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Elucidation of the mechanism of protective responses induced by a new vaccine with glycolipid against pneumococcal infection

Research Project

Project/Area Number 16H05349
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Infectious disease medicine
Research InstitutionJikei University School of Medicine (2018)
National Institute of Infectious Diseases (2016-2017)

Principal Investigator

KINJO Yuki  東京慈恵会医科大学, 医学部, 教授 (20570831)

Co-Investigator(Kenkyū-buntansha) 高塚 翔吾  国立感染症研究所, 真菌部, 研究員 (90609398)
Research Collaborator Hayashizaki Koji  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywords肺炎球菌 / 糖脂質 / ワクチン / 感染防御 / NKT細胞 / 抗体 / 蛋白 / 肺炎 / 感染症
Outline of Final Research Achievements

Streptococcus pneumoniae (Pneumococcus) is a bacterium that causes pneumonia and meningitis especially in children and adults aged 65 years and above. Current pneumococcal vaccines are effective. However, in recent years, the serotypes that are not included in the current vaccines are increasing. Therefore, development of new vaccines that provide broad protection against pneumococcal infection is desired.
In this study, we invested the protective effect of a new protein and glycolipid vaccine. Our results indicate that this vaccine induces protective antibody production and long-term protection against pneumococcal infection. Furthermore, we performed immunological analyses to understand the mechanisms of antibody production and elucidated a part of mechanisms of B cell antibody production that is induced with the help of a lymphocyte called as NKT cell.

Academic Significance and Societal Importance of the Research Achievements

本研究にて,新規肺炎球菌蛋白・糖脂質ワクチンの接種により,肺炎球菌に結合するIgG抗体の産生および感染防御効果が長期間持続することが明らかになった。また,感染防御効果をもたらす抗体の産生が持続する免疫学的機序の一端を解明することができた。本研究の結果に基づき今後の研究が進展することで,新規肺炎球菌蛋白ワクチンによる抗体産生の持続機構が明らかになるものと考えられる。さらに,その知見を応用することで,有効性の高いワクチンの開発に繋がり,国内のみならず世界中で主な死因の1つになっている肺炎球菌感染症の制御に貢献できる可能性が期待される。

Report

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

    (32 results)

All 2019 2018 2017 2016

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 5 results) Presentation (21 results) (of which Invited: 7 results)

  • [Journal Article] Neutrophil-mediated antifungal activity against highly virulent Cryptococcus gattii strain R2652019

    • Author(s)
      Ueno Keigo、Yanagihara Nao、Otani Yoshiko、Shimizu Kiminori、Kinjo Yuki、Miyazaki Yoshitsugu
    • Journal Title

      Medical Mycology

      Volume: 印刷中 Issue: 8 Pages: 1046-1054

    • DOI

      10.1093/mmy/myy153

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Redundant and Distinct Roles of Secreted Protein Eap and Cell Wall-Anchored Protein SasG in Biofilm Formation and Pathogenicity of Staphylococcus aureus2019

    • Author(s)
      Yonemoto Keigo、Chiba Akio、Sugimoto Shinya、Sato Chikara、Saito Mitsuru、Kinjo Yuki、Marumo Keishi、Mizunoe Yoshimitsu
    • Journal Title

      Infection and Immunity

      Volume: 87(4) Issue: 4

    • DOI

      10.1128/iai.00894-18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epidemiological and clinical features of invasive pneumococcal disease caused by serotype 12F in adults, Japan2019

    • Author(s)
      Shimbashi R、Chang B、Tanabe Y、Takeda H、Watanabe H、Kubota T、Kasahara K、Oshima K、Nishi J、Maruyama T、Kuronuma K、Fujita J、Ikuse T、Kinjo Y、Suzuki M、Kerdsin A、Shimada T、Fukusumi M、Tanaka-Taya K、Matsui T、Sunagawa T、Ohnishi M、Oishi K、and the Adult IPD Study Group
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 2 Pages: e0212418-e0212418

