Nanoparticle-Based Tolerogenic Vaccines: Next-Generation Strategies for Autoimmune and Allergic Disease Therapies.

The concurrent rise of autoimmune diseases, which affect nearly 10% of the global population, along with allergic conditions such as asthma, food allergy, and atopic disease, together pose substantial health and economic burdens. Traditional therapies rely on systemic immunosuppression that temporarily mitigates symptoms but often compromises protective immunity, increases infection and malignancy risk, and fails to restore central or peripheral tolerance. These limitations underscore the need for antigen-specific strategies capable of re-establishing durable immune balance. Tolerogenic vaccines have emerged as a promising solution by retraining the immune system to restore antigen-specific tolerance while preserving normal host defense, though challenges remain in efficiently targeting antigen-presenting cells (APCs), avoiding their overactivation, and minimizing off-target effects. Nanoparticles provide a versatile platform to address these hurdles, as their size, composition, and surface modifications can be tailored to direct biodistribution, enhance antigen delivery, and modulate immune signaling. By co-delivering antigens and immunomodulators in programmable ways, nanoparticles offer a pathway to overcome key translational barriers and achieve precise immune reprogramming. This review explores how advances in nanomedicine are being applied to tolerogenic vaccines, focusing on three areas: (1) current nanoparticle platforms, (2) the role of biomaterial selection, and (3) multifunctional engineering strategies, while also considering the clinical outlook and translational challenges of bringing these therapies from bench to bedside.