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Gingival vaccination strategy to induce both humoral and cellular immunity ideal for elderly vaccination

Research Project

Project/Area Number 22K09932
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionNihon University

Principal Investigator

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

Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Granted (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2024: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsSARS-CoV-2 spike / influenza HA / gingival vaccination / protein modelling / SARS-CoV-2 / influenza hemagglutinin / vaccine / SARS CoV 2 / Influenza
Outline of Research at the Start

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.

Outline of Annual Research Achievements

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.

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

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.

Strategy for Future Research Activity

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.

Report

(2 results)
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (4 results)

All 2023 2022

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (2 results) (of which Int'l Joint Research: 2 results)

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

    • Author(s)
      Cueno Marni E.、Taketsuna Keiichi、Saito Mitsuki、Inoue Sara、Imai Kenichi
    • Journal Title

      Journal of Molecular Graphics and Modelling

      Volume: 119 Pages: 108396-108396

    • DOI

      10.1016/j.jmgm.2022.108396

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] 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

    • Author(s)
      Cueno Marni E.、Wada Kanta、Tsuji Arisa、Ishikawa Kouta、Imai Kenichi
    • Journal Title

      Journal of Theoretical Biology

      Volume: 558 Pages: 111376-111376

    • DOI

      10.1016/j.jtbi.2022.111376

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Presentation] Structural comparison of differing spike protein structures relative to conformation changes observed among the various SARS-CoV-2 variants.2023

    • Author(s)
      Marni E. Cueno, Kenichi Imai
    • Organizer
      EMBO Workshop: Computational structural biology
    • Related Report
      2023 Research-status Report
    • Int'l Joint Research
  • [Presentation] Network analysis of autophagy in relation to various autophagy-targeted proteins found among SARS-CoV-2 variants of concern2022

    • Author(s)
      Cueno Marni E.、Taketsuna Keiichi、Saito Mitsuki、Inoue Sara、Imai Kenichi
    • Organizer
      10th International Symposium on Autophagy
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research

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Published: 2022-04-19   Modified: 2024-12-25  

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