Tolerogenic Reverse\nMicelle Nanovaccine Prevents Onset\nand Progression of Multiple Sclerosis

Exhilarating breakthroughs in the treatment of autoimmune\ndiseases\nthrough antigen-specific therapies offer new hope for patients. Herein,\na novel antigen-specific reverse micelle platform is proposed: blank\nliposomes prepared with 1, 2-diolyl-<i>sn</i>-glycerol-3-phosphocholine\n(DOPC) and cholesterol (Chol) are mixed with an aqueous solution of\nthe encapsulated antigens and immunomodulators, lyophilized, and then\nreconstituted in oil. Subcutaneous injection of 100 μL of a\nreverse micelle vaccine loaded with 10 μg of MOG<sub>35–55</sub> and 30 μg of dexamethasone sodium phosphate (DSP) before experimental\nautoimmune encephalomyelitis (EAE, a multiple sclerosis model) establishment\ndirectly blocked the development of clinical symptoms. Furthermore,\nthe same vaccine delayed and attenuated clinical symptoms in an established\nmouse model of EAE. Conversely, the reverse micelle vaccine loaded\nwith an unrelated antigen OVA failed to alleviate paralysis in mice,\nhighlighting the crucial aspect of antigen specificity. Dose-dependent\neffects were observed in both the prevention and treatment of EAE,\nwith clinical scores of 0 being achieved during the treatment at single\nDSP doses of up to 50 μg at the MOG<sub>35–55</sub> dose\nof 10 μg. The treatment of the reverse micelle vaccine induced\nTreg cell proliferation, accounting for the tolerance to the pathogenic\nantigens and improved outcomes. Overall, the designed reverse micelle\nvaccine provided a universal platform to encapsulate antigens and\nimmunomodulators that restore tolerance of antigens and then demonstrated\nthe therapeutic promise in autoimmune diseases.