Sublingual vaccine with groel attenuates atherosclerosis

M. Hagiwara, T. Kurita-Ochiai, R. Kobayashi, T. Hashizume-Takizawa, K. Yamazaki, M. Yamamoto

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29 Citations (Scopus)


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 (Apoeshl) 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.

Original languageEnglish
Pages (from-to)382-387
Number of pages6
JournalJournal of Dental Research
Issue number4
Publication statusPublished - Apr 2014


  • atherosclerosis
  • GroEL
  • HSP60
  • mucosal immunization
  • periodontopathic bacteria
  • Porphyromonas gingivalis


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