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2006 Fiscal Year Final Research Report Summary

Novel Vaccines against Pseudomonas aeruginosa and Other Microorganisms

Research Project

Project/Area Number 17390129
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionYokohama city university

Principal Investigator

OKUDA Kenji  Yokohama city university, School of medicine, professor, 医学部, 教授 (40124862)

Co-Investigator(Kenkyū-buntansha) SHINADA Masaru  Yokohama city university, School of medicine, Associate Professor, 医学部, 準教授 (40301452)
TAKESHITA Fumihiko  Yokohama city university, School of medicine, Associate Professor, 医学部, 準教授 (60333572)
Project Period (FY) 2005 – 2006
Keywordsnatural immunity (TLR5 etc..) / Pseudomonas aeruginosa / DNA vaccine / triple vaccine / flagella antigen / type III secretion mechanism protein / clinical investigation
Research Abstract

Novel Vaccines against Pseudomonas aeruginosa and Other Microorganisms
Infection of Pseudomonas aeruginosa (P. aeruginosa) is one of the most common infectious diseases in the opportunistic infection group. The goal of the present study is to develop a vaccine against multi-antibiotic-resistant P.aeruginosa. Inactive vaccine of P.aeruginosa has been used in humans for many years. This vaccine however, contains a lot of non-immunogenic protein and strong side-effects such as fever are well documented.
In this study, a DNA vaccine was developed.
1) It was found that immunization with a vaccine containing PcrV, OprF/I and flagella genes induced strong protective immune responses. On the other hand, immunity was not observed from a DNA vaccine containing elastase or protease genes. The construction, of a vaccine containing PcrV, OprF/I and flagella genes is being carried out in collaboration with a Chinese company (Hisun Pharmaceutical Co.).
2) An amino acid sequence in the flagella gene, which activates Toll-like receptor5 (TLK.5), was identified. It was observed that the enhanced immunogenecity of the P.aeruginosa DNA vaccine contained a point-mutant flagella gene. The mutant vaccine greatly suppressed the product of the anti-TLR5 antibody and induced persistent protective immune responses against P.aeruginosa.
Previously most vaccines were composed of inactive microbes but such vaccines usually generate strong side effects. The refined component vaccine of the present study will greatly contribute to modern medicine.

  • Research Products

    (49 results)

All 2007 2006 2005

All Journal Article (46 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Blocking of the TLR5 activation domain hampers protective potential of flagellin DNA vaccine.2007

    • Author(s)
      Saha S et al.
    • Journal Title

      J. Immunology (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Blocking the TLR5 activation domain hampers protective protential of flagellin DNA vaccine.2007

    • Author(s)
      Saha S et al.
    • Journal Title

      J.Iminunology (In Press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Multivalent DNA vaccine protects mice against pulmonary infection caused by Pseudomonas aeruginosa.2006

    • Author(s)
      Saha S et al.
    • Journal Title

      Vaccine 24・37-39

      Pages: 6240-6249

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Induction of robust immune responses against human immunodeficiency virus is supported by the inherent tropism of adeno-associated virus type 5 for dendritic cells.2006

    • Author(s)
      Xin KQ et al.
    • Journal Title

      J Virol 80・24

      Pages: 11899-11910

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Activator protein 1-mediated transcriptional regulation strategy sustains long-term expression of a xenogeneic gene product in vivo : An implication for gene therapy targeting congenital protein deficiencies.2006

    • Author(s)
      Sasaki S
    • Journal Title

      Int. J. Mol. Med. 18・12

      Pages: 289-297

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Isolation and identification of adenovirus from conjunctival scrapings over a two-year period (between 2001 and 2003) in Yokohama, Japan.2006

    • Author(s)
      Matsui K et al.
    • Journal Title

      J Med Virol 79・2

      Pages: 200-205

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Human immunodeficiency virus-type 1 specific cellular immunity in chronic infected patients on prolonged highly active antiretroviral treatment and on structured treatment interruption.2006

    • Author(s)
      Matsuda R et al.
    • Journal Title

      Microbiol Immunol 50・8

      Pages: 629-635

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] TLR-adaptor molecules enhance DNA-raised adaptive immune responses against flu and tumor challenge trough the activation of innate immunity.2006

    • Author(s)
      Takeshita F et al.
    • Journal Title

      J. Virol 80・13

      Pages: 6218-6224

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A fused gene of nucleoprotein (NP) and herpes simplex virus genes (VP22) induces highly protective immunity against different subtypes of influenza virus.2006

    • Author(s)
      Saha S et al.
    • Journal Title

      Virology 35・1

      Pages: 48-57

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Oral administration of the adenovirus vector induces systemic immunity rather than intestinal mucosal immunity.2006

    • Author(s)
      Oomura K et al.
    • Journal Title

      Vaccine 24・8

      Pages: 1045-1046

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Robust HIV-specific immune responses were induced by DNA vaccine prime followed by attenuated recombinant vaccinia virus (LC16m8 strain) boost.2006

