DNA vaccination for treatment of multiple sclerosis and insulin-dependent diabetes mellitus
A pro-inflammatory T cell response is specifically suppressed by the injection into a recipient of DNA encoding an autoantigen associated with autoimmune disease. The recipient may be further treating by co-vaccination with a DNA encoding a Th2 cytokine, particularly encoding IL4. In response to the vaccination, the proliferation of autoantigen-reactive T cells and the secretion of Th1 cytokines, including IL-2, IFN-γ and IL-15, are reduced.
1. A method for reducing the destruction of β cells in a human in need thereof, the method comprising administering intramuscularly to the human a plasmid DNA vector comprising an expression cassette, the expression cassette comprising a DNA encoding at least one immunodominant epitope of a human autoantigen targeted in IDDM, wherein the plasmid DNA vector has a low number of CpG motifs compared to the unmodified plasmid DNA vector, so as to thereby reduce the destruction of β cells in the human.
2. The method of claim 1 , wherein the autoantigen is a polypeptide.
3. The method of claim 1 , wherein the autoantigen is a peptide.
4. The method of claim 1 , wherein the autoantigen is insulin B chain.
5. The method of claim 1 , wherein the autoantigen is proinsulin.
6. The method of claim 1 , wherein the autoantigen is pre-proinsulin.
7. The method of claim 1 , wherein the autoantigen is selected from the group consisting of insulin, insulin B chain, pre-proinsulin, proinsulin, glutamic acid decarboxylase 65 (GAD65); islet cell antigen ICA512, islet cell antigen ICA12, islet cell antigen ICA69, IA-2, and IA-2beta.