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Induction of HIV neutralizing antibodies by anti-idiotype antibodies

Research Project

Project/Area Number 18H02854
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 54030:Infectious disease medicine-related
Research InstitutionKumamoto University

Principal Investigator

Matsushita Shuzo  熊本大学, ヒトレトロウイルス学共同研究センター, 教授 (00199788)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords感染症 / 内科 / ウイルス / HIV-1 / AIDS / 中和抗体 / 抗イディオタイプ抗体 / イディオタイプワクチン / エイズワクチン開発
Outline of Final Research Achievements

We established a panel of anti-idiotype antibodies against the HIV neutralizing antibodies such as V3 antibody (1C10) and CD4i antibodies (4E9C, 916B2). B cells recognized by these anti-idiotype antibodies are obtained from the peripheral blood of HIV-infected cases by single cell sorting, and their biological activities are under investigation. In addition, in the analysis using 5 anti-idiotype antibodies against 1C10, # 102-reactive cells were found in the early stage of infection, # 87 in the middle stage of infection, # 103 in the late stage of infection were found. In the case of # 92 the binding cells were found in the early to middle stage, and #103 cells that bound in the middle to late stages were observed. These data suggest the stepwise induction of neutralizing antibody-producing B cells with multiple anti-idiotype antibodies.

Academic Significance and Societal Importance of the Research Achievements

HIV感染予防に有効なワクチンが開発できない理由として、中和抗体の誘導が困難という問題がある。近年、広範囲のHIVを中和する抗体分離されたが、その誘導は成功していない。我々は、single cell sortingによって、中和抗体に対する多様な抗イディオタイプ抗体を作成する方法を確立した。抗イディオタイプ抗体は、中和抗体の抗原認識部位に反応し、一部は標的エピトープに類似した構造を取る。本研究の目的は、多様な抗イディオタイプ抗体パネルを作成して、中和抗体産生B細胞集団を解析し、その前駆細胞を同定することにある。これによってHIVワクチン開発への新しい道が開ける。

Report

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

    (28 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (11 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 11 results,  Open Access: 10 results) Presentation (12 results) (of which Int'l Joint Research: 3 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 2 results)

  • [Int'l Joint Research] NYU School of Medicine(米国)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] A Potent Anti-Simian Immunodeficiency Virus Neutralizing Antibody Induction Associated with a Germ Line Immunoglobulin Gene Polymorphism in Rhesus Macaques2021

    • Author(s)
      Matsuoka Saori、Kuwata Takeo、Ishii Hiroshi、Sekizuka Tsuyoshi、Kuroda Makoto、Sano Masato、Okazaki Midori、Yamamoto Hiroyuki、Shimizu Mikiko、Matsushita Shuzo、Seki Yohei、Saito Akatsuki、Sakawaki Hiromi、Hirsch Vanessa M.、Miura Tomoyuki、Akari Hirofumi、Matano Tetsuro
    • Journal Title

      Journal of Virology

      Volume: 95 Issue: 7

    • DOI

      10.1128/jvi.02455-20

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hybrids of Small-Molecule CD4 Mimics with Polyethylene Glycol Units as HIV Entry Inhibitors2021

    • Author(s)
      Kobayakawa Takuya、Tsuji Kohei、Konno Kiju、Himeno Ai、Masuda Ami、Yang Tingting、Takahashi Kohei、Ishida Yusuke、Ohashi Nami、Kuwata Takeo、Matsumoto Kaho、Yoshimura Kazuhisa、Sakawaki Hiromi、Miura Tomoyuki、Harada Shigeyoshi、Matsushita Shuzo、Tamamura Hirokazu
    • Journal Title

      Journal of Medicinal Chemistry

      Volume: 64 Issue: 3 Pages: 1481-1496

    • DOI

      10.1021/acs.jmedchem.0c01153

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prediction of Contact Residues in Anti-HIV Neutralizing Antibody by Deep Learning2020

    • Author(s)
      Kaku Yu、Kuwata Takeo、Gorny Miroslaw K.、Matsushita Shuzo
    • Journal Title

      Japanese Journal of Infectious Diseases

      Volume: 73 Issue: 3 Pages: 235-241

    • DOI

      10.7883/yoken.JJID.2019.496

    • NAID

      130007845455

    • ISSN
      1344-6304, 1884-2836
    • Year and Date
      2020-05-29
    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Existence of replication-competent minor variants with different coreceptor usage in plasma from HIV-1-infected individuals2020

    • Author(s)
      Maeda Y, Takemura T, Chikata T, Kuwata T, Terasawa H, Fujimoto R, Kuse N, Akahoshi T, Murakoshi H, Van Tran G, Zhang Y, Pham CH, Pham AHQ, Monde K, Sawa T, Matsushita S, Nguyen TV, Van Nguyen K, Hasebe F, Yamashiro T, Takiguchi M.
    • Journal Title

