An Antigen-Free Nanovaccine-Enabled Holo-Immunotherapy for Establishing Robust Memory Immune Tolerance in Autoimmune Diseases

T cell subsets. By bridging innate and adaptive immunity, this multitargeted strategy synergistically reshapes the inflammatory microenvironment, establishes robust memory immune tolerance, and promotes immune homeostasis restoration, leading to sustained efficacy and delayed relapse in the collagen-induced arthritis (CIA) mouse model. Unlike traditional vaccines, the antigen-free design eliminates reliance on exogenous antigens, minimizes off-target immune risks, and holds promise for broader clinical applicability. The nanovaccine outperforms anti-TNF-α antibodies in treating models of CIA, adjuvant-induced arthritis, and chronic ulcerative colitis, highlighting its potential as a universal vaccine platform for AID therapy. Overall, this work provides a strategy to address AID challenges through precise immune regulation and durable therapeutic benefits.