    • Author(s)
      Shinoda K et al.
    • Journal Title

      Clin Immunol 119・1

      Pages: 32-37

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A modified HIV challenge assay in mice by using luciferase-expressing vaccinia virus.2006

    • Author(s)
      Shinoda K et al.
    • Journal Title

      Vaccine 24・15

      Pages: 2751-2754

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Double stranded B-DNA activates type-l IFNs gene program via IPS-1/TBK1 pathway.2006

    • Author(s)
      Ishii KJ et al.
    • Journal Title

      Nat. Immunol 7・4

      Pages: 40-48

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Induction of positive cellular and humoral immune responses by a prime-boost vaccine encoded with simian immunodeficiency virus gag/pol.2006

    • Author(s)
      Someya K et al.
    • Journal Title

      J Immunol 176・3

      Pages: 1784-1795

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Removal of Empty Capsids from Type 1 Adeno-Associated Virus Vector Stocks by Anion-Exchange Chromatography Potentiates Transgene Expression.2006

    • Author(s)
      Urabe M et al.
    • Journal Title

      Mol Ther 13・4

      Pages: 823-828

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Scalable generation of high-titer recombinant adeno-associated virus type 5 in insect cells.2006

    • Author(s)
      Urabe M et al.
    • Journal Title

      J Virol 80・4

      Pages: 1874-1885

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Multivalent DNA vaccine protects mice against pulmonary infection caused by Pseudomonas aeruginosa.2006

    • Author(s)
      Saha S et al.
    • Journal Title

      Vaccine 24, 37-39

      Pages: 6240-6249

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Induction of robust immune responses against human immunodeficiency virus is supported by the inherent tropism of adeno-associated virus type 5 for dendritic cells.2006

    • Author(s)
      Xin KQ et al.
    • Journal Title

      J Virol 80, 24

      Pages: 11899-11910

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Activator protein 1-mediated transcriptional regulation strategy sustains long-term expression of a xenogeneic gene product in vivo : An implication for gene therapy targeting congenital protein deficiencies.2006

    • Author(s)
      Sasaki S
    • Journal Title

      Int.J.Mol.Med 18, 12

      Pages: 289-297

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Isolation and identification of adenovirus from conjunctival scrapings over a two-year period (between 2001 and 2003) in Yokohama, Japan.2006

    • Author(s)
      Matsui K et al.
    • Journal Title

      J Med Virol 79, 2

      Pages: 200-205

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Human immunodeficiency virus-type 1 specific cellular immunity in chronic infected patients on prolonged highly active antiretroviral treatment and on structured treatment interruption.2006

    • Author(s)
      Matsuda R et al.
    • Journal Title

      Microbiol Immunol 50, 8

      Pages: 629-635

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] TLR-adaptor molecules enhance DNA-raised adaptive immune responses against flu and tumor challenge trough the activation of innate immunity.2006

    • Author(s)
      Takeshita F et al.
    • Journal Title

      J.Virol 80, 13

      Pages: 6218-6224

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A fused gene of nucleoprotein (NP) and herpes simplex virus genes (VP22) induces highly protective immunity against different subtypes of influenza virus.2006

    • Author(s)
      Saha S et al.
    • Journal Title

      Virology 35, 1

      Pages: 48-57

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Oral administration of the adenovirus vector induces systemic immunity rather than intestinal mucosal immunity.2006

    • Author(s)
      Oomura K et al.
    • Journal Title

      Vaccine 24, 8

      Pages: 1045-1046

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Robust HIV-specific immune responses were induced by DNA vaccine prime followed by attenuated recombinant vaccinia virus (LC16m8 strain) boost.2006

    • Author(s)
      Shimoda K et al.
    • Journal Title

      Olin Immunol 119, 1

      Pages: 32-37

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A modified HIV challenge assay in mice by using luciferase-expressing vaccinia virus.2006

    • Author(s)
      Shimoda K et al.
    • Journal Title

      Vaccine 24, 15

      Pages: 2751-2754

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Double stranded B-DNA activates type-I.IFNs gene program via IPS-1/TBK1 pathway.2006

    • Author(s)
      Ishii KJ et al.
    • Journal Title

      Nat Immunol 176, 3

      Pages: 40-48

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Induction of positive cellular and humoral immune responses by a prime-boost vaccine encoded with simian immunodeficiency virus gag/pol.2006

    • Author(s)
      Someya K et al.
    • Journal Title

      I Immunol 176, 3

      Pages: 1784-1795

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Removal of Empty Capsids from Type 1 Adeno-Associated Virus Vector Stocks by Anion-Exchange Chromatography Potentiates Transgene Expression.2006

    • Author(s)
      Urabe M et al.
    • Journal Title

      Mol Ther 13, 4

      Pages: 823-828

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Scalable generation of high-titer recombinant adeno-associated virus type 5 in insect cells.2006

    • Author(s)
      Urabe M at al.
    • Journal Title

      J Virol 80, 4

      Pages: 1874-1885

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Prime-boost vaccination with plasmid DNA and a chimeric adenovirus type 5 vector with type 35 fiber induces persistent protective immunity against HIV.2005

