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Mucosal Vaccines : Vectors and Adjuvants for Novel Th1 and Th2 cells

Research Project

Project/Area Number 08044285
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research Field Immunology
Research InstitutionOsaka University

Principal Investigator

KIYONO Hiroshi  Osaka Univ., RIMD., Professor, 微生物病研究所, 教授 (10271032)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Masafumi  Univ.of Alabama, Immunobiology Vaccine Center, Res.Instractor, バーミングハム校・免疫ワクチンセンター, 助手
FUJIHASHI Kuhtaro  Univ.of Alabama, Immunobiology Vaccine Center, Assistant Professor, バーミングハム校・免疫ワクチンセンター, 助教授
MCGHEE Jerry  Univ.of Alabama, Immunobiology Vaccine Center, Professor, バーミングハム校・免疫ワクチンセンター, 教授
HIROI Takachika  Osaka Univ., RIMD., Instractor, 微生物病研究所, 助手 (80228824)
TAKAHASHI Ichiro  Osaka Univ., RIMD., Assistant Professor, 微生物病研究所, 講師 (20206791)
島岡 要  大阪大学, 医学部, 助手 (40281133)
VANCOTT John  アラバマ大学, バーミングハム校免疫ワクチンセンター, 主任 研究員
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1997: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1996: ¥3,700,000 (Direct Cost: ¥3,700,000)
KeywordsMucosal Immune System / Mucosal Vaccine / Mucosal Intranet / IgA / Mucosal Modulator / Mucosal Adjuvant / Mucosal Th1 / Mucosal Th2 / 無毒化リコンビナントサルモネラ菌 / 経口免疫 / IFN-γ遺伝子欠損マウス / Th1型 / Th2型応答 / レベル2 Th2型 / 経口ワクチン
Research Abstract

A major goal of this Internationa1 Collaborative Research Project was to investigate molecular and cellular mechanisms of mucosal modulators including choelera toxin (CT), Labile enterotoxin (LT) and IL-12 for the induction of antigen-specific Th1 and Th2 cells in the IgA inductive and effector compartments. Our findings demonstrated that mucosal immunization of vaccine protein antigen and CT as mucosal adjuvant resulted in the dominant Th2 type response which lead to the generation of antigen-specific IgG and IgA antibodies in both systemic and mucopsal compartments. In contrast to CT,co-administered LT as a mucosal modulator resulted in the generation of both antigen-specific Th1 and Th2 cells. Further, it was shown that mucosally-administered IL-12 shifts a dominant Th2 to Th1 type response in vivo. These findings suggested that using the different mucosal modulators, one can mimic outcome of mucosal and systemic Th1/Th2 and B cell responses. These interesting and important findings which will contribute for the development of Mucosal Vaccine were generated by the collaborative effort between Osaka University and the University of Alabama at Birmingham (UAB). Through this project, 28 original articles and 15 reviews were published in high quality journals such as J.Exp.Med., Proc.Natl.Acad.Sci.USA., J.Immunol., Gastroenterology and etc.
On behalf of Osaka and UAB Mucosal Immunology Laboratories, I would like to express our appreciation for this kind support to establish new concept for Mucosal immunology Trans-Pacific Research System.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (51 results)

All Other

All Publications (51 results)

