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Analysis of the immune mechanism for protection of intrarectal HIV infection

Research Project

Project/Area Number 21H02745
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49060:Virology-related
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

Matano Tetsuro  国立感染症研究所, 副所長, 副所長 (00270653)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2023: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2022: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2021: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywords感染免疫学 / 感染症 / 微生物 / 細胞傷害性T細胞 / 粘膜免疫 / ウイルス / ワクチン / 免疫学 / 微生物学 / 微生物學
Outline of Research at the Start

経粘膜感染は主要なウイルス伝播経路の一つであり、その防御に結びつく免疫機序の解明は学術的にも感染症克服の観点からも重要である。本研究では、経粘膜感染を生じる代表的ウイルスであるHIV(ヒト免疫不全ウイルス)を対象とし、粘膜上皮バリア通過後の粘膜下感染・増殖の阻止による感染成立防御の可能性を検討し、その防御免疫機序の解明を進める。本研究で得られる成果は、ウイルス経粘膜感染防御に向けたワクチン開発等の戦略基盤として極めて重要と考えられる。

Outline of Final Research Achievements

Elucidation of the viral transmission mechanism is a key for the control of infectious disease epidemic. In the process of HIV/SIV transmission, viruses do not infect mucosal epithelial cells but go through the injured mucosal barrier or penetrate it by transcytosis, followed by viral proliferation at the submucosal area. Control of submucosal viral proliferation is important for protection of the establishment of systemic HIV/SIV infection. This study aims at investigating the protective process of submucosal HIV/SIV replication by vaccine-induced immune responses. We established a method for analysis of viral proliferation and immune responses in the rectum mucosa of macaques in several days after intrarectal SIV challenge. We obtained results indicating reduced viral proliferation in the rectum mucosa by vaccine-induced virus-specific CD8+ T cell responses after SIV challenge. This study contributes to elucidation of the protective process against mucosal HIV transmission.

Academic Significance and Societal Importance of the Research Achievements

本研究は、個体から個体へのウイルス感染伝播の防御機序の解明をテーマとし、主要な感染伝播経路である経粘膜感染のうち、粘膜上皮細胞に感染せず粘膜上皮バリアを通過する代表的ウイルスであるHIVの経粘膜感染防御過程の解明に結びつくものである。ワクチン開発を含む、HIV感染防御法の開発への貢献という観点で社会的意義は大きい。粘膜下局所の防御過程に関する知見獲得は、新規性が高く、学術的にも高い意義を有している。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (35 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (7 results) Journal Article (16 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 16 results,  Open Access: 12 results) Presentation (12 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results)

  • [Int'l Joint Research] NIHE(国立衛生疫学研究所)(ベトナム)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] NMIMR(野口記念医学研究所)(ガーナ)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] George Washington University/NIH/NIAID/Northwestern University(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] NMIMR(ガーナ)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] NIHE(ベトナム)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] George Washington University/NIH(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of Ghana(ガーナ)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] HIV-1 RNAs whose transcription initiates from the third deoxyguanosine of GGG tract in the 5′ long terminal repeat serve as a dominant genome for efficient provirus DNA formation2024

    • Author(s)
      Yoshida Takeshi、Kasuya Yuho、Yamamoto Hiroyuki、Kawai Gota、Hanaki Ken-ichi、Matano Tetsuro、Masuda Takao
    • Journal Title

      Journal of Virology

      Volume: 98 Issue: 2

    • DOI

      10.1128/jvi.01825-23

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Longitudinal analysis of microbiome composition in Ghanaians living with HIV-12024

    • Author(s)
      Runtuwene Lucky Ronald、Parbie Prince Kofi、Mizutani Taketoshi、Ishizaka Aya、Matsuoka Saori、Abana Christopher Zaab-Yen、Kushitor Dennis、Bonney Evelyn Yayra、Ofori Sampson Badu、Kiyono Hiroshi、Ishikawa Koichi、Ampofo William Kwabena、Matano Tetsuro
    • Journal Title

      Frontiers in Microbiology

      Volume: 15 Pages: 1359402-1359402

    • DOI

      10.3389/fmicb.2024.1359402

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Plasmacytoid dendritic cells stimulated with Lactococcus lactis strain Plasma produce soluble factors to suppress SARS-CoV-2 replication2023

