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Elucidation of infection establishment of Bordetella pertussis and application for the vaccine development

Research Project

Project/Area Number 16K19131
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Bacteriology (including mycology)
Research InstitutionOsaka University

Principal Investigator

Hiramatsu Yukihiro  大阪大学, 微生物病研究所, 助教 (90739210)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords百日咳 / ワクチン / BipA / バイオフィルム
Outline of Final Research Achievements

Current acellular pertussis vaccine protect against disease but fail to prevent infection and transmission of Bordetella pertussis, which is epidemiological agent of pertussis (whooping cough). This causes that detailed infection mechanisms of the bacterium are well not understood. To resolve the problem, I focused on Bordetella intermediate protein A (BipA) that is strongly expressed in B. pertussis grown on upper airway temperature (30°C), and analyzed its function. The experiment using BipA-deficient mutant of B. pertussis demonstrated that BipA plays a role in bacterial adhesion to human lung cell line. Furthermore, I generated a novel pertussis vaccine that contains not only current vaccine antigens, but also BipA. In addition, I found a B. pertussis isolate not expressing major virulence factors due to impaired function of BvgAS system in the course of this study.

Academic Significance and Societal Importance of the Research Achievements

百日咳はワクチン予防可能疾患とされているが、ワクチンが普及した日本や欧米においても感染制御に苦慮する状況が続いている。この問題を解決するために、百日咳菌の感染成立機構を解明するとともに、現行ワクチンを感染防御能を持つものに改良する必要がある。本研究では、BipAが百日咳菌の細胞接着因子であることを実証するとともに、BipAを抗原として含む新規百日せきワクチンの作製に成功した。本成果は、日本において年間数千人が報告される百日咳患者を減らすための有益な基礎データとなる。また、本研究の過程で発見した主要抗原を産生しない百日咳菌株はワクチンが無効である可能性が高く、今後の流行を監視していく必要がある。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (16 results)

All 2019 2018 2017 2016

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 9 results,  Acknowledgement Compliant: 1 results) Presentation (6 results)

  • [Journal Article] Lactobacillus plantarum induces genomic DNA-dependent and TLR9-mediated elafin secretion from Caco-2 cells2019

    • Author(s)
      Yukihiro Hiramatsu, Daisuke Sakamoto, Tomomitsu Satho, Keiichi Irie, Fumio Miake, Minoru Maeda, Nobuhiro Kashige
    • Journal Title

      Asian Pacific Journal of Allergy and Immunology

      Volume: 37 Pages: 36-42

    • DOI

      10.12932/ap-021017-0174

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Eukaryotic Host Factor 14-3-3 Inactivates Adenylate Cyclase Toxins of Bordetella bronchiseptica and B.?parapertussis, but Not B.?pertussis2018

    • Author(s)
      Fukui-Miyazaki Aya、Toshima Hirono、Hiramatsu Yukihiro、Okada Keisuke、Nakamura Keiji、Ishigaki Keisuke、Shinzawa Naoaki、Abe Hiroyuki、Horiguchi Yasuhiko
    • Journal Title

      mBio

      Volume: 9 Issue: 4 Pages: 1-15

    • DOI

      10.1128/mbio.00628-18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bordetella pertussis population dynamics and phylogeny in Japan after adoption of acellular pertussis vaccines2018

    • Author(s)
      Aldert Zomer, Nao Otsuka, Yukihiro Hiramatsu, Kazunari Kamachi, Naoko Nishimura, Takao Ozaki, Jan Poolman, Jeroen Geurtsen
    • Journal Title

      Microbial genomics

      Volume: 印刷中 Issue: 5

    • DOI

      10.1099/mgen.0.000180

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Significant Decrease in Pertactin-Deficient Bordetella pertussis Isolates, Japan2017

    • Author(s)
      Hiramatsu Yukihiro, Miyaji Yusuke, Otsuka Nao, Arakawa Yoshichika, Shibayama Keigo, Kamachi Kazunari
    • Journal Title

      Emerging Infectious Diseases

      Volume: 23 Issue: 4 Pages: 699-701

    • DOI

      10.3201/eid2304.161575

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A high seroprevalence of antibodies to pertussis toxin among Japanese adults: Qualitative and quantitative analyses2017

    • Author(s)
      Moriuchi Takumi, Otsuka Nao, Hiramatsu Yukihiro, Shibayama Keigo, Kamachi Kazunari
    • Journal Title