    • DOI

      10.1371/journal.pone.0212418

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functions of CD1d-Restricted Invariant Natural Killer T Cells in Antimicrobial Immunity and Potential Applications for Infection Control2018

    • Author(s)
      Kinjo Yuki、Takatsuka Shogo、Kitano Naoki、Kawakubo Shun、Abe Masahiro、Ueno Keigo、Miyazaki Yoshitsugu
    • Journal Title

      Frontiers in Immunology

      Volume: 9 Pages: 1266-1266

    • DOI

      10.3389/fimmu.2018.01266

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A dendritic cell-based systemic vaccine induces long-lived lung-resident memory Th17 cells and ameliorates pulmonary mycosis2018

    • Author(s)
      Ueno Keigo、Urai Makoto、Sadamoto Sota、Shinozaki Minoru、Takatsuka Shogo、Abe Masahiro、Otani Yoshiko、Yanagihara Nao、Shimizu Kiminori、Iwakura Yoichiro、Shibuya Kazutoshi、Miyazaki Yoshitsugu、Kinjo Yuki
    • Journal Title

      Mucosal Immunology

      Volume: 12 Issue: 1 Pages: 265-276

    • DOI

      10.1038/s41385-018-0094-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 真菌感染に対する防御免疫機構:Th1細胞及びTh17細胞の役割2018

    • Author(s)
      金城雄樹, 上野圭吾,宮﨑義継
    • Journal Title

      化学療法の領域

      Volume: 34 Pages: 564-570

    • Related Report
      2017 Annual Research Report
  • [Journal Article] クリプトコックス症の診断と治療2017

    • Author(s)
      宮﨑義継, 中村茂樹,金城雄樹
    • Journal Title

      日本医師会雑誌

      Volume: 146 Pages: 495-498

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Immunization with Antigen-Pulsed Dendritic Cells Against Highly Virulent Cryptococcus gattii Infection: Analysis of Cytokine-Producing T Cells2017

    • Author(s)
      Ueno Keigo、Urai Makoto、Takatsuka Shogo、Abe Masahiro、Miyazaki Yoshitsugu、Kinjo Yuki
    • Journal Title

      Methods Mol Biol.

      Volume: 1625 Pages: 327-339

    • DOI

      10.1007/978-1-4939-7104-6_22

    • ISBN
      9781493971039, 9781493971046
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disrupting ceramide-CD300f interaction prevents septic peritonitis by stimulating neutrophil recruitment.2017

    • Author(s)
      Izawa K, Maehara A, Isobe M, Yasuda Y, Urai M, Hoshino Y, Ueno K, Matsukawa T, Takahashi M, Kaitani A, Shiba E, Takamori A, Uchida S, Uchida K, Maeda K, Nakano N, Yamanishi Y, Oki T, Voehringer D, Roers A, Nakae S, Ishikawa J, Kinjo Y, Shimizu T, Ogawa H, Okumura K, Kitamura T, Kitaura J
    • Journal Title

      Sci Rep.

      Volume: 7(1) Issue: 1 Pages: 4298-4298

    • DOI

      10.1038/s41598-017-04647-z

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dendritic Cell-Based Vaccine Against Fungal Infection2016

    • Author(s)
      Ueno K, Urai M, Ohkouchi K, Miyazaki Y, Kinjo Y.
    • Journal Title

      Methods Mol Biol

      Volume: 1403 Pages: 537-4

    • DOI

      10.1007/978-1-4939-3387-7_30

    • ISBN
      9781493933853, 9781493933877
    • Related Report
      2016 Annual Research Report
  • [Journal Article] Human CD4- CD8- invariant natural killer T cells promote IgG secretion from B cells stimulated by cross-linking of their antigen receptors2016

    • Author(s)
      Miyasaka T, Watanabe Y, Akahori Y, Miyamura N, Ishii K, Kinjo Y, Miyazaki Y, Liu T-Y, Uemura Y, Kawakami K
    • Journal Title

