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Developmdent of BCG vaccines based on ehausted T cell re-activation

Research Project

Project/Area Number 26293098
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Bacteriology (including mycology)
Research InstitutionKyushu University

Principal Investigator

yoshikai yasunobu  九州大学, 生体防御医学研究所, 教授 (90158402)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2015: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2014: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Keywords細菌学 / BCG / IL-21 / IL-7 / ワクチン / T細胞 / 感染症 / 細菌 / 免疫学 / 微生物
Outline of Final Research Achievements

Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine confers incomplete protection against tuberculosis because it is not effective for inducing long-term immunity. Therefore, it is urgently required to develop improved vaccines. We found that IL-7 and IL-21 are pleiotropic common cytokines that affect IL-17+γδT cells and CD8+T cells, respectively. Based on these results, we examined the effects of recombinant BCG secreting fusion protein Ag85B/IL-7, or IL-21 (rBCG-Ag85B-IL7, rBCG-Ag85B-IL21) on cell-mediated immune responses against BCG. The levels of effector CD8+ T cells were significantly higher butexhausted CD8+ T cells were lower after immunization with rBCG-Ag85B-IL21 compared with rBCG-Ag85B. The levels of IL-17+γδ T cells and CD4+ Th1 cells were higher in rBCG-Ag85B-IL7-immunized mice than rBCG-Ag85B-immunized mice. rBCG-Ag85B-IL-7 or IL-21 vaccination capable of inducing long-term efficient immunity might be used as an effective vaccine for tuberculosis.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (35 results)

All 2017 2016 2015 2014

All Journal Article (15 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 15 results,  Acknowledgement Compliant: 7 results,  Open Access: 11 results) Presentation (16 results) (of which Invited: 2 results) Book (4 results)

  • [Journal Article] Recombinant Mycobacterium bovis Bacillus Calmette-Guerin expressing IL-7-Ag85B fusion protein enhances IL-17A-producing innate γδ T cells.2016

    • Author(s)
      Hatanoa S., Tamura T. Umemura M., Matsuzaki G., Ohara N., and Yoshikai Y.
    • Journal Title

      Vaccine.

      Volume: 34 Issue: 22 Pages: 2490-2495

    • DOI

      10.1016/j.vaccine.2016.03.096

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] C-Type Lectin Receptor DCAR Recognizes Mycobacterial Phosphatidyl-Inositol Mannosides to Promote a Th1 Response during Infection2016

    • Author(s)
      Toyonaga K, Torigoe S, Motomura Y, Kamichi T, Hayashi JM, Morita YS, Noguchi N, Chuma Y, Kiyohara H, Matsuo K, Tanaka H, Nakagawa Y, Sakuma T, Ohmuraya M, Yamamoto T, Umemura M, Matsuzaki G, Yoshikai Y, Yano I, Miyamoto T, Yamasaki S.
    • Journal Title

      Immunity

      Volume: 45 Issue: 6 Pages: 1245-1257

    • DOI

      10.1016/j.immuni.2016.10.012

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Two types of IL-17A-producing γδ T cells in protection against pulmonary infection with Klebsiella pneumoniae2016

    • Author(s)
      Murakami T., Hatano S., Yamada H., Iwakura Y., Yoshikai Y.
    • Journal Title

      J. Infect.Dis.

      Volume: 214 Issue: 11 Pages: 1752-1761

    • DOI

      10.1093/infdis/jiw443

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] IL-21 inhibits IL-17A-producing γδ T cell response after infection with Bacillus Calmette-Guerin via induction of apoptosis2016

    • Author(s)
      Huang Y., Matsumura Y., Hatano, S., Noguchi N., Murakamia, T., Iwakura Y., Sun X., Oharad N., Yoshikai Y.
    • Journal Title

      Innate Immun.

      Volume: 22 Issue: 8 Pages: 588-597

    • DOI

      10.1177/1753425916664125

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] IL-21/IL-21R signaling suppresses intestinal inflammation induced by DSS through regulation of Th responses in lamina propria in mice2016

    • Author(s)
      Wang, Y. Jiang, X., Zhu, J., Yue, D., Zhang, X., Wang, X., You, Y., Wang, B., Xu, Y., Lu, C, Sun, X., Yoshikai Y.
    • Journal Title

      Sci. Rep.

      Volume: 22 Issue: 1 Pages: 31881-31881

    • DOI

      10.1038/srep31881

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Interleukin-21-signaling in B cells, but not in T cells, is indispensable for the development of collagen-induced arthritis in mice2016

    • Author(s)
      Sakuraba K., Oyamada A., Fujimura K., Spolski R., Iwamoto Y., Leonard I.W., Yoshikai Y., Yamada H.
    • Journal Title

      Arthritis Research & Therap.

