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An epidemiological investigation of serum titers of anti-Pseudomonas aeruginosa virulent antigens and a trial of a specific anti-Pseuomonal gamma-globulin product

Research Project

Project/Area Number 18H02905
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 55060:Emergency medicine-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Sawa Teiji  京都府立医科大学, 医学(系)研究科(研究院), 教授 (10206013)

Co-Investigator(Kenkyū-buntansha) 森山 潔  杏林大学, 医学部, 教授 (10296717)
木下 真央  京都府立医科大学, 医学(系)研究科(研究院), 助教 (20816384)
天谷 文昌  京都府立医科大学, 医学(系)研究科(研究院), 教授 (60347466)
清水 優  京都府立医科大学, 医学(系)研究科(研究院), 助教 (40800131)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywords緑膿菌 / 肺炎 / 多剤耐性菌 / ガンマグロブリン / Ⅲ型分泌システム / 受動免疫 / PcrV / 急性肺傷害 / 細菌性肺炎 / 3型分泌システム / 抗体価 / 免疫療法 / 抗原 / 抗体療法 / ガンマグロブリン療法 / 血清抗体価 / グラム陰性菌 / 重症感染症 / 三型分泌システム / 重症肺炎
Outline of Final Research Achievements

Pneumonia caused by Pseudomonas aeruginosa has no effective treatment other than antibacterial agents, and it is difficult to treat it due to the addition of multidrug resistance. While working on the development of the anti-Pseudomonas aeruginosa vaccine and antibody therapy, we prototyped a high-potency gamma globulin preparation for the Pseudomonas aeruginosa toxin secretion system and verified its anti-P. aeruginosa action using an animal P.aeruginosa pneumonia model. As a result, the existence of antibody titers against not only P. aeruginosa but also other bacterial type III secretion proteins could be identified, and it is speculated that cross-antigenicity and natural infection may be involved. It has been shown that the development of a gamma globulin preparation leading to a high titer in the toxin secretion system of pathogenic Gram-negative bacteria may be effective as a therapeutic drug for infection with multidrug-resistant bacteria.

Academic Significance and Societal Importance of the Research Achievements

高齢化社会進行や医療高度化に伴い、致死的な細菌性肺炎が増加している。中でも日和見感染菌として代表的な緑膿菌による肺炎は、抗菌剤以外に未だ有効な治療法は無く、多剤耐性化が加わって治療に難渋する。申請者は、抗緑膿菌ワクチン・抗体療法の開発に取り組む中で、ヒトの血液中のガンマグロブリンには、緑膿菌毒素分泌システムを阻害できる抗体分画が多く含まれていることを発見した。このことから、今回の研究成果では、ヒト血清由来のガンマグロブリンが持つ抗緑膿菌作用について動物緑膿菌性肺炎モデルにて検証し、緑膿菌肺炎治療に有効な特殊ガンマグロブリン製剤の開発につなげられる結果を示した。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (35 results)

All 2022 2021 2020 2019 2018 Other

All Journal Article (16 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 14 results,  Open Access: 12 results) Presentation (9 results) (of which Int'l Joint Research: 5 results,  Invited: 4 results) Book (8 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Adverse reactions to the first and second doses of Pfizer-BioNTech COVID-19 vaccine among healthcare workers.2022

    • Author(s)
      Maruyama A, Sawa T, Teramukai S, Katoh N.
    • Journal Title

      J Infect Chemothe

      Volume: Mar 25 Issue: 7 Pages: 934-942

    • DOI

      10.1016/j.jiac.2022.03.015

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Difficult Airway Management in Neonates and Infants: Knowledge of Devices and a Device-Oriented Strategy2021

    • Author(s)
      Sawa Teiji、Kainuma Atsushi、Akiyama Koichi、Kinoshita Mao、Shibasaki Masayuki
    • Journal Title

      Frontiers in Pediatrics

      Volume: 9 Pages: 654291-654291

    • DOI

      10.3389/fped.2021.654291

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Power spectrum and spectrogram of EEG analysis during general anesthesia: Python-based computer programming analysis.2021

    • Author(s)
      Sawa T, Yamada T, Obata Y
    • Journal Title

      J Clin Monit Comput

      Volume: Oct 29 Issue: 3 Pages: 1-1

    • DOI

      10.1007/s10877-021-00771-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Poincar? Plot Area of Gamma-Band EEG as a Measure of Emergence From Inhalational General Anesthesia2021

    • Author(s)
      Hayase Kazuma、Kainuma Atsushi、Akiyama Koichi、Kinoshita Mao、Shibasaki Masayuki、Sawa Teiji
    • Journal Title

      Frontiers in Physiology

      Volume: 12 Pages: 627088-627088

    • DOI

      10.3389/fphys.2021.627088

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epidemiological survey of serum titers from adults against various Gram-negative bacterial V-antigens.2020

    • Author(s)
      Kinoshita M, Shimizu M, Akiyama K, Kato H, Moriyama K, Sawa T.
    • Journal Title

      PLoS One

      Volume: 15 Issue: 3 Pages: 15-15

    • DOI

      10.1371/journal.pone.0220924

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular diversity of extended-spectrum β-lactamases and carbapenemases, and antimicrobial resistance.2020

