DNA-based vaccines for multiple sclerosis: current status and future directions

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that mainly affects young adults between 20 and 40 years of age and leads to significant disability. Although MS is considered to be an immune-mediated disorder, current immunosuppressive therapies fail to inhibit disease progression, and some of them are associated with serious adverse reactions. DNA vaccination is a strategy of immunization based on the injection of genes encoding for target proteins. Depending on the route as well as the dosage of administration, exposure to certain molecules may either stimulate effector responses or induce immune tolerance. A large body of data from the animal model, experimental autoimmune encephalomyelitis (EAE), has demonstrated efficacy of DNA vaccination at inhibiting the disease through the induction of basic tolerizing mechanisms such as anergy, clonal deletion, immune deviation, or induction of regulatory cells. Interestingly, recent phase I and II clinical trials in MS with DNA vaccines have shown positive results in reducing MRI-measured disease activity in patients with relapse-onset MS, and inducing antigen-specific tolerance to myelin-specific B and T cells. Thus, DNA vaccines represent a promising therapeutic approach for MS which also seem to overcome the safety concerns raised by other currently tested therapeutic strategies. Here, we will review existing data from MS and EAE studies on DNA vaccination and discuss on further optimization of the DNA technology in order to improve treatment efficacy.