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

Klingenberg, Roland; Lebens, Michael; Hermansson, Andreas; Nordin Fredrikson, Gunilla LU ; Strodthoff, Daniela; Rudling, Mats; Ketelhuth, Daniel F. J.; Gerdes, Norbert; Holmgren, Jan and Nilsson, Jan LU , et al. (2010) In Arteriosclerosis, Thrombosis and Vascular Biology 30(5). p.148-946
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... (More)
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.) (Less)
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publication status
published
subject
keywords
lipoproteins, atherosclerosis, immune system, regulatory T cells, vaccination
in
Arteriosclerosis, Thrombosis and Vascular Biology
volume
30
issue
5
pages
148 - 946
publisher
American Heart Association
external identifiers
  • wos:000276677700010
  • scopus:77951433369
ISSN
1524-4636
DOI
10.1161/ATVBAHA.109.202671
language
English
LU publication?
yes
id
810b2d7a-9a83-4e7e-8653-77f8f1470a30 (old id 1603304)
date added to LUP
2010-05-19 09:14:17
date last changed
2018-07-15 03:09:48
@article{810b2d7a-9a83-4e7e-8653-77f8f1470a30,
  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.)},
  author       = {Klingenberg, Roland and Lebens, Michael and Hermansson, Andreas and Nordin Fredrikson, Gunilla and Strodthoff, Daniela and Rudling, Mats and Ketelhuth, Daniel F. J. and Gerdes, Norbert and Holmgren, Jan and Nilsson, Jan and Hansson, Goran K.},
  issn         = {1524-4636},
  keyword      = {lipoproteins,atherosclerosis,immune system,regulatory T cells,vaccination},
  language     = {eng},
  number       = {5},
  pages        = {148--946},
  publisher    = {American Heart Association},
  series       = {Arteriosclerosis, Thrombosis and Vascular Biology},
  title        = {Intranasal Immunization With an Apolipoprotein B-100 Fusion Protein Induces Antigen-Specific Regulatory T Cells and Reduces Atherosclerosis},
  url          = {http://dx.doi.org/10.1161/ATVBAHA.109.202671},
  volume       = {30},
  year         = {2010},
}