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.