Mesoporous polydopamine nanoparticle-based tolerogenic vaccine induces antigen-specific immune tolerance to prevent and treat autoimmune multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic neurological disorder derived from autoreactive immune system attacking the protective myelin sheath that surrounds nerves in the central nervous system (CNS). Here, a tolerogenic nanovaccine for generating an antigen-specific immune tolerance for treating MS is proposed. It consisted of a mesoporous polydopamine (mPDA) nanoparticle, characterized by high reactive oxygen species (ROS)-scavenging property, loaded with MS-derived autoantigen. Intravenous vaccination of autoantigen-loaded mPDA could induce tolerogenic dendritic cells (DCs) with low expression of co-stimulatory molecules while presenting peptide epitopes. The tolerogenic DCs induced peripheral regulatory T-cells (Tregs), thereby reducing infiltration of autoreactive CD4⁺ T-cells and inflammatory antigen-presenting cells (APCs) into the CNS. In MS-mimicking mouse model, the tolerogenic nanovaccine prevented MS development in the early therapeutic setup and exhibited an enhanced recovery from complete paralysis in the late therapeutic model. The current platform could be exploited to treat other autoimmune diseases where disease-dependent autoantigen peptides are delivered.