Analysis of vaccine-mediated immune induction in Mucopolysaccharidosis-specific iPS cells

• Project/Area Number: 25461558
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Osaka City University
• Principal Investigator: Tokuhara Daisuke 大阪市立大学, 大学院医学研究科, 講師 (60448751)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: ワクチン / 自然免疫 / 小児 / 感染症 / 単球 / サイトカイン / 免疫 / アジュバント / 樹状細胞 / Toll-様受容体 / ムコ多糖症

Outline of Final Research Achievements

When Toll-like receptor (TLR)-mediated innate immune response was compared between Mucopolysaccharidosis (MPS)-specific cells and control iPS cells, zymosan or MALP2-mediated cytokine levels were significantly lower in MPS-specific iPS cells-derived dendritic cells compared to control iPS cells-derived dendritic cells. Then, when TLR-mediated innate immune response was compared between healthy neonates and healthy adults, immaturity of TLR-mediated immune response was disclosed to depend on cell types and TLR types in neonates, however zymosan provided comparable immune response between neonates and adults. Therefore, vaccine using zymosan as an adjuvant may play a key role in vaccine development for MPS children.

Research Products

• [Journal Article] Zymosan Induces Immune Responses Comparable with Those of Adults in Monocytes, Dendritic Cells, and Monocyte-Derived Dendritic Cells from Cord Blood. (2015)
  • Author(s): Nohmi K, Tokuhara D, Tachibana D, Saito M, Sakashita Y, Nakano A, Terada H, Katayama H, Koyama M, Shintaku H.
  • Journal Title: Journal of Pediatrics Volume: 167 Issue: 1 Pages: 155-162
  • DOI: 10.1016/j.jpeds.2015.03.035
  • Acknowledgement Compliant
• [Journal Article] Zymosan induces immune responses comparable with those of adults in monocytes, dendritic cells, and monocyte-derived dendritic cells from cord blood (2015)
  • Author(s): Kyoko Nohmi, Daisuke Tokuhara, Daisuke Tachibana, Mika Saito, Yuko Sakashita, Akemi Nakano, Hiroyuki Terada, Hiroko Yamamoto, Masayasu Koyama, Haruo Shintaku
  • Journal Title: Journal of Pediatrics Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 臍帯血由来免疫細胞の自然免疫応答を基盤とした、乳幼児の消化管感染症に対するワクチンアジュバント開発 (2015)
  • Author(s): 能見恭子、徳原大介、齊藤三佳、新宅治夫
  • Organizer: 第４２回日本小児栄養消化器肝臓学会
  • Place of Presentation: 広島国際会議場（広島県広島市）
  • Year and Date: 2015-10-16
• [Presentation] Zymosan but not other TLR agonists, induces immune responses comparable to those of adults in monocytes, DCs, and monocyte-derived DCs of neonates. (2015)
  • Author(s): Daisuke Tokuhara, Nohmi Kyoko, Saito Mika, Shintaku Haruo
  • Organizer: European Academy of Paediatrics Congress and Mastercourse 2015
  • Place of Presentation: Holmenkollen Park Hotel(Oslo, Norway)
  • Year and Date: 2015-09-17
  • Int'l Joint Research
• [Presentation] TLR2リガンドは成人と同等の自然免疫応答を新生児に誘導する (2015)
  • Author(s): 能見恭子、徳原大介、齊藤三佳、新宅治夫
  • Organizer: 第１１８回日本小児科学会
  • Place of Presentation: 大阪国際会議場（ 大阪府・大阪市）
  • Year and Date: 2015-04-17 – 2015-04-19
• [Presentation] ヒト臍帯血細胞を用いた新生児の自然免疫機構の解明：TLR2リガンドは成人と同等の自然免疫応答を新生児に誘導しうる (2014)
  • Author(s): 能見恭子、徳原大介、齊藤三佳、新宅治夫
  • Organizer: 日本未熟児新生児学会
  • Place of Presentation: ひめぎんホール（ 愛媛県・松山市）
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] ZYMOSAN BUT NOT LPS, PAM3CSK4, OR FLAGELLIN INDUCES IMMUNE RESPONSES IN MONOCYTES, DCS, AND MONOCYTE-DERIVED DCS OF NEONATES COMPARABLE TO THOSE OF ADULTS (2014)
  • Author(s): Daisuke Tokuhara, Kyoko Nohmi, Haruo Shintaku
  • Organizer: The 5th Congress of the European Academy of Paediatric Societies
  • Place of Presentation: Barcelona (Spain)
  • Year and Date: 2014-10-17 – 2014-10-21