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MucosaI immunity in the upper respiratory tract and vaccine development

Research Project

Project/Area Number 19591979
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Otorhinolaryngology
Research InstitutionOita University

Principal Investigator

SUZUKI Masashi  Oita University, 医学部, 教授 (60211314)

Co-Investigator(Kenkyū-buntansha) HIRANO Takashi  大分大学, 医学部, 講師 (20305056)
KODAMA Satoru  大分大学, 医学部, 講師 (40325717)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords上気道 / 粘膜免疫 / ワクチン / 粘膜粘液 / 樹状細胞
Research Abstract

Dendritic cells (DCs) are essential for the induction of antigen (Ag)-specific immune responses, DC-targeted vaccination might be an effective strategy for the induction of the specific immune responses. Flt3 ligand (Flt3L) mobilizes and stimulates myeloid and lymphoid progenitor cells, and DCs. The purpose of this study is to investigate the effect of Flt3L on the induction of Ag-specific immune responses in nasal mucosa. Mice were administered with Flt3L 10Hg intranasally or intraperitoneally, on day 0. After the Flt3L application, mice were further immunized with P6 outer membrane protein of nontypeable Haemophilus influenzae (NTHi) 10μg on day 6, 13, and 20, and mice were killed on day 27. Control were not given Flt3L. The number and subset of DCs in nasal-associated lymphoid tissue (NALT) were analyzed by flow cytometry. P6-specific antibody titers in nasal wash and serum were measured by enzyme-linked immunosorbent assay (ELISA), and P6-specific antibody-producing cells were examined by enzyme-linked immunospot (ELISPOT) assay. CD11c^+ DCs increased in NALT after nasal Flt3L administration. In addition, P6-specific nasal IgA and systemic IgG titers were significantly elevated in nasally Flt3L-treated mice, possessing higher number of the specific IgA-producing in nasal mucosa. This study showed that nasal but not peritoneal application with a single dose of Flt3L induced increase of NALT DCs, resulted in enhanced local and systemic immune responses. These findings suggest that nasal application with Flt3L might be a useful vaccine strategy.

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (21 results)

All 2010 2009 2008 2007 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (7 results) Book (1 results) Remarks (4 results)

  • [Journal Article] A single nasal dose of fms-like tyrosine kinase receptor-3 ligand, but not peritoneal application, enhances nontypeable Haemophilus influenzae-specific long term mucosal immune responses in the nasopharynx.2010

    • Author(s)
      Kodama S, Hirano T, Noda K, Abe N, Suzuki M
    • Journal Title

      Vaccine 28

      Pages: 2510-2516

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] The role of toll-like receptor 4 in eliciting acquired immune responses against nontypeable Haemophilus influenzae following intranasal immunization with outer membrane protein.2009

    • Author(s)
      Hirano T, Kodama S, Suzuki M
    • Journal Title

      Int J Pediatr Otorhinolaryngol 73

      Pages: 1657-1665

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] The role of toll-like receptor 4 in eliciting acquired immune responsed against nontypeable Haemophilus influenzae following intranasal immunization with outer membrane protein2009

    • Author(s)
      Hirano T, Kodama S, Moriyama M, Kawano T, Suzuki M.
    • Journal Title

      Int J Pediatr Otorhinolaryngol 73

      Pages: 1657-1665

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic impact of phosphorylcholine expression in nontypeable Haemophilus influenzae in otitis media with effusion2009

    • Author(s)
      Fujita K, Hirano T, Kodama S, Suzuki M.
    • Journal Title

      Acta Otolaryngol 129

      Pages: 832-838

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 中耳炎に対するワクチン療法2009

    • Author(s)
      鈴木正志, 平野隆
    • Journal Title

      日本医師会雑誌 137

      Pages: 2346-2348

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 上気道粘膜免疫ワクチン2008

    • Author(s)
      鈴木正志, 児玉悟
    • Journal Title

      耳鼻咽喉科免疫アレルギー 26

      Pages: 11-16

    • NAID

      10021295196

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of toll-like receptor 4 in innate immune responses in a mouse model of otitis media.2007

