Intranasal Immunization With an Apolipoprotein B-100 Fusion Protein Induces Antigen-Specific Regulatory T Cells and Reduces Atherosclerosis

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@article{810b2d7a9a834e7e865377f8f1470a30,
title = "Intranasal Immunization With an Apolipoprotein B-100 Fusion Protein Induces Antigen-Specific Regulatory T Cells and Reduces Atherosclerosis",
abstract = "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 of 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. Conclusion-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. (Arterioscler Thromb Vasc Biol. 2010;30:946-952.)",
keywords = "lipoproteins, atherosclerosis, immune system, regulatory T cells, vaccination",
author = "Roland Klingenberg and Michael Lebens and Andreas Hermansson and {Nordin Fredrikson}, Gunilla and Daniela Strodthoff and Mats Rudling and Ketelhuth, {Daniel F. J.} and Norbert Gerdes and Jan Holmgren and Jan Nilsson and Hansson, {Goran K.}",
year = "2010",
doi = "10.1161/ATVBAHA.109.202671",
language = "English",
volume = "30",
pages = "946--U148",
journal = "Arteriosclerosis, Thrombosis and Vascular Biology",
issn = "1524-4636",
publisher = "Lippincott Williams & Wilkins",
number = "5",

}