Development of safety vaccine using spleen- and dendritice cells-targeted nano device

• Project/Area Number: 24590198
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Nagasaki University
• Principal Investigator: KITAHARA Takashi 長崎大学, 病院(医学系), 准教授 (30380934)
• Co-Investigator(Kenkyū-buntansha): SASAKI Hitoshi 長崎大学, 病院(医学系), 教授 (00170689)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ワクチン / ナノ材料 / 癌 / 感染症 / DNAワクチン / ナノデバイス / マラリア / 遺伝子デリバリー / メラノーマ

Outline of Final Research Achievements

In this study, we developed the novel melanoma vaccine and malaria vaccine using spleen-targeted nano-device. We used pUb-M which expresses melanoma-related antigen (gp100 and tyrosinase-related protein 2 (TRP2)) as melanoma DNA vaccine. We successfully prepared the stable nanoparticles (pUb-M/PEI/γ-PGA complexes) by optimization of the mix ratio. The pUb-M/PEI/γ-PGA complex significantly inhibited the growth and metastasis of a melanoma cell line, B16-F10 cells, and improved the survival time of metastasis model mice. For the development of malaria DNA nano-vaccine, PyGPI8p-transamidase-related protein (PyTAM) was selected as a possible candidate vaccine antigen. The pyTAM/PEI/γ-PGA complexes suppressed parasitemia and prolonged survival.

Research Products

• [Journal Article] Secure and effective gene delivery system of plasmid DNA coated by polynucleotide. (2015)
  • Author(s): Kodama Y, Ohkubo C, Kurosaki T, Egashira K, Sato K, Fumoto S, Nishida K, Higuchi N, Kitahara T, Nakamura T, Sasaki H.
  • Journal Title: J Drug Target. Volume: 23 Issue: 1 Pages: 43-51
  • DOI: 10.3109/1061186x.2014.950665
  • NAID: 120006986293
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Splenic gene delivery system using self-assembling nano-complex with phosphatidylserine analog. (2015)
  • Author(s): Kurosaki T, Nakasone C, Kodama Y, Egashira K, Harasawa H, Muro T, Nakagawa H, Kitahara T, Higuchi N, Nakamura T, Sasaki H.
  • Journal Title: Biol Pharm Bull. Volume: 38 Pages: 23-29
  • NAID: 130004872233
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Biodegradable nanoparticles composed of dendrigraft poly-L-lysine for gene delivery. (2014)
  • Author(s): Kodama Y, Nakamura T, Kurosaki T, Egashira K, Mine T, Nakagawa H, Muro T, Kitahara T, Higuchi N, Sasaki H.
  • Journal Title: Eur J Pharm Biopharm. Volume: 87 Issue: 3 Pages: 472-479
  • DOI: 10.1016/j.ejpb.2014.04.013
  • NAID: 120006986334
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Novel siRNA delivery system using a ternary polymer complex with strong silencing effect and no cytotoxicity. (2014)
  • Author(s): Kodama Y, Shiokawa Y, Nakamura T, Kurosaki T, Aki K, Nakagawa H, Muro T, Kitahara T, Higuchi N, Sasaki H.
  • Journal Title: Biol Pharm Bull Volume: 37 Pages: 1274-1281
  • NAID: 130004677533
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Secure splenic delivery of plasmid DNA and its application to DNA vaccine. (2013)
  • Author(s): Kurosaki T, Kodama Y, Muro T, Higuchi N, Nakamura T, Kitahara T, Miyakoda M, Yui K, Sasaki H.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 36 Pages: 1800-1806
  • NAID: 130003382044
  • Peer Reviewed
• [Presentation] Dendrigraft poly-L-lysineを構成成分とした生分解型siRNAベクターの構築 (2014)
  • Author(s): 藏本 悠、兒玉 幸修、北原 隆志、佐々木 均
  • Organizer: 日本薬剤学会第29年会
  • Place of Presentation: 大宮ソニックシティビル（大宮）
  • Year and Date: 2014-05-20 – 2014-05-22
• [Presentation] 医療用医薬品を用いたGMP基準の新規遺伝子ベクターの開発 (2014)
  • Author(s): 西垣 和香、兒玉 幸修、北原 隆志、佐々木 均
  • Organizer: 日本薬剤学会第29年会
  • Place of Presentation: 大宮ソニックシティビル（大宮）
  • Year and Date: 2014-05-20 – 2014-05-22
• [Presentation] Nanoparticles electrostatically coated with folic acid for effective and safe gene delivery (2014)
  • Author(s): Hitoshi Sasaki, Yukinobu Kodama, Tamami Morishita, Takashi Kitahara
  • Organizer: 5th Pharmaceutical Sciences World Congress
  • Place of Presentation: Melbourne Convention and Exhibition Centre（メルボルン）
  • Year and Date: 2014-04-13 – 2014-04-16
• [Presentation] Secure and effective gene vector of polyamidoamine dendrimer pharmaceutically modified with anionic polymer (2014)
  • Author(s): Yukinobu Kodama, Yumi Yamashita, Takashi Kitahara, Sasaki Hitoshi
  • Organizer: 5th Pharmaceutical Sciences World Congress
  • Place of Presentation: Melbourne Convention and Exhibition Centre（メルボルン）
  • Year and Date: 2014-04-13 – 2014-04-16