    • Author(s)
      Sawa T, Kooguchi K, Moriyama K.
    • Journal Title

      J Intensive Care

      Volume: 28 Issue: 1 Pages: 13-13

    • DOI

      10.1186/s40560-020-0429-6

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular epidemiology of clinically high-risk Pseudomonas aeruginosa strains: Practical overview.2020

    • Author(s)
      Sawa T, Momiyama K, Mihara
    • Journal Title

      Microbiol Immunol

      Volume: - Issue: 5 Pages: 1-1

    • DOI

      10.1111/1348-0421.12776

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Secondary in-hospital epidemiological investigation after an outbreak of Pseudomonas aeruginosa ST3572020

    • Author(s)
      Mihara T, Kimura T, Momiyama K, Kainuma A, Akiyama K, Ohara J, Inoue K, Kinoshita M, Shimizu M, Moriyama K, Fujita N, Sawa T.
    • Journal Title

      J Infect Chemother

      Volume: 26 Issue: 3 Pages: 257-265

    • DOI

      10.1016/j.jiac.2019.09.014

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immunoglobulin for Treating Bacterial Infections: One More Mechanism of Action. Development of Therapeutic Antibodies against Toxins and Pathogens.2019

    • Author(s)
      Sawa T, Kinoshita M, Inoue K, Ohara J, Moriyama K.
    • Journal Title

      Antibodies

      Volume: 8 Issue: 4 Pages: 52-52

    • DOI

      10.3390/antib8040052

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 当院で分離された薬剤耐性緑膿菌株にけるclass 1 integron遺伝子解析2019

    • Author(s)
      三原聡仁, 甲斐沼篤, 籾山恭子, 小原潤也, 井上敬太, 木下真央, 清水優, 木村武史, 佐和貞治.
    • Journal Title

      第53回緑膿菌感染症研究会公演記録

      Volume: 53 Pages: 55-57

    • Related Report
      2019 Annual Research Report
  • [Journal Article] The protective effects of nasal PcrV-CpG oligonucleotide vaccination against Pseudomonas aeruginosa pneumonia.2018

    • Author(s)
      Naito Y, Hamaoka S, Kinoshita M, Kainuma A, Shimizu M, Katoh H, Moriyama K, Ishii KJ, Sawa T.
    • Journal Title

      Microbiol Immunol

      Volume: 12 Issue: 12 Pages: 774-785

    • DOI

      10.1111/1348-0421.12658

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] An outbreak of fluoroquinolone-resistant Pseudomonas aeruginosa ST357 harboring the exoU gene.2018

    • Author(s)
      Kainuma A, Momiyama K, Kimura T, Akiyama K, Inoue K, Naito Y, Kinoshita M, Shimizu M, Kato H, Shime N, Fujita N, Sawa T.
    • Journal Title

      J Infect Chemother.

      Volume: in press Issue: 8 Pages: 615-622

    • DOI

      10.1016/j.jiac.2018.03.008

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dopamine D2-receptor Antagonist Droperidol Deepens Sevoflurane Anesthesia2018

    • Author(s)
      Araki, R. Hayashi, K. Sawa, T.
    • Journal Title

      Anesthesiology

      Volume: 128 Issue: 4 Pages: 754-763

    • DOI

      10.1097/aln.0000000000002046

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of surgical and conservative treatment outcomes for type A aortic dissection in elderly patients.2018

    • Author(s)
      Aoyama T, Kunisawa S, Fushimi K, Sawa T, Imanaka Y.
    • Journal Title

      Journal of Cardiothoracic Surgery

      Volume: 13 Issue: 1 Pages: 129-129

    • DOI

      10.1186/s13019-018-0814-6

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pulmonary Regnase-1 orchestrates the interplay of epithelium and adaptive immune systems to protect against pneumonia2018

    • Author(s)
      Nakatsuka Yoshinari、Vandenbon Alexis、Mino Takashi、Yoshinaga Masanori、Uehata Takuya、Cui Xiaotong、Sato Ayuko、Tsujimura Tohru、Suzuki Yutaka、Sato Atsuyasu、Handa Tomohiro、Chin Kazuo、Sawa Teiji、Hirai Toyohiro、Takeuchi Osamu
    • Journal Title

      Mucosal Immunology

      Volume: AOP Issue: 4 Pages: 1203-1218

    • DOI

      10.1038/s41385-018-0024-5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 多剤耐性緑膿菌に対する免疫療法.2018

    • Author(s)
      内藤慶史、佐和貞治.
    • Journal Title

      医学のあゆみ

      Volume: 264 Pages: 444-449

    • Related Report
      2018 Annual Research Report
  • [Presentation] 多剤耐性緑膿菌の治療:ワクチン・ガンマグロブリン療法のポテンシャル.2020

    • Author(s)
      佐和貞治
    • Organizer
      第2回神奈川ICT・ASTセミナー
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 多剤耐性緑膿菌の治療:ワクチン・ガンマグロブリン療法のポテンシャル.2020

