Dvelopment of novel adjuvant which constructed by DNA origami technology

• Project/Area Number: 24659836
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Niigata University
• Principal Investigator: TERAO Yutaka 新潟大学, 医歯学系, 教授 (50397717)
• Co-Investigator(Kenkyū-buntansha): KAWABATA Shigetada 大阪大学, 大学院歯学研究科, 教授 (50273694) ; NAKATA Masanobu 大阪大学, 大学院歯学研究科, 准教授 (90444497) ; SUMITOMO Tomoko 大阪大学, 大学院歯学研究科, 助教 (50423421)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: アジュバント / DNAオリガミ / ワクチン

Research Abstract

Recently, pathogenic microorganisms acquired drug-resistance, and they are spreading throughout the world. Antibiotics were presented as "magic bullets" against infectious diseases in the 20th century, however, the heavy usage of antibiotics has led to the appearance of drug-resistant microorganisms. Thus, it has become difficult to treat most infantile diarrhea with basic antibiotics in the developing countries. Now, it is important to develop and improve the enteric and general immune activators on the basis of fundamental investigations. In this proposal, we focus on a CpG motif among the DNA sequence. The CpG motif is observed at high frequency in the genomes of pathogenic microorganisms. It works as an immune activator to boost production of antigen-specific immune responses. In this study, we constructed "DNA origami" immune activators being fixed the GpG motifs to the outside using M13 DNA, aiming to obtain the immunopotentiating effect.

Research Products

• [Journal Article] Penetration kinetics of four mouthrinses into Streptococcus mutans biofilms analyzed by direct time-lapse visualization (2014)
  • Author(s): Wakamatsu, R., Takenaka, S., Ohsumi, T., Terao, Y., Ohshima, H., and Okiji, T
  • Journal Title: Clin. Oral Invest Volume: 8 Pages: 625-34
  • Peer Reviewed
• [Journal Article] Penetration kinetics of four mouthrinses into Streptococcus mutans biofilms analyzed by direct time-lapse visualization. (2014)
  • Author(s): Wakamatsu, R., Takenaka, S., Ohsumi, T., Terao, Y., Ohshima, H., and Okiji, T.
  • Journal Title: Clin. Oral Invest. Volume: 8 Pages: 625-634
  • Peer Reviewed
• [Journal Article] STO feeder cells are useful for propagation of primarily cultured human deciduous dental pulp cells in view of elimination of contaminated bacteria and promotion of cellular outgrowth (2013)
  • Author(s): Murakami, T., Saitoh, I., Inada, E., Kurosawa, M., Iwase, Y., Noguchi, H., Terao, Y., Yamasaki, Y., Hayasaki, H., and Sato, M
  • Journal Title: Cell Medicine Volume: 6 Pages: 75-81
  • Peer Reviewed
• [Journal Article] Streptococcus pneumoniae invades erythrocytes and utilizes them to evade human innate immunity (2013)
  • Author(s): Yamaguchi, M., Terao, Y., Mori-Yamaguchi, M., Domon, H., Sakaue, Y., Yagi, T., Nishino, K., Yamaguchi, A., Nizet, V., and Kawabata, S
  • Journal Title: PLoS one Volume: 8 Pages: 77282-77282
  • Peer Reviewed
• [Journal Article] Cysteine proteinase from Streptococcus pyogenes enables to evade innate immunity via degradation of complement factors (2013)
  • Author(s): Honda-Ogawa, M., Ogawa, T., Terao, Y., Sumitomo, T., Nakata, M., Ikebe, K., Maeda, Y., and Kawabata, S
  • Journal Title: J. Biol. Chem Volume: 288 Pages: 15854-15864
  • Peer Reviewed
• [Journal Article] Group A streptococcal cysteine protease cleaves epithelial junctions and contributes to bacterial translocation (2013)
  • Author(s): Sumitomo, T., Nakata, M., Higashino, M., Terao, Y., and Kawabata, S
  • Journal Title: J. Biol. Chem Volume: 288 Pages: 13317-24
  • Peer Reviewed
• [Journal Article] The virulence factors and pathogenic mechanisms on Streptococcus pyogenes (2013)
  • Author(s): Yamaguchi, M., Terao, Y., and Kawabata, S
  • Journal Title: Cell Microbiol Volume: 15 Pages: 503-511
  • Peer Reviewed
• [Journal Article] Hydrogen peroxide produced by oral streptococci induces macrophage cell death (2013)
  • Author(s): Okahashi, N., Nakata, M., Sumitomo, T., Terao, Y., and Kawabata, S
  • Journal Title: PLoS one Volume: 8 Pages: 62563-62563
  • Peer Reviewed
• [Journal Article] MicroRNA fragments derived from Streptococcus pyogenes enable activation of neutrophil phagocytosis : in vitro study (2013)
  • Author(s): Ogawa T., Terao Y., Honda-Ogawa M., Hashimoto S., Ikebe K., Maeda Y., and Kawabata S
  • Journal Title: Microb Infect Volume: 15 Pages: 212-218
  • Peer Reviewed
• [Journal Article] STO feeder cells are useful for propagation of primarily cultured human deciduous dental pulp cells in view of elimination of contaminated bacteria and promotion of cellular outgrowth. (2013)
  • Author(s): Murakami, T., Saitoh, I., Inada, E., Kurosawa, M., Iwase, Y., Noguchi, H., Terao, Y., Yamasaki, Y., Hayasaki, H., and Sato, M.