    • Author(s)
      Ishii Hiroshi、Jounai Kenta、Tsuji Ryohei、Ohshio Konomi、Kaneda Daiki、Okazaki Midori、Harada Shigeyoshi、Fujiwara Daisuke、Matano Tetsuro
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 662 Pages: 26-30

    • DOI

      10.1016/j.bbrc.2023.04.046

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HTLV-1 Proliferation after CD8 + Cell Depletion by Monoclonal Anti-CD8 Antibody Administration in Latently HTLV-1-Infected Cynomolgus Macaques2023

    • Author(s)
      Midori Nakamura-Hoshi, Takushi Nomura, Masako Nishizawa, Trang Thi Thu Hau, Hiroyuki Yamamoto, Midori Okazaki, Hiroshi Ishii, Kenzo Yonemitsu, Yuriko Suzaki, Yasushi Ami, and Tetsuro Matano
    • Journal Title

      Microbiology Spectrum

      Volume: 11(4) Issue: 4

    • DOI

      10.1128/spectrum.01518-23

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Breadth and Durability of SARS-CoV-2-Specific T Cell Responses following Long-Term Recovery from COVID-192023

    • Author(s)
      Dang Thi Thu Thao、Anzurez Alitzel、Nakayama-Hosoya Kaori、Miki Shoji、Yamashita Kazuo、de Souza Mark、Matano Tetsuro、Kawana-Tachikawa Ai
    • Journal Title

      Microbiology Spectrum

      Volume: 11 Issue: 4

    • DOI

      10.1128/spectrum.02143-23

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sendai virus particles carrying target virus glycoproteins for antibody induction2022

    • Author(s)
      Ishii Hiroshi、Nakamura-Hoshi Midori、Shu Tsugumine、Matano Tetsuro
    • Journal Title

      Vaccine

      Volume: 40 Issue: 16 Pages: 2420-2431

    • DOI

      10.1016/j.vaccine.2022.03.008

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Env-independent protection of intrarectal SIV challenge by vaccine induction of Gag/Vif-specific CD8+ T cells but not CD4+ T cells2022

    • Author(s)
      Ishii Hiroshi、Terahara Kazutaka、Nomura Takushi、Okazaki Midori、Yamamoto Hiroyuki、Shu Tsugumine、Sakawaki Hiromi、Miura Tomoyuki、Watkins David I.、Matano Tetsuro
    • Journal Title

      Molecular Therapy

      Volume: 30 Issue: 5 Pages: 2048-2057

    • DOI

      10.1016/j.ymthe.2022.02.023

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Super high-resolution single-molecule sequence-based typing of HLA class I alleles in HIV-1 infected individuals in Ghana2022

    • Author(s)
      Nii-Trebi Nicholas I.、Matsuoka Saori、Kawana-Tachikawa Ai、Bonney Evelyn Y.、Abana Christopher Z.、Ofori Sampson B.、Mizutani Taketoshi、Ishizaka Aya、Shiino Teiichiro、Ohashi Jun、Naruse Taeko K.、Kimura Akinori、Kiyono Hiroshi、Ishikawa Koichi、Ampofo William K.、Matano Tetsuro
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 6 Pages: e0269390-e0269390

    • DOI

      10.1371/journal.pone.0269390

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Association of envelope-specific B-cell differentiation and viral selective pressure signatures in HIV-1 CRF01_AE infection2022

    • Author(s)
      Hau Trang Thi Thu、Nishizawa Masako、Harada Shigeyoshi、Phan My Ha、Kanno Yoshiaki、Nomura Takushi、Matsuoka Saori、Kawana-Tachikawa Ai、Hall William W.、Matano Tetsuro、Nguyen Lan Anh Thi、Yamamoto Hiroyuki
    • Journal Title

      AIDS

      Volume: 36 Issue: 12 Pages: 1629-1641

    • DOI

      10.1097/qad.0000000000003323

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Neutralizing-antibody-independent SARS-CoV-2 control correlated with intranasal-vaccine-induced CD8+ T?cell responses2022

