A single-dose, tolerizing vaccine induces antigen-specific regulatory T cells and durable remission while preserving healthy immunity in a mouse model of Multiple sclerosis

Abstract Multiple sclerosis (MS) is an inflammatory disorder that occurs when autoreactive lymphocytes mistakenly attack myelin, resulting in motor deficits and cognitive deterioration. Current drugs are non-curative require life-long treatment make compliance challenging, existing therapeutics can leave patients vulnerable to opportunistic infections. An experimental approach overcome these hurdles drive long-lasting, antigen-specific regulatory T cells (Tregs) dampen responses autoantigens. Here, we co-deliver antigen rapamycin micron-sized, diffusion-limited, polymer microparticles (MPs) directly lymph nodes (LNs) where immune orchestrated. Using adoptive transfer of transgenic cells, show MPs generate Tregs response two different MP-derived peptides – evidence do not interfere with induction peripheral tolerance LNs. In autoimmune encephalomyelitis (EAE), a mouse model MS, single-dose demonstrates potent, long-lasting efficacy (up three months) following single treatment. Tolerizing effects observed during chronic disease the most challenging for regimens. Efficacy accompanied by reduced demyelination spinal cords treated mice, cause paralysis EAE MS. Thus, reprogramming LNs reshapes inflammation distal tissues without need systemic or repeated dosing. Importantly, MP-treated mice mount healthy vaccine challenge. This work advances strategy locally reprogram antigen-specific, tolerogenic preserve immunity hurdle faced current MS therapeutics. Supported grants from NIH (R01 AI169686).