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Development of new immunotherapy treatments toward a cure for HIV

Research Project

Project/Area Number 17H05087
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Infectious disease medicine
Research InstitutionNational Institutes of Biomedical Innovation, Health and Nutrition

Principal Investigator

Yamamoto Takuya  国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 免疫老化プロジェクト, プロジェクトリーダー (60752368)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥24,830,000 (Direct Cost: ¥19,100,000、Indirect Cost: ¥5,730,000)
Fiscal Year 2019: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2018: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2017: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Keywordsエイズ / 潜伏感染 / 免疫療法 / アジュバント / HIV / SIV / CTL / 自然免疫
Outline of Final Research Achievements

Elimination of the hidden HIV-1 is required for the cure from diseases related to HIV-1 infection. The latently infected cells under cART located mainly in lymph tissues. For the eradication of such cells, an appropriate animal model, which recapitulate pathological features after HIV-1 infection is essentially required. Here, we have established the macaque model under cART during chronic phase of infection, which potentially reflects many clinical features of HIV-1 infected individuals under cART. On the other hand, we found the potential usages of STING ligands for HIV treatment because STING ligands could stimulate latently infected cells and also activate immune responses simultaneously at least in vitro. Thus, we injected either a STING ligand or saline in two cART treated monkeys. However, we couldn't see any significant difference between them, therefore we are going to increase the number of monkeys for further investigation.

Academic Significance and Societal Importance of the Research Achievements

HIV-1に対する抗ウイルス薬は広く普及しているが、依然としてHIV-1感染症に対する根治療法の開発は世界的にも望まれており、本研究を含む新規治療法の開発研究の学術的、社会的意義は高いと考えられる。その目的達成のため、これまでサルを用いた急性期治療モデルは世界的にも多数報告されていたが、本研究により実臨床に近い慢性期治療モデルを世界に先駆けて樹立できたことは、エイズ根治に向けた大きな一歩を踏み出せたと考えられる。さらに、新規免疫療法となる可能性をもつ免疫賦活化剤としてのSTINGリガンドを同定することができたことで、本研究成果が、今後より具体的な新規治療法の確立へと繋がることが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (23 results)

All 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 5 results) Presentation (13 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results)

  • [Int'l Joint Research] INSERM(フランス)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] VRC, NIAID, NIH(米国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Principles Governing Establishment versus Collapse of HIV-1 Cellular Spread2019

    • Author(s)
      Hataye Jason M.、Casazza Joseph P.、Best Katharine、Liang C. Jason、Immonen Taina T.、Ambrozak David R.、Darko Samuel、Henry Amy R.、Laboune Farida、Maldarelli Frank、Douek Daniel C.、Hengartner Nicolas W.、Yamamoto Takuya、Keele Brandon F.、Perelson Alan S.、Koup Richard A.
    • Journal Title

      Cell Host & Microbe

      Volume: 26 Issue: 6 Pages: 748-763.e20

    • DOI

      10.1016/j.chom.2019.10.006

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Priming of HIV-1-specific CD8+ T cells with strong functional properties from naive T cells2019

    • Author(s)
      Kuse Nozomi、Sun Xiaoming、Akahoshi Tomohiro、Lissina Anna、Yamamoto Takuya、Appay Victor、Takiguchi Masafumi
    • Journal Title

      EBioMedicine

      Volume: 42 Pages: 109-119

    • DOI

      10.1016/j.ebiom.2019.03.078

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The STING ligand cGAMP potentiates the efficacy of vaccine-induced CD8+ T cells2019

    • Author(s)
      Gutjahr Alice、Papagno Laura、Nicoli Francesco、Kanuma Tomohiro、Kuse Nozomi、Cabral-Piccin Mariela Pires、Rochereau Nicolas、Gostick Emma、Lioux Thierry、Perouzel Eric、Price David A.、Takiguchi Masafumi、Verrier Bernard、Yamamoto Takuya、Paul Stephane、Appay Victor
    • Journal Title

      JCI Insight

      Volume: 4 Issue: 7 Pages: 1-11

    • DOI

      10.1172/jci.insight.125107

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] STING agonists activate latently infected cells and enhance SIV-specific responses ex vivo in naturally SIV controlled cynomolgus macaques2019

    • Author(s)
      Yamamoto Takuya、Kanuma Tomohiro、Takahama Shokichi、Okamura Tomotaka、Moriishi Eiko、Ishii Ken J.、Terahara Kazutaka、Yasutomi Yasuhiro
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 1-11

    • DOI

      10.1038/s41598-019-42253-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A unique nanoparticulate TLR9 agonist enables a HA split vaccine to confer FcγR-mediated protection against heterologous lethal influenza virus infection2018

    • Author(s)
      Yamamoto Takuya、Masuta Yuji、Momota Masatoshi、Kanekiyo Masaru、Kanuma Tomohiro、Takahama Shoukichi、Moriishi Eiko、Yasutomi Yasuhiro、Saito Takashi、Graham Barney S、Takahashi Yoshimasa、Ishii Ken J
    • Journal Title

      International Immunology

      Volume: 31 Issue: 2 Pages: 81-90

    • DOI

      10.1093/intimm/dxy069

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Elderly human hematopoietic progenitor cells express cellular senescence markers and are more susceptible to pyroptosis2018

