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Keywords:

  • Autoimmune diseases;
  • IL-17;
  • Vaccination;
  • Virus-like particles

Abstract

Interleukin 17 is a T cell-derived cytokine that induces the release of pro-inflammatory mediators in a wide range of cell types. Recently, a subset of IL-17-producing T helper cells (Th17) distinct from Th1 and Th2 cells has been described, which constitutes a new T cell polarization state. Aberrant Th17 responses and overexpression of IL-17 have been implicated in a number of autoimmune disorders including rheumatoid arthritis and multiple sclerosis. Molecules blocking IL-17 such as IL-17-specific monoclonal antibodies have proved to be effective in ameliorating disease in animal models. Hitherto, active immunization targeting IL-17 is an untried approach. Herein we explore the potential of neutralizing IL-17 by active immunization using virus-like particles conjugated with recombinant IL-17 (IL-17-VLP). Immunization with IL-17-VLP induced high levels of anti-IL-17 antibodies thereby overcoming natural tolerance, even in the absence of added adjuvant. Mice immunized with IL-17-VLP had lower incidence of disease, slower progression to disease and reduced scores of disease severity in both collagen-induced arthritis and experimental autoimmune encephalomyelitis. Active immunization against IL-17 therefore represents a novel therapeutic approach for the treatment of chronic inflammatory diseases.

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