2022 Fiscal Year Final Research Report

Rejuvenation of mucosal immunosenescence by the sublingual vaccine: The prevention and treatment for periodontal disease and arteriosclerosis

Research Project

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Project/Area Number	20H03856
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 57020:Oral pathobiological science-related
Research Institution	Chiba University (2022) The University of Tokyo (2020-2021)
Principal Investigator	Fujihashi Kohtaro 千葉大学, 医学部附属病院, 特任教授 (50820354)
Co-Investigator(Kenkyū-buntansha)	片岡宏介徳島大学, 大学院医歯薬学研究部(歯学域), 教授 (50283792) 中橋理佳千葉大学, 医学部附属病院, 特任准教授 (80391887) 落合智子 (栗田智子) 日本大学, 松戸歯学部, 教授 (20130594)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	舌下ワクチン / 歯周病 / 老化 / 高原特異的IgA / サイトカイン / 歯槽骨吸収
Outline of Final Research Achievements	In order to prevent periodontal disease and its-associated diseases including arteriosclerosis and aspiration pneumonia for the elderly, we aimed to develop a sublingual vaccine using outer membrane protein from Porphyromonas gingivalis as a vaccine antigen. Mice have sublingually immunized with OMP40 plus CpG ODN and plasmid Flt3 ligand plasmid as a mucosal adjuvant. The vaccinated mice showed increased levels of OMP-specific salivary IgA and serum IgG antibody responses. Similarly, when aged mice (>18 month-old) were given the sublingual vaccine, these mice showed elevated levels of OMP-specific antibody responses in serum and saliva. Importantly, when mice given a sublingual vaccine were infected with P. gingivalis, reduced levels of periodontal bone loss were observed. These results indicate that the OMP40-based sublingual vaccine is a potent strategy for the prevention of periodontal disease-associated systemic diseases.
Free Research Field	粘膜免疫・粘膜ワクチン
Academic Significance and Societal Importance of the Research Achievements	主要原因菌の１つであるP. gingivalis口腔感染症としての歯周病は、動脈硬化、リウマチ、誤嚥性肺炎、糖尿病など様々な全身系疾患の引き金となると報告されており、加齢による口腔感染症に対する免疫力の低下は高齢者に重篤な健康被害を引き起こす。そこで、高齢者の口腔内局所とそれに関連する全身系の両方の疾患を予防・治療する有効な対策の開発が求められている。経口・経鼻免疫に代表される粘膜免疫法は粘膜局所と全身系に二段構えのバリアを構築することができ、歯周病と全身疾患の予防に有効と考えられ、高齢者の生活資質を向上に貢献し、健全な健康長寿社会を構築・維持することはできる。