    • Author(s)
      Hirano T, Kodama S, Fujita K, Maeda K, Suzuki M.
    • Journal Title

      FEMS Immunol Med Microbiol 49

      Pages: 75-83

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Local application of CpG oligonucleotide enhances nontypeable Haemophilus influenza-specific mucosal IgA responses in the middle ear.2007

    • Author(s)
      Kodama S, Hirano T, Abe N, Suzuki M.
    • Journal Title

      Acta Otolaryngol 127

      Pages: 809-815

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antibody responses to survivin and their clinical significance in patients with head and neck cancer.2007

    • Author(s)
      Eto M, Kodama S, Uemura N, Suzuki M.
    • Journal Title

      Head Neck 29

      Pages: 1128-1135

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Role of toll-like receptor (TLR) 4 and efficacy of TLR9 ligand in the middle ear protective immunity.2009

    • Author(s)
      Kodama S, Hirano T, Suzuki M
    • Organizer
      6th Extraordinary International Symposium on Recent Advances in Otitis Media
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2009-08-05
    • Related Report
      2009 Final Research Report
  • [Presentation] Isolated sphenoid sinus disease : a clinical analysis2008

    • Author(s)
      Suzuki M, Kodama S, Kawano T.
    • Organizer
      22nd ERS & 27th ISIAN
    • Place of Presentation
      Crete, Greece
    • Year and Date
      2008-06-15
    • Related Report
      2008 Annual Research Report
  • [Presentation] インフルエンザ菌に対する経鼻DNAワクチン作成の試みと新しいワクチンデリバリーシステム2008

    • Author(s)
      児玉 悟、安倍伸幸、平野 隆、鈴木正志
    • Organizer
      第26回日本耳鼻咽喉科免疫アレルギー学会
    • Place of Presentation
      大阪市
    • Year and Date
      2008-02-22
    • Related Report
      2007 Annual Research Report
  • [Presentation] 長期中耳炎病態の解析2008

    • Author(s)
      平野 隆、児玉 悟、前田一彦、藤田佳吾、鈴木正志
    • Organizer
      第26回日本耳鼻咽喉科免疫アレルギー学会
    • Place of Presentation
      大阪市
    • Year and Date
      2008-02-22
    • Related Report
      2007 Annual Research Report
  • [Presentation] A single nasal dose of Flt3 ligand enhances mucosal immune responses in the nasopharynx.2007

    • Author(s)
      Kodama S, Hirano T, Abe N, Suzuki M.
    • Organizer
      9th International Symposium on Recent Advances in Otitis Media
    • Place of Presentation
      St. Pete Beach, Florida, USA
    • Year and Date
      2007-06-07
    • Related Report
      2007 Annual Research Report
  • [Presentation] A sing le nasal dose of Flt3 ligand enhances m ucosal immune responses in the nasophar ynx.2007

    • Author(s)
      Kodama S, Hirano T, Suzuki M
    • Organizer
      9th International Symposium on Rece nt Advances in Otitis Media
    • Place of Presentation
      St. Pete Beach, Florida, USA
    • Year and Date
      2007-06-05
    • Related Report
      2009 Final Research Report
  • [Presentation] Analysis of the cellular immune responses to influenza virus infection in the middle ear.2007

    • Author(s)
      Hirano T, Tomiguchi, Mabuchi H, Kodama S, Suzuki M.
    • Organizer
      9th International Symposium on Recent Advances in Otitis Media
    • Place of Presentation
      St. Pete Beach, Florida, USA
    • Year and Date
      2007-06-05
    • Related Report
      2007 Annual Research Report
  • [Book] 実験医学 粘膜免疫からの感染と免疫応答機構.中耳・耳管の免疫システム2007

    • Author(s)
      児玉 悟、鈴木正志
    • Publisher
      羊土社
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.oita-u.ac.jp/ent/

    • Related Report
      2009 Final Research Report
  • [Remarks]

    • URL

      http://.www.med.oita-u.ac.jp/ent/index.html

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.oita-u.ac.jp

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.oita-u.ac.jp

    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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