  • [Publications] Kiyono,H.et al: "Molecular and cellular mechanisms for periodontal diseases:role of Th1 and Th2 type cytokines ininduction of mucosal inflamation." J.Peridontal.Res.32. 115-119 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kiyono,H.et al: "Functional γδ T lymphocyte defect associated with human immunodeficiency virus infection." Mol.Med.3. 60-71 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kiyono,H.et al: "Oral immunization of PspA elicits protective humoral immunity from Streptococcus pneumoniae infection." Infect.Immun.65. 640-644 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kiyono,H.et al: "CD4^+ T Cell population mediates development of inflammatory bowel disease in T cell receptor α-chain dificient mice." Gastoroenterology. 112. 1876-1886 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kiyono,H.et al: "Mucosal IL-2 switches type 2 help to an oral vaccine containing cholera toxin as adjuvant to type 1 help with secretory IgA responses." J.Exp.Med.185. 415-427 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kiyono,H.et al: "Oral immunization with simian immunodeficiency virus(SIV)p55 gag and cholera toxin (CT)elicits both mucosal IgA and systemic IgG immune response in non-human primates." J.Immunol.158. 5321-5329 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kiyono,H.et al: "Respiratory immunity to a replication-deficient adenovirus 5(Ade5)vector and to its transgene:segregation of T helper cell responses." J.Immunol.685-693 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kiyono,H.et al: "Mutants in the putative ADP-ribosy transferase cleft of cholera toxinlack diarrhoeagenisity but retain adjuvanticity." J.Exp.Med.185. 1203-1210 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kiyono,H.et al: "A nontoxic mutant of cholera toxin elicits Th2-type responses for enhanced mucosal immunity." Proc.Natl.Acad.Sci.94. 5267-5272 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kiyono,H.et al: "Cholera toxin reverses the T cell dysfunction in spontaneously hypertensive rats via the stimulation of Th2-type responses." Am.J.Physiol. 273. 1509-1518 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kiyono,H.et al: "Bacterial invasion induces interleukin-7(IL-7)receptor expression in colonic epitjelial cell line." Eur.J.Immunol.27. 3456-3460 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kiyono,H.et al: "A novel alkaline phosphatase-based isolation method allows characterization of intraepithelial lymphocytes from villi tip and crypt regions of murine small intestine." Biochem.Biophy.Res.Commun.241. 797-802 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kiyono,H.et al: "An interleukin 7 internet for intestinal intraepithelial γδ T cell development knockout of ligand or receptor reveal deifferences in the immunodeficient state." Eur.J.Immunol.27. 2123-2132 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takahashi, I., Kiyono, H., and Hamada, H.: "CD4^+T Cell population mediates development of inflamatory bowel disease in T cell receptor alpha-chain deficient mice." Gastoroenterology. 112. 1876-1886 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kubota, M., Miller, C.J., Imaoka, K., Kawabata, K., Fujihashi, K., McGhee, J.R., and Kiyono, H.: "Oral immunization with simian immunodeficiency virus (SIV) p55 gag and cholera toxin (CT) elicits both mucosal IgA and systemic IgG immune responses in non-human primates." J.Immunol.158. 5321-5329 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamamoto, S., Kiyono, H., Yamamoto, M., Imamoka, K., Yamamoto, M., Fujihashi, K., van Ginkel, F.W., Takeda, Y.and McGhee, J.R.: "A nontoxic mutant of cholera toxin elicits Th2-type responses for enhanced mucosal immunity." Proc.Nat1.Acad.Sci.USA. 94. 5267-5272 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamamoto, S., Yamamoto, , M., Kurazono, H., Imamoka, K., Yamamoto, M., Fujihashi, K., McGhee, J.R., Fujihashi, K., Noda, M., Kiyono, H., Takeda, Y., and McGhee, J.R.: "Mutants in the putative ADP-ribosy transferase cleft of cholera toxin lack diarrheagenicity but retain adjuvanticity." J.Exp.Med.185. 1203-1210 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujihashi, K., McGhee, J.R., Yamamoto, M., and Kiyono, H.: "An interleukin 7 internet for intestinal intraepithelial gammadelta T cell development : Knockout of ligand or receptor reveal differences in the immunodeficient state." Eur.J.Immunol.27. 2123-2132 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Marinaro, M., Boyaka, P., Finkelman, F.D., Kiyono, H., Jackson, R.J., Jirillo, E., and McGhee, J.R.: "Mucosal lL-12 switches type 2 help to an oral vaccine containing cholera toxin as adjuvant to type 1 help with secretory IgA responses." J.Exp.Med.185. 415-427 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamamoto, M., McDaniel, L.S., Kawabata, K., Briles, D.E., Jackson, R.J., McGhee, J.R., and Kiyono, H.: "Oral immunization of PspA elicits protective humoral immunity from Streptococcus pneumoniae infection." Infect.Immun.65. 640-644 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] van Ginkel, F.W., Liu.C-G., Simecka, J.W., Frizzell, R.A.., McGhee, J.R., Kiyono, H., and Pascua1, D.W.: "Respiratory immunity to a replication-deficient adenovirus 5 (Ade 5) vector and to its transgene : segregation of T helper cell responses." J.Immunol. 59. 685-693 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamamoto, M., Fujihashi, K., Hiroi, T., McGhee, J.R., Van Dyke, T.E.and Kiyono, H: "Molecular and cellular mechanisms for periodontal diseases : role of Th1 and Th2 type cytokine for the induction of mucosal inflamation." J.Periodontal.Res.32. 115-119 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Wallace, M., Scharko, A.M., Pauge, C.O., Fisch, P., Imaoka, K., Kawabata, S., Fujihashi, K., Kiyono, H., Tanaka, Y., Bloom, B.R.and Malkovsky, M.: "Functional gammadelta T lymphocyte defect associated with human immunodeficiency virus infection." Mol.Med.3. 