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

2016 Fiscal Year Final Research Report

• 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
• Keywords: 粘膜免疫 / ワクチン / 粘液

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.

Free Research Field

粘膜免疫