    • Author(s)
      Ishii H, Nomura T, Yamamoto H, Nishizawa M, Thu Hau TT, Harada S, Seki S, Nakamura-Hoshi M, Okazaki M, Daigen S, Kawana-Tachikawa A, Nagata N, Iwata-Yoshikawa N, Shiwa N, Suzuki T, Park ES, Ken M, Onodera T, Takahashi Y, Kusano K, Shimazaki R, Suzaki Y, Ami Y, Matano T
    • Journal Title

      Cell Reports Medicine

      Volume: 3 Issue: 2 Pages: 100520-100520

    • DOI

      10.1016/j.xcrm.2022.100520

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hierarchy of multiple viral CD8+ T-cell epitope mutations in sequential selection in simian immunodeficiency infection2022

    • Author(s)
      Ntim Nana Afia Asante、Ishii Hiroshi、Jomori Moe、Yamamoto Hiroyuki、Matano Tetsuro、Nomura Takushi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 607 Pages: 124-130

    • DOI

      10.1016/j.bbrc.2022.03.108

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dysbiotic Fecal Microbiome in HIV-1 Infected Individuals in Ghana2021

    • Author(s)
      Parbie Prince Kofi、Mizutani Taketoshi、Ishizaka Aya、Kawana-Tachikawa Ai、Runtuwene Lucky Ronald、Seki Sayuri、Abana Christopher Zaab-Yen、Kushitor Dennis、Bonney Evelyn Yayra、Ofori Sampson Badu、Uematsu Satoshi、Imoto Seiya、Kimura Yasumasa、Kiyono Hiroshi、Ishikawa Koichi、Ampofo William Kwabena、Matano Tetsuro
    • Journal Title

      Frontiers in Cellular and Infection Microbiology

      Volume: 11 Pages: 646467-646467

    • DOI

      10.3389/fcimb.2021.646467

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neutralizing Antibody Induction Associated with a Germline Immunoglobulin Gene Polymorphism in Neutralization-Resistant SIVsmE543-3 Infection2021

    • Author(s)
      Nomura Yuto、Matsuoka Saori、Okazaki Midori、Kuwata Takeo、Matano Tetsuro、Ishii Hiroshi
    • Journal Title

      Viruses

      Volume: 13 Issue: 6 Pages: 1181-1181

    • DOI

      10.3390/v13061181

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Late-phase dominance of a single epitope-specific CD8+ T-cell response in passive neutralizing antibody-infused simian immunodeficiency virus controllers2021

    • Author(s)
      Kanno Yoshiaki、Hau Trang Thi Thu、Kurokawa Rise、Nomura Takushi、Nishizawa Masako、Matano Tetsuro、Yamamoto Hiroyuki
    • Journal Title

      AIDS

      Volume: 35 Issue: 14 Pages: 2281-2288

    • DOI

      10.1097/qad.0000000000003013

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+?T cells in?cynomolgus?macaques2021

    • Author(s)
      Nomura T, Yamamoto H, Nishizawa M, Hau TTT, Harada S, Ishii H, Seki S, Nakamura-Hoshi M, Okazaki M, Daigen S, Kawana-Tachikawa A, Nagata N, Iwata-Yoshikawa N, Shiwa N, Iida S, Katano H, Suzuki T, Park ES, Maeda K, Suzaki Y, Ami Y, Matano T
    • Journal Title

      PLOS Pathogens

      Volume: 17 Issue: 7 Pages: 1-16

    • DOI

      10.1371/journal.ppat.1009668

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nef‐specific CD107a+ CD4+ T‐cell responses in a rhesus macaque (Macaca mulatta) showing partial simian immunodeficiency virus control following passive neutralizing antibody infusion2021

    • Author(s)
      Hau Trang Thi Thu、Kanno Yoshiaki、Nishizawa Masako、Nomura Takushi、Matano Tetsuro、Yamamoto Hiroyuki
    • Journal Title

      Journal of Medical Primatology

      Volume: 51 Issue: 1 Pages: 56-61

    • DOI

      10.1111/jmp.12551

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 感染症基礎研究:ベンチからベットへ2023

    • Author(s)
      俣野哲朗
    • Organizer
      第97回日本感染症学会総会・学術講演会/第71回日本化学療法学会学術集会合同学会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Protective efficacy of intranasal vaccination with a Sendai virus vector expressing a spike antigen against SARS-CoV-2 infection in mice.2023