      PLoS One

      Volume: 12 Issue: 7 Pages: e0181181-e0181181

    • DOI

      10.1371/journal.pone.0181181

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular epidemiology of Bordetella pertussis in Cambodia determined by direct genotyping of clinical specimens2017

    • Author(s)
      Moriuchi Takumi, Vichit Ork, Vutthikol Yong, Hossain Md. Shafiqul, Samnang Chham, Toda Kohei, Grabovac Varja, Hiramatsu Yukihiro, Otsuka Nao, Shibayama Keigo, Kamachi Kazunari
    • Journal Title

      International Journal of Infectious Diseases

      Volume: 62 Pages: 56-58

    • DOI

      10.1016/j.ijid.2017.07.015

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The proline residue at position 319 of BvgS is essential for BvgAS activation in Bordetella pertussis.2017

    • Author(s)
      Yukihiro Hiramatsu, Shuji Yoshino, Yoshiko Yamamura, Nao Otsuka, Keigo Shibayama, Mineo Watanabe, Kazunari Kamachi
    • Journal Title

      Pathogens and Disease

      Volume: 75(1) Issue: 1

    • DOI

      10.1093/femspd/ftx011

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Evaluation of a commercial loop-mediated isothermal amplification assay for diagnosis of Bordetella pertussis infection2017

    • Author(s)
      Kazunari Kamachi, Takumi Moriuchi, Yukihiro Hiramatsu, Nao Otsuka, Keigo Shibayama
    • Journal Title

      Journal of Microbiological Methods

      Volume: 133 Pages: 20-22

    • DOI

      10.1016/j.mimet.2016.12.009

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] BipA is associated with preventing autoagglutination and promoting biofilm formation in Bordetella holmesii.2016

    • Author(s)
      Yukihiro Hiramatsu, Momoko Saito, Nao Otsuka, Eri Suzuki, Mineo Watanabe, Keigo Shibayama, Kazunari Kamachi
    • Journal Title

      PLoS One

      Volume: 11(7) Issue: 7 Pages: e0159999-e0159999

    • DOI

      10.1371/journal.pone.0159999

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhancement and regulation effect of myrcene on antibody response in immunization with ovalbumin and Ag85B in mice.2016

    • Author(s)
      Saori Uyeda, Tanjina Sharmin, Tomomitsu Satho, Keiichi Irie, Mieno Watanabe, Masato Hosokawa, Yukihiro Hiramatsu, Takayuki Koga, Yukihiko Nakashima, Nobuhiro Kashige, Akihisa Toda, Kenji Mishima, Fumio Miake
    • Journal Title

      Asian Pacific Journal of Allergy and Immunology

      Volume: 34(4) Pages: 314-323

    • DOI

      10.12932/ap0734

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Lactobacillus plantarum D2905株のEPSの産生に関わる遺伝子の同定とその性状2019

    • Author(s)
      坂本大輔、平松征洋、萩原大樹、佐藤朝光、入江圭一、前田稔、中島幸彦、見明史雄、鹿志毛信広
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 百日咳菌のV型分泌装置Vag8の機能的解析2018

    • Author(s)
      小野田直記、平松征洋、照屋志帆乃、鈴木孝一朗、堀口安彦
    • Organizer
      第71回日本細菌学会関西支部総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Functional analysis of Bordetella pertussis autotransporter, Vag82018

    • Author(s)
      小野田直記、平松征洋、照屋志帆乃、鈴木孝一朗、堀口安彦
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Construction of a novel vaccine strain Bordetella pertussis Tohama co-producing Fim2 and Fim32018

    • Author(s)
      大塚菜緒、平松征洋、柴山恵吾、蒲地一成
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] クルマエビの腸管から単離された乳酸菌のゲノム解析2018

    • Author(s)
      坂本大輔、佐藤朝光、平松征洋、入江圭一、中島幸彦、前田稔、鹿志毛信広、見明史雄
    • Organizer
      日本薬学会 第138年会
    • Related Report
      2017 Research-status Report
  • [Presentation] わが国の小児と成人における百日咳抗体の量的・質的解析2016

    • Author(s)
      森内巧, 文元礼, 品川文乃, 新谷亮, 宮地悠輔, 勝田友博, 大塚菜緒, 平松征洋, 柴山恵吾, 蒲地一成
    • Organizer
      第48回日本小児感染症学会
    • Place of Presentation
      岡山コンベンションセンター(岡山県岡山市)
    • Year and Date
      2016-11-19
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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