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高齢者における安全で 特異免疫誘導効果の高い歯肉経由免疫法の開発

研究課題

研究課題/領域番号 22K09932
研究種目

基盤研究(C)

配分区分基金
応募区分一般
審査区分 小区分57020:病態系口腔科学関連
研究機関日本大学

研究代表者

Cueno Marni  日本大学, 歯学部, 専修研究員 (20569967)

研究期間 (年度) 2022-04-01 – 2025-03-31
研究課題ステータス 交付 (2023年度)
配分額 *注記
4,290千円 (直接経費: 3,300千円、間接経費: 990千円)
2024年度: 1,040千円 (直接経費: 800千円、間接経費: 240千円)
2023年度: 1,560千円 (直接経費: 1,200千円、間接経費: 360千円)
2022年度: 1,690千円 (直接経費: 1,300千円、間接経費: 390千円)
キーワードSARS-CoV-2 spike / influenza HA / gingival vaccination / protein modelling / SARS-CoV-2 / influenza hemagglutinin / vaccine / SARS CoV 2 / Influenza
研究開始時の研究の概要

Research Activity 1: Virulence factor entry through the gingival crevice can affect the body systemically by altering immune-related and ageing-related biochemical networks.
Research Activity 2: Virulence factor entry through the gingival crevice can affect the brain and nerve cells in vivo.
Research Activity 3: Identifying target amino acid residues in the SARS CoV 2 spike and influenza A/B hemagglutinin proteins that could affect structural evolution
and viral infection among seasonal and pandemic influenza strains.
Research Activity 4: Vaccination design and antigen production strategies.

研究実績の概要

We were able to design the molecular structures related to the following: SARS-CoV-2 spike protein, influenza A H3N2 hemagglutinin (HA) and H5N1 HA, and influenza B/Yamagata HA proteins. Additionally, we were also able to do in silico xanthan gel molecular docking and confirmed that protein epitopes associated with activating B- and T-cell immune responses are readily exposed after xanthan gel molecule docking. We were able to optimize the antigen:gel ratio for influenza A H3N2 HA, H5N1 HA, and influenza B/Yamagata HA while antigen:gel ratio optimization for SARS-CoV-2 spike proteins are on-going.

現在までの達成度 (区分)
現在までの達成度 (区分)

2: おおむね順調に進展している

理由

We successfully designed and produced all our desired target antigen proteins (SARS-CoV-2 alpha, beta, gamma, delta, omicron spike proteins, influenza A H3N2 HA, influenza A H5N1 HA, influenza B/Yamagata HA) in silico. Additionally, antigen:gel ratio optimization for influenza A H3N2 HA, influenza A H5N1 HA, influenza B/Yamagata HA were done while antigen:gel ratio optimization for SARS-CoV-2 alpha, beta, gamma, delta, and omicron spike proteins are on-going. Three manuscripts have been written and submitted to internationally peer-reviewed journals and are currently under review.

今後の研究の推進方策

Vaccination of the optimized antigen:gel ratio along the gingival crevice will be performed. ELISA (B-cell immunity) and ELISPOT (T-cell immunity) will be performed following previously published work. Immune response from all all protein antigens (SARS-COV-2 spike, influenza A HA, and influenza B HA) will be checked to establish immune efficacy of the gel vaccine. In addition, results will be compared to direct gingival, sublingual, oral, and intramuscular vaccination strategies.

報告書

(2件)
  • 2023 実施状況報告書
  • 2022 実施状況報告書
  • 研究成果

    (4件)

すべて 2023 2022

すべて 雑誌論文 (2件) (うち査読あり 2件) 学会発表 (2件) (うち国際学会 2件)

  • [雑誌論文] Network analysis of the autophagy biochemical network in relation to various autophagy-targeted proteins found among SARS-CoV-2 variants of concern2023

    • 著者名/発表者名
      Cueno Marni E.、Taketsuna Keiichi、Saito Mitsuki、Inoue Sara、Imai Kenichi
    • 雑誌名

      Journal of Molecular Graphics and Modelling

      巻: 119 ページ: 108396-108396

    • DOI

      10.1016/j.jmgm.2022.108396

    • 関連する報告書
      2022 実施状況報告書
    • 査読あり
  • [雑誌論文] Structural patterns of SARS-CoV-2 variants of concern (alpha, beta, gamma, delta) spike protein are influenced by variant-specific amino acid mutations: A computational study with implications on viral evolution2023

    • 著者名/発表者名
      Cueno Marni E.、Wada Kanta、Tsuji Arisa、Ishikawa Kouta、Imai Kenichi
    • 雑誌名

      Journal of Theoretical Biology

      巻: 558 ページ: 111376-111376

    • DOI

      10.1016/j.jtbi.2022.111376

    • 関連する報告書
      2022 実施状況報告書
    • 査読あり
  • [学会発表] Structural comparison of differing spike protein structures relative to conformation changes observed among the various SARS-CoV-2 variants.2023

    • 著者名/発表者名
      Marni E. Cueno, Kenichi Imai
    • 学会等名
      EMBO Workshop: Computational structural biology
    • 関連する報告書
      2023 実施状況報告書
    • 国際学会
  • [学会発表] Network analysis of autophagy in relation to various autophagy-targeted proteins found among SARS-CoV-2 variants of concern2022

    • 著者名/発表者名
      Cueno Marni E.、Taketsuna Keiichi、Saito Mitsuki、Inoue Sara、Imai Kenichi
    • 学会等名
      10th International Symposium on Autophagy
    • 関連する報告書
      2022 実施状況報告書
    • 国際学会

URL: 

公開日: 2022-04-19   更新日: 2024-12-25  

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