Minimalist Adjuvant‐Free Nano‐Vaccine Based on Antigen Self‐Assembled Amyloid‐Like Fibrils to Induce Potent Immune Response

Abstract The development of cancer vaccines is at the forefront of cancer immunotherapy. Most existing strategies to induce an efficient anti‐tumor immune response rely on molecular adjuvants and the incorporation of complex synthetic vectors into vaccine formulations. In contrast, this study introduces a one‐step engineering technique to assemble the model antigen, Ovalbumin (OVA), into amyloid aggregates, leveraging biomimetic folding and aggregation to create non‐fibrillar OVA globular aggregates and OVA amyloid‐like fibrils as single‐component, adjuvant‐free vaccines. Notably, the OVA amyloid‐like fibrils induced stronger immune responses compared to the native form, as evidenced by robust humoral immune reactions and the establishment of immune memory. These enhanced responses can be attributed to the self‐adjuvant effect of the unique assembled structure, which preserves antigenic epitopes, improves antigen stability, facilitates antigen internalization, prolongs retention at the injection site, enhances antigen trafficking to the lymphoid organs, and promotes increased secretion of antibodies and cytokines. Furthermore, the efficacy of the vaccine was validated in a high OVA‐expressing tumor model, demonstrating the potential of OVA amyloid‐like fibrils as an effective vaccine for cancer immunoprevention. This minimalist self‐adjuvant vaccine strategy holds promising implications for cancer immunotherapy and can inform the design of other protein antigen‐based vaccines.