Development of an anti-IL-17A auto-vaccine that prevents experimental auto-immune encephalomyelitis.
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.
Uyttenhove
Catherine
C
Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium. catherine.uyttenhove@bru.licr.org
Van Snick
Jacques
J
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control*; D020381:Interleukin-17 / Q000037:antagonists & inhibitors*; D051379:Mice; D008815:Mice, Inbred Strains; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology / Q000627:therapeutic use*
D001323:Autoantibodies; D020381:Interleukin-17; D014614:Vaccines, Synthetic