Chitosan-based Oral DNA vaccine elicits mucosal immunity and reduces Helicobacter pylori colonization in mice

Oral vaccination offers a promising strategy for controlling Helicobacter pylori infection, particularly in the face of rising antibiotic resistance and reinfection rates. In this study, we developed a chitosan nanoparticle-mediated oral DNA vaccine encoding the urease B subunit of H. pylori. The chitosan-DNA nanoparticles exhibited stability under simulated gastric and duodenal conditions and demonstrated efficient transgene expression in vivo without cytotoxicity. Oral administration of the vaccine induced strong mucosal IgA and systemic IgG responses, accompanied by elevated IFN-γ and IL-17 production. Immunized mice exhibited a 150-fold reduction in gastric H. pylori colonization and significant inhibition of urease activity compared to controls. Histological analysis revealed enhanced immune cell infiltration associated with bacterial clearance. These findings suggest that chitosan-based oral DNA vaccination can elicit protective mucosal and systemic immunity and represents a promising approach for the prevention of H. pylori infection.