Creation of vaccines and RNA acaricides targeting tick antioxidative molecules for controlling ticks

• Project/Area Number: 16H05028
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Kagoshima University
• Principal Investigator: TANAKA TETSUYA 鹿児島大学, 農水産獣医学域獣医学系, 教授 (00322842)
• Co-Investigator(Kenkyū-buntansha): 黒田 俊一 大阪大学, 産業科学研究所, 教授 (60263406) ; 宮田 健 鹿児島大学, 農水産獣医学域農学系, 准教授 (20448591)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2017: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2016: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
• Keywords: マダニ / 抗酸化分子 / ペルオキシレドキシン / グルタチオンSトランスフェラーゼ / フェリチン / 抗マダニワクチン / RNA殺ダニ剤 / リポソーム / 過酸化水素

Outline of Final Research Achievements

The purpose of this study was to clarify the characteristics of the redox balance control mechanism of ticks, to provide new knowledge to the development, research of tick suppression, and to create anti-tick vaccines and RNA acaricides targeting them. Therefore, we worked on the theme of antioxidant molecules, and identified and characterized peroxiredoxin (Prx), glutathione S-transferase (GST), and ferritin (Fer). We investigated the role of antioxidant molecules against acaricides and embryonic development of ticks. Thus, exploiting the properties of antioxidant molecules has been demonstrated to be a promising target molecule for combating ticks.

Academic Significance and Societal Importance of the Research Achievements

[学術的意義] マダニの吸血における酸化ストレス応答の重要性と抗酸化分子の機能・動態を明らかにした。本研究の成果は、マダニ生存基盤である吸血消化・繁殖を根本的にたたき、神経毒性などのないこれまでの化学的殺ダニ剤とは全く作用機序の異なるRNA殺ダニ剤として分子創薬による抗マダニ薬の先駆けになる可能性が高い。
[社会的意義] 本研究はマダニだけでなく、マダニ媒介性感染症をもたらす病原体伝播の阻止効果も期待できることから、安全性や畜産物への薬物残留など化学的殺ダニ剤が抱えている諸問題を根本から解決できる革新的技術を提供できる。

