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

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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; Strodthoff, Daniela; Rudling, Mats; Ketelhuth, Daniel F. J.; Gerdes, Norbert; Holmgren, Jan; Nilsson, Jan; Hansson, Goran K.

In: Arteriosclerosis, Thrombosis and Vascular Biology, Vol. 30, No. 5, 2010, p. 946-U148.

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Harvard

Klingenberg, R, Lebens, M, Hermansson, A, Nordin Fredrikson, G, Strodthoff, D, Rudling, M, Ketelhuth, DFJ, Gerdes, N, Holmgren, J, Nilsson, J & Hansson, GK 2010, 'Intranasal Immunization With an Apolipoprotein B-100 Fusion Protein Induces Antigen-Specific Regulatory T Cells and Reduces Atherosclerosis', Arteriosclerosis, Thrombosis and Vascular Biology, vol. 30, no. 5, pp. 946-U148. https://doi.org/10.1161/ATVBAHA.109.202671

APA

Klingenberg, R., Lebens, M., Hermansson, A., Nordin Fredrikson, G., 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-U148. https://doi.org/10.1161/ATVBAHA.109.202671

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Klingenberg, Roland ; Lebens, Michael ; Hermansson, Andreas ; Nordin Fredrikson, Gunilla ; Strodthoff, Daniela ; Rudling, Mats ; Ketelhuth, Daniel F. J. ; Gerdes, Norbert ; Holmgren, Jan ; Nilsson, Jan ; Hansson, Goran K. / Intranasal Immunization With an Apolipoprotein B-100 Fusion Protein Induces Antigen-Specific Regulatory T Cells and Reduces Atherosclerosis. In: Arteriosclerosis, Thrombosis and Vascular Biology. 2010 ; Vol. 30, No. 5. pp. 946-U148.

RIS

TY - JOUR

T1 - Intranasal Immunization With an Apolipoprotein B-100 Fusion Protein Induces Antigen-Specific Regulatory T Cells and Reduces Atherosclerosis

AU - Klingenberg, Roland

AU - Lebens, Michael

AU - Hermansson, Andreas

AU - Nordin Fredrikson, Gunilla

AU - Strodthoff, Daniela

AU - Rudling, Mats

AU - Ketelhuth, Daniel F. J.

AU - Gerdes, Norbert

AU - Holmgren, Jan

AU - Nilsson, Jan

AU - Hansson, Goran K.

PY - 2010

Y1 - 2010

N2 - 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.)

AB - 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.)

KW - lipoproteins

KW - atherosclerosis

KW - immune system

KW - regulatory T cells

KW - vaccination

U2 - 10.1161/ATVBAHA.109.202671

DO - 10.1161/ATVBAHA.109.202671

M3 - Article

C2 - 20167655

VL - 30

SP - 946-U148

JO - Arteriosclerosis, Thrombosis and Vascular Biology

JF - Arteriosclerosis, Thrombosis and Vascular Biology

SN - 1524-4636

IS - 5

ER -