Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-32206
Klingenberg, R; Lebens, M; Hermansson, A; Fredrikson, G N; Strodthoff, D; Rudling, M; Ketelhuth, D F J; Gerdes, N; Holmgren, J; Nilsson, J; Hansson, G K (2010). Intranasal immunization with an Apolipoprotein B-100 fusion protein induces antigen-specific regulatory T cells and reduces Atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology, 30(5):946-952.
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OBJECTIVE: Atherosclerosis is an inflammatory disease. Autoimmune responses to low-density lipoproteins (LDL) contribute to its progression, whereas immunization with LDL may induce atheroprotective or proatherogenic responses. The objective of this study was to develop an atheroprotective vaccine by targeting a peptide of the LDL protein constituent apolipoprotein B-100 (apoB-100) to the nasal mucosa to induce a protective mucosal immune response. METHODS AND RESULTS: A peptide comprising amino acids 3136 to 3155 of apoB-100 (p210) was fused to the B subunit of cholera toxin (CTB), which binds to a ganglioside on mucosal epithelia. The effect of nasal administration of the p210-CTB fusion protein on atherogenesis was compared with that of an ovalbumin peptide fused to CTB and with untreated controls. Immunization with p210-CTB for 12 weeks caused a 35% reduction in aortic lesion size in Apoe(-/-) mice. This effect was accompanied by induction regulatory T cells that markedly suppressed effector T cells rechallenged with apoB-100 and increased numbers of interleukin (IL)-10(+) CD4(+) T cells. Furthermore, a peptide-specific antibody response was observed. Atheroprotection was also documented in apoe(-/-) mice lacking functional transforming growth factor-beta receptors on T cells. CONCLUSIONS: Nasal administration of an apoB-100 peptide fused to CTB attenuates atherosclerosis and induces regulatory Tr1 cells that inhibit T effector responses to apoB-100.
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|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology|
|DDC:||610 Medicine & health|
|Deposited On:||26 Mar 2010 07:40|
|Last Modified:||27 Nov 2013 18:24|
|Publisher:||Lippincott Wiliams & Wilkins|
|Additional Information:||This is an un-copyedited author manuscript that was accepted for publication in "Arteriosclerosis Thrombosis and Vascular Biology", copyright The American Heart Association. This may not be duplicated or reproduced, other than for personal use or within the “Fair Use of Copyrighted Materials” (section 107, title 17, U.S. Code) without prior permission of the copyright owner, The American Heart Association. The final copyedited article, which is the version of record, can be found at http://atvb.ahajournals.org/cgi/content/abstract/ATVBAHA.109.202671v1. The American Heart Association disclaims any responsibility or liability for errors or omissions in this version of the manuscript or in any version derived from it by the National Institutes of Health or other parties.|
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