title: A VLP-based vaccine against interleukin-1α protects mice from atherosclerosis.
abstract: 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.
authors.affiliation: Cytos Biotechnology AG, Zurich-Schlieren, Switzerland.
authors.forename: Alain C
authors.initials: AC
authors.lastname: Tissot
authors.forename: Gunther
authors.initials: G
authors.lastname: Spohn
authors.forename: Gary T
authors.initials: GT
authors.lastname: Jennings
authors.forename: Abdijapar
authors.initials: A
authors.lastname: Shamshiev
authors.forename: Michael O
authors.initials: MO
authors.lastname: Kurrer
authors.forename: Renata
authors.initials: R
authors.lastname: Windak
authors.forename: Marco
authors.initials: M
authors.lastname: Meier
authors.forename: Miriam
authors.initials: M
authors.lastname: Viesti
authors.forename: Martin
authors.initials: M
authors.lastname: Hersberger
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kündig
authors.forename: Romeo
authors.initials: R
authors.lastname: Ricci
authors.forename: Martin F
authors.initials: MF
authors.lastname: Bachmann
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053582:Interleukin-1alpha / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000276:immunology / Q000473:pathology; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000906:Antibodies; D057134:Antibodies, Neutralizing; D001057:Apolipoproteins E; D053582:Interleukin-1alpha; D058425:Vaccines, Virus-Like Particle