      Volume: 17 Issue: 1 Pages: 188-188

    • DOI

      10.1186/s13075-016-1086-y

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Equol inhibits prostate cancer growth via degradation of the androgen receptor by Skp2.2016

    • Author(s)
      Itsumi M, Shiota M, Takeuchi A, Kashiwagi E, Inokuchi J, Tatsugami K, Kajioka S, Uchiumi T, Naito S, Eto M, Yokomizo A.
    • Journal Title

      Cancer Sci

      Volume: in press Pages: 327-331

    • DOI

      10.1016/j.intimp.2016.03.007

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Antitumor activity of recombinant Bacille Calmette-Guerin secreting interleukin-15-Ag85B fusion protein against bladder cancer.2016

    • Author(s)
      Takeuchi A., , Eto M., Yamada H., Shita M., Tatsugami K., Kiyoshima K., Inokuchi J., Itsumi M., Takahashi R., Yokomizo A., Ohara N. Yoshikai Y.
    • Journal Title

      Int Immunopharmacol.

      Volume: 16;35 Pages: 327-331

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recombinant Mycobacterium bovis Bacillus Calmette-Guerin Expressing IL-7-Ag85B Fusion Protein Enhances IL-17A-producing Innate γδ T Cells.2016

    • Author(s)
      Hatanoa S. , Tamurab, T. Umemura M., Matsuzaki G., Ohara N., and Yoshikai Y.
    • Journal Title

      Vaccine

      Volume: in press

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Dermal Vγ4+ γδ T cells possess a migratory potency to the draining lymph nodes and modulate CD8+ T cell activity through TNF-α production.2015

    • Author(s)
      Nakamizo S., Egawa G., Tomura M., Sakai S., Tsuchiya S., Kitoh A., Honda T., Otsuka A., Nakajima S., Dainichi T., Tanizaki H., Mitsuyama M., Sugimoto Y., Kawai K., Yoshikai Y., Miyachi Y. and Kabashima K.
    • Journal Title

      J. Invest. Dermatology.

      Volume: 135 Pages: 1007-15

    • NAID

      120005621945

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] An enhancer of the IL-7 receptor alpha-chain locus controls IL-7 receptor expression and maintenance of peripheral T cells.2015

    • Author(s)
      Abe, A., Tani-ichi, S., Shitara, S., Cui, G., Yamada, H., Miyachi, H., Kitano, S., Hara, T., Abe, R., Yoshikai, Y., and Ikuta, K.
    • Journal Title

      J. Immunol.

      Volume: 195 Pages: 3129-38

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] IL-1 receptor antagonist-deficient mice develop autoimmune arthritis due to intrinsic activation of IL-17-producing CCR2+Vγ6+γδ T cells.2015

    • Author(s)
      Akitsu, A., Ishigame, H., Kakuta, S., Chung SH, Ikeda, S., Shimizu, K., Kubo, S., Liu, Y., Umemura, M., Matsuzaki, G., Yoshikai, Y., Saijo, S., and Iwakura Y.
    • Journal Title

      Nature Communication

      Volume: 6 Pages: 7464-7464

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A genome-wide analysis identifies a notch-RBP-Jκ-IL-7Rα axis that controls IL-17-producing γδ T cell homeostasis in mice.2015

    • Author(s)
      Nakamura M, Shibata K, Hatano S, Sato T, Ohkawa Y, Yamada H, Ikuta K, and Yoshikai Y.
    • Journal Title

      J.Immunol

      Volume: 194 Pages: 243-251

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tyk2-dependent bystander activation of conventional and non-conventional Th1 cell subsets contributes to innate host defense against Listeria monocytogenes infection.2014

    • Author(s)
      Hashiguchi T., Oyamada A., Sakuraba K., Iwamoto Y., Yoshikai, Y. and Yamada H.
    • Journal Title

      J.Immunol.

      Volume: 192 Pages: 4739-4747

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IFN-γ-producing and IL-17-producing γδ T cells differentiate at distinct developmental stages in murine fetal thymus.2014

    • Author(s)
      Shibata K. , Yamada H., Nakamura M., Katsuragi Y., Kominami R. and Yoshikai Y.
    • Journal Title

      J.Immunol.

      Volume: 192 Pages: 2210-2218

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Presentation] γδ型 T細胞-原始的T細胞として-2017

    • Author(s)
      吉開泰信
    • Organizer
      第90回日本細菌学会総会
    • Place of Presentation
      仙台市
    • Year and Date
      2017-03-19
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] A critical role of primitive γδ T cells developing (from DN2a stage) independently of Bcl11b in early host defense.2016

    • Author(s)
      Shinya Hatano, Tesshin Murakami, Yumiko Matsumura, Hisakata Yamada, Yasunobu Yoshikai
    • Organizer
      第45回日本免疫学会総会
    • Place of Presentation
      宜野湾市
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] CD153-CD30 interaction is involved in immunosenescence of T cells and spontaneous germinal center reactions.2016

    • Author(s)
      Yuji Fukushima, Hisakata Yamada, Yasunobu Yoshikai, Nagahiro Minato, Masakazu Hattori
    • Organizer
      第45回日本免疫学会総会
    • Place of Presentation
      宜野湾市
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] In vivo blockade of T cell development defines developmental pathways of intraepithelial lymphocytes in mice.2016

