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2007 Fiscal Year Final Research Report Summary

Development of a novel nasal vaccine having wide spectrum activity for upper respiratory infections

Research Project

Project/Area Number 17390463
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

KURONO Yuichi  Kagoshima University, Graduate School of Medical and Dental Sciences, Professor (80153427)

Co-Investigator(Kenkyū-buntansha) MATSUNE Shoji  Kagoshima University, Graduate School of Medical and Dental Sciences, Associate Professor (00253899)
NISHIMOTO Kengo  Kagoshima University, Medical and Dental Hospital, Senior Assistant Professor (50305132)
FUKUIWA Tatsuya  Kagoshima University, Medical and Dental Hospital, Senior Assistant Professor (60325785)
ODA Hiroshi  Kagoshima University, Graduate School of Medical and Dental Sciences, Professor (40107868)
Project Period (FY) 2005 – 2007
KeywordsPhosphorylcholine / Intra-nasal vaccine / Wide spectrum vaccine / Mucosal immunity / Mucosal adjuvant / IgA / Haemophilus influenzae / Streptococcus pneumoniae
Research Abstract

1. Immunogenicity of phosphorylcholine (PC). PC-specific antibody activities in serum obtained from patients with acute epiglottitis and peri-tonsillar abscess were examined by ELISA. The results showed increased antibody titers against PC, suggesting that PC has immunogenicity and an ability to induce protecting antibodies.
2. Relationship between the expression of PC and bacterial virulence. The expression of PC on bacterial surfaces determined by ELISA was significantly increased in log-phase and decreased in lag-phase. Further, the adherence ability of bacteria highly expressing PC was greater than that of bacteria scarcely expressing PC. Those findings indicate that PC is associated with the phase variation of bacteria and the virulence of bacteria.
3. Mucosal immune responses against PC PC was intra-nasally administered to mice and mucosal as well as systemic immune responses were investigated. The results demonstrated that PC is capable of inducing IgA immune responses in nasal mucosa. The immune responses had impact on wide spectrum of bacteria including Haemophilus influenzae and Streptococcus pneumonia. However, IgE immune responses against cholera toxin, mucosal adjuvant administered with PC, as well as PC were reduced, indicating the safety of PC as mucosal vaccine.
4. Development of new mucosal adjuvant CpG and Flt3-ligand are known to activate dendritic cell and are candidates of mucosal adjuvant. When both CpG and Flt3-ligand were intra-nasally administered to mice with ovalbumin, Th1- and Th2-type immune responses were induced and long-lasting IgA as well as IgG immune responses were observed. The results suggest that PC might be a candidate of mucosal vaccine having wide spectrum activity against most bacteria such as Haemophilus influenzae and Streptococcus pneumonia causing upper respiratory infections.

  • Research Products

    (57 results)

All 2008 2007 2006 2005

All Journal Article (29 results) (of which Peer Reviewed: 9 results) Presentation (27 results) Book (1 results)

  • [Journal Article] 粘膜免疫による耳鼻咽喉科疾患の制御2007

    • Author(s)
      黒野 祐一
    • Journal Title

      医学のあゆみ 221(11)

      Pages: 887-890

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 経鼻粘膜ワクチンの現況と展望2007

    • Author(s)
      黒野 祐一
    • Journal Title

      耳鼻咽喉科展望 50(3)

      Pages: 136-141

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Vascular endothelial cells and eosinophil infiltration in allergic rhinitis2007

    • Author(s)
      Matsune S.
    • Journal Title

      Clinical and Experimental Allergy Reviews 7

      Pages: 5-10

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] IL-4 and TNF-α increased the secretion of eotaxin from cultured fibroblasts of nasal polyps with eosinophil infiltration2007

    • Author(s)
      K.Yoshifuku
    • Journal Title

      Rhinology 45

      Pages: 235-241

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Intranasal immunization with Phosphorylcholine induces antigen specific mucosal and systemic immune responses in mice2007

    • Author(s)
      Norimitsu Tanaka
    • Journal Title

      Vaccine 25(14)

      Pages: 2680-2687

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] TNF-α upregulates VCAM-1 and NF-κB in fibroblasts from nasal polyps2007

    • Author(s)
      Ohori J.
    • Journal Title

      Auris Nasus Larynx 34

      Pages: 177-183

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Application of mucosal immunity to upper respiratory diseases2007

