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

Author:
  • Roland Klingenberg
  • Michael Lebens
  • Andreas Hermansson
  • Gunilla Nordin Fredrikson
  • Daniela Strodthoff
  • Mats Rudling
  • Daniel F. J. Ketelhuth
  • Norbert Gerdes
  • Jan Holmgren
  • Jan Nilsson
  • Goran K. Hansson
Publishing year: 2010
Language: English
Pages: 148-946
Publication/Series: Arteriosclerosis, Thrombosis and Vascular Biology
Volume: 30
Issue: 5
Document type: Journal article
Publisher: Lippincott Williams Wilkins Hagerstown, MD

Abstract english

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

  • Cardiac and Cardiovascular Systems
  • lipoproteins
  • atherosclerosis
  • immune system
  • regulatory T cells
  • vaccination

Other

Published
  • Cardiovascular Research - Immunity and Atherosclerosis
  • ISSN: 1524-4636
E-mail: jan [dot] nilsson [at] med [dot] lu [dot] se

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