Research Products

• [Journal Article] シリーズ：ダニ研究の最前線とダニ媒介性感染症制御の可能性を探る (2020)
  • Author(s): 川端寛樹、田仲哲也
  • Journal Title: 衛生動物 Volume: 70（1） Pages: 1-2
  • Peer Reviewed
• [Journal Article] A Peroxiredoxin From the Haemaphysalis longicornis Tick Affects Langat Virus Replication in a Hamster Cell Line (2020)
  • Author(s): Kusakisako Kodai、Morokuma Haruki、Talactac Melbourne Rio、Hernandez Emmanuel Pacia、Yoshii Kentaro、Tanaka Tetsuya
  • Journal Title: Frontiers in Cellular and Infection Microbiology Volume: 10 Pages: 7-7
  • DOI: 10.3389/fcimb.2020.00007
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expression analysis of glutathione S-transferases and ferritins during the embryogenesis of the tick Haemaphysalis longicornis (2020)
  • Author(s): Hernandez, E. P., Shimazaki, K., Niihara, H., Umemiya-Shirafuji, R., Fujisaki, K. and Tanaka, T
  • Journal Title: Heliyon Volume: 6(3) Issue: 3 Pages: e03644-e03644
  • DOI: 10.1016/j.heliyon.2020.e03644
  • Peer Reviewed / Open Access
• [Journal Article] マダニの吸血生理と抗マダニワクチン (2020)
  • Author(s): 田仲哲也
  • Journal Title: 衛生動物 Volume: -
  • NAID: 130007864247
  • Peer Reviewed
• [Journal Article] The case for oxidative stress molecule involvement in the tick-pathogen interactions-an omics approach (2019)
  • Author(s): Hernandez, E. P., Talactac, M. R., Fujisaki, K. and Tanaka, T.
  • Journal Title: Dev. Comp. Immunol. Volume: 100 Pages: 103409-103409
  • DOI: 10.1016/j.dci.2019.103409
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Immunofluorescent detection in the ovary of host antibodies against a secretory ferritin injected into female Haemaphysalis longicornis ticks (2018)
  • Author(s): Galay, R. L., Matsuo, T., Hernandez, E. P., Talactac, M. R., Kusakisako, K., Umemiya-Shirafuji, R., Mochizuki, M., Fujisaki, K. and Tanaka, T.
  • Journal Title: Parasitol. Int. Volume: 67 (2) Issue: 2 Pages: 119-122
  • DOI: 10.1016/j.parint.2017.10.006
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Evaluation of vaccine potential of 2-Cys peroxiredoxin from the hard tick Haemaphysalis longicornis (2018)
  • Author(s): Kusakisako, K., Miyata, T., Tsujio, M., Galay, R. L., Talactac, M. R., Hernandez, E. P., Fujisaki, K. and Tanaka, T.
  • Journal Title: Exp. Appl. Acarol. Volume: 74 (1) Issue: 1 Pages: 73-84
  • DOI: 10.1007/s10493-018-0209-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Peroxiredoxins are important for the regulation of hydrogen peroxide concentrations in ticks and tick cell line (2018)
  • Author(s): Kusakisako, K., Hernandez, E. P., Talactac, M. R., Yoshii, K., Umemiya-Shirafuji, R., Fujisaki, K. and Tanaka, T.
  • Journal Title: Ticks Tick Borne Dis. Volume: In press Issue: 4 Pages: 870-881
  • DOI: 10.1016/j.ttbdis.2018.03.016
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] マダニの鉄代謝を制御するフェリチンの展望 (2017)
  • Author(s): 田仲哲也、レミル リングガートン ガライ、白藤(梅宮)梨可、藤崎幸蔵
  • Journal Title: 細胞 Volume: 49 (14) Pages: 25-29
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] マダニペルオシレドキシンの役割－特に吸血における抗酸化機構と宿主の免疫応答について－ (2017)
  • Author(s): 草木迫浩大、藤崎幸蔵、田仲哲也
  • Journal Title: 獣医寄生虫学会誌 Volume: 16 (1・2) Pages: 22-28
  • Peer Reviewed
• [Journal Article] 2-Cys peroxiredoxin is required in successful blood-feeding, reproduction, and antioxidant response in the hard tick Haemaphysalis longicornis (2016)
