title: Sublingual vaccine with GroEL attenuates atherosclerosis.
abstract: Autoimmune responses to heat-shock protein 60 (HSP60) contribute to the progression of atherosclerosis, whereas immunization with HSP60 may induce atheroprotective responses. We assessed the capacity of an atheroprotective vaccine that targeted a recombinant HSP60 from Porphyromonas gingivalis (rGroEL) to induce a protective mucosal immune response. Female apolipoprotein E-deficient spontaneously hyperlipidemic (Apoe(shl)) mice received sublingual delivery of rGroEL prior to P. gingivalis 381 injection. The animals were euthanized 16 weeks later. Sublingual immunization with rGroEL induced significant rGroEL-specific serum IgG responses. Antigen-specific cells isolated from spleen produced significantly high levels of IL-10 and IFN-γ after antigen re-stimulation in vitro. Flow cytometric analysis indicated that the frequencies of both IL-10(+) and IFN-γ(+) CD4(+) Foxp3(+) cells increased significantly in submandibular glands (SMG). Furthermore, sublingual immunization with rGroEL significantly reduced atherosclerosis lesion formation in the aortic sinus and decreased serum CRP, MCP-1, and ox-LDL levels. These findings suggest that sublingual immunization with rGroEL is associated with the increase of IFNγ(+) or IL-10(+) Foxp3(+) cells in SMG and a systemic humoral response, which could be an effective strategy for the prevention of naturally occurring or P. gingivalis-accelerated atherosclerosis.
authors.affiliation: Department of Oral Surgery.
authors.forename: M
authors.initials: M
authors.lastname: Hagiwara
authors.forename: T
authors.initials: T
authors.lastname: Kurita-Ochiai
authors.forename: R
authors.initials: R
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Hashizume-Takizawa
authors.forename: K
authors.initials: K
authors.lastname: Yamazaki
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D000286:Administration, Sublingual; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000473:pathology / Q000517:prevention & control*; D001324:Autoantigens / Q000097:blood; D001428:Bacterial Vaccines / Q000008:administration & dosage*; D002097:C-Reactive Protein / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018834:Chaperonin 60 / Q000276:immunology*; D018932:Chemokine CCL2 / Q000097:blood; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D006949:Hyperlipidemias / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology; D007114:Immunization / Q000379:methods*; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D008077:Lipoproteins, LDL / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D016966:Porphyromonas gingivalis / Q000276:immunology; D011897:Random Allocation; D012850:Sinus of Valsalva / Q000473:pathology; D013363:Submandibular Gland / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000032:analysis
chemical_list: D000907:Antibodies, Bacterial; D001057:Apolipoproteins E; D001324:Autoantigens; D001428:Bacterial Vaccines; C491768:Ccl2 protein, mouse; D018834:Chaperonin 60; D018932:Chemokine CCL2; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C556062:IL10 protein, mouse; D007074:Immunoglobulin G; D008077:Lipoproteins, LDL; D016212:Transforming Growth Factor beta; C099252:oxidized low density lipoprotein; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D002097:C-Reactive Protein
keywords: GroEL; HSP60; Porphyromonas gingivalis; atherosclerosis; mucosal immunization; periodontopathic bacteria