    • Author(s)
      Xin K-Q et al.
    • Journal Title

      Gen. Ther 12・24

      Pages: 1769-1777

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] TRAF4 acts as a silencer in TLR-mediated signaling through the association with TRAF6 and TRIF.2005

    • Author(s)
      Takeshita F et al.
    • Journal Title

      Eur. J. Immunol 35・8

      Pages: 2477-2485

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Identification and characterization of a novel Delphilin variant with an alternative N-terminus.2005

    • Author(s)
      Yamashita T et al.
    • Journal Title

      Mol. Brain. Res 141・1

      Pages: 83-94

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Hyperproduction of IFN-□ by CpG oligodeoxynucleotide-induced exacerbation of atopic dermatitis-like skin lesion in some NC/Nga mice.2005

    • Author(s)
      Takakura M et al.
    • Journal Title

      J. Invest. Dermatol 125・6

      Pages: 1156-1162

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The F(ab')_2 fragment of an Aβ-specific monoclonal antibody reduces Aβ-deposits in the brain.2005

    • Author(s)
      Tamura Y et al.
    • Journal Title

      Neurobiology of Disease 20・2

      Pages: 541-549

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Combination of DNA vaccine and adenovirus vector by cutaneous administration induced strong HIV-specific cellular immune responses in mice.2005

    • Author(s)
      Takakura M et al.
    • Journal Title

      Vaccine 23・7

      Pages: 847-848

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Comparison of antigen-specific cellurar immune responses between individual PBMCs and splenocytes.2005

    • Author(s)
      Xin K-Q et al.
    • Journal Title

      Vaccine 23・23

      Pages: 2954-2955

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Vaccination of rhesus macaques with recombinant mycobacterium bovis calmette-guerin env V3 elicites neutralizing antibody-mediated protection against simian-human immunodeficiency virus with a homologous but not a heterologous V3 motif.2005

    • Author(s)
      Someya K et al.
    • Journal Title

      J. Virol 79・3

      Pages: 1452-1462

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Prime-boost vaccination with plasmid DNA and a chimeric adenovirus type 5 vector with type 35 fiber induces persistent protective immunity against HIV.2005

    • Author(s)
      Xin K-Q et al.
    • Journal Title

      Gen.Ther 12, 24

      Pages: 1769-1777

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] TRAF4 acts as a silencer in TLR-mediated signaling through the association with TRAF6 and TRIF.2005

    • Author(s)
      Takeshita F et al.
    • Journal Title

      Eur.J.Immunol 35, 8

      Pages: 2477-2485

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Identification and characterization of a novel Delphilin variant with an alternative N-terminus.2005

    • Author(s)
      Yamashita T et al.
    • Journal Title

      Mol.Brain.Res 141, 1

      Pages: 83-94

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Hyperproduction of IFN-□ by CpG oligodeoxynucleotide-induced exacerbation of atopic dermatitis-like skin lesion in some NC/Nga mice.2005

    • Author(s)
      Takakura M et al.
    • Journal Title

      J.Invest.Dermatol 125, 6

      Pages: 1156-1162

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The F(ab')2 fragment of an Aβ-specific monoclonal antibody reduces Aβ-deposits in the brain.2005

    • Author(s)
      Tamura Y et al.
    • Journal Title

      Neurobiology of Disease 20, 2

      Pages: 541-549

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Combination of DNA vaccine and adenovirus vector by cutaneous administration induced strong HIV-specific cellular immune responses in mice.2005

    • Author(s)
      Takakura M et al.
    • Journal Title

      Vaccine 23, 7

      Pages: 847-848

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Comparison of antigen-specific cellurar immune responses between individual PBMCs and splenocytes.2005

    • Author(s)
      Xin K-Q et al.
    • Journal Title

      Vaccine 23, 23

      Pages: 2954-2955

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Vaccination of rhesus macaques with recombinant mycobacterium bovis calmette-guerin env V3 elicites neutralizing antibody-mediated protection against simian-human immunodeficiency virus with a homologous but not a heterologous V3 motif.2005

    • Author(s)
      Someya K et al.
    • Journal Title

      J.Virol 79, 3

      Pages: 1452-1462

    • Description
      「研究成果報告書概要(欧文)」より
  • [Patent(Industrial Property Rights)] プラスミドを抱合するシアノアクリレートポリマー粒子であるプラスミド送達用粒子2007

    • Inventor(s)
      奥田研爾
    • Industrial Property Rights Holder
      奥田研爾
    • Industrial Property Number
      06-35,2007-46529
    • Filing Date
      2007-02-27
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] フラジェリン変異体ワクチン2007

    • Inventor(s)
      奥田研爾
    • Industrial Property Rights Holder
      奥田研爾
    • Industrial Property Number
      06-37, 2007-17446
    • Filing Date
      2007-01-29
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] フラジェリン変異体ワクチン2006

    • Inventor(s)
      奥田研爾
    • Industrial Property Rights Holder
      奥田研爾
    • Industrial Property Number
      6-12, 2006-199361
    • Filing Date
      2006-07-21
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2008-05-27  

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