    • Author(s)
      Kurono, Y
    • Journal Title

      Igaku no ayumi Vol.221(11)

      Pages: 887-890

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Application of nasal vaccine for infectious and allergic diseases in upper respiratory tract2007

    • Author(s)
      Kurono, Y
    • Journal Title

      OTO-RHINO-LARYNGOLOGY,TOKYO Vol.50(3)

      Pages: 136-141

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Vascular endothelial cells and eosinophil infiltration in allergic rhinitis2007

    • Author(s)
      Matsune, S
    • Journal Title

      Clinical and experimental Allergy Reviewa Vol.7

      Pages: 5-10

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] IL-4 and TNF-a increased the secretion of eotaxin from cultured fibroblasts of nasal polyps with eosinophil infiltration2007

    • Author(s)
      Yoshifuku, K
    • Journal Title

      Rhinology Vol.45

      Pages: 235-241

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Intranasal immunization with Phosphorylcholine induces antigen specific mucosal and systemic immune responses in mice2007

    • Author(s)
      Tanaka, N
    • Journal Title

      Vaccine Vol.25(14)

      Pages: 2680-2687

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] TNF-a upregulates VCAM-1 and NF-KB in fibroblasts from nasal polyps2007

    • Author(s)
      Ohori, J
    • Journal Title

      Auris Nasus Larynx Vol.34

      Pages: 177-183

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Mucosal vaccine against nontypeable Haemophilus influenzae2007

    • Author(s)
      Kurono, Y
    • Journal Title

      Expeimental Medicne(Yodosha) Vol.25(20)

      Pages: 43-47

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] 上気道粘膜免疫と経鼻ワクチン2006

    • Author(s)
      黒野 祐一
    • Journal Title

      日耳鼻専門医通信 86

      Pages: 16-17

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 副鼻腔感染とアレルギー2006

    • Author(s)
      黒野 祐一
    • Journal Title

      呼吸 25(10)

      Pages: 927-932

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Uniqueness of lymphoid chemokine requirement for the initiation and maturation of nasopharynx-associated lymphoid tissue organogenesis2006

    • Author(s)
      Fukuyama S.
    • Journal Title

      J.Immunol 177(7)

      Pages: 4276-4280

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] 予防ワクチンの可能性について2006

    • Author(s)
      黒野 祐一
    • Journal Title

      小児科臨床 59(12)

      Pages: 2524-2528

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Mucosal ifmmunology in upper respiratory tract and intra-nasal vaccine2006

    • Author(s)
      Kurono, Y
    • Journal Title

      Nippon Jibiinkoka Senmoni Tushin Vol.86

      Pages: 16-17

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The impact of allergy on paranasal sinusitis2006

    • Author(s)
      Kurono, Y
    • Journal Title

      Respiration Research Foundation Vol.25(10)

      Pages: 927-932

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Uniqueness of lymphoid chemokine requirement for the initiation and maturation of nasopharynx-associated lymphoid tissue organogenesis2006

    • Author(s)
      Fukuyama, S
    • Journal Title

      J. Immunol Vol.177(7)

      Pages: 4276-4280

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Application of mucosal vaccine to prevent upper respiratory infections2006

    • Author(s)
      Kurono, Y
    • Journal Title

      Japanese Journal of Pediatrics Vol.59 (12)

      Pages: 2524-2528

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] TNF-α and endotoxin increase hypoxia-induced VEGF production by cultured human nasal fibroblasts in synergistic fashion2005

    • Author(s)
      Dung Sun
    • Journal Title

      Auris Nasus Larynx 32(3)

      Pages: 243-249

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] 特集・反復性中耳炎「ワクチン療法の現況と可能性」2005

    • Author(s)
      黒野 祐一
    • Journal Title

      MB ENT 56

      Pages: 71-76

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 上気道粘膜免疫機構とアレルギー予防・治療戦略2005

    • Author(s)
      黒野 祐一
    • Journal Title

      アレルギー科 20(5)

      Pages: 473-477

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Inhibition of vascular endothelial growth factor by macrolides in cultured fibroblasts from nasal polyps2005

    • Author(s)
      Matsune S.
    • Journal Title

      Laryngoscope 115(11)

      Pages: 1953-1956

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] TNF-a and endotoxin increase hypoxia-induced VEGF production by cultured human nasal fibroblasts in synergistic fashion2005

    • Author(s)
      Dung, Sun
    • Journal Title

      Auris Nasus Larynx Vol.32(3)

