Vaccination with DNA encoding a myelin autoantigen exacerbates experimental autoimmune encephalitis

The ultimate goal in the treatment of autoimmune diseases is to reestablish tolerance to self antigens. One strategy to induce tolerance is to express the target autoantigen by DNA vaccination. In this work, the potential of vaccination with a DNA construct encoding the myelin oligodendrocyte glycoprotein (MOG), an important candidate autoantigen in multiple sclerosis, to induce tolerance and protect against experimental autoimmune encephalomyelitis (EAE) was assessed. Unexpectedly, mice vaccinated with MOG-DNA develop an exacerbated form of EAE when challenged with either MOG or an unrelated encephalitogen, myelin proteolipid protein. Disease exacerbation is due to the inability of DNA vaccination to tolerise the MOG specific T cell response and to the concomitant induction of a MOG-specific autoantibody response which is pathogenic, enhancing demyelination, inflammation and disease severity. These results suggest that tolerogenic strategies for autoimmune diseases based on DNA vaccination should be approached with caution.