A Prussian Blue Nanozyme‐Adjuvanted Vaccine Presenting Phosphocholine Antigens for Induction of Immunotolerance in Inflammatory Bowel Disease

ABSTRACT Inflammatory bowel disease (IBD) is a complex disorder characterized by chronic intestinal inflammation and impaired barrier function, for which effective long‐term therapies remain elusive. To address this challenge, we developed a novel nano‐vaccine that combines Prussian blue nanozymes (PBNZs) adjuvants with a ferritin carrier loaded with phosphorylcholine (PC), an autoimmune‐related antigen (Ferritin‐PC@PBNZs). This vaccine aims to provide sustained protection and therapeutic benefits for IBD through an active immunization strategy. This vaccine leverages the ferritin carrier to effectively present PC antigens, while simultaneously enhancing antigen uptake and activating dendritic cells with the PBNZs adjuvant. This dual action induces a durable humoral immunity characterized by a high‐titer, antigen‐specific antibody response with a balanced Th1/Th2 immune profile. In the dextran sulfate sodium (DSS)‐induced acute colitis model, vaccination with the Ferritin‐PC@PBNZs vaccine markedly alleviated disease severity. This protective effect was attributed to the induction of high levels of specific antibody against inflammation‐associated PC antigen and the restoration of intestinal barrier integrity. Overall, this vaccine‐based immunotolerance therapy represents a promising long‐term therapeutic strategy for IBD.