DNA-based vaccines: The future of multiple sclerosis therapy?

Olaf Stüve, Petra D. Cravens, Todd N. Eagar

Research output: Contribution to journalReview articlepeer-review

10 Scopus citations

Abstract

Multiple sclerosis (MS) is the most common human inflammatory, demyelinating and degenerative disorder of the CNS. Based mostly on work in experimental autoimmune encephalomyelitis, CD4+ T cells were long thought to play the crucial role in MS pathogenesis. Only more recently has it been recognized that other effector cell types, including CD8+ T cells, γδ-T cells and B lymphocytes may also have an important role in disease initiation and perpetuation. The expression of soluble inflammatory mediators, including cytokines and free radicals, may be one of the late pathways mediating CNS tissue damage. In addition, in virtually all patients with MS, an oligoclonal banding pattern of antibodies can be detected in the cerebrospinal fluid (CSF). However, the cause of MS still remains unknown. Specifically, no single foreign or self antigen has been identified to account for clinical disease activity or the presence of surrogate disease markers. All approved pharmacotherapies have antiinflammatory or immunoregulatory properties and work in early stages of the disease. In a recent clinical trial, BHT-3009, a DNA vaccine encoding full-length human myelin basic protein, was tested in patient with MS. BHT-3009 was safe and well tolerated. In addition, immunization with BHT-3009 induced anti-inflammatory antigen-specific immune changes consisting of a marked decrease in T-cell proliferation of IFN? production and a reduction in titers of myelin-specific autoantibodies in the CSF. This review will discuss these intriguing observations and the overall potential of DNA vaccination in MS.

Original languageEnglish (US)
Pages (from-to)351-360
Number of pages10
JournalExpert review of neurotherapeutics
Volume8
Issue number3
DOIs
StatePublished - Mar 2008

Keywords

  • Autoimmune disease
  • Bystander suppression
  • Clinical trial
  • DNA
  • Deoxyribonucleic acid
  • EAE
  • Experimental autoimmune encephalomyelitis
  • Immunization
  • MS
  • Multiple sclerosis
  • Pharmacotherapy
  • Therapy
  • Tolerance
  • Treatment
  • Vaccine

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Neurology
  • Pharmacology (medical)

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