A VLP‐based vaccine against interleukin‐1α protects mice from atherosclerosis

Interleukin (IL)‐1α is a potent proinflammatory cytokine that has been implicated in the development of atherosclerosis. We investigated whether a vaccine inducing IL‐1α neutralizing antibodies could interfere with disease progression in a murine model of atherosclerosis. We immunized Apolipoprothin E (ApoE)‐deficient mice with a vaccine (IL‐1α‐C‐Qβ) consisting of full‐length, native IL‐1α chemically conjugated to virus‐like particles derived from the bacteriophage Qβ. ApoE^?/? mice were administered six injections of IL‐1α‐C‐Qβ or nonconjugated Qβ 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‐1α 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‐1α reduced both the inflammatory reaction in the plaque as well as plaque progression. In summary, vaccination against IL‐1α protected ApoE^?/? mice against disease, suggesting that this may be a potential treatment option for atherosclerosis.