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The mucosal immune system of the upper respiratory tract and development of nasal vaccine for upper respiratory tract infection

Research Project

Project/Area Number 10307040
Research Category

Grant-in-Aid for Scientific Research (A)

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

Principal Investigator

MOGI Goro  Oita Medical University, vice president, 副学長 (20035190)

Co-Investigator(Kenkyū-buntansha) OKAMOTO Yoshitaka  Yamanashi Medical University, Professor, 医学部, 教授 (40169157)
KIYONO Hiroshi  Osaka University, Professor, 微生物病研究所, 教授 (10271032)
SUZUKI Masashi  Oita Medical University, Professor, 医学部, 教授 (60211314)
KURONO Yuichi  Kagoshima University, Professor, 医学部, 教授 (80153427)
KAWAUCHI Hideyuki  Shimane Medical University, Professor, 医学部, 教授 (50161279)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥23,500,000 (Direct Cost: ¥23,500,000)
Fiscal Year 1999: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1998: ¥17,500,000 (Direct Cost: ¥17,500,000)
KeywordsNALT / Intranasal immunization / vaccine / Mucosal immune system / Haemophilus influenzae / Streptococcus pneumoniae / IgA / RS virue / 鼻粘膜 / 中耳粘膜 / マウス / CD4^+T細胞 / P6
Research Abstract

A. Experimental Study
1. Mucosal immune function of NALT
Selected Th2-type cytokine expressing CD4ィイD1+ィエD1 T cells were induced in intranasally-immunized mice NALT. M cells were observed in rat NALT. Antigen-specific IgA antibody titers in nasal wash were increased after immunization of mice without Peyers patches. These findings strongly suggest that NALT functions as an inductive site of nasal IgA response.
2. Induction of antigen-specific IgA by intranasal immunization in mice
The greatest antigen-specific IgA response was observed in mice intranasally immunized with P6, an antigen of nontypeable Haemophilus influenzae (NTHi) that is a major pathogen of otitis media. This response was induced not only in the nose but also in the middle ear. In mice immunized intranasally with fimbrial protein of Porhyromonas gingivalis, a causative agent for destructive chronic inflammation in the periodontium, antigen-specific IgA antibodies were induced in nasal mucosae and salivary glands. Thus, int … More ranasal vaccination may be the most effective means for induction of antigen-specific mucosal immune responses in the upper respiratory tract.
3. Prevention of virus infection by intranasal immunization
Inflammatory reaction was mild in mice with Rs virus injected into the nasal cavity after intranasal immunization with vaccina virus. Nasal administrations of Fab antibodies against RS virus restricted viral proliferation and decreased the inflammatory reaction. These findings also lead us to the conclusion that intranasal immunization is useful for prevention of virus infection in the upper respiratory tract.
B. Clinical Study
1. The number of P6-specific IgA-secreting cells was greater in the tonsils showing no NTHi than in the samples with the bacteria. The number of P6-specific IgA-secreting cells in tonsils was correlated with IgA antibody titers in nasal secretions. Intratonsillar as well as intranasal immunization with OK-432 increased the number of M-protein-specific antibody-secreting cells in tonsils and antigen-specific antibody activity in nasal secretions. CD4ィイD1+ィエD1 T cells produced Th2-and Th1-type cytokines in response to stimulation with P6 or M-protein. These findings suggest that the palatine tonsils are important as an effector site.
2. Adenoid involvement in otitis media with effusion (OME)
NTHi was cultured more frequently in adenoids from patients with OME than in patients without OME. A tendency toward increased stratified squamous epithelium was apparent, and reticular epithelium extension was greater in patients with OME. The data suggest that adenoid inflammation is implicated in the pathogenesis of OME.
3. Antigen specific-antibody responses in otitis-prone children
Otitis-prone children exhibited reduced IgGィイD22ィエD2 responses to S. pneumoniae and IgG responses to NTHi. Otitis proneness appears to be related to numerous immunological deficiencies. Less

