Mucosal Vaccine in Next Generation: Mechanisms of Nasal Vaccine

下一代粘膜疫苗：鼻疫苗的机制

基本信息

批准号：
11670294
负责人：
HIROI Takachika
金额：
$ 2.24万
依托单位：
Osaka Universrty
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670294/
关键词：
Nasal Immunization IgA B-1 cell Vaccine Mucosal Immunity IL-15 NALT Th1 Th2 IL-5 IL-5R B-2細胞 CMIS

项目摘要

I show a new development results of the mechanisms of nasal vaccine system in this report supported by Grand-in-Aid for Scientific Research (C) (1999 - 2001) of