  • Author(s): Kusakisako K, Galay RL, Umemiya-Shirafuji R, Hernandez EP, Maeda H, Talactac MR, Tsuji N, Mochizuki M, Fujisaki K, Tanaka T.
  • Journal Title: Parasites and Vectors Volume: 9 Issue: 1 Pages: 457-457
  • DOI: 10.1186/s13071-016-1748-2
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] フタトゲチマダニ胚発生における抗酸化分子の発現動態 (2019)
  • Author(s): 島崎 慧, Emmanuel Pacia Hernandez, 新原博子, 藤崎幸蔵, 田仲哲也
  • Organizer: 第27回ダニと疾患のインターフェイスに関するセミナー
• [Presentation] Elucidation of the role of a glutathione S-transferase(GST) during langat virus(LGTV) infection of Ixodes scapularis-dervied tick cells(ISE6) (2019)
  • Author(s): Emmauel Pacia Hernandez, Melbourne Rio Talactac, Kentaro Yoshii, Tetsuya Tanaka
  • Organizer: 第27回ダニと疾患のインターフェイスに関するセミナー
• [Presentation] The Haemaphysalis longicornis larvae needs glutathione S-transferase in the metabolism of flumethrin (2019)
  • Author(s): Emmauel Pacia Hernandez, Kodai Kusakisako, Melbourne Rio Talactac, Remil Linggatong Galay, Takeshi Hatta, Kozo Fujisaki, Naotoshi Tsuji, Tetsuya Tanaka
  • Organizer: 27th Conference of the World Association for the Advancement of Veterinary Parasitology(WAAVP)
  • Int'l Joint Research
• [Presentation] Glutathion S-transferase (HlGST2) are important in oxidative stress management and acaricide metabolisum in the hard ticks Haemaphysalis longicornis (2019)
  • Author(s): Emmauel Hernandez, 草木迫 浩大, Melbourne Talactac, Remil Galay, 八田岳士, 藤崎幸蔵, 辻 尚利, 田仲哲也
  • Organizer: 第162回日本獣医学会学術集会
  • Invited
• [Presentation] 為生殖系フタトゲチマダニ胚発生における鉄イオンの動態と抗酸化分子の局在 (2019)
  • Author(s): 島崎 慧, Emmanuel Pacia Hernandez, 新原博子, 藤崎幸蔵, 田仲哲也
  • Organizer: 第72回日本寄生虫学会南日本支部大会・第69回日本衛生動物学会南日本支部大会合同大会
• [Presentation] ランガットウイルスに感染したフタトゲチマダニにおける抗酸化分子の発現動態 (2019)
  • Author(s): 山田智大, Emmanuel Pacia Hernandez, 新原博子, 藤崎幸蔵, 好井健太郎, 田仲哲也
  • Organizer: 第72回日本寄生虫学会南日本支部大会・第69回日本衛生動物学会南日本支部大会合同大会
• [Presentation] フタトゲチマダニ由来カタラーゼ遺伝子の同定ならびに組換え体を用いた抗酸化活性の検証 (2019)
  • Author(s): 草木迫浩大, 中尾 亮, 田仲哲也, 野中成晃
  • Organizer: 第65 回日本寄生虫学会・日本衛生動物学会 北日本支部合同大会
• [Presentation] Peroxiredoxins are important for blood feeding and reproduction through the regulation of concentrations in the hard tick Haemaphysalis longicornis (2017)
  • Author(s): Kodai Kusakisako, Remil Linggatong Galay, Rika Umemiya-Shirafuji, Emmauel Pacia Hernandez, Hiroki Maeda, Melbourne Rio Talactac, Naotoshi Tsuji, Masami Mochizuki, Kozo Fujisaki, Tetsuya Tanaka
  • Organizer: International Symposium in Veterinary Science: Strengthening The Collaboration between Indonesian and Japanesse Veterinary School
  • Int'l Joint Research
• [Presentation] Interaction of different acaricides with the recombinant glutathione S-transferases of Haemaphysalis longicornis (2017)
  • Author(s): Emmauel Pacia Hernandez, Kodai Kusakisako, Remil Linggatong Galay, Hiroki Maeda, Melbourne Rio Talactac, Masami Mochizuki, Kozo Fujisaki, Tetsuya Tanaka
  • Organizer: International Symposium in Veterinary Science: Strengthening The Collaboration between Indonesian and Japanesse Veterinary School
  • Int'l Joint Research
• [Presentation] The potential of recombinant ferritins as anti-tick vaccine against Haemaphysalis longicornis (2017)
  • Author(s): Remil Linggatong Galay, Takeshi Miyata, Rika Umemiya-Shirafuji, Hiroki Maeda, Kodai Kusakisako, Masami Mochizuki, Kozo Fujisaki, Tetsuya Tanaka