      World J Vaccines

      Volume: 6 Issue: 02 Pages: 34-41

    • DOI

      10.4236/wjv.2016.62005

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] The application of glycolipid-mediated NKT cell activation for a pneumococcal vaccine2019

    • Author(s)
      Yuki Kinjo
    • Organizer
      第12回次世代アジュバント研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 糖脂質に着目した肺炎球菌感染防御2019

    • Author(s)
      金城雄樹, 高塚翔吾, 川久保俊, 林﨑浩史, 宮﨑義継
    • Organizer
      第5回糖鎖免疫研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] iNKT細胞を介する生体防御(シンポジウム)2018

    • Author(s)
      金城雄樹
    • Organizer
      第62回日本薬学会関東支部大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 肺炎球菌感染症:ワクチンの研究(教育講演)2018

    • Author(s)
      金城雄樹
    • Organizer
      第67回日本感染症学会東日本地方学術集会・第65回日本化学療法学会東日本支部総会 合同学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] NKT細胞のαガラクトシルセラミド類似細菌糖脂質の認識および感染免疫における役割(シンポジウム)2018

    • Author(s)
      金城雄樹
    • Organizer
      第24回日本エンドトキシン・自然免疫研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] The critical role of IL-21+ NKT cells in the formation of germinal center B cells by a protein-based pneumococcal vaccine2018

    • Author(s)
      Shogo Takatsuka, Koji Hayashizaki, Keigo Ueno, Masato Kubo, Yuki Kinjo
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 肺炎球菌蛋白・糖脂質経鼻ワクチンによる感染防御効果と免疫応答メカニズムの解析2018

    • Author(s)
      高塚 翔吾, 川久保 俊, 仲原 真貴子, 浦井 誠, 上野 圭吾, 林﨑 浩史, 竹山 春子, 大石 和徳, 宮﨑 義継, 金城 雄樹
    • Organizer
      第29回日本生体防御学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 高病原性真菌の莢膜多糖による免疫回避及び樹状細胞ワクチンによる感染防御2018

    • Author(s)
      金城 雄樹,上野 圭吾,浦井 誠,宮﨑 義継
    • Organizer
      糖鎖免疫 Glyco-Immunology 2018
    • Related Report
      2017 Annual Research Report
  • [Presentation] 肺炎球菌感染症の制圧へむけて-感染防御免疫の解析からワクチン開発まで-2018

    • Author(s)
      金城 雄樹
    • Organizer
      第3回免疫関連希少・難治性疾患に対する革新的治療創生研究シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] シンポジウム「日本生体防御学会共催:生体防御学的視点から見た細菌感染」NKTFH cells induce the protective effect of protein and glycolipid vaccine against pneumococcal infection2017

    • Author(s)
      Yuki Kinjo, Makiko Nakahara, Shogo Takatsuka, Masahiro Abe, Keigo Ueno, Bin Chang, Zhenyu Piao, Yukihiro Akeda, Kazuyoshi Kawakami, Kazunori Oishi
    • Organizer
      第90回 日本細菌学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-19
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 糖脂質によるNKT細胞活性化を介した抗体産生誘導と感染防御2017

    • Author(s)
      金城 雄樹
    • Organizer
      Glyco-Immunology 2017
    • Place of Presentation
      東京
    • Year and Date
      2017-01-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] ワクチン非含有血清型の臨床分離肺炎球菌における病原性の検討2017

    • Author(s)
      宮崎治子, 渋谷理恵, 緑川直子, 常彬,金城雄樹, 大西真, 松本哲哉
    • Organizer
      第91回日本感染症学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 侵襲性真菌感染症の病態の基礎的解析2017

    • Author(s)
      金城雄樹
    • Organizer
      第7回小児Febrile Neutropenia研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] シンポジウム ワクチン創製の理論とその展開 「肺炎球菌感染症を予防する新規ワクチン~防御免疫誘導機構及び今後の展望~」2017