  • Journal Title: Cell Medicine Volume: 6 Pages: 75-81
  • Peer Reviewed
• [Journal Article] Streptococcus pneumoniae invades erythrocytes and utilizes them to evade human innate immunity. (2013)
  • Author(s): Yamaguchi, M., Terao, Y.*, Mori-Yamaguchi, M., Domon, H., Sakaue, Y., Yagi, T., Nishino, K., Yamaguchi, A., Nizet, V., and Kawabata, S.
  • Journal Title: PLoS one Volume: 8
  • Peer Reviewed
• [Journal Article] Cysteine proteinase from Streptococcus pyogenes enables to evade innate immunity via degradation of complement factors. (2013)
  • Author(s): Honda-Ogawa, M., Ogawa, T., Terao, Y.*, Sumitomo, T., Nakata, M., Ikebe, K., Maeda, Y., and Kawabata, S.
  • Journal Title: J. Biol. Chem. Volume: 288 Pages: 15854-15864
  • Peer Reviewed
• [Journal Article] Group A streptococcal cysteine protease cleaves epithelial junctions and contributes to bacterial translocation. (2013)
  • Author(s): Sumitomo, T., Nakata, M., Higashino, M., Terao, Y., and Kawabata, S.
  • Journal Title: J. Biol. Chem. Volume: 288 Pages: 13317-13324
  • Peer Reviewed
• [Journal Article] The virulence factors and pathogenic mechanisms on Streptococcus pyogenes. (2013)
  • Author(s): Yamaguchi, M., Terao, Y., and Kawabata, S.
  • Journal Title: Cell. Microbiol. Volume: 15 Pages: 503-511
  • Peer Reviewed
• [Journal Article] Hydrogen peroxide produced by oral streptococci induces macrophage cell death. (2013)
  • Author(s): 8. Okahashi, N., Nakata, M., Sumitomo, T., Terao, Y., and Kawabata, S.
  • Journal Title: PLoS one Volume: 8
  • Peer Reviewed
• [Journal Article] MicroRNA fragments derived from Streptococcus pyogenes enable activation of neutrophil phagocytosis: in vitro study. (2013)
  • Author(s): Ogawa T., Terao Y.*, Honda-Ogawa M., Hashimoto S., Ikebe K., Maeda Y., and Kawabata S.
  • Journal Title: Microb. Infect Volume: 15 Pages: 212-218
  • Peer Reviewed
• [Journal Article] Hydrogen peroxide produced by oral streptococci induces macrophage cell death. (2013)
  • Author(s): Okahashi, N., Nakata, M., Sumitomo, T., Terao, Y., and Kawabata, S.
  • Journal Title: PLoS one Volume: in press
  • Peer Reviewed
• [Journal Article] Neonatal pleural empyema caused by emm type 6 group A Streptococcus. (2013)
  • Author(s): Nohara, F., Nagaya, K., Asai, H., Tsuchida, E., Okamoto, T., Hayashi, T., Sakata, H., Terao, Y., and Azuma, H.