    • Author(s)
      Surenchimeg Mondoon, Kensuke Shibata, Yasunobu Yoshikai
    • Organizer
      第45回日本免疫学会総会
    • Place of Presentation
      宜野湾市
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] Recognition of mycobacterial lipid by Dendritic cell immunoactivating receptor.2016

    • Author(s)
      Kenji Toyonaga, Shota Torigoe, Yoshitomo Motomura, Takane Kamichi, Kazuhiro Matuo, Yasunobu Yoshikai, Sho Yamasaki.
    • Organizer
      第45回日本免疫学会総会
    • Place of Presentation
      宜野湾市
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] Bcl11b非依存性primitive γδT cellによる感染防御機構2016

    • Author(s)
      畑野晋也、村上哲晋、野口直人、松村友美子、山田久方、吉開泰信
    • Organizer
      第27回日本生体防御学会学術総会
    • Place of Presentation
      福岡市
    • Year and Date
      2016-07-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] 異なる活性化経路をもつ2種類のIL-17A産生γδT細胞が、肺炎桿菌に対する感染防御に重要な役割を果たす。2016

    • Author(s)
      村上哲晋、畑野晋也、山田久方、岩倉洋一郎、吉開泰信
    • Organizer
      第27回日本生体防御学会学術総会
    • Place of Presentation
      福岡市
    • Year and Date
      2016-07-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] γδ型 T細胞と生体防御2016

    • Author(s)
      吉開泰信
    • Organizer
      第27回日本生体防御学会学術総会
    • Place of Presentation
      福岡市
    • Year and Date
      2016-07-07
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Newly identified BCL11b-independent γδ T cell subset in the periphery in mice.2016

    • Author(s)
      畑野晋也、村上哲晋、松村友美子、山田久方、吉開泰信
    • Organizer
      第89回日本細菌学会総会
    • Place of Presentation
      大阪市
    • Year and Date
      2016-03-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] Two types of IL-17A-producing γδ T cells play critical roles against Klebsiella pneumoniae.2016

    • Author(s)
      村上哲晋、畑野晋也、山田久方、岩倉洋一郎、吉開泰信
    • Organizer
      第89回日本細菌学会総会
    • Place of Presentation
      大阪市
    • Year and Date
      2016-03-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] Analysis of a novel subset of IFN-γ-producing DN2a γδT cells in the periphery of mice.2015

    • Author(s)
      Shinya Hatano, Tesiin Murakami, Hisakata Yamada, and Yasunobu Yoshikai
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌市
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Two types of IL-17A-producing γδ T cells play critical roles in protection against pulmonary infection with Klebsiella pneumoniae in different activation manners.2015

    • Author(s)
      Tesshin Murakami, Shinya Hatano, Naoto Noguchi, Yasunobu Yoshikai
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌市
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] マウスにおける新規IFN-γ産生γδ細胞サブセットの解析2015

    • Author(s)
      畑野晋也、柴田健輔、山田久方、吉開泰信
    • Organizer
      第26回日本生体防御学会学術総会
    • Place of Presentation
      東京都
    • Year and Date
      2015-07-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] IL-17A+ γδ cells are required for the protection against Klebsiella pneumonia at infant stage.2015

    • Author(s)
      村上哲晋, 畑野晋也,柴田健輔, 山田久方, 吉開泰信
    • Organizer
      第88回日本細菌学会総会
    • Place of Presentation
      岐阜市
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] Development of a recombinant BCG expressing murine IL-7 as a novel vaccine against tuberculosis.2015

    • Author(s)
      畑野晋也, 柴田健輔, 山田久方, 大原直也, 田村敏生, 吉開泰信
    • Organizer
      第88回日本細菌学会総会
    • Place of Presentation
      岐阜市
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] IFN-γ-producing and IL-17-producing γδ T cells differentiate at distinct developmental stages in murine fetal thymus.2014

    • Author(s)
      Shinya Hatano, Kensuke Shibata, Hisakata Yamada, Yasunobu Yoshikai.
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      京都市
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Book] ウイルスによる膵島細胞障害 -ウイルス糖尿病予防ワクチンの開発は可能か?-2017

    • Author(s)
      永淵正法、勝田仁、三根敬一朗、吉開泰信
    • Total Pages
      236
    • Publisher
      羊土社
    • Related Report
      2016 Annual Research Report
  • [Book] 次世代アジュバント開発のためのメカニズム解明と安全性評価2017

    • Author(s)
      吉開 泰信
    • Total Pages
      249
    • Publisher
      シーエムシー出版
    • Related Report
      2016 Annual Research Report
  • [Book] 化学療法の領域「γδ型T細胞と細菌感染防御」2015

    • Author(s)
      吉開 泰信
    • Publisher
      医薬ジャーナル社
    • Related Report
      2015 Annual Research Report
  • [Book] 臨床免疫 アレルギー 科 「γδ型 T 細胞からのIL-17産生」2014

    • Author(s)
      吉開 泰信
    • Total Pages
      7
    • Publisher
      科学評論社
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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