Development of Nasal Vaccine agaisnt RS virus based on neonatal innate immunity

• Project/Area Number: 26670514
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Osaka City University
• Principal Investigator: Saito Mika 大阪市立大学, 大学院医学研究科, 講師 (40419700)
• Co-Investigator(Kenkyū-buntansha): 徳原 大介 大阪市立大学, 大学院医学研究科, 講師 (60448751)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ワクチン / アジュバント / 新生児 / 自然免疫 / RSウイルス / ウイルス / 臍帯血 / 感染症

Outline of Final Research Achievements

Adjuvant is necessary for the development of vaccine against RSV, because the immune response against recombinant RSV protein is weak in neonates and adults. Zymosan, a cell wall extract from Saccharomyces cervisiae, gave comparable innate immune response via TLR2/TLR6 heterodimer in the immune cells of cord blood and adult blood, thus may be useful as a nasal vaccine adjuvant against RSV in neonates and infants.

Research Products

• [Journal Article] Rejuvenation of mucosal immunosenescence by adipose tissue-derived mesenchymal stem cells (2017)
  • Author(s): Akitoshi Tsuruhara, Kazuyoshi Aso, Daisuke Tokuhara, Junichiro Ohori, Masaki Kawabata, Yuichi Kurono, Jerry R McGhee, Kohtaro Fujihashi
  • Journal Title: International Immunology Volume: 29 Issue: 1 Pages: 5-10
  • DOI: 10.1093/intimm/dxx001
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Diabetic pregnancy activates the innate immune response through TLR5 or TLR1/2 on neonatal monocyte. (2016)
  • Author(s): Yanai S, Tokuhara D, Tachibana D, Saito M, Sakashita Y, Shintaku H, Koyama M.
  • Journal Title: J Reprod Immuno Volume: 117 Pages: 17-23
  • DOI: 10.1016/j.jri.2016.06.007
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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] Diabetic pregnancy activates innate immune response through TLR5 or TLR1/2 on cord blood-derived monocytes. (2016)
  • Author(s): Daisuke Tokuhara, Sakika Yanai, Daisuke Tachibana, Mika Saito, Yuki Cho, Masayasu Koyama, Haruo Shintaku.
  • Organizer: 6th International Congress of UENPS.
  • Place of Presentation: バレンシア、スペイン
  • Year and Date: 2016-11-23
  • Int'l Joint Research
• [Presentation] TLR2/TLR6 heterodimer-mediated innate immune response in cord blood immune cells. (2016)
  • Author(s): Yuki Cho, Daisuke Tokuhara, Kyoko Nohmi, Mika Saito, Daisuke Tachibana, Masayasu Koyama, Haruo Shintaku.
  • Organizer: 6th International Congress of UENPS.
  • Place of Presentation: バレンシア、スペイン
  • Year and Date: 2016-11-23
  • Int'l Joint Research
• [Presentation] 妊娠中の糖代謝異常は新生児における過剰な自然免疫応答を惹起する． (2016)
  • Author(s): 柳井咲花，徳原大介，橘大輔，斎藤三佳，新宅治夫，古山将康．
  • Organizer: 第１１９回日本小児科学会学術集会．
  • Place of Presentation: ロイトン札幌、札幌
  • Year and Date: 2016-05-13
• [Presentation] 臍帯血由来免疫細胞の自然免疫機構を基盤とした, 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] Zymosan induces innate immune responses in neonates comparable to adults. (2015)
  • Author(s): Nohmi Kyoko, Daisuke Tokuhara, Saito Mika, Shintaku Haruo
  • Organizer: Asian Society for Pediatric Research 2015.
  • Place of Presentation: Osaka International Convention Center (Osaka, Japan)
  • Year and Date: 2015-04-15
  • Int'l Joint Research
• [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