA-VLP) can provide superior protection against homologous virus and antigenically different strains of influenza viruses in aged (15-18 months old) BALB/c mice compared to the current HA-based vaccine. In this study, I examined a strategy of co-immunization of HA-VLP and M2e-VLP as a potential approach for effective vaccination for the immunosuppressed and elderly against a wide-range of influenza strains.