Combination of gene delivery and DNA vaccination to protect from and reverse Th1 autoimmune disease via deviation to the Th2 pathway

Using a combination of local gene delivery and tolerizing DNA vaccination, we demonstrate that codelivery of the interieukin-4 (IL-4) gene and a DNA v accine encoding the self-peptide proteolipid protein 139-151 (PLP139-151) p rovides protective immunity against experimental autoimmune encephalomyelit is (EAE). We provide evidence for a mechanism whereby IL-4 expressed from t he naked DNA is secreted and acts locally on autoreactive T cells via activ ation of STAT6 to shift their cytokine profile to T helper 2. We also show that DNA vaccines can be used to reverse established EAE by covaccination w ith the genes for myelin oligodendrocyte glycoprotein and IL-4. This treatm ent strategy combines the antigen-specific effects of DNA vaccination and t he beneficial effects of local gene delivery.