    • Author(s)
      佐和貞治
    • Organizer
      第52回日本小児感染症学会総会・学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 生体防御とストレス反応ー細菌感染から血液凝固までー.2020

    • Author(s)
      佐和貞治.
    • Organizer
      麻酔科学セミナー2020
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 緑膿菌に学び,緑膿菌を操る. タイプ III 毒素分泌機構2020

    • Author(s)
      佐和貞治.
    • Organizer
      第94回日本感染症学会学術講演会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Frequency analysis-linked Poincare plot-integrated score (f-PIS) of the electroencephalogram during general anesthesia.2018

    • Author(s)
      Sawa T, Hayashi K, Kainuma A, Inoue K, Kinoshita M.
    • Organizer
      IARS 2018. Annual Meeting and International Science Symposium.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Energetic performance index improvement after Glenn and Damus-Kaye-Stansel procedure using vector flow mapping analysis.2018

    • Author(s)
      Kainuma A, Hayase K, Akiyama K, Naito Y, Shimizu M, Itatani K, Sawa T.
    • Organizer
      IARS 2018. Annual Meeting and International Science Symposium.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The effect of aortic regurgitant jet directionality on energy loss.2018

    • Author(s)
      Akiyama K, Wu I, Kainuma A, Nakajima Y, Sawa T, Itatani K, Takayama H.
    • Organizer
      IARS 2018. Annual Meeting and International Science Symposium.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Experience exchange session. Arterial pulse waveform analysis.2018

    • Author(s)
      Sawa T.
    • Organizer
      Edwards Life Science Limited, Irvine, CA, USA.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Airway Management.2018

    • Author(s)
      Sawa T
    • Organizer
      Smith Medical Airway Advisory Panel Meeting.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Book] Construction of a recombinant single-chain antibody fragment against bacterial type III secretion. Antibody Engineering,2018

    • Author(s)
      Sawa T, Kainuma A, Moriyama K, Naito Y.
    • Total Pages
      15
    • Publisher
      InTech
    • Related Report
      2018 Annual Research Report
  • [Book] 専門医認定試験の概要:何のためにどのような試験が行われるか. 麻酔科研修ノート 改訂第3版.2018

    • Author(s)
      佐和貞治.
    • Total Pages
      5
    • Publisher
      診断と治療社
    • ISBN
      9784787824011
    • Related Report
      2018 Annual Research Report
  • [Book] 麻酔科研修ノート 改訂第3版. 感染症.2018

    • Author(s)
      木下真央、佐和貞治.
    • Total Pages
      6
    • Publisher
      診断と治療社
    • ISBN
      9784787824011
    • Related Report
      2018 Annual Research Report
  • [Book] 褐色細胞腫. リスクを有する患者の周術期管理の実際. 麻酔科医のためのリスクを有する患者の周術期管理.2018

    • Author(s)
      早瀬一馬,佐和貞治.
    • Total Pages
      6
    • Publisher
      中山書店
    • ISBN
      9784521743264
    • Related Report
      2018 Annual Research Report
  • [Book] 敗血症患者. リスクを有する患者の緊急手術での対応. 麻酔科医のためのリスクを有する患者の周術期管理.2018

    • Author(s)
      甲斐沼 篤,佐和貞治.
    • Total Pages
      7
    • Publisher
      中山書店
    • ISBN
      9784521743264
    • Related Report
      2018 Annual Research Report
  • [Book] Arterial Pulse Wave Analysis法におけるオンラインlog10(SVV)-SVI プロットとリアルタイム回帰直線分析. 麻酔・集中治療とテクノロジー20172018

    • Author(s)
      佐和貞治,竹下秀祐, 橋本悟.
    • Total Pages
      6
    • Publisher
      日本麻酔集中治療テクノロジー学会
    • ISBN
      4894671581
    • Related Report
      2018 Annual Research Report
  • [Book] ClearSight SystemTM によるオンラインSVV-SVIプロット解析. 麻酔・集中治療とテクノロジー20172018

    • Author(s)
      竹下秀祐, 佐和貞治, 橋本悟.
    • Total Pages
      6
    • Publisher
      日本麻酔集中治療テクノロジー学会
    • ISBN
      4894671581
    • Related Report
      2018 Annual Research Report
  • [Book] TLR9リガンド添加緑膿菌V抗原ワクチンによる粘膜免疫誘導の検討. 第52回緑膿菌感染症研究会公演記録2018

    • Author(s)
      内藤慶史、濱岡早枝子、井上敬太、甲斐沼篤、石井健、佐和貞治.
    • Total Pages
      3
    • Publisher
      日本緑膿菌感染症研究会
    • Related Report
      2018 Annual Research Report
  • [Remarks] 京都府立医科大学麻酔科学教室 佐和貞治

    • URL

      http://www.f.kpu-m.ac.jp/k/anesth/index.php?TeijiSawa

    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 病原性グラム陰性菌に対するワクチン2018

    • Inventor(s)
      佐和貞治、濱岡早枝子、内藤慶史、石井健
    • Industrial Property Rights Holder
      京都府公立大学法人、国立研究開発法人医薬基盤・健康・栄養研究所
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
    • Overseas

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Published: 2018-04-23   Modified: 2023-01-30  

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