BACKGROUND: is a zoonotic pathogen that poses a threat to human and animal health. However, no vaccine exists for controlling this bacterium. AIMS: This study aimed to evaluate the immune efficacy of a chitosan nanoparticle DNA vaccine of the gene from . METHODS: The naked DNA vaccine based on the gene of was constructed. Then, the chitosan nanoparticle DNA vaccine of the gene was prepared and the shape, size, encapsulation efficiency, stability, and ability of anti-DNA enzyme degradation were detected. Chickens were divided into five groups, namely the naked DNA vaccine group (poprH group), chitosan nanoparticle DNA vaccine group (CpoprH group), outer membrane protein vaccine group (OMP group), inactive vaccine group, and PBS group. After being vaccinated with corresponding vaccines, the levels of serum antibodies, lymphocyte proliferation assays, interferon-γ (IFN-γ), interleukin-2 (IL-2), and interleukin-4 (IL-4) concentrations were detected. Groups of chickens were challenged with live virulent 2 weeks after the last vaccination and the survival numbers were counted until day 15 post challenge. Then, the protective rates were calculated. RESULTS: The particle size of the chitosan nanoparticle DNA vaccine was approximately 200 nm and close to spherical; the encapsulation efficiency was 95.88%, and it could effectively resist degradation by DNase. Following vaccination, serum antibodies, stimulation index (SI) value, and concentrations of IFN-γ, IL-2, and IL-4 in chickens immunized with the chitosan nanoparticle DNA vaccine were significantly higher than those that were vaccinated with the naked DNA vaccine (P<0.05). The protective rates of poprH, CoprH, OMP vaccine, and inactive vaccine groups were 55%, 75%, 75%, and 90%, respectively. CONCLUSION: Chitosan could significantly enhance the immune response and protection provided by the naked DNA vaccine of the gene.