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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（DC）对于诱导抗原（Ag）特异性免疫反应至关重要，DC靶向疫苗接种可能是诱导特异性免疫反应的有效策略。 Flt3 配体 (Flt3L) 动员并刺激骨髓和淋巴祖细胞以及 DC。本研究的目的是探讨 Flt3L 对诱导鼻粘膜 Ag 特异性免疫反应的影响。第0天对小鼠鼻内或腹膜内给予Flt3L 10Hg。应用Flt3L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。对照不给予Flt3L。通过流式细胞术分析鼻相关淋巴组织（NALT）中 DC 的数量和子集。通过酶联免疫吸附测定（ELISA）测量鼻洗液和血清中的P6特异性抗体滴度，并通过酶联免疫斑点（ELISPOT）测定检查产生P6特异性抗体的细胞。经鼻 Flt3L 给药后，CD11c^+ DC 的 NALT 增加。此外，经鼻 Flt3L 处理的小鼠中，P6 特异性鼻 IgA 和全身 IgG 滴度显着升高，鼻粘膜中产生的特异性 IgA 数量较多。这项研究表明，鼻腔而不是腹腔应用单剂量的 Flt3L 会诱导 NALT DC 的增加，从而增强局部和全身免疫反应。这些发现表明，鼻腔应用 Flt3L 可能是一种有用的疫苗策略。