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2022 年度 実施状況報告書

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
キーワードprotein modelling / SARS-CoV-2 / influenza hemagglutinin
研究実績の概要

We were able to produce the molecular structure of one of the protein antigens that would be used throughout the study. More specifically, the SARS-CoV-2 spike protein from the original, alpha, beta, gamma, and delta variants were successfully designed in silico. We were able to publish our preliminary results related to the in silico design of the SARS-CoV-2 in a peer-reviewed journal. At present, we are likewise designing molecular structures related to the influenza A H3N2 and influenza B/Yamagata hemagglutinin (HA) proteins. Additionally, we also decided to add additional proteins for molecular structure design, namely: SARS-CoV-2 omicron spike and influenza A H5N1 HA proteins since the on-going pandemic is mainly associated with the omicron variant while the on-going bird flu epidemic might have the potential to cross to humans. Protein structures that have already been designed are currently undergoing epitope screening to identify potential B- and T-cell-related conformational epitopes associated with immune response. Moreover, we were also able to perform and confirm xanthan gel and antigen docking involving some of the SARS-CoV-2 spike proteins. We are currently confirming whether epitopes associated with activating B- and T-cell immune responses are readily exposed after xanthan gel molecule docking.

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 one of our target antigen protein (SARS-CoV-2 spike protein) in silico. Multiple spike proteins related to the original, alpha, beta, gamma, and delta variants were made. Other antigen protein targets (influenza A H3N2 and B/Yamagata hemagglutinin) are currently being designed. In addition, the spike protein from the SARS-CoV-2 omicron variant and the hemagglutinin protein from the influenza A H5N1 are also being considered. Similarly, xanthan gel and antigen docking were likewise done and confirmed involving some of the SARS-CoV-2 spike proteins. We are currently confirming whether epitopes associated with activating B- and T-cell immune responses are readily exposed after xanthan gel molecule docking. Two papers were successfully accepted for publication in two different peer-reviewed journals.

今後の研究の推進方策

Commercially available SARS-CoV-2 spike, influenza A H3N2 HA, and influenza B HA at varying concentrations will be used for antigen:gel ratio optimization. Industrial-grade xanthum gum will be used as the gel component. Varying mixing options will be considered in order to establish the optimal antigen:gel ratios for all three target antigens. Additionally, optimization for liquid vaccination mixture for use in alternative vaccination strategies (sublingual, oral, intramuscular) and direct gingival injection will likewise be performed.

次年度使用額が生じた理由

Savings from the previous year is due to the reduction in price of several of the materials needed which include the SARS-CoV-2 protein antigen. Industrial-grade xanthum gum will be purchased and used as the gel component. For the subsequent year, varying mixing options will be considered in order to establish the optimal antigen:gel ratios for all target antigens.

  • 研究成果

    (3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 (1件) (うち国際学会 1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

    • 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

    • 査読あり
  • [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
    • 国際学会

URL: 

公開日: 2023-12-25  

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