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Utilizing the sulcular epithelium as a vaccination route ideal for elderly vaccination

Research Project

Project/Area Number 16K11525
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionNihon University

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) 落合 智子 (栗田智子)  日本大学, 松戸歯学部, 教授 (20130594)
落合 邦康  日本大学, 歯学部, 特任教授 (50095444)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsgel vaccine / gingival vaccination / elderly / gingival vaccine / gel-encapsulated / oral-supplementation / gingival crevice / mixed antigen / separated antigen / antigen:gel ratio / vaccine design / oral vaccination / influenza / elderly vaccination / インフルエンザ / ワクチン
Outline of Final Research Achievements

We first simulated xanthan gel-encapsulation of two representative antigens (Dengue virus envelope subtype-2 and Influenza A nucleoprotein) through molecular docking in order to confirm exposure of target epitopes. Subsequently, we orally supplemented two sets of rats with two different antigen doses: mixed low-dose (50 ug/mL per antigen) and separated high-dose (100 ug/mL per antigen). Throughout this study, we were able to establish the following: (1) total number of xanthan molecules encapsulating an antigen depends on the number of residues in the target antigen; (2) gel-encapsulation enhances antigen structural stability; (3) gel-encapsulated antigens putatively elicit high affinity antibodies; and (4) the more stable a gel-encapsulated antigen is, the more antibody titer amount is elicited. Overall, we propose that gel-encapsulation of mixed low-dose antigens and, subsequently, orally-supplementing these components via the GC route are able to elicit a systemic immune response.

Academic Significance and Societal Importance of the Research Achievements

老化は口腔内歯肉溝(GC)を拡大することから、歯肉溝内の歯周病原性細菌が歯肉粘膜に入り込み易くなり、その結果これらが全身に影響をもたらす可能性が高い。これまでの我々の研究において、GCは細菌の侵入経路であることを模倣し、ゲルカプセル化し経口補給した単一の抗原が同様の経路で全身性免疫応答を引き起こす可能性を明らかにした。この研究の結果から、本実験結果は将来、高齢者が使用可能な歯肉ワクチン接種法の開発に有用であると思われます。この提案された歯肉ワクチン接種は,簡便かつ安全であり、高齢者が予防接種を受けたときに有害な副作用がないものと考えられます。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (9 results)

All 2019 2018 2017 2016

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Structural significance of residues 158-160 in the H3N2 hemagglutinin globular head: A computational study with implications in viral evolution and infection2019

    • Author(s)
      Marni E. Cueno, Hayato Shiotsu, Karin Nakano, Emiko Sugiyama, Mari Kikuta, Rikuya Usui, Riku Oya, Kenichi Imai
    • Journal Title

      Journal of Molecular Graphics and Modelling

      Volume: 89 Pages: 33-40

    • DOI

      10.1016/j.jmgm.2019.02.007

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gingival Periodontal Disease (PD) Level-Butyric Acid Affects the Systemic Blood and Brain Organ: Insights Into the Systemic Inflammation of Periodontal Disease2018

    • Author(s)
      Marni E. Cueno, Kuniyasu Ochiai
    • Journal Title

      Frontiers in Immunology

      Volume: 9 Pages: 1-13

    • DOI

      10.3389/fimmu.2018.01158

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Network analytics approach towards identifying potential antivirulence drug targets within the Staphylococcus aureus staphyloxanthin biosynthetic network2018

    • Author(s)
      Marni E. Cueno, Kenichi Imai
    • Journal Title

      Archives of Biochemistry and Biophysics

      Volume: 645 Pages: 81-86

    • DOI

      10.1016/j.abb.2018.03.010

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Various cellular components change as the rat ages: An insight into the putative overall age-related cellular stress network2018

    • Author(s)
      Cueno ME, Imai K
    • Journal Title

      Experimental Gerontology

      Volume: 102 Pages: 36-42

    • DOI

      10.1016/j.exger.2017.11.021

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Structural comparison among the 2013-2017 avian influenza A H5N6 hemagglutinin proteins: A computational study with epidemiological implications2018

    • Author(s)
      Cueno ME, Suzuki I, Shimotomai S, Yokoyama T, Nagahisa K, Imai K
    • Journal Title

      Journal of Molecular Graphics and Modelling

      Volume: 79 Pages: 185-191

    • DOI

      10.1016/j.jmgm.2017.11.013

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Periodontal disease- level butyric acid putatively contributes to the ageing blood: A proposed linked between periodontal diseases and the ageing process2017

    • Author(s)
      Cueno ME, Seki K, Ochiai K, Imai K
    • Journal Title

      Mechanisms of Aging and Development

      Volume: 162 Pages: 100-105

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Gingival vaccination as a potential non-invasive route for elderly2018

    • Author(s)
      Marni E. Cueno, Kenichi Imai
    • Organizer
      Mucosal Immunology Course and Symposium (MICS) 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Network analysis of the varying components involved in Staphylococcus aureus staphyloxanthin biosynthesis: Prospects for antivirulence strategies2017

    • Author(s)
      Cueno ME, Imai K
    • Organizer
      18th International Carotenoid Symposium
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Gingival vaccination for the elderly population2016

    • Author(s)
      Cueno ME, Tamura M, Imai K
    • Organizer
      10th Vaccine Congress
    • Place of Presentation
      Amsterdam (Netherlands)
    • Year and Date
      2016-09-04
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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