Composition and method for prevention and treatment of type I diabetes
A composition for the prevention or treatment of type I diabetes in a subject, said composition comprising a fusion protein selected from the group consisting of GLP-1/IgG or variant or fragment thereof and an Ex4/IgG or variant or fragment thereof and an autoimmune suppressor for silencing an autoimmune response against islet beta cells.
1. A composition for the treatment of type I diabetes in a subject, said composition comprising:
a GLP-1/IgG fusion protein, wherein said GLP-1 polypeptide is selected from the group consisting of GLP-1(7-37)OH, GLP-1(7-36)amide (SEQ ID NO:1), a DPPIV resistant GLP-1 Ala 8 mutant and a DPPIV resistant GLP-1 His 7 mutant; and the IgG is human IgG2: and
an autoimmune suppressor comprising at least one antigenic target epitope of a pancreatic beta-cell associated antigen for decreasing autoimmunity against islet beta cells, wherein said pancreatic beta-cell associated antigen is pre-proinsulin comprising SEQ ID NO:8, GAD65 comprising SEQ ID NO:9, 10 and/or 11, or pre-proinsulin/GAD65 (PPI/GAD65) comprising SEQ ID NO:8 and SEQ ID NO: 9, 10 and/or 11.
2. The composition of claim 1 , wherein said IgG comprises an Fc portion of the IgG or a fragment or variant of the Fc portion.
3. The composition of claim 1 , further comprising B7-1wa molecule which is a T cell negative regulatory molecule.
4. The composition of claim 1 , wherein said DPPIV resistant GLP-1 Ala 8 mutant is GLP-1A8G.