Epitopes described in "Intranasal immunization with an apolipoprotein B-100 fusion protein induces antigen-specific regulatory T cells and reduces atherosclerosis."

Article Authors:Roland Klingenberg; Michael Lebens; Andreas Hermansson; Gunilla Nordin Fredrikson; Daniela Strodthoff; Mats Rudling; Daniel F J Ketelhuth; Norbert Gerdes; Jan Holmgren; Jan Nilsson; Göran K Hansson
Article Title:Intranasal immunization with an apolipoprotein B-100 fusion protein induces antigen-specific regulatory T cells and reduces atherosclerosis.
Reference Detail
Reference ID:1019902
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.
Affiliations:Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden.
Reference Type:Literature
PubMed ID:20167655
Journal:Arterioscler Thromb Vasc Biol
Journal Volume:30
Article Pages:946-52
Journal ISSN:1524-4636
Article Chemical List:Aerosols;Apolipoprotein B-100;Apolipoproteins E;Forkhead Transcription Factors;Foxp3 protein, mouse;Immunoconjugates;Peptide Fragments;RNA, Messenger;Receptors, Transforming Growth Factor beta;Vaccines, Synthetic;Interleukin-10;Ovalbumin;Cholera Toxin;Protein-Serine-Threonine Kinases;transforming growth factor-beta type II receptor
Article MeSH List:Administration, Intranasal; Aerosols; Animals; Aortic Diseases(genetics; immunology; metabolism; pathology; prevention & control); Apolipoprotein B-100(administration & dosage; immunology); Apolipoproteins E(deficiency; genetics); Atherosclerosis(genetics; immunology; metabolism; pathology; prevention & control); Cholera Toxin(administration & dosage; immunology); Disease Models, Animal; Female; Forkhead Transcription Factors(genetics); Humans; Immunity, Cellular(drug effects); Immunity, Humoral(drug effects); Immunity, Mucosal(drug effects); Immunoconjugates(administration & dosage; immunology); Interleukin-10(genetics); Mice; Mice, Knockout; Nasal Mucosa(drug effects; immunology); Ovalbumin(administration & dosage; immunology); Peptide Fragments(administration & dosage; immunology); Protein-Serine-Threonine Kinases(metabolism); RNA, Messenger(metabolism); Receptors, Transforming Growth Factor beta(metabolism); T-Lymphocytes, Regulatory(drug effects; immunology); Vaccines, Synthetic(administration & dosage; immunology)
Curation Last Updated:2015-04-22 20:01:50