    • Author(s)
      金城 雄樹, 高塚 翔吾, 仲原 真貴子, 阿部 雅広, 上野 圭吾, 宮武 浩, 朴 貞玉, 明田 幸宏, 常 彬, 相内 章, 鈴木 忠樹, 大島 謙吾, 武田 博明, 川上 和義, 長谷川 秀樹, 大西 真, 生田 和良, 大石 和徳, 宮﨑 義継
    • Organizer
      第28回日本生体防御学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Development of recombinant pneumococcal surface protein A (PspA)-based vaccine against Streptococcus pneumoniae2017

    • Author(s)
      Ryutaro Ogura, Hiroshi Miyatake, Hiroki Nakayama, Yuji Inoue, Shunsuke Kano, Noriyuki Kanzawa, Zhenyu Piao, Yuka Koizumi, Yuriko Tanaka, Daisuke Ono, Naokuni Ueda, Yukihiro Akeda, Yuki Kinjo, Kazunori Oishi, Kazuyoshi Ikuta
    • Organizer
      The 16th Awaji International Forum on Infection and Immunity
    • Related Report
      2017 Annual Research Report
  • [Presentation] Follicular helper NKT cells augment germinal center B cell formation by a protein-based pneumococcal vaccine2017

    • Author(s)
      Shogo Takatsuka, Keigo Ueno, Masato Kubo and Yuki Kinjo
    • Organizer
      第46回日本免疫学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Dendritic cell-based vaccination induces lung resident memory Th17 cells that ameliorate pulmonary infection with highly virulent Cryptococcus gattii2017

    • Author(s)
      Keigo Ueno, Shogo Takatsuka and Yuki Kinjo
    • Organizer
      第46回日本免疫学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Follicular helper NKT cells induce protective effect of a protein-based pneumococcal vaccine through stimulation of IgG production by B cells2016

    • Author(s)
      Makiko Nakahara, Shogo Takatsuka, Keigo Ueno, Taishi Onodera, Yoshimasa Takahashi, Kazuyoshi Kawakami, Masato Kubo, Yuki Kinjo
    • Organizer
      第45回 日本免疫学会総会
    • Place of Presentation
      沖縄
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] 肺炎球菌蛋白経鼻ワクチンによる肺炎球菌感染防御効果~インフルエンザ続発性の肺炎球菌感染防御効果も含めて~2016

    • Author(s)
      金城 雄樹, 酒井 純, 阿部 雅広, 上野 圭吾, 浦井 誠, 朴 貞玉, 明田 幸宏, 二木 芳人, 川上 和義, 賀来 満夫, 前崎 繁文, 大石 和徳, 宮﨑 義継
    • Organizer
      第86回 日本感染症学会西日本地方会学術集会
    • Place of Presentation
      沖縄
    • Year and Date
      2016-11-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] 肺炎球菌蛋白・糖脂質経鼻ワクチンによる感染防御効果の解析~インフルエンザ続発性肺炎球菌感染に対する防御効果も含めて~2016

    • Author(s)
      仲原 真貴子, 大河内 香代, 高塚 翔吾, 水口 裕紀, 酒井 純, 浦井 誠, 井澤 由衣奈, 上野 圭吾, 相内 章, 鈴木 忠樹, 川上 和義, 竹山 春子, 長谷川 秀樹, 宮﨑 義継, 大石 和徳,金城 雄樹
    • Organizer
      第27回 日本生体防御学会総会
    • Place of Presentation
      福岡
    • Year and Date
      2016-07-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] 肺炎球菌蛋白・糖脂質経鼻ワクチンによる感染防御効果の免疫学的解析2016

    • Author(s)
      金城 雄樹、酒井 純、浦井 誠、上野 圭吾、金子 幸弘、朴 貞玉、明田 幸宏、前崎 繁文、二木 芳人、川上 和義、大石 和徳、宮崎 義継
    • Organizer
      第90回 日本感染症学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2016-04-15
    • Related Report
      2016 Annual Research Report

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

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