| 研究課題/領域番号 |
22K09932
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| 研究種目 |
基盤研究(C)
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| 配分区分 | 基金 |
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| 応募区分 | 一般 |
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| 審査区分 |
小区分57020:病態系口腔科学関連
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| 研究機関 | 日本大学 |
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研究代表者 |
Cueno Marni 日本大学, 歯学部, 専修研究員 (20569967)
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| 研究期間 (年度) |
2022-04-01 – 2025-03-31
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| 研究課題ステータス |
交付 (2022年度)
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| 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)
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| キーワード | protein modelling / SARS-CoV-2 / influenza hemagglutinin / vaccine / SARS CoV 2 / Influenza |
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| 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.
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| 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.
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| 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.
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| 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.
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