  • Journal Title: Pediatirics International Volume: in press
  • Peer Reviewed
• [Journal Article] The virulence factors and pathogenic mechanisms on Streptococcus pyogenes. (2013)
  • Author(s): Yamaguchi, M., Terao, Y., and Kawabata, S.
  • Journal Title: Cell. Microbiology Volume: in press
  • Peer Reviewed
• [Journal Article] MicroRNA fragments derived from Streptococcus pyogenes enable activation of neutrophil phagocytosis: in vitro study. (2013)
  • Author(s): Ogawa, T., Terao, Y., Honda-Ogawa, M., Hashimoto, S., Ikebe, K., Maeda, Y., and Kawabata, S.
  • Journal Title: Microb. Infect. Volume: 15 Pages: 212-218
  • Peer Reviewed
• [Journal Article] Group A streptococcus adheres to pharyngeal epithelial cells with salivary proline-rich proteins via GrpE chaperone protein (2012)
  • Author(s): Murakami, J., Terao, Y., Morisaki, I., Hamada, S., and Kawabata, S
  • Journal Title: J. Biol. Chem Volume: 287 Pages: 22266-22275
  • Peer Reviewed
• [Journal Article] α-enolase of Streptococcus pneumoniae induces formation of neutrophil extracellular traps (2012)
  • Author(s): Mori, Y., Yamaguchi, M., Terao, Y., Hamada, S., Ooshima, T., and Kawabata, S
  • Journal Title: J. Biol. Chem Volume: 287 Pages: 10472-10481
  • Peer Reviewed
• [Journal Article] Long-term survival of salivary streptococci on dental devices made of EVA (2012)
  • Author(s): Ogawa, T., Yamasaki, S., Honda, M., Terao, Y., Kawabata, S., and Maeda, Y
  • Journal Title: Int J. Oral Science Volume: 4 Pages: 14-8
  • Peer Reviewed
• [Journal Article] Involvement of T6 pili in biofilm formation by serotype M6 Streptococcus pyogenes (2012)
  • Author(s): Kimura, K. R., Nakata, M., Sumitomo, T., Kreikemeyer, B., Podbielski, A., Terao, Y., and Kawabata, S
  • Journal Title: J. Bacteriol Volume: 194 Pages: 804-812
  • Peer Reviewed
• [Journal Article] S-carboxymethylcysteine inhibits adherence of Streptococcus pneumoniae to human alveolar epithelial cells (2012)
  • Author(s): Sumitomo, T., Nakata, M., Yamaguchi, M., Terao, Y., and Kawabata S
  • Journal Title: J. Med. Microbiol Volume: 61 Pages: 101-108
  • Peer Reviewed
• [Journal Article] Group A streptococcus adheres to pharyngeal epithelial cells with salivary proline-rich proteins via GrpE chaperone protein. (2012)
  • Author(s): Murakami, J., Terao, Y., Morisaki, I., Hamada, S., and Kawabata, S.
  • Journal Title: J. Biol. Chem. Volume: 287 Pages: 22266-22275
  • Peer Reviewed
• [Journal Article] α-enolase of Streptococcus pneumoniae induces formation of neutrophil extracellular traps. (2012)
  • Author(s): Mori, Y., Yamaguchi, M., Terao, Y., Hamada, S., Ooshima, T., and Kawabata, S.
  • Journal Title: J. Biol. Chem. Volume: 287 Pages: 10472-10481
  • Peer Reviewed
• [Journal Article] Long-term survival of salivary streptococci on dental devices made of EVA. (2012)
  • Author(s): Ogawa, T., Yamasaki, S., Honda, M., Terao, Y., Kawabata, S., and Maeda, Y.
  • Journal Title: Int. J. Oral Science Volume: 4 Pages: 14-18
  • Peer Reviewed
• [Journal Article] Involvement of T6 pili in biofilm formation by serotype M6 Streptococcus pyogenes. (2012)
  • Author(s): Kimura, K. R., Nakata, M., Sumitomo, T., Kreikemeyer, B., Podbielski, A., Terao, Y., and Kawabata, S.
  • Journal Title: J. Bacteriol. Volume: 194 Pages: 804-812
  • Peer Reviewed
• [Journal Article] S-carboxymethylcysteine inhibits adherence of Streptococcus pneumoniae to human alveolar epithelial cells. (2012)
  • Author(s): Sumitomo, T., Nakata, M., Yamaguchi, M., Terao, Y., and Kawabata S.
