Tolerogenic nanodisc vaccination for the treatment of experimental autoimmune encephalomyelitis 2747

Abstract Description Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system, impairing vision, coordination, and movement. Current standard treatments involve broad immunosuppressants that can cause toxicity with prolonged use. Regulatory T cell (Treg)-based immunotherapies offer an alternative by employing Tregs to restore immune tolerance with long-term protection. One such approach is antigen-specific immunotherapy, in which Tregs are generated to suppress autoantigen-specific Th1 and Th17 cells, allowing immune tolerance while preserving overall immune function. Our lab has developed a synthetic high-density lipoprotein nanodisc (ND) for targeted delivery of autoantigens to antigen-presenting cells in lymphoid tissues. We have shown that NDs carrying both autoantigens and the immunomodulator rapamycin can induce antigen-specific Tregs, thereby serving as a platform for tolerogenic vaccination. We evaluated the therapeutic potential of tolerogenic vaccination with NDs carrying myelin oligodendrocyte glycoprotein (MOG) peptide and rapamycin in an experimental autoimmune encephalomyelitis (EAE) model, a murine model of MS. Tolerogenic ND vaccination initiated at the peak of the disease (with EAE score > 3) significantly reduced the EAE score to less than 1. NDs induce robust expansion of antigen-specific Tregs both in vitro and in vivo. Our results show NDs as a promising platform for treating MS and potentially other autoimmune diseases. Funding Sources Supported by Cellular Biotechnology Training Program T32-GM008353. Topic Categories Vaccines and Immunotherapy (VAC)