Immunological involvement of airway cilium function in the pneumococcal nasal vaccine using claudin-4 binder

• Project/Area Number: 15K18950
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: National Institutes of Biomedical Innovation, Health and Nutrition
• Principal Investigator: Suzuki Hidehiko 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 ワクチンマテリアルプロジェクト, プロジェクト研究員 (10710296)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 粘膜免疫 / ワクチン / 粘液 / 粘膜ワクチン

Outline of Final Research Achievements

Nasal physical barrier (ex. mucus) prevents the entry of exogenous materials. Nasal vaccine is probably affected by nasal physical barrier, but it remains unknown. In this study, I used Ttll1 kockout (KO) mice, which showed accumulation of nasal mucus, to check whether claudin-4-targeting vaccine (PspA-C-CPE) was affected by nasal physical barrier.
Ttll1 KO mice showed accumulation of nasal mucus around NALT, which was an immune induction site in nose. PspA-C-CPE was trapped by nasal mucus, and PspA-C-CPE could not effectively bind to NALT. Furthermore, PspA-specific nasal IgA was impaired with decrease of germinal center formation in Ttll1 KO mice. Thus, insufficient binding of PspA-C-CPE to NALT led to the impaired PspA-specific nasal IgA responses. Ttll1 KO mice treated with mucus remover showed recover of immune induction of PspA-specific nasal IgA. These findings indicated that accumulation of nasal mucus is an interfering factor in claudin-4-targeting nasal vaccine.

Research Products

• [Journal Article] C-terminal Clostridium perfringens enterotoxin-mediated antigen delivery for nasal pneumococcal vaccine (2015)
  • Author(s): H. Suzuki, A. Watari, E. Hashimoto, M. Yonemitsu, H. Kiyono, K. Yagi, M. Kondoh, and J. Kunisawa
  • Journal Title: PLoS ONE Volume: 10 Issue: 5 Pages: e0126352-e0126352
  • DOI: 10.1371/journal.pone.0126352
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Central role of core binding factor β2 in mucosa-associated lymphoid tissue organogenesis in mouse (2015)
  • Author(s): T. Nagatake, S. Fukuyama, S. Sato, H. Okura, M. Tachibana, I. Taniuchi, K. Ito, M. Shimojou, N. Matsumoto, H, Suzuki, J. Kunisawa, and H. Kiyono
  • Journal Title: PLoS ONE Volume: 10 Issue: 5 Pages: e0127460-e0127460
  • DOI: 10.1371/journal.pone.0127460
  • NAID: 120006987038
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Dietary ω3 fatty acid exerts anti-allergic effect through the conversion to 17,18-epoxyeicosatetraenoic acid in the gut (2015)
  • Author(s): J. Kunisawa, M. Arita, T. Hayasaka, T. Harada, R. Iwamoto, R. Nagasawa, S. Shikata, T. Nagatake, H. Suzuki, E. Hashimoto, Y. Kurashima, Y. Suzuki, H. Arai, M. Setou, and H. Kiyono
  • Journal Title: Sci Rep Volume: 5 Issue: 1 Pages: 9750-9750
  • DOI: 10.1038/srep09750
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Vitamin-mediated immune regulation in the development of inflammatory diseases (2015)
  • Author(s): H. Suzuki and J. Kunisawa
  • Journal Title: Endocrine, Metabolic & Immune Disorders - Drug Targets Volume: 15 Issue: 3 Pages: 212-215
  • DOI: 10.2174/1871530315666150316122128
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mode of bioenergetic metabolism during B cell differentiation in the intestine determines the distinct requirement for vitamin B1 (2015)
  • Author(s): J. Kunisawa, Y. Sugiura, T. Wake, T. Nagatake, H. Suzuki, R. Nagasawa, S. Shikata, K. Honda, E. Hashimoto, Y. Suzuki, M. Setou, M. Suematsu, H. Kiyono
  • Journal Title: Cell Rep Volume: 13 Issue: 1 Pages: 122-131
  • DOI: 10.1016/j.celrep.2015.08.063
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Claudin-4指向型経鼻ワクチンにおける鼻腔物理的バリアの影響 (2017)
  • Author(s): 鈴木 英彦、長竹 貴広、那須 彩香、池上 浩司、瀬藤 光利、濱崎 洋子、清野 宏、八木 清仁、近藤 昌夫、國澤 純
  • Organizer: 第10回次世代アジュバント研究会
  • Place of Presentation: 大阪 千里ライフサイエンスセンター
  • Year and Date: 2017-01-23
• [Presentation] Mucus accumulation caused by impaired mucociliary function is an interfering factor in the C-CPE-based claudin-4-targeting nasal vaccine (2016)
  • Author(s): SUZUKI Hidehiko, NAGATAKE Takahiro, KIYONO Hiroshi, KUNISAWA Jun
  • Organizer: 第45回日本免疫学会学術集会
  • Place of Presentation: 沖縄 沖縄コンベンションセンター
  • Year and Date: 2016-12-05
• [Presentation] Immunological involvement of airway mucociliary function in the claudin-4-targeting pneumococcal nasal vaccine (2016)
  • Author(s): SUZUKI Hidehiko, NAGATAKE Takahiro, NASU Ayaka, IKEGAMI Koji, SETOU Mitsutoshi, KIYONO Hiroshi, YAGI Kiyohito, KONDOH Masuo and KUNISAWA Jun
  • Organizer: 16th International Congress of Immunology
  • Place of Presentation: オーストラリア メルボルン Melbourne Convention and Exhibition Centre
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] クローディン４標的型経鼻ワクチンシステムにおける鼻腔物理的機能の影響 (2016)
  • Author(s): 鈴木 英彦、長竹 貴広、那須 彩香、池上浩司、瀬藤光利、清野 宏、八木 清仁、近藤 昌夫、國澤 純
  • Organizer: 第9回次世代アジュバント研究会
  • Place of Presentation: 大阪府、吹田市
  • Year and Date: 2016-01-19
• [Presentation] Immunological involvement of airway cilium in the induction of antigen-specific i (2015)
  • Author(s): SUZUKI Hidehiko, NAGATAKE Takahiro, KIYONO Hiroshi, KUNISAWA Jun
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 北海道、札幌市
  • Year and Date: 2015-11-18
• [Presentation] Claudin標的型経鼻ワクチンにおける鼻腔物理的機能の影響 (2015)
  • Author(s): 鈴木 英彦 , 長竹 貴広 , 那須 彩香 , 渡利 彰浩 , 池上 浩司 , 瀬藤 光利 , 清野 宏 , 八木 清仁, 近藤 昌夫, 國澤 純
  • Organizer: 第4回感染症若手フォーラム
  • Place of Presentation: 兵庫県、淡路市
  • Year and Date: 2015-09-06