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MucosaI immunity in the upper respiratory tract and vaccine development

上呼吸道粘膜免疫和疫苗开发

基本信息

批准号：
19591979
负责人：
SUZUKI Masashi
金额：
$ 2.83万
依托单位：
Oita University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2007
资助国家：
日本
起止时间：
2007 至 2009
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19591979/
关键词：
上気道粘膜免疫ワクチン粘膜粘液樹状細胞

项目摘要

Dendritic cells (DCs) are essential for the induction of antigen (Ag)-specific immune responses, DC-targeted vaccination might be an effective strategy for the induction of the specific immune responses. Flt3 ligand (Flt3L) mobilizes and stimulates myeloid and lymphoid progenitor cells, and DCs. The purpose of this study is to investigate the effect of Flt3L on the induction of Ag-specific immune responses in nasal mucosa. Mice were administered with Flt3L 10Hg intranasally or intraperitoneally, on day 0. After the Flt3L application, mice were further immunized with P6 outer membrane protein of nontypeable Haemophilus influenzae (NTHi) 10μg on day 6, 13, and 20, and mice were killed on day 27. Control were not given Flt3L. The number and subset of DCs in nasal-associated lymphoid tissue (NALT) were analyzed by flow cytometry. P6-specific antibody titers in nasal wash and serum were measured by enzyme-linked immunosorbent assay (ELISA), and P6-specific antibody-producing cells were examined by enzyme-linked immunospot (ELISPOT) assay. CD11c^+ DCs increased in NALT after nasal Flt3L administration. In addition, P6-specific nasal IgA and systemic IgG titers were significantly elevated in nasally Flt3L-treated mice, possessing higher number of the specific IgA-producing in nasal mucosa. This study showed that nasal but not peritoneal application with a single dose of Flt3L induced increase of NALT DCs, resulted in enhanced local and systemic immune responses. These findings suggest that nasal application with Flt3L might be a useful vaccine strategy.

树突状细胞（Dendritic cells，DC）是诱导抗原特异性免疫应答的关键细胞，DC靶向疫苗可能是诱导特异性免疫应答的有效策略。Flt3配体（Flt3L）动员并刺激骨髓和淋巴祖细胞以及DC。本研究旨在探讨Flt3L对鼻粘膜Ag特异性免疫应答的诱导作用。在第0天，鼻内或腹膜内向小鼠施用Flt3L 10Hg。在Flt3L应用后，在第6、13和20天用不可分型流感嗜血杆菌（NTHi）的P6外膜蛋白10μg进一步免疫小鼠，并在第27天处死小鼠。对照组不给予Flt3L。流式细胞术检测鼻相关淋巴组织（NALT）中DC的数量和亚群。用酶联免疫吸附试验（ELISA）检测鼻洗液和血清中P6特异性抗体滴度，用酶联免疫斑点试验（ELISPOT）检测P6特异性抗体产生细胞。鼻内给予Flt3L后，NALT中CD11c^+ DCs增加。此外，鼻用Flt3L处理的小鼠中P6特异性鼻伊加和全身IgG滴度显著升高，在鼻粘膜中具有更高数量的特异性IgA产生。该研究表明，鼻腔而非腹腔应用单剂量的Flt3L诱导NALT DC的增加，导致增强的局部和全身免疫应答。这些发现表明，鼻内应用Flt3L可能是一种有用的疫苗策略。