Development of an anti-IL-17A auto-vaccine that prevents experimental auto-immune encephalomyelitis

Authors

  • Catherine Uyttenhove Dr.,

    Corresponding author
    1. Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium
    2. Cellular Genetics Unit, Christian de Duve Institute of Cellular Pathology, Université Catholique de Louvain, Brussels, Belgium
    • Ludwig Institute for Cancer Research, Brussels Branch, 74 av. Hippocrate UCL 7459, B-1200 Brussels, Belgium, Fax: +32-2-762-9405
    Search for more papers by this author
  • Jacques Van Snick

    1. Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium
    2. Experimental Medicine Unit, Christian de Duve Institute of Cellular Pathology, Université Catholique de Louvain, Brussels, Belgium
    Search for more papers by this author

Abstract

IL-17 has been associated with multiple inflammatory disorders such as rheumatoid arthritis, asthma and multiple sclerosis. As these diseases require long-term treatment we turned to an auto-vaccine strategy for IL-17 neutralization in vivo. Mouse IL-17A was covalently linked to ovalbumin and used to immunize C57BL/6 mice. This vaccine induced the production of antibodies that blocked IL-17A bioactivity in vitro but did not react with the other IL-17 isoforms, including IL-17F. As the half-life of the Ab titers after the last immunogen administration was approximately 4 months, the vaccine provides for long lasting and selective inhibition of IL-17A activity in vivo. A monoclonal Ab (mAb) derived from these mice showed the same specificity for IL-17A. To test the ability of the vaccine to confer protection against an IL-17-dependent disorder, SJL mice were vaccinated with IL-17-OVA and encephalomyelitis (EAE) was induced by proteolipid protein (PLP) peptide 139–151. Vaccinated mice were completely protected against the disease. The above-mentioned anti-IL-17A mAb also prevented EAE development. The absence of clinical symptoms contrasted with unaltered PLP-induced cytokine production in vitro and unmodified anti-PLP IgG titers and isotypes. These results suggest that an anti-IL-17A auto-vaccine offers new perspectives for therapy of autoimmune diseases.

See accompanying commentary: http://dx.doi.org/10.1002/eji.200636760

Ancillary