  • Journal Title: J. Med. Microbiol. Volume: 61 Pages: 101-108
  • Peer Reviewed
• [Journal Article] Neonatal pleural empyema caused by emm type 6 group A streptococcus
  • Author(s): Nohara, F., Nagaya, K., Asai, H., Tsuchida, E., Okamoto, T., Hayashi, T., Sakata, H., Terao, Y., and Azuma, H
  • Journal Title: Pediatirics International Volume: (in press)
  • Peer Reviewed
• [Presentation] Hydrogen peroxide produced by oral streptococci induces macrophage cell deth (2014)
  • Author(s): N. Okahashi,, M. Nakata, S. Sumitomo, Y. Terao, S. Kawabata
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 東京都，タワーホール船堀
• [Presentation] バイオイメージング研究から始まる感染制御 (2013)
  • Author(s): 寺尾豊
  • Organizer: 金沢医科大学大学院医学研究セミナー講演
  • Place of Presentation: 石川市
  • Year and Date: 2013-05-22
• [Presentation] ヒト補体免疫系回避機構におけるStreptococcus pyogenes分泌型プロテアーゼSpeBの機能解析 (2013)
  • Author(s): 本多真理子,寺尾豊,住友倫子,中田匡宣,川端重忠
  • Organizer: 第5回口腔環境制御」カテゴリー集会
  • Place of Presentation: 長﨑市
  • Year and Date: 2013-02-01
• [Presentation] Lion Award受賞講演 (2013)
  • Author(s): 寺尾豊
  • Organizer: 第55回歯科基礎医学会学術大会
  • Place of Presentation: 岡山市
• [Presentation] Moleculara mechanisms of complement evasion by Streptococcus pyogenes cysteine protease SpeB (2013)
  • Author(s): 本多真理子,寺尾豊,住友倫子,中田匡宣,川端重忠
  • Organizer: 第86回日本細菌学会総会
  • Place of Presentation: 千葉市
• [Presentation] Group A streptococcal cysteine proteases, SpeB and Sib35, cleave epithelial junctions (2013)
  • Author(s): Tomoko Sumitomo, Miharu Higashino, Akari Kominami, Masanobu Nakata, Yutaka Terao, and Shigetada Kawabata
  • Organizer: 第86回日本細菌学会総会
  • Place of Presentation: 千葉市
• [Presentation] Cell wall anchoring mechanism of FCT region type 3 pili in Streptococcus pyogenes (2013)
  • Author(s): Masanobu Nakata, Tomoko Sumitomo, Yutaka Terao, Shigeyuki Hamada, and Shigetada Kawabata
  • Organizer: 第86回日本細菌学会総会
  • Place of Presentation: 千葉市
• [Presentation] Streptococcus sanguinis induces foam cell formation and cell death of macrophages (2013)
  • Author(s): N. Okahashi, T. Okinaga, A. Sakurai, Y. Terao, M. Nakata, S. Kawabata, T. Nishihara
  • Organizer: 第86回日本細菌学会総会
  • Place of Presentation: 千葉市
• [Presentation] Group A streptococcal pyrogenic exotoxin B cleaves epithelial junctions and contributes to bacterial translocation (2013)
  • Author(s): Tomoko Sumitomo, Masanobu Nakata, Miharu Higashino, Yutaka Terao, and Shigetada Kawabata
  • Organizer: ASM 113th General Meeting
  • Place of Presentation: Denver, Colorado, USA
• [Presentation] Group A Streptococcus translocates across an epithelial barrier via calpain activation (2013)
  • Author(s): 住友 倫子，中田 匡宣，寺尾 豊，川端 重忠
  • Organizer: 第55回歯科基礎医学会学術大会