      Pages: 243-249

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effectiveness of mucosal vaccine for recurrent atitis media2005

    • Author(s)
      kurono, Y
    • Journal Title

      MB ENT Vol.56

      Pages: 71-76

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Application of mucosal immune system for the prevention and treatment of allergic rhinitis2005

    • Author(s)
      Kurono, Y
    • Journal Title

      Allergology Vol.20(5)

      Pages: 473-477

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Inhibition of vascular endothelial growth factor by macrolides in cultured fibroblasts from nasal polyps2005

    • Author(s)
      Matsune, S
    • Journal Title

      Laryngoscope Vol.115(11)

      Pages: 1953-1956

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 舌下免疫によるPhosphorylcholine特異的粘膜免疫応答2008

    • Author(s)
      田中 紀充
    • 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
      2008-02-21
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Phosphorylcholine specific immune responses induced by sublingual immunization2008

    • Author(s)
      Tanaka, N
    • Organizer
      26th Japan Society of Immunology in Otolaryngology.
    • Place of Presentation
      Osaka
    • Year and Date
      2008-02-21
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Intranasal immunization with Phosphorylcholine reduced Typel allergic responses in mice2007

    • Author(s)
      Kurono Yuichi
    • Organizer
      9th International Symposium on Recent Advances in Otitis Media
    • Place of Presentation
      Florida
    • Year and Date
      20070703-07
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Nasal vaccination with new DNA aduvants elicit long lasting immunity mediated by both Th 1-and Th2-type cvtokine and NALT dentritic cells2007

    • Author(s)
      Fukuiwa Tatsuya
    • Organizer
      9th International Symposium on Recent Advances in Otitis Media
    • Place of Presentation
      Florida
    • Year and Date
      20070603-07
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Intranasal immunization with Phosphorylcholine enhanced the clearance of S.pneumonae and Nontypeable H.influenzae from the nasal cavity2007

    • Author(s)
      Tanaka Norimitsu
    • Organizer
      9th International Symposium on Recent Advances in Otitis Media
    • Place of Presentation
      Florida
    • Year and Date
      20070603-07
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Intranasal Immunization with Phosphorylcholine Reduced Type I Allergic Responses in Mice2007

    • Author(s)
      Kurono, Y
    • Organizer
      9th International Symposium on Recent Advances in Otitis Media
    • Place of Presentation
      Florida
    • Year and Date
      20070603-07
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Nasal vaccination with new DNA aduvants elicit long lasting immunity mediated by both Th 1- and Th2-type cytokine and NALT dentritic cells2007

    • Author(s)
      Fukuiwa, T
    • Organizer
      9th International Symposium on Recent Advances in Otitis Media
    • Place of Presentation
      Florida
    • Year and Date
      20070603-07
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] InIntranasal immunization with Phosphorylcholine enhanced the clearance of S. pneumonae and Nontypeable H. influenzae from the nasal cavity2007

    • Author(s)
      Tanaka, N
    • Organizer
      9th International Symposium on Advances in Otitis Media
    • Place of Presentation
      Florida
    • Year and Date
      20070603-07
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] マウス鼻粘膜B1細胞の特異性2007

    • Author(s)
      田中 紀充
    • Organizer
      第25回日本耳鼻咽喉科免疫アレルギー学会
    • Place of Presentation
      甲府
    • Year and Date
      20070329-31
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] アレルギー性鼻炎マウスモデルにおけるPhosphorylcholineのアレルギー抑制作用についての検討2007

    • Author(s)
      宮下 圭一
    • Organizer
      第25回日本耳鼻咽喉科免疫アレルギー学会
    • Place of Presentation
      甲府
    • Year and Date
      20070329-31
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] The Uniqueness of murine nasal B1 cells2007

    • Author(s)
      Tanaka, N
    • Organizer
      25th Japan Society of Immunology in Otolaryngology
    • Place of Presentation
      Koufu
    • Year and Date
      20070329-31
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Phosphorylcholine suppressed the allergic rhinitis in mice2007

    • Author(s)
      Miyashita, K
    • Organizer
      25th Japan Society of Immunology in Otolaryngology
    • Place of Presentation
      Koufu
    • Year and Date
      20070329-31
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Phosphoylcholine経鼻免疫による鼻腔内細菌クリアランスの変化2007