      Journal of Virology

      Volume: 94 Issue: 12

    • DOI

      10.1128/jvi.00193-20

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance2020

    • Author(s)
      Pisil Yalcin、Yazici Zafer、Shida Hisatoshi、Matsushita Shuzo、Miura Tomoyuki
    • Journal Title

      Pathogens

      Volume: 9 Issue: 3 Pages: 181-181

    • DOI

      10.3390/pathogens9030181

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Synergistic inhibition of cell-to-cell HIV-1 infection by combinations of single chain variable fragments and fusion inhibitors2019

    • Author(s)
      Alam Mohammad Mamun、Kuwata Takeo、Tanaka Kazuki、Alam Muntasir、Takahama Shokichi、Shimura Kazuya、Matsuoka Masao、Fukuda Natsuki、Morioka Hiroshi、Tamamura Hirokazu、Matsushita Shuzo
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 20 Pages: 100687-100687

    • DOI

      10.1016/j.bbrep.2019.100687

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The role of conventional antibodies targeting the CD4 binding site and CD4-induced epitopes in the control of HIV-1 CRF01_AE viruses.2019

    • Author(s)
      Thida W, Kuwata T, Maeda Y, Yamashiro T, Tran GV, Nguyen KV, Takiguchi M, Gatanaga H, Tanaka K, Matsushita S
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 508 Issue: 1 Pages: 46-51

    • DOI

      10.1016/j.bbrc.2018.11.063

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Total HIV-1 DNA dynamics and influencing factors in long-term ART-treated Japanese adults: a retrospective longitudinal analysis.2018

    • Author(s)
      Stanoeva KR, König A, Fukuda A, Kawanami Y, Kuwata T, Satou Y, Matsushita S.
    • Journal Title

      J Acquir Immune Defic Syndr

      Volume: - Issue: 2 Pages: 239-247

    • DOI

      10.1097/qai.0000000000001662

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Apolipoprotein E is an HIV-1-inducible inhibitor of viral production and infectivity in macrophages2018

    • Author(s)
      Siddiqui Rokeya、Suzu Shinya、Ueno Mikinori、Nasser Hesham、Koba Ryota、Bhuyan Farzana、Noyori Osamu、Hamidi Sofiane、Sheng Guojun、Yasuda-Inoue Mariko、Hishiki Takayuki、Sukegawa Sayaka、Miyagi Eri、Strebel Klaus、Matsushita Shuzo、Shimotohno Kunitada、Ariumi Yasuo
    • Journal Title

      PLOS Pathogens

      Volume: 14 Issue: 11 Pages: 1007372-1007372

    • DOI

      10.1371/journal.ppat.1007372

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Flexibility of small molecular CD4 mimics as HIV entry inhibitors.2018

    • Author(s)
      KOBAYAKAWA T, OHASHI N, HIROTA Y, TAKAHASHI K, YAMADA Y, NARUMI T, YOSHIMURA K, MATSUSHITA S, HARADA S, TAMAMURA H
    • Journal Title

      Bioorganic & Medical Chemistry

      Volume: 26 Issue: 21 Pages: 5664-5671

    • DOI

      10.1016/j.bmc.2018.10.011

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Osteoporosis-related fractures in HIV-infected patients receiving long-term tenofovir disoproxil fumarate: an observational cohort study2018

    • Author(s)
      Komatsu, A., Ikeda, A., Kikuchi, A., Minami, C., Tan, M., Matsushita, S.
    • Journal Title

      Drug Safety

      Volume: 印刷中 Issue: 9 Pages: 843-848

    • DOI

      10.1007/s40264-018-0665-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Synergistic Inhibition of cell-to-cell infection of HIV-1 by thecombination of single chain fragment variables (scFvs) and fusion inhibitors.2019

    • Author(s)
      Mohammad Mamun Alam, Takeo Kuwata, Kazuki Tanaka, Muntasir Alam, Shokichi Takahama, Kazuya Shimura, Masao Matsuoka, Natsuki Fukuda, Hiroshi Morioka, Hirokazu Tamamura and Shuzo Matsushita
    • Organizer
      10th IAS Conference on HIV Science
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] VH gene polymorphism associated with potent anti-SIV neutralizing antibody induction.2019

    • Author(s)
      Kuwata T, Ishii H, Matsuoka S, Sekizuka T, Kuroda M, Harada S, Matsushita S, Seki Y, Sakawaki H, Miura T, Akari H, Matano T.
    • Organizer
      The Conference on Retroviruses and Opportunistic Infections (CROI 2020)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] single cell sortingとdeep learningを用いた抗イディオタイプ抗体による抗V3 loop抗体分化の系統学的検討.2019