  • Place of Presentation: 岡山市, 岡山コンベンションセンター
• [Presentation] Lion Award 受賞講演 (2013)
  • Author(s): 寺尾 豊
  • Organizer: 第55回歯科基礎医学会学術大会
  • Place of Presentation: 岡山市, 岡山コンベンションセンター
  • Invited
• [Presentation] Streptococcus pyogenesのシステインプロテアーゼSpeBが補体免疫機構に及ぼす影響 (2012)
  • Author(s): 本多真理子,寺尾豊,川端重忠
  • Organizer: 第65回日本細菌学会関西支部総会
  • Place of Presentation: 神戸市
  • Year and Date: 2012-11-17
• [Presentation] 細菌の感染制御に向けた次世代の基礎的研究展開 (2012)
  • Author(s): 寺尾豊
  • Organizer: 「第60回日本化学療法西日本支部総会」「第55回日本感染症学会中日本地方会学術集会」「第82回日本感染症学会西日本地方会学術集会」三学会合同集会
  • Place of Presentation: 福岡市
  • Year and Date: 2012-11-06
• [Presentation] Streptococcus pyogenesのシステインプロテアーゼSpeBによる補体免疫回避機構の解析 (2012)
  • Author(s): 本多真理子,橋本栄,寺尾豊,川端重忠
  • Organizer: 第21回Lancefieldレンサ球菌研究会
  • Place of Presentation: 吹田市
  • Year and Date: 2012-06-08
• [Presentation] T6線毛のバイオフィルム形成と菌体凝集への関与 (2012)
  • Author(s): 森田知里,中田匡宣,木村敬次Richard,住友倫子,寺尾豊,川端重忠
  • Organizer: 第21回Lancefieldレンサ球菌研究会
  • Place of Presentation: 吹田市
  • Year and Date: 2012-06-08
• [Presentation] Streptococcus pyogenesのシステインプロテアーゼSpeBによる補体免疫回避機構の解析
  • Author(s): 本多 真理子，橋本 栄，寺尾 豊，川端 重忠
  • Organizer: 第21回Lancefieldレンサ球菌研究会
  • Place of Presentation: 吹田市
• [Presentation] T6線毛のバイオフィルム形成と菌体凝集への関与
  • Author(s): 森田 知里，中田 匡宣，木村 敬次Richard，住友 倫子，寺尾 豊，川端 重忠
  • Organizer: 第21回Lancefieldレンサ球菌研究会
  • Place of Presentation: 吹田市
• [Presentation] Streptococcus pyogenesのシステインプロテアーゼSpeBが補体免疫機構に及ぼす影響
  • Author(s): 本多 真理子，寺尾 豊，川端 重忠
  • Organizer: 第65回日本細菌学会関西支部総会
  • Place of Presentation: 神戸市
• [Presentation] ヒト補体免疫系回避機構におけるStreptococcus pyogenes 分泌型プロテアーゼSpeBの機能解析
  • Author(s): 本多 真理子，寺尾 豊，住友 倫子，中田 匡宣，川端 重忠
  • Organizer: 第5回口腔環境制御」カテゴリー集会
  • Place of Presentation: 長崎市
• [Book] ナノスケールの研究を歯科医学に,日本歯科評論 (2014)
  • Author(s): 寺尾豊
  • Total Pages: 74
  • Publisher: ヒョーロン・パブリッシャーズ社
• [Book] 日本歯科評論 (2014)
  • Author(s): 寺尾 豊
  • Total Pages: 3
  • Publisher: ヒョーロン・パブリッシャーズ
• [Book] レンサ球菌感染症の予防・治療法の確立に向けた展望,化学療法の領域 (2013)
  • Author(s): 寺尾豊
  • Publisher: 医薬ジャーナル社
• [Book] 化学療法の領域 (2013)
  • Author(s): 寺尾 豊
  • Total Pages: 4
  • Publisher: 医薬ジャーナル
• [Book] 化学療法の領域（レンサ球菌感染症の予防・治療法の確立に向けた展望） (2013)
  • Author(s): 寺尾 豊
  • Publisher: 株式会社医薬ジャーナル社
• [Remarks]
  • URL: http://www.dent.niigata-u.ac.jp/microbio/microbio.html
• [Remarks] 研究成果発表HP
  • URL: http://www.niigata-univ-mid.net/study/index2.html
• [Remarks] 新潟大学大学院医歯学総合研究科微生物感染症学分野
  • URL: http://www.dent.niigata-u.ac.jp/microbio/microbio.html
• [Remarks] 微生物DNAのナノスケール解析
  • URL: http://www.niigata-univ-mid.net/study/index2.html
• [Remarks] アウトリーチ活動の案内
  • URL: http://www.niigata-univ-mid.net/about_us/index.html
• [Remarks] 研究内容とアウトリーチ活動の問合せ
  • URL: http://www.niigata-univ-mid.net/contact/index.html