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Suzuki M., Mogi G. et al.: "Immune responses to Haemophilus influenzae before and after tonsillectomy"Recent Advances in Otitis Media ed. by DJ Lim et al.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] kodama S., Suzuki m., mogi G. et al.: "Induction of specific immunoglobulin A and Th2 immune responses to P6 outer memarane protein of nontypeable Haemophilus influenzae in middle ear mucos a by intranasal immunization"Infection and immunity. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kurono Y., Suzuki M., Mogi G., Kiyono H., et al.: "nasal immunization induces Haemophilus influenzae-specific Th1 and Th2 responses with mucosal IgA and systemic IgG antibodies for protective immunity"TheJournal of Infectious Diseases. 180. 122-132 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kurono Y., Suzuki M., Mogi G., Kiyono H., et al.: "Effcts of intranasal immunization on protective immunity against otitis media"International Journal of Pediatric Otorthinolaryngology. 49(1). 277-229 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hotomi M., Yamanaka N. et al.: "Antibody responses to the outer membrane protein P6 of non-typeable Haemophilus influenzae and pneumococal capsular polysaccharides in otitis prone children"Acta Otolaryngol (Stockh). 119. 703-707 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yanagita M., Kiyono H., et al.: "Nasopharyngeal-associated lymphoreticular tissues (NALT) immunity"The Journal of Immunology. 162. 3559-3565 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawaguchi H. et al.: "T-cell mucosal immunity in the nasopharynx, In "New Frontiers in Immunobiology""ed by JE Veldman, D Passali, DJ Lim Kugler Publications, The Hague, The Netherlandas. 65-71 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kurono Y., DJ Lim, Mogi G.: "Middle ear and eustachian tube. In 2Mucosal immunology""de by PL Ogra, J Mestecky, JR McGhee et al.academic Press. 1305-1311, 1628 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suzuki M., Kodama S., Sakamoto N., Mogi G: "Immune responses to Haemophilus influenzae before and after tonsillectomy"Proceedings of 7th International Symposium on Recent Advances in Otitis Media. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kodama S., Suenaga S., Hirano T., Suzuki M., Mogi G.: "lnduction of specific immunTh2 immune responses to P6 outer membrane protein of nontypeable Haemophilus influenzae in middle ear mucosa by intranasal immunization"Infection and Immunity. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kurono Y., Yamamoto M., Fujihashi K, Kodama S., Suzuki M., Mogi G., McGhee J.R., Kiyono H.: "Nasal immunization induces Haemophilus influenzae-specific Th1 and Th2 responses with mucosal IgA and systemic IgG antibodies for protective immunity"J Infect Dis.. 180(1). 122-132 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kurono Y., Suzuki M., Mogi G., Fujihashi K, McGhee J.R., Kiyono H: "Effects of intranasal immunization on protective immunity against otitis media"Int J Pediatric Otorhinolaryngology. 49 Suppl. 1. 227-229 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hotomi M., Yamanaka N., Saito T., Shimada J., Suzumoto M., Suetake M., Faden H.: "Antibody responses to the outer membrane protein P6 of non-typeable Haemophilus influenzae and pneumococcal capsular polysacharides in otitis-prone children"Acta Otolaryngol (Stockh). 119. 703-707 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yanagita M., Hiroi T., Kitagaki N., Hamada S., Ito H., Shimauchi H., Murakami S., Okada H., Kiyono H.: "Nasopharyngeal-associated lymphoreticular tissue (NALT) immunity: fimbriae-specific Th1 and Th2 cell-regulated IgA responses for the inhibition of bacterial attachment to epithelial cells and subsequent inflammatory cytokine production"J Immunol. 162. 3559-3565 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawauchi H., Sano K., Shiba H., Sano C., Yamada T., Suzuki T.: "T-cell mucosal immunity in the nasopharynx"New Frontiers in Immunobiology, (ed. By J.E. Veldman, D.Passali and D.J.Lim), 65-71, Kugler Publications, The Hague, The Netherlands. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kurono Y., LimD.J., Mogi G.: "Middle ear and eustachian tube"Mucosal Immunology, (ed. By P.L Ogra, J.Mestecky, M.E.Lamm, W.Strober, J.R.MaGhee, J.Bienenstock), 1305-1311, Academic Press. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suzuki M.,Mogi G.et al.: "Immune reponses to Haemophilus influenzae before and after tonsillectomy"Recent Advances in Otitis Media ed.by DJ Lim et al.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Kodama S.,Suzuki M.,Mogi G.et al.: "Induction of specific immunoglobulin A and Th2 immune responses to P6 outer membrane protein of nonty.peable Haemo philus influenzae in middle ear mucos a by intranasal immunization"Infection and immunity. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Kurono Y.,Suzuki M.,Mogi G.,Kiyono H.et al.: "Nasal immunization induces Haemo philus influenzaw-specific Th1 and Th2 responses with mucosal IgA and systemic IgG antib odres for protective"The Journal of Infectious Diseases. 180. 122-132 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kurono Y.,Suzuki M.,Mogi G.,Kiyono H.et al.: "Effects of intranasal immunization on protective immunity against otitis media"International Journal of Pediatric Otorhinolaryngology. 49(1). 227-229 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hotomi M.,Yamanaka N.et al.: "Autibody responses to the outer membrane protein P6 of non-typeable Haemo philus influenzae and pneumococcal capsular polysaccharides in otitis-prone children"Acta Otolaryngol(Stockh). 119. 703-707 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yanagita M.,Kiyono H.,et al.: "Nasopharyngeal-associated lymph oreticular tissues(NALT)immunity"The Journal of Immunology. 3559-3565 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawauchi H.et al.: "T-cell muscosal immunity in the nasopharynx.In "New Frontiers in Immunobiology""ed by JE Veldman,D Passali,DJ Lim Kugler Publications,The Hague,The Netherlandas(in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Kurono Y.,DJ Lim,Mogi G.: "Middle ear and eustachian tube.In "Mucosal Immunology""ed by PL Ogra J Mestecky,JR McGhee et al.Academic Press. (1305-1311)1628 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 黒野祐一・他: "ヒト扁桃の細菌抗原に対する免疫応答." 口腔咽頭科. 10(2). 161-167 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sakamoto N.,Suzuki M.,Mogi G.,et al.: "Immune responses of adenoidal lymphocytes specific to Haemophilus influenzae in the nasopharynx." Laryngoscope. 108. 1036-1041 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Suzuki M.,et al.: "Enhancement of nasal clearance of nontypeable Haemophilus influenzae by oral immunization with outer membrane proteins." Acta Otolarngol(Stockh). in press.

