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Development of mucosal vaccines for prevention of prevention of respiratory infectious diseases

Research Project

Project/Area Number 14370095
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionNagoya City University

Principal Investigator

TOCHIKUBO Kunio  Nagoya City University, Graduate School of Medical Sciences, Professor and Chair, 大学院・医学研究科, 教授 (30079991)

Co-Investigator(Kenkyū-buntansha) ISAKA Masanori  Nagoya City University, Graduate School of Medical Sciences, Research Associate, 大学院・医学研究科, 助手 (40336673)
TANIGUCHI Tooru  Nagoya City University, Graduate School of Medical Sciences, Assistant Professor, 大学院・医学研究科, 講師 (00285199)
YASUDA Yoko  Nagoya City University, Graduate School of Medical Sciences, Associate Professor, 大学院・医学研究科, 助教授 (70080009)
OHKUMA Kunio  The Chem-Sero-Therapeutic Research Institute, First Production Department, Manager, 第一製造部, 部長
GOTO Norihisa  National Institute of Infectious Diseases, Department of Safety Research on Blood and Biological Products, Chief, 血液・安全性研究部, 室長 (10100108)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥3,700,000 (Direct Cost: ¥3,700,000)
KeywordsRecombinant / Mucosal adjuvant / Intranasal administration / Mucosal vaccine / Influenza HA vaccine / Capsular polysaccharide vaccine of Streptococcus pneumoniae / Respiratory infectious diseases / 組換えコレラ毒素Bサブユキット / 粘膜アジュバント
Research Abstract

