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

## TL;DR

A new nano-vaccine combining Prussian blue nanozymes and a ferritin carrier with phosphocholine antigens shows promise for treating inflammatory bowel disease by inducing immunotolerance.

## Contribution

A novel nano-vaccine (Ferritin-PC@PBNZs) is developed for IBD treatment through active immunization and adjuvant-enhanced antigen presentation.

## Key findings

- The vaccine significantly reduces disease severity in a DSS-induced colitis model.
- It induces high-titer, antigen-specific antibodies and restores intestinal barrier integrity.
- The nanozyme adjuvant enhances dendritic cell activation and T-cell help for B-cell differentiation.

## 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.

This study developed a novel nano‐vaccine (Ferritin‐PC@PBNZs) comprising a ferritin‐based scaffold for the multivalent display of phosphorylcholine (PC) antigens, integrated with Prussian blue nanozymes (PBNZs) as a potent adjuvant. By leveraging the ferritin carrier for high‐density and ordered antigen display, the nano‐vaccine significantly augments BCR recognition. PBNZs‐induced lysosomal ROS signaling facilitates DCs maturation and antigen presentation to drive Tcell activation. This synergistic process provides critical T‐cell help, orchestrating the differentiation of B cells into plasma cells for the production of high‐affinity, PC‐specific IgG. This active immunization strategy represents a promising paradigm for the long‐term management of IBD.