Tolerizing agents

Abstract

Described herein is the development of fusion proteins useful for inducing tolerance in a subject. In particular embodiments, the tolerizing agents are useful for influence autoimmune, inflammatory, and/or allergic reactions. Example tolerizing fusion proteins contain a targeting portion (which delivers the fusion protein) and a toleragen or allergen or other antigen to which tolerance is desired in a subject. In particular examples, it is demonstrated that a pσ1 fusion protein, when administered orally, facilitates systemic and mucosal tolerance. Also described is the nasal delivery of fusion proteins, for instance for restoring immunogenicity.

1 . A method of treating an autoimmune or inflammatory disease in a subject, comprising administering to the subject a therapeutically effective amount of a tolerizing fusion protein, wherein the tolerizing fusion protein comprises (1) a targeting portion comprising a reovirus protein σ1 (pσ1) and (2) an antigen to which tolerance is desired, thereby treating the autoimmune or inflammatory disease in the subject. 
     
     
         2 . The method of  claim 1 , wherein the autoimmune or inflammatory disease is multiple sclerosis, arthritis, diabetes, Hashimoto's disease, Graves' disease or Sjögren syndrome. 
     
     
         3 . The method of  claim 2 , wherein the autoimmune disease is multiple sclerosis. 
     
     
         4 . The method of  claim 1 , wherein the antigen comprises a protein, nucleic acid, carbohydrate, lipid or any combination thereof. 
     
     
         5 . The method of  claim 4 , wherein the antigen comprises a protein. 
     
     
         6 . The method of  claim 5 , wherein the antigen comprises a myelin protein and the autoimmune disease is multiple sclerosis. 
     
     
         7 . The method of  claim 6 , wherein the myelin protein is myelin oligodendrocyte glycoprotein (MOG). 
     
     
         8 . The method of  claim 6 , wherein the myelin protein comprises MOG 29-146 . 
     
     
         9 . The method of  claim 1 , wherein the tolerizing fusion protein is administered in a single dose. 
     
     
         10 . The method of  claim 9 , wherein the single dose of the tolerizing fusion protein comprises 1 mg or less of the antigen. 
     
     
         11 . The method of  claim 9 , wherein the single dose of the tolerizing fusion protein comprises 500 μg or less of the antigen. 
     
     
         12 . The method of  claim 9 , wherein the single dose of the tolerizing fusion protein comprises 250 μg or less of the antigen. 
     
     
         13 . The method of  claim 9 , wherein the single dose of the tolerizing fusion protein comprises 100 μg or less of the antigen. 
     
     
         14 . The method of  claim 1 , wherein the tolerizing fusion protein is administered orally or nasally.