Vaccination against interleukin 17 attenuates atherosclerosis in LDLr -/- m ice

Interleukin 17 (IL-17) is a T cel-derived pro-inflammatory cytokine that has been linked to several autoimmune diseases. IL-17 exhibits pleiotropic effects on atheroma-associated cel types and induces the secretion of proinflammatory cytokines, chemokines and matrix metaloproteinases, which enhances the inflammatory response in atherosclerotic lesions. In the present study we aimed to study the effect of IL-17blockade by vaccination on the initiation of atherosclerosis. A plasmid (pcDNA3.1) encoding IL-17 and the dominant T helper cel epitope HEL was used to vaccinate LDL receptor deficient mice prior to induction of atherosclerosis by feeding a Western type diet and colar placement. Successful functional blockade of IL-17 upon vaccination was shown by reduced induction of serum IL-6 levels after administration of IL-17. DNA vaccination by intramuscular injection of the HEL-IL-17 plasmid or by oral administration of S. typhimurium transformed with this plasmid resulted in a decrease in atherosclerosis of 90% and 75%, respectively. Oral vaccination of LDLr -/mice with S. typhimurium transformed with an IL-17 plasmid without the HEL sequence did not affect atherosclerosis. We conclude that effective interruption of the IL-17 pathway by DNA vaccination depended on the presence of the HEL epitope in the IL17 DNA vaccine. Effective blockade of IL-17 by DNA vaccination resulted in a vast decrease in atherosclerosis and it may be speculated that IL-17 production by the newly identified IL-17 memory cels form a major target for IL-17 vaccination. Chapter 4

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