    • Author(s)
      田中 紀充
    • Organizer
      第19回気道病態シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2007-02-24
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] The clearance of bacteria from the nasal cavity was enhanced by intranasal immunization with Phosphorylcholine2007

    • Author(s)
      Tanaka, N
    • Organizer
      The 19th Symposium of Respiratory Diseases
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-02-24
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Intranasal immunization with Phosphorylcholine induced protective immune responses against S.pneumoniae and nontypeable H.influenzae2006

    • Author(s)
      N.Tanaka
    • Organizer
      Thellth Asian Research Symposium in Rhinology
    • Place of Presentation
      Seoul,Korea
    • Year and Date
      20061130-1202
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Intranasal immunization with Phosphorylcholine induced protective immune responses against S. pneumoniae and nontypeable H. influenzae2006

    • Author(s)
      Tanaka, N
    • Organizer
      The 11th Asian Research Symposium in Rhinology
    • Place of Presentation
      Seoul Korea
    • Year and Date
      20061130-1202
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] アレルギー性鼻炎マウスモテ"ルにおけるPhosphorylcholine前投与のアレルギー抑制効果の検討2006

    • Author(s)
      田中 紀充
    • Organizer
      第56回日本アレルギー学会秋季学術大会
    • Place of Presentation
      東京
    • Year and Date
      20061102-04
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] The immune responses against Phosphorylcholine suressed the allergic rhinitis mouse model2006

    • Author(s)
      Tanaka, N
    • Organizer
      The 56th Autumn Meeting of Japanese Society of Allergology
    • Place of Presentation
      Tokyo
    • Year and Date
      20061102-04
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Applicatiion of mucosal vaccine to inhibit IgE production as preserving IgA immune responses2006

    • Author(s)
      Kurono, Y
    • Organizer
      ERS & ISIAN 2006
    • Place of Presentation
      Tampere. Finland
    • Year and Date
      20060611-15
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] The role of nasal B1 cells on Phosphorylcholine specific mucosal immune responses2006

    • Author(s)
      Tanaka, N
    • Organizer
      24th Japan Society of Immunology in Otolaryngology
    • Place of Presentation
      Mie
    • Year and Date
      20060502-04
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Mucosal adjuvants to inhibit IgE production as preserving IgE immune responses2006

    • Author(s)
      Y.Kurono
    • Organizer
      Thellth Korea-Japan
    • Place of Presentation
      Busan Korea
    • Year and Date
      20060406-08
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Mucosal adjuvants to inhibit IgE production as preserving IgE immune responses2006

    • Author(s)
      Kurono, Y
    • Organizer
      The 11th Korea-Japan
    • Place of Presentation
      Busan
    • Year and Date
      20060406-08
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Dentritic cell(DC)-targeting nasal adjuvant elicits prolonged mucosal and systemic immune responses2006

    • Author(s)
      Fukuiwa, T
    • Organizer
      24th Japan Society of Immunology in Otolaryngology
    • Place of Presentation
      Mie
    • Year and Date
      20060302-0604
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 記憶型樹状細胞を介した長期持続性粘膜免疫を誘導する経鼻粘膜アジュバントについて2006

    • Author(s)
      福岩 達哉
    • Organizer
      第24回日本耳鼻咽喉科免疫アレルギー学会
    • Place of Presentation
      三重
    • Year and Date
      20060302-04
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Phosphorylcholine特異的粘膜免疫応答における鼻粘膜B1細胞の役割2006

    • Author(s)
      田中 紀充
    • Organizer
      第24回日本耳鼻咽喉科免疫アレルギー学会
    • Place of Presentation
      三重
    • Year and Date
      20060302-04
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Applicatiion of mucosal vaccine to inhibit IgE production as preserving IgA immune responses2006

    • Author(s)
      Y.Kurono
    • Organizer
      ERS & ISIAN 2006
    • Place of Presentation
      Tampere.Finland
    • Year and Date
      20060211-15
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Immune responses against Phosphorylcholine and it's application for mucosal vaccine2005

    • Author(s)
      Y.Kurono
    • Organizer
      XVIII IFOS WORLD CONGRESS
    • Place of Presentation
      Rome.Italy
    • Year and Date
      20050125-30
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 実験医学「インフルエンザ菌感染と粘膜ワクチン」2007

    • Author(s)
      黒野 祐一
    • Total Pages
      43-47
    • Publisher
      羊土社
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2010-02-04  

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