Tolerogenic Reverse Micelle Nanovaccine Prevents Onset and Progression of Multiple Sclerosis

Abstract

Exhilarating breakthroughs in the treatment of autoimmune diseases through antigen-specific therapies offer new hope for patients. Herein, a novel antigen-specific reverse micelle platform is proposed: blank liposomes prepared with 1, 2-diolyl-sn-glycerol-3-phosphocholine (DOPC) and cholesterol (Chol) are mixed with an aqueous solution of the encapsulated antigens and immunomodulators, lyophilized, and then reconstituted in oil. Subcutaneous injection of 100 μL of a reverse micelle vaccine loaded with 10 μg of MOG_35–55 and 30 μg of dexamethasone sodium phosphate (DSP) before experimental autoimmune encephalomyelitis (EAE, a multiple sclerosis model) establishment directly blocked the development of clinical symptoms. Furthermore, the same vaccine delayed and attenuated clinical symptoms in an established mouse model of EAE. Conversely, the reverse micelle vaccine loaded with an unrelated antigen OVA failed to alleviate paralysis in mice, highlighting the crucial aspect of antigen specificity. Dose-dependent effects were observed in both the prevention and treatment of EAE, with clinical scores of 0 being achieved during the treatment at single DSP doses of up to 50 μg at the MOG_35–55 dose of 10 μg. The treatment of the reverse micelle vaccine induced Treg cell proliferation, accounting for the tolerance to the pathogenic antigens and improved outcomes. Overall, the designed reverse micelle vaccine provided a universal platform to encapsulate antigens and immunomodulators that restore tolerance of antigens and then demonstrated the therapeutic promise in autoimmune diseases.