    • Related Report
      1998 Annual Research Report
  • [Publications] Hiroi T.,Kiyono H.,et al.: "Distinctive Th0 and Th1/Th2 type enviroments in murine nasal associated associated lymphoid tisues and nasal passage,respectively." Eur J Immunol. 28. 3346-3353 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Imaoka K.,Kiyono H.,et al.: "Nasal immunization of non-human primates with simian immunodeficiency virus p55gag and cholera toxin adjuvant induces Th1/Th2 help for anti-viral immunity." J immunol. 161. 5952-5958 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hotomi M.,Yamanaka N.,et al.: "Specific mucosal immunity and enhanced nasopharyngeal clearance of nontypeable Haemophilus influenzac after intranasal immunization with outer membrane protein P6 and cholera toxin." Vaccine. 16. 1950-1956 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kurono Y.,et al.: "Application of mucosal vaccine against otitis media.Immuno- and Molecular Biology in ORL-State of the Art." (ed.)Veldman JE.,Passali D.,Lim DJ.,Kugler Publications,The Hague,The Netherlands,in press.,

    • Related Report
      1998 Annual Research Report
  • [Publications] Kurono Y.,et al: "Effects of intranasal immunization on protective immunity against otitis media.Proceedings of the 7th International Congress of Pediatric Otolaryngology." (ed.)Ruben RJ.,Elsevier Science,Amsterdam,The Netherlands,in press.,

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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