Anti-IL-17A Autovaccination Prevents Clinical and Histological Manifestations of Experimental Autoimmune Encephalomyelitis

Ann N Y Acad Sci. 2007 Sep;1110:330-6. doi: 10.1196/annals.1423.035.

Abstract

Excessive or inappropriate production of IL-17A has been reported in diseases such as rheumatoid arthritis, asthma, and multiple sclerosis. The potential clinical relevance of these correlations was suggested by the protective effects of anti-IL-17A monoclonal antibodies in various mouse disease models. However, the chronic nature of the corresponding human afflictions raises great challenges for Ab-based therapies. An alternative to passive Ab therapy is autovaccination. Covalent association of self-cytokines with foreign proteins has been reported to induce the production of antibodies capable of neutralizing the biological activity of the target cytokine. We recently reported that cross-linking of IL-17A to ovalbumin produced highly immunogenic complexes that induced long-lasting IL-17A-neutralizing antibodies. Vaccinated SJL mice were completely protected against experimental autoimmune encephalomyelitis (EAE) induced by proteolipid protein peptide (PLP 139-151), and a monoclonal anti-IL-17A Ab (MM17F3), derived from C57Bl/6 mice vaccinated against IL-17A-OVA, also prevented disease development. Here we report that this Ab also protects C57Bl/6 mice from myelin oligdendrocyte glycoprotein (MOG)-induced EAE. Histological analysis of brain sections of C57Bl/6 mice treated with MM17F3 showed a complete absence of inflammatory infiltrates and evidence for a marked inhibition of chemokine and cytokine messages in the spinal cord. These results further extend the analytical and therapeutic potential of the autovaccine procedure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / therapy*
  • Immunotherapy
  • Interleukin-17 / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Vaccination*

Substances

  • Cytokines
  • Interleukin-17