In this issue of the Archives, Bar-Or and coworkers1 report on a successful attempt to induce antigen-specific tolerance with a DNA encoding myelin basic protein (MBP) vaccine in patients with multiple sclerosis (MS). Two questions immediately arise: (1) why vaccinate patients with MS with a self antigen, and (2) why use a DNA plasmid vaccine?
Multiple sclerosis is the most common inflammatory, demyelinating, and neurodegenerative disorder of the central nervous system (CNS) in humans. A pathological hallmark of MS is the infiltration of leukocytes into the brain and spinal cord. Not surprisingly, controlling the migration of T cells, B cells, and other immunocompetent myeloid cells into the brain and spinal cord has been a major target of drug development over the last 15 years. Substantial evidence for the role of myelin-specific T cells in CNS demyelinating disorders has been derived from investigations of experimental autoimmune encephalomyelitis (EAE), the archetypal model for MS.2 Specifically, activated CD4+ T cells that recognize one of several myelin antigens mediate EAE, causing relapsing paralysis and CNS inflammation. Given this knowledge, why would an immunization with a CNS autoantigen possibly be a good treatment strategy?
Stüve O, Eagar TN, Frohman EM, Cravens PD. DNA Plasmid Vaccination for Multiple Sclerosis. Arch Neurol. 2007;64(10):1385–1386. doi:10.1001/archneur.64.10.1385