    • Author(s)
      Fali T, Fabre-Mersseman V, Yamamoto T, Bayard C, Papagno L, Fastenackels S, Zoorab R, Koup RA, Boddaert J, Sauce D, Appay V.
    • Journal Title

      JCI Insight

      Volume: 3 Issue: 13 Pages: 1-14

    • DOI

      10.1172/jci.insight.95319

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] An Antigen-Free, Plasmacytoid Dendritic Cell-Targeting Immunotherapy To Bolster Memory CD8+ T Cells in Nonhuman Primates.2018

    • Author(s)
      Masuta Y, Yamamoto T, Natsume-Kitatani Y, Kanuma T, Moriishi E, Kobiyama K, Mizuguchi K, Yasutomi Y, Ishii KJ.
    • Journal Title

      J Immunol.

      Volume: 200(6) Issue: 6 Pages: 2067-2075

    • DOI

      10.4049/jimmunol.1701183

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CD63-Mediated Antigen Delivery into Extracellular Vesicles via DNA Vaccination Results in Robust CD8+T Cell Responses2017

    • Author(s)
      Kanuma Tomohiro、Yamamoto Takuya、Kobiyama Kouji、Moriishi Eiko、Masuta Yuji、Kusakabe Takato、Ozasa Koji、Kuroda Etsushi、Jounai Nao、Ishii Ken J.
    • Journal Title

      The Journal of Immunology

      Volume: 198 Issue: 12 Pages: 4707-4715

    • DOI

      10.4049/jimmunol.1600731

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] Evaluating broadly neutralizing antibodies for targeted ADCC cure strategies in the Asia Pacific region.2019

    • Author(s)
      Yamamoto T., and Lynch RM.
    • Organizer
      U.S.-Japan Cooperative Medical Sciences Program (USJCMSP) 22nd International Conference on Emerging Infectious Diseases in the Pacific Rim.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Effects of cART interruption during the chronic phase of SIV Infection on T-cell responses.2019

    • Author(s)
      Yamamoto T.
    • Organizer
      United States-Japan Cooperative Medical Sciences Program (AIDS Panel)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 機能的治癒を目指したSIV潜伏感染cARTモデルの構築2019

    • Author(s)
      高濱正吉、升田雄士、岡村智崇、保富康宏、山本拓也
    • Organizer
      第33回日本エイズ学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] HIV治癒を目指したSIV潜伏感染cARTモデルの構築.2019

    • Author(s)
      髙濱正吉、神沼智裕、升田雄士、岡村智崇、保富康宏、山本拓也
    • Organizer
      第33回近畿エイズ研究会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Establishment of a new strategy to eradicate SIV-latently infected cells for a cure treatment.2019

    • Author(s)
      Kanuma T, Takahama S, Okamura T, Masuta1 Y, Ise T, Nagata S, Yasutomi Y, and Yamamoto T.
    • Organizer
      17th International Congress of Immunology (IUIS 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] リンパ組織におけるSIV潜伏感染細胞排除の可能性.2019

    • Author(s)
      升田 雄士、髙濱正吉、岡村智崇、 伊勢知子、永田諭志、保富康宏、山本拓也
    • Organizer
      第33回日本エイズ学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 免疫賦活化剤によるSIV潜伏感染細胞排除の可能性2018

    • Author(s)
      髙濱正吉、岡村智崇、神沼智裕、滝口雅文、保富康宏、山本拓也
    • Organizer
      第32回近畿エイズ研究会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] SIV潜伏感染細胞排除を目指した自然免疫賦活化剤の応用2018

    • Author(s)
      髙濱正吉、神沼智裕、岡村智崇、保富康宏、山本拓也
    • Organizer
      第32回日本エイズ学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] STING ligand re-activates latently SIV infected cells and enhances SIV-specific CTL responses.2018

    • Author(s)
      Kanuma T, Takahama S, Okamura T, Yasutomi Y, Yamamoto T.
    • Organizer
      The 47th Annual Meeting of the Japanese Society for Immunology.
    • Related Report
      2018 Annual Research Report
  • [Presentation] Adjuvant effect of a nanoparticulate TLR9 agonist for protection against heterologous influenza challenge through FcRγ-mediated effector functions.2018

    • Author(s)
      Yamamoto T, Masuta Y, Momota M, Takahashi Y, Ishii KJ.
    • Organizer
      The 47th Annual Meeting of the Japanese Society for Immunology.
    • Related Report
      2018 Annual Research Report
  • [Presentation] ユニバーサルインフルエンザワクチン開発に向けたK3-SPGアジュバントの応用2018

    • Author(s)
      3.升田雄士, 山本拓也, 百田匡寿, 高橋宜聖, 石井健
    • Organizer
      第22回日本ワクチン学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] How can we improve CTL functions during cART?2017

    • Author(s)
      Takuya Yamamoto
    • Organizer
      18th Kumamoto AIDS seminar
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ART開始時期の違いによるHIV特異的CD8T細胞機能変化2017

    • Author(s)
      山本拓也
    • Organizer
      第31会日本エイズ学会
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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