    • Author(s)
      Hiroshi Ishii, Kosuke Miyauchi, Shigeyoshi Harada, Midori Nakamura-Hoshi, Sayuri Seki, Daiki Kaneda, Midori Okazaki, Tetsuro Matano
    • Organizer
      The 12th IAS Conference on HIV Science (IAS 2023)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 抗体誘導ワクチンでHTLV-1感染が制御されたカニクイサルにおけるCD8陽性細胞枯渇実験2023

    • Author(s)
      中村碧、石井洋、野村拓志、岡﨑みどり、米満研三、須崎百合子、網康至、俣野哲朗
    • Organizer
      第70回日本ウイルス学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 経鼻S抗原発現ワクチンのマウスにおけるSARS-CoV-2感染防御効果2023

    • Author(s)
      石井洋、宮内浩典、原田恵嘉、中村碧、関紗由里、金田大樹、岡崎みどり、俣野哲朗
    • Organizer
      第70回日本ウイルス学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 抗HTLV-1 Env抗体誘導ワクチンのカニクイサルでのHTLV-1感染防御効果2023

    • Author(s)
      中村碧、石井洋、野村拓志、岡﨑みどり、相内章、長谷川秀樹、米満研三、須崎百合子、網康至、俣野哲朗
    • Organizer
      第27回日本ワクチン学会・第64回日本臨床ウイルス学会合同学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ワクチン誘導中和抗体のHTLV-1感染防御効果2023

    • Author(s)
      中村碧、石井洋、野村拓志、岡﨑みどり、相内章、長谷川秀樹、米満研三、須崎百合子、網康至、俣野哲朗
    • Organizer
      第9回日本HTLV-1学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Protection against HTLV-1 challenge by vaccination inducing antibodies in macaques.2023

    • Author(s)
      Midori Nakamura-Hoshi, Hiroshi Ishii, Takushi Nomura, Midori Okazaki, Yuriko Suzaki, Kenzo Yonemitsu, Yasushi Ami, Tetsuro Matano.
    • Organizer
      The 30th Conference on Retroviruses and Opportunistic Infections (CROI2023)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Protective efficacy of a vaccine inducing anti-Env antibodies against HTLV-1 challenge in cynomolgus macaques.2022

    • Author(s)
      Hiroshi Ishii, Midori Nakamura-Hoshi, Takushi Nomura, Midori Okazaki, Yuriko Suzaki, Yasushi Ami, Tetsuro Matano.
    • Organizer
      The 39th Annual Symposium on Nonhuman Primate Models for AIDS, Portland
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] カニクイサルにおけるEnv抗原発現ワクチン接種がSHIV感染急性期に及ぼす影響の解析.2022

    • Author(s)
      石井洋、野村拓志、中村碧、岡崎みどり、俣野哲朗.
    • Organizer
      第36回日本エイズ学会学術集会・総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Neutralizing antibody induction associated with a germline immunoglobulin gene polymorphism in rhesus macaques after neutralization-resistant SIVsmE543-3 infection2021

    • Author(s)
      Hiroshi Ishii, Saori Matsuoka, Yuto Nomura, Takeshi Kuwata, Tetsuro Matano
    • Organizer
      The 11th IAS Conference on HIV Science (IAS2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 中和抗体抵抗性SIV感染サルにおいて免疫グロブリン遺伝子多型が中和抗体誘導に及ぼす影響の解析2021

    • Author(s)
      野村柚仁、松岡佐織、岡崎みどり、桑田岳夫、俣野哲朗、石井洋
    • Organizer
      第35回日本エイズ学会学術集会・総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Hierarchy of CD8+ T-cell responses targeting protective MHC-I-associated epitopes and selection of viral escape mutations in a macaque AIDS model2021

    • Author(s)
      Nana Afia Asante Ntim, Takushi Nomura, Hiroshi Ishii, Tetsuro Matano
    • Organizer
      第35回日本エイズ学会学術集会・総会
    • Related Report
      2021 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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