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Improvement of vaccines against human papilloma viruses and evaluation of treatments of human papillomavirus vaccination-associated neuro-immunopathic syndrome with pathological model mice

Research Project

Project/Area Number 17K08671
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionTokyo Medical University

Principal Investigator

Aratani Satoko  東京医科大学, 医学部, 講師 (40387064)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsHANS / モデルマウス / 視床下部 / HPVワクチン / 脳神経疾患
Outline of Final Research Achievements

Cervical cancer is the most common type of cancer in women and is associated with the most death in young women. Because infection with human papilloma viruses (HPVs) is necessary for the occurrence of cervical cancer, protection from HPV is effective in avoiding the disease. Vaccines against HPVs were developed. However, adverse reactions related to the vaccination, such as myalgia, chronic fatigue, and neurological manifestations were reported. We have coined these reactions as human papillomavirus vaccination-associated neuro-immunopathic syndrome (HANS). This syndrome is the important problem that we have to take initiative to elucidate. To elucidate the mechanism of HANS, we established an animal model of the syndrome with HPV vaccine. The mice indicated HANS like phenotypes such as tail reflex, decrease of motor coordination. We analyzed the changes of gene expression level inthe model mice. It was suggested that expression of autoimmune disease-related factors were activated.

Academic Significance and Societal Importance of the Research Achievements

HPV ワクチンは子宮頸がん予防に対して効果的である一方で、各国より慢性の有害な副反応が報告されている。健康であった若い女性が後遺症に悩まされるなど社会的に大きな問題となっており、病因・病態の解明が急務とされている。その症状は疼痛、運動障害、高次機能障害、内分泌異常など多岐にわたり、現在ワクチン投与による侵襲的な障害は検出されておらず HANS の発症機構、なぜ同ワクチンでのみ高頻度で発症するのかなどほとんど明らかになっていない。そこでHANS モデルマウスの樹立、病因解析を行うことは、ワクチンの改良や同疾患の予防・治療に関して多くの知見を与えるものであると期待できる。

Report

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

    (16 results)

All 2019 2018 2017 Other

All Journal Article (5 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (9 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (2 results)

  • [Journal Article] The NRF2-PGC-1β pathway activates kynurenine aminotransferase 4 via attenuation of an E3 ubiquitin ligase, Synoviolin, in a cecal ligation/perforation -induced septic mouse model.2018

    • Author(s)
      Ishida Y, Fujita H, Aratani S, Chijiiwa M, Taniguchi N, Yokota M, Ogihara Y, Uoshima N, Nagashima F, Uchino H, Nakajima T.
    • Journal Title

      Mol. Med. Rep.

      Volume: 18(2) Pages: 2467-2475

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of the inhibitory activity of E3 ligase Syvn1 in walnut extract.2018

    • Author(s)
      Fujita H, Aratani S, Yagishita N, Nishioka K, Nakajima T.
    • Journal Title

      Mol. Med. Rep

      Volume: 8(6) Pages: 5701-5708

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 線維筋痛症の病態・病因2018

    • Author(s)
      荒谷 聡子、中島 利博
    • Journal Title

      日本臨牀

      Volume: 76 (11) Pages: 1921-1926

    • Related Report
      2018 Research-status Report
  • [Journal Article] What occurs in human papilloma virus vaccination-associated neuro-immunopathic syndrome (HANS)? : implications of previous animal model studies2018

    • Author(s)
      Aratani S, Kuroiwa Y, Fujita H, Usui C, Yokota S, Nakamura I, Nishioka K, Nakajima T
    • Journal Title

      The Autonomic Nervous System

      Volume: 55 Pages: 915-919

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibitory effects of ubiquitination of synoviolin by PADI42017

    • Author(s)
      Aratani S、Fujita H、Yagishita N、Yamano 、Okubo Y、Nishioka K、Nakajima T
    • Journal Title

      Molecular Medicine Reports

      Volume: 16 Issue: 6 Pages: 9203-9209

    • DOI

      10.3892/mmr.2017.7764

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] シノビオリンを介した全身性エリテマトーデスの病因・病態制御メカニズムの解析2019

    • Author(s)
      荒谷 聡子、宮川 聡美、藤田 英俊、中島 利博
    • Organizer
      第 6 回JCRベーシックリサーチカンファレンス
    • Related Report
      2019 Annual Research Report
  • [Presentation] リウマチ滑膜細胞の新規増殖機構の解明2019

    • Author(s)
      藤田 英俊、荒谷 聡子、横田 真穂、中島 利博
    • Organizer
      第 6 回JCRベーシックリサーチカンファレンス
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脳内炎症に関わるキヌレニンの代謝機構の解明2018

    • Author(s)
      藤田 英俊、石田 裕介、荒谷 聡子、横田 真穂、内野 博之、中島 利博
    • Organizer
      日本線維筋痛症学会第 10 回学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 線維筋痛症における当院での関節超音波検査の取り組み2018

    • Author(s)
      西森 美佐子、中平 律子、山口 結花、梅原由加里、荒谷 聡子、中島 若巳、北川 中行、中谷  孝、中島 利博
    • Organizer
      日本線維筋痛症学会第 10 回学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] A study on our novel murine model of Humanpapillomavirus-associated Neuroimmunopathic Syndrome (HANS)2017

    • Author(s)
      Nakajima T, Aratani S, Fujita H, Kuroiwa Y, Usui C, Yokota S, Nakamura I, Nishioka K
    • Organizer
      国際自律神経学会 ISAN2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 新規ヒトパピローマウイルスワクチン関連神経免疫異常症候群モデルマウスの樹立とその病態解析2017

    • Author(s)
      荒谷聡子
    • Organizer
      第18回 運動器科学研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] モデルマウスを用いたヒトパピローマウイルスワクチン関連神経免疫異常症候群の病態解析2017

    • Author(s)
      荒谷聡子、藤田英俊、黒岩義之、臼井千恵、横田俊平、中村郁郎、西岡久寿樹、中島利博
    • Organizer
      日本線維筋痛症学会  第9回学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 線維筋痛症における関節超音波検査の活用法2017

    • Author(s)
      西森美佐子、中平律子、山口結花、梅原由加里、荒谷聡子、中島若巳、北川中行、中谷孝、中島利博
    • Organizer
      日本線維筋痛症学会 第9回学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Development of novel regulatory methods of mitochondrial functions2017

    • Author(s)
      Fujita H, Aratani S, Yokota M, Nakajima T
    • Organizer
      The 16th International Symposium on Advanced Technology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Remarks] 東京医科大学医学総合研究所運動器科学研究部門

    • URL

      http://toshinakajima2014.wixsite.com/tokyomed

    • Related Report
      2019 Annual Research Report
  • [Remarks] 東京医科大学 医学総合研究所 運動器科学研究部門

    • URL

      http://toshinakajima2014.wixsite.com/tokyomed

    • Related Report
      2018 Research-status Report 2017 Research-status Report

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

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