    • Author(s)
      郭 悠, MD Hassan Zahid, Shashwata Biswas, 桑田岳夫, 松下修三.
    • Organizer
      第33回日本エイズ学会学術集会・総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Anti-idiotype antibodies of neutralizing antibodies targeting CD4-induced (CD4i) epitope on HIV-1 gp120.2019

    • Author(s)
      Shashwata B., Tanaka K., Kaku Y., Kuwata T., Matsushita S.
    • Organizer
      第33回日本エイズ学会・学術集会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Isolation of a monoclonal antibody from a patient infected with HIV-1 subtype AG2019

    • Author(s)
      Hasan MD Zahid, Kaku Yu, Kazuki Tanaka, Takahama Shokichi, Kuwata, Takeo., Matsushita Shuzo.
    • Organizer
      第33回日本エイズ学会学術集会・総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Role of Conventional Antibodies in Control of HIV-1 CRF01_AE viruses2018

    • Author(s)
      Thida W, Kuwata T, Maeda Y, Tran G V, Nguyen K V, Takiguchi M, Gatanaga H and Matsushita S
    • Organizer
      HIV Research for Prevention 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analysis of the envelope gene in the patient treated with maraviroc2018

    • Author(s)
      Lin K H, Kuwata T, Thida W, Shimizu M and Matsushita S
    • Organizer
      第32回日本エイズ学会学術集会・総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Synergistic inhibition by single chain fragment variables and fusion inhibitors in both cell-free and cell-associated HIV-1 infections2018

    • Author(s)
      Mamun M A, Maruta Y, Tanaka K, Alam M, Thida W, Takahama S, Kuwata T and Matsushita S
    • Organizer
      第32回日本エイズ学会学術集会・総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 抗イディオタイプ抗体による抗V3中和単クローン抗体産生B細胞単離方法の検討2018

    • Author(s)
      郭悠、桑田岳夫、田中和樹、Biswas Shashwata、Zahid MD Hassan、松下修三
    • Organizer
      第32回日本エイズ学会学術集会・総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Synergistic inhibition of both cell-free and cell-associated HIV-1 infections by single chain fragment variables and fusion inhibitors.2018

    • Author(s)
      Mamun M., Maruta Y., Tanaka K., Muntasir A, Thida W., Takahama S., Kuwata T., Shimura K., Matsuoka M., Tamamura H., Matsushita S.
    • Organizer
      19th Kumamoto AIDS seminar.
    • Related Report
      2018 Annual Research Report
  • [Presentation] ADCC activity of HIV-1 Env-specific monoclonal antibodies against subtype B and CRF01_AE viruses from Japan and Vietnam.2018

    • Author(s)
      Thida W., Kuwata T., Maeda Y., Yamashiro T., Tran G.V., Nguyen K.V., Takiguchi M., Gatanaga H., Tanaka K., Matsushita S.
    • Organizer
      19th Kumamoto AIDS seminar
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of anti-idiotypic antibodies for neutralizing antibodies against V3-loop of HIV-1.2018

    • Author(s)
      Kaku Y., Tanaka K., Shashwata B., Hassan Z., Kuwata T., Matsushita S.
    • Organizer
      19th Kumamoto AIDS seminar
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 抗HIV-1 V3抗体1C10(0.5γ)に結合する抗体及びその抗原結合断片並びにその応用2019

    • Inventor(s)
      松下修三、桑田岳夫、郭悠
    • Industrial Property Rights Holder
      松下修三、桑田岳夫、郭悠
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-180305
    • Filing Date
      2019
    • Acquisition Date
      2019
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 抗HIV抗体の製造方法2019

    • Inventor(s)
      松下修三、桑田岳夫、清水衛、冨田正浩、道下眞弘
    • Industrial Property Rights Holder
      松下修三、桑田岳夫、清水衛、冨田正浩、道下眞弘
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Acquisition Date
      2019
    • Related Report
      2019 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 抗HIV抗体及びその製造方法2019

    • Inventor(s)
      松下修三、桑田岳夫、清水衛、冨田正浩、道下眞弘
    • Industrial Property Rights Holder
      松下修三、桑田岳夫、清水衛、冨田正浩、道下眞弘
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Acquisition Date
      2019
    • Related Report
      2019 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 抗HIV抗体の製造方法2018

    • Inventor(s)
      松下修三;桑田岳夫; 清水 衛; 冨田正浩; 道下眞弘
    • Industrial Property Rights Holder
      松下修三;桑田岳夫; 清水 衛; 冨田正浩; 道下眞弘
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-203114
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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