Vaccination against IL-17 suppresses autoimmune arthritis and encephalomyelitis.
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.
Röhn
Till A
TA
Cytos Biotechnology AG, Immunodrugs, Zürich, Switzerland.
Jennings
Gary T
GT
Hernandez
Marcela
M
Grest
Paula
P
Beck
Markus
M
Zou
Yu
Y
Kopf
Manfred
M
Bachmann
Martin F
MF
D000818:Animals; D001169:Arthritis, Experimental / Q000473:pathology / Q000517:prevention & control*; D001323:Autoantibodies / Q000097:blood; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control*; D005121:Extremities / Q000473:pathology; D005260:Female; D016233:Immunotherapy, Active; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000627:therapeutic use; D051379:Mice; D008815:Mice, Inbred Strains; D017510:Protein Folding; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D022721:Vaccines, Virosome / Q000627:therapeutic use*
D001323:Autoantibodies; D020381:Interleukin-17; D011994:Recombinant Proteins; D022721:Vaccines, Virosome