A VLP-based vaccine against interleukin-1?? protects mice from atherosclerosis

摘要

Interleukin (IL)-1?? is a potent proinflammatory cytokine that has been implicated in the development of atherosclerosis. We investigated whether a vaccine inducing IL-1?? neutralizing antibodies could interfere with disease progression in a murine model of atherosclerosis. We immunized Apolipoprothin E (ApoE)-deficient mice with a vaccine (IL-1??-C-Q??) consisting of full-length, native IL-1?? chemically conjugated to virus-like particles derived from the bacteriophage Q??. ApoE-/- mice were administered six injections of IL-1??-C-Q?? or nonconjugated Q?? over a period of 160 days while being maintained on a western diet. Atherosclerosis was measured in the descending aorta and in cross-sections at the aortic root. Macrophage infiltration in the aorta was measured using CD68. Expression levels of VCAM-1, ICAM-1, and MCP-1 were quantified by RT-PCR. Immunization against IL-1?? reduced plaque progression in the descending aorta by 50% and at the aortic root by 37%. Macrophage infiltration in the aorta was reduced by 22%. Inflammation was also reduced in the adventitia, with a decrease of 54% in peri-aortic infiltrate score and reduced expression levels of VCAM-1 and ICAM-1. Active immunization targeting IL-1?? reduced both the inflammatory reaction in the plaque as well as plaque progression. In summary, vaccination against IL-1?? protected ApoE-/- mice against disease, suggesting that this may be a potential treatment option for atherosclerosis. ? 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.