BACKGROUND: Despite the importance of influenza vaccination in asthma patients, the efficacy of this vaccine in asthma has not been well elucidated. We aimed to compare the efficacy of an influenza vaccine of the asthmatic and control mice. We also evaluated the efficacy of AddaVax™ as an adjuvant candidate, which is equivalent to the MF59 influenza vaccine adjuvant in the elderly. METHOD: House dust mite extracts were intranasally injected into six-week-old female BALB/c mice to induce chronic allergic asthma. Antibody responses after split-inactivated A/Puerto Rico/8/34 H1N1 influenza vaccination with or without AddaVax™ adjuvant were measured using ELISA. Homologous viral protection was determined by measuring the survival rate, lung inflammation level, and lung virus titer after challenge with the human influenza virus strain A/Puerto Rico/8/1934 H1N1. Antigen-specific T cell responses were determined using flow cytometry. RESULT: The chronic asthma mice immunized with split-inactivated A/Puerto Rico/8/34 H1N1 influenza vaccine showed significant weight loss and higher lung viral load after homologous influenza infection than naïve vaccinated mice. Antigen-specific IgG, IgG1, and IgG2a production did not differ between the naïve and asthma mice. However, serum HI titer was lower in asthma-vaccinated mice after infection. The application of AddaVax™ to a vaccine for mice with asthma enhanced the efficacy of homologous antiviral protection but elicited eosinophil infiltration in the lungs after homologous influenza virus infection. CONCLUSION: The immune response after split inactivated A/PR8 vaccine differed between asthma and naïve mice, particularly in terms of antibody activity and T cell populations. This study enhances our understanding of how asthma status may influence the effectiveness of influenza vaccine and offers insights into the AddaVax™-induced eosinophilic inflammation, guiding the development of virus vaccine strategies for both healthy individuals and asthma patients.