  • Organizer: International Symposium in Veterinary Science: Strengthening The Collaboration between Indonesian and Japanesse Veterinary School
  • Int'l Joint Research
• [Presentation] Preliminary evaluation of vaccine efficacy of potential anti-tick vaccine antigens using a laboratory animal (2017)
  • Author(s): Remil Linggatong Galay, Takeshi Miyata, Rika Umemiya-Shirafuji, Hiroki Maeda, Kodai Kusakisako, Masami Mochizuki, Kozo Fujisaki, Tetsuya Tanaka
  • Organizer: 84th PVMA Annual Convention and Scientific Conference
  • Int'l Joint Research
• [Presentation] マダニの過酸化水素消去酵素2-Cysペルオキシレドキシンの特性解明 (2017)
  • Author(s): 田仲哲也、草木迫浩大、白藤(梅宮)梨可
  • Organizer: 帯広畜産大学原虫病研究センター共同研究成果報告会
  • Invited
• [Presentation] Expression profile of glutathione S-transferases during blood feeding of the hard tick Haemaphysalis longicornis (2017)
  • Author(s): Emmanuel Pacia Hernandez, 草木迫浩大, Melbourne Rio Talactac, Remil Linggatong Galay, 藤崎幸蔵, 田仲哲也
  • Organizer: 第86回日本寄生虫学会大会
• [Presentation] ペルオキシレドキシンは連携して細胞内過酸化水素濃度を制御する (2017)
  • Author(s): 草木迫浩大, Emmanuel Pacia Hernandez, Melbourne Rio Talactac, 好井健太郎, 田仲哲也
  • Organizer: 第86回日本寄生虫学会大会
• [Presentation] The use of laboratory animals in tick rearing and research (2017)
  • Author(s): Remil Linggatong Galay, Hiroki Maeda, Tetsuya Tanaka
  • Organizer: 29th Philippine Association for Laboratory Animal Science (PALAS) Annual Scientific Conference and Workshop
  • Int'l Joint Research
• [Presentation] Peroxiredoxins are important for blood feeding and reproduction through the regulation of hydrogen peroide concentrations in the hard tick Haemaphysalis longicornis (2017)
  • Author(s): Kodai Kusakisako, Tatsunori Masatani, Takeshi Miyata, Remil Linggatong Galay, Rika Umemiya-Shirafuji, Emmauel Pacia Hernandez, Hiroki Maeda, Melbourne Rio Talactac, Naotoshi Tsuji, Masami Mochizuki, Kozo Fujisaki, Tetsuya Tanaka
  • Organizer: One Health 9th Tick and Tick-borne Pathogen Conference and 1st Asia Pacific Rikettsia Conference(TTP9-APRC1)
  • Int'l Joint Research / Invited
• [Presentation] Induction of Ferritin1 expression in Ixodes scapularis embryo derived cell line (ISE6) (2017)
  • Author(s): Emmanuel Pacia Hernandez, 草木迫浩大, RemilGalay, Melbourne Talactac, 好井健太朗, 田仲哲也
  • Organizer: 第160回日本獣医学会学術集会
• [Presentation] マダニの過酸化水素消去酵素2-Cysペルオキシレドキシンの特性解明(－ペルオキシレドキシンの性状解析並びに吸血・産卵に果たす役割について－) (2017)
  • Author(s): 草木迫浩大, 正谷達謄, 宮田 健, Remil Galay, 田仲哲也, 白藤(梅宮)梨可, 前田大輝, Melbourne Talactac, Emmanuel Hernandez, 辻 尚利, 望月雅美, 藤崎幸蔵, 田仲哲也
  • Organizer: 第160回日本獣医学会学術集会
  • Invited
• [Presentation] Glutathione S-transferases could play a role in coping with oxidative stress during blood feeding of the hard tick Haemaphysalis longicornis (2017)
  • Author(s): Emmanuel Pacia Hernandez, Kodai Kusakisako, Melbourne Rio Talactac, Remil Linggatong Galay, Tomohide Matsuo, Takeshi Hatta, Kozo Fujisaki, Tetsuya Tanaka
  • Organizer: The 5th Sapporo Summer Seminar for One Health
  • Int'l Joint Research
• [Book] 犬のライム病（動物の感染症<第四版>） (2019)
  • Author(s): 田仲哲也（編集：明石博臣、内田郁夫、大橋和彦、後藤義孝、須永藤子、高井伸二、宝達 勉）
  • Total Pages: 301
  • Publisher: （株）近代出版
  • ISBN: 9784874022504
• [Book] Ⅳ節足動物 1. ダニ類（動物寄生虫病学<四訂版>） (2019)
  • Author(s): 田仲哲也（編集：板垣 匡、藤﨑幸蔵）
  • Total Pages: 359
  • Publisher: （株）朝倉書店
  • ISBN: 9784254460377
• [Remarks] 鹿児島大学 共同獣医学部獣医学科 病態予防獣医学講座 感染症学分野
  • URL: http://www.vet.kagoshima-u.ac.jp/kadai/V-Infection/sinkoukansen/index.html