Recombinant cholera toxin B subunit (rCTB) which is produced by Bacillus brevis carrying pNU212-CTB acts as a mucosal adjuvant and induces constantly protective levels of diphtheria and tetanus toxin-neutralizing antibodies and high levels of anti-hepatitis B vaccine serum IgG antibodies when each vaccine is intranasally co-administered with rCTB in mice. On the basis of these results adjuvanticity of rCTB was investigated on influenza hemagglutinin (HA) vaccine and capsular polysaccharide (PS) vaccine of Sreptococus pneumoniae. [1]HA vaccines were prepared from influenza viruses A/New Caledonia (NC)/20/99 (H1N1) and B/Johannesburg (JB)/5/99, and mice were intranasally immunized with 1μg of each HA vaccine in the presence and absence of rCTB on days 0, 14.21 and 28, and sacrificed on day 35. The presence of rCTB showed significantly high levels of A/NCHA vaccine-and B/JB HA vaccine-specific serum ELISA IgG antibody titers and hemagglutination inhibition (HI) antibody titers and mucosal IgA antibody responses in the lungs and the nasal cavities. [2]Mice immunized intranasally with A/NCHA vaccine with and without rCTB were intranasally infected with mouse-adapted influenza virus A/Aichi/88/02 (H1N1). All mice receiving HA with rCTB were completely protected from infection, but 3 of 8 mice receiving HA alone died within 4 days and all nonimmunized mice died within 6 days. [3]Mice were intranasally immunized with rCTB-conjugated PS vaccine with and without rCTB based on the above conditions. Serum PS-specific IgG, IgA and IgM antibody titers elevated irrespective of rCTB and mucosal PS-specific IgA antibody titers in the lungs werre significantly high in the presence of rCTB, suggesting the possibility of rCTB-conjugated PS vaccine.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Yasuda Y, Yasuda Y, Tochikubo K, Tsuji T, Morita A.: "Development of a new protein transduction system by fusing N-terminal peptide of partial cholera toxin B subunit"Nagoya Medical Journal. Vol.46,No.1-2. 17-26 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Isaka M, Yasuda Y, Taniguchi T, Kozuka S, Matano K, Maeyama J, Morokuma K, Ohkuma K, Goto N, Tochikubo K: "Mucosal and systemic antibody responses against an acellular pertussis vaccine in mice after intranasal co-administration with recombinant cholera toxin B subunit as an adjuvant"Vaccine. Vol.21,No.11-12. 1165-1173 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuda Y, Isaka M, Taniguchi T, Zhao Y, Matano K, Matsui H, Morokuma K, Maeyama J, Ohkuma K, Goto N, Tochikubo K: "Frequent nasal administrations of recombinant cholera toxin B subunit (rCTB)-containing tetanus and diphtheria toxoid vaccines induced antigen-specific serum and mucosal immune responses in the presence of anti-rCTB antibodies"Vaccine. Vol.21,No.21-22. 2954-2963 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 趙 艶秋: "組換えコレラ毒素Bサブユニットを粘膜アジュバントとしたインフルエンザ赤血球凝集素(hemagglutinin, HA)ワクチンのマウスへの経鼻免疫(学位論文:指導 杤久保邦夫)"名古屋市立大学医学会雑誌. Vol.54,No.4. 135-153 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Isaka M, Komiya T, Takahashi M, Yasuda Y, Taniguchi T, Zhao Y, Matano K, Matsui H, Maeyama J, Morokuma K, Ohkuma K, Goto N, Tochikubo K: "Recombinant cholera toxin B subunit (rCTB) as a mucosal adjuvant enhances induction of diphtheria and tetanus antitoxin antibodies in mice by intranasal administration with diphtheria-pertussis-tetanus (DPT) combination vaccine"Vaccine. (accepted).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Maeyama J, Isaka M, Yasuda Y, Matano K, Morokuma K, Ohkuma K, Tochikubo K, Yammamoto S, Goto N: "Effects of recombinant cholera toxin B subunit (rCTB) on cellular immune responses: Enhancement of delayed-type hypersensitivity following intranasal co-administration of Mycobacterium bovis-BCG with rCTB"Microbiology and Immunology. (accepted).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuda Y, Yasuda Y, Tochikubo K et al.: "Development of a new protein transduction system by fusing N-terminal peptide of partial cholera toxin B subunit"Nagoya Medical Journal. 46(1/2). 17-26 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Isaka M, Yasuda Y, Taniguchi T et al.: "Mucosal and systemic antibody responese against an acellular pertussis vaccine in mice after intranasal co-administration with recombinant cholera toxin B subunit as an adjuvant"Vaccine. 21(11/12). 1165-1173 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuda Y, Isaka M, Taniguchi T et al.: "Frequent nasal administrations of recombinant cholera toxin B subunit (rCTB)-containing tetanus and diphtheria toxoid vaccines induced antigen-specific serum and mucosal immune responses in the presence of anti-rCTB antibodies"Vaccine. 21(21/22). 2954-2963 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Zhao Y: "Intranasal immunization in mice with influenza hemagglutinin (HA) vaccine and recombinant cholera toxin B subunit as a mucosal adjuvant (in Japanese)"The Journal of the Nagoya City University Medical Association. 54(4). 135-153 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Isaka M, Komiya T, Takahashi M et al.: "Recombinant cholera toxin B subunit (rCTB) as a mucosal adjuvant enhances induction of diphtheria and tetanus antitoxin antibodies in mice by intranasal administration with diphtheria-pertussis-tetanus (DPT) combination vaccine"Vaccine. (accepted).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Maeyama J, Isaka M, Yasuda Y et al.: "Effects of recombinant cholera toxin B subunit (rCTB) on cellular immune responses : Enhancement of delayed-type hypersensitiviety following intranasal co-administration of Mycobacterium bovis-BCG with rCTB"Microbiology and Immunology. (accepted).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuda Y, Yasuda Y, Tochikubo K, Tsuji T, Morita A.: "Development of a new protein transduction system by fusing N-terminal peptide of partial cholera toxin B subunit"Nagoya Medical Journal. Vol.46, No.1-2. 17-26 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Isaka M, Yasuda Y, Taniguchi T, Kozuka S, Matano K, Maeyama J, Morokuma K, Ohkuma K, Goto N, Tochikubo K: "Mucosal and systemic antibody responses against an acellular pertussis vaccine in mice after intranasal co-administration with recombinant cholera toxin B subunit as an adjuvant"Vaccine. Vol.21, No.11-12. 1165-1173 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yasuda Y, Isaka M, Taniguchi T, Zhao Y, Matano K, Matsui H, Morokuma K, Maeyama J, Ohkuma K, Goto N, Tochikubo K: "Frequent nasal administrations of recombinant cholera toxin B subunit(rCTB)-containing tetanus and diphtheria toxoid vaccines induced antigen-specific serum and mucosal immune responses in the presence of anti-rCTB antibodies"Vaccine. Vol.21, No.21-22. 2954-2963 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 趙 艶秋: "組換えコレラ毒素Bサブユニットを粘膜アジュバントとしたインフルエンザ赤血球凝集素(hemagglutinin, HA)ワクチンのマウスへの経鼻免疫(学位論文:指導 析久保邦夫)"名古屋市立大学医学会雑誌. Vol.54, No.4. 135-153 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Isaka M, Komiya T, Takahashi M, Yasuda Y, Taniguchi T, Zhao Y, Matano K, Matsui H, Maeyama J, Morokuma K, Ohkuma K, Goto N, Tochikubo K: "Recombinant cholera toxin B subunit(rCTB) as a mucosal adjuvant enhances induction of diphtheria and tetanus antitoxin antibodies in mice by intranasal administration with diphtheria-pertussis-tetanus(DPT) combination vaccine"Vaccine. (accepted).

    • Related Report
      2003 Annual Research Report
  • [Publications] Miyashita M, Joh T, Watanabe K, Todoroki I, Seno K, Ohara H, Nomura T, Miyata M, Kasugai K, Tochikubo K, Itoh M, Nitta M: "Immune responses in mice to intranasal and intracutaneous administration of a DNA vaccine encoding Helicobacter pylori-catalase"Vaccine. Vol.20, No.17-18. 2336-2342 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Maeyama J, Isaka M, Yasuda Y, Matano K, Taniguchi T, Morokuma K, Ohkuma K, Tochikubo K, Goto N: "Effects of recombinant cholera toxin B subunit on IL-1β production by macrophages in vitro"Microbiology and Immunology. Vol.46,No.9. 593-599 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 谷口暢, 本田武司: "感染症の変貌とワクチン開発(総説:特集 最近のワクチン)"最新医学. 第57巻,第9号. 1889-1893 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Isaka M, Yasuda Y, Taniguchi T, Kozuka S, Matano K, Maeyama J, Morokuma K, Ohkuma K, Goto N, Tochikubo K: "Mucosal and systemic antibody responses against an acellular pertussis vaccine in mice after intranasal co-administration with recombinant cholera toxin B subunit as an adjuvant"Vaccine. Vol.21,No.11-12. 1165-1173 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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