Transcutaneous immunization with phosphorylcholine induces antigen-specific mucosal and systemic immune responses

• Project/Area Number: 16K11238
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Kagoshima University
• Principal Investigator: Nagano Hiromi 鹿児島大学, 医歯学域医学系, 講師 (60613148)
• Co-Investigator(Kenkyū-buntansha): 地村 友宏 鹿児島大学, 附属病院, 医員 (10709596) ; 宮下 圭一 鹿児島大学, 医歯学域附属病院, 助教 (30585063) ; 牧瀬 高穂 鹿児島大学, 医歯学域医学系, 助教 (30585120) ; 黒野 祐一 鹿児島大学, 医歯学域医学系, 教授 (80153427)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ホスホリルコリン / 経皮免疫 / 特異的IgA / 粘膜免疫応答 / 経皮ワクチン / 粘膜免疫 / ﾏｲｸﾛニードル / 感染症

Outline of Final Research Achievements

Objective: Transcutaneous immunization (TCI) is a novel route of vaccination through application of a topical vaccine antigen on the skin. The purpose of the study was to examine the effect of TCI using PC in BALB/c mice.　Methods: TCI was performed in BALB/c mice using PC-keyhole limpet hemocyanin (KLH) plus cholera toxin (CT). Immunogenicity was evaluated by measuring PC-specific IgG and specific IgG1, IgG2a, IgM, IgA, and secretory IgA antibodies by ELISA.　Results: Six months after immunization, IgG after TCI using PC plus CT was significantly higher than in controls, but this was not found for IgA. In saliva, secretory IgA antibodies decreased with a peak level at two to three months.　Conclusions: These results suggest that TCI using PC plus CT with BALB/c mice is a simple approach for induction of systemic and mucosal immune responses.

Academic Significance and Societal Importance of the Research Achievements

本研究より、背部の皮膚を用いた経皮免疫は、簡単な投与方法であるが一定期間血清中や唾液中に抗原特異的免疫グロブリンを確認でき、新たな投与経路としての可能性を示唆することができた。

Research Products

• [Journal Article] Transcutaneous immunization in auricle skin induces antigen-specific mucosal and systemic immune responses in BALB/c mice (2017)
  • Author(s): Nagano H., Jimura T., Nagano M., Miyashita K., Kurono Y.
  • Journal Title: Auris Nasus Larynx Volume: 44 Issue: 4 Pages: 411-416
  • DOI: 10.1016/j.anl.2016.08.006
  • Peer Reviewed
• [Presentation] Transcutaneous immunization with pneumococcal surface protein A in mice (2018)
  • Author(s): Hiromi Nagano
  • Organizer: The 17th Japan-Korea Joint Meeting of Otorhinolaryngology-Head and Neck Surgery
  • Int'l Joint Research
• [Presentation] PspA経皮ワクチンによる免疫応答の誘導 (2018)
  • Author(s): 永野広海
  • Organizer: 第１１９回日本耳鼻咽喉科学会総会・学術講演会
• [Presentation] PspA点眼投与による上気道粘膜免疫応答の誘導 (2018)
  • Author(s): 永野広海
  • Organizer: 第３６回日本耳鼻咽喉科免疫アレルギー学会
• [Presentation] PspA点眼投与による上気道粘膜免疫応答の誘導 (2017)
  • Author(s): 永野広海
  • Organizer: 第３０回日本口腔・咽頭科学会総会ならびに学術講演会
• [Presentation] Poly:ICをアジュバントとして用いたPC経鼻免疫による免疫応答の検討 (2016)
  • Author(s): 地村友宏
  • Organizer: 第５５回日本鼻科学会総会・学術講演会
  • Place of Presentation: 栃木県総合文化センター（栃木県・宇都宮市）
  • Year and Date: 2016-10-13
• [Presentation] 耳介経皮免疫によるホスホリルコリン特異的粘膜免疫応答の誘導 (2016)
  • Author(s): 永野広海
  • Organizer: 第１１７回日本耳鼻咽喉科学会通常総会・学術講演会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2016-05-18