60-71 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Pascual, D.W., Caste, M., Boyaka, P.N., Kiyono, H., and McGhee, J.R.: "Spontaneously hypertensive rat : Cholera toxin converts suppression to immunity through a Th2 cell-IL-4 pathway." Amer.J.Physiol.273. R1509-R1518 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamada, K., Shimaoka, M., Nagayama, K., Hiroi, T., Kiyono, H., and Honda, T.: "Bacterial invasion induces interleukin-7 (IL-7) receptor expression in colonic epitjelial cell line T84." Eur.J.Immunol.27. 3546-3460 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Bon, E.M., van Ginkel, F,W., Simeka, J.W., Kiyino, H,Robinson, H.L.and McGhee, J.R.: "Mucosal immunization with DNA encoding influenza hemmagglutinin" Vaccine. 15. 811-813 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kiyono, H.et al: "Molecular and cellular mechanisms for periodontal diseasee : role of Th1 and Th2 type cytokines ininduction of mucosal inflamation." J.Peridontal.Res.32. 115-119 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kiyono, H.et al: "Functional _γδ T lymphocyte defect associated with human immunodeficiency virus infection." Mol.Med.3. 60-71 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kiyono, H.et al: "Oral immunization of PspA elicits protective humoral immunity from Streptococcus pneumoniae infection." Infect.Immun.65. 640-644 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kiyono, H.et al: "CD4^+T Cell population mediates development of inflammatory bowel disease in T cell receptor α-chain dificient mice." Gastoroenterology. 112. 1876-1886 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kiyono, H.et al: "Mucosal IL-2 switches type 2 help to an oral vaccine containing cholera toxin as adjuvant to type 1 help with secretory IgA responses." J.Exp.Med.185. 415-427 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kiyono, H.et al: "Oral immunization with simian immunodeficiency virus (SIV) p55 gag and cholera toxin (CT) elicits both mucosal IgA and systemic IgG immune responses in non-human primates." J.Immunol.158. 5321-5329 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kiyono, H.et al: "Respiratory immunity to a replication-deficient adenovirus 5 (Ade5) vector and to its transgene : segregation of T helper cell responses." J.Immunol.685-693 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kiyono, H.et al: "Mutants in the putative ADP-ribosy transferase cleft of cholera toxinlack diarrhoeagenisity but retain adjuvanticity." J.Exp.Med.185. 1203-1210 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kiyono, H.et al: "A nontoxic mutant of cholera toin elicits Th2-type responses for enhanced mucosal immunity." Proc.Natl.Acad.Sci.94. 5267-5272 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kiyono, H.et al: "Cholera toxin reverses the T cell dysfunction in spontaneously hypertensive rats via the stimulation of Th2-type responses." Am.J.Physiol.273. 1509-1518 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kiyono, H.et al: "Bacterial invasion induces interleukin-7 (IL-7) receptor expression in colonic epitjelial cell line." Eur.J.Immunol.27. 3456-3460 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kiyono, H.et al: "A novel alkaline phosphatase-based isolation method allows characterization of intraepithelial lymphocytes from villi tip and crypt regions of murine small intestine." Biochem.Biophy.Res.Commun.241. 797-802 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kiyono, H.et al: "An interleukin 7 internet for intestinal intraepithelial _γδ T cell development : knockout of ligand or receptor reveal deifferences in the immunodeficient state." Eur.J.Immunol.27. 2123-2132 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] VanCott,J.L.,et al.: "Regulation of mucosal and systemic antibody responses by T helper subsets,macrophages and derived cytokines following oral immunization with live recombinant Salmonella." J.Immunol.156. 1504-1514 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takahashi,I.,et al.: "Mechanisms for mucosal immunogenicity and adjuvancy of Escherichia coli labile enterotoxin." J.Infect.Dis.173. 627-635 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takahashi,I.,et al.: "Epitope maps of Escherichia coli labile toxin B subunit for development,of a synthetic oral vaccine." Infect.Immune.64. 1290-1298 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakagawa,I.,et al.: "Oral lmmunization with the B subnit of the heat-labile entrerotoxin of Escherichia coil induces early Th1 and Th2 cytokines expression in Peyer′s patches." J.Infect.Dis.173. 1428-1426 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Okahashi,N.,et al.: "Mucosal immunity in IL-4 knockout mice:orala dministration of recombinant Salmonella or cholea toxin elicits CD4^+Th2 cells producing IL-6 and IL-10 and IgA responses." Infect.Immune.64. 1516-1525 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujihashi,K.,et al.: "γδT cell deficient mice have imparied mucosal IgA responses." J.Exp.Med.183. 1929-1935 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kiyono,H.,et al.: "Mucosal vaccine:New Trends in Immunization." Academic Press,San Diego., 479 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kagnoff,M.F.,et al.: "Essential of Mucosal Immunology." Academic Press,San Diego, 597 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujihashi,K.,et al.: "Role of γδT cells in regulation of mucosal IgA response and oral tolarance.778" Ann.NY Acad.Sci., 55-63 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamamoto,M.,et al.: "The role of Th1 and Th2 cells for mucosal IgA responses.778" Ann.NY Acad.Sci, 64-71 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] VanCott,J.L.,et al.: "Optimization of mucosal vaccine delivery systems for the induction of mucosal and systemic immune responses and advances in detection of mucosal antibodies Vaccine 96" Cold Spring Harbor Laboratory Ptess, 175 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Pascual,D.W.,et al.: "Mucosal immunity:molecular and cellular aspects of immune protection to enteric infections.In:Enteric Infections and Immune Responses" Plenum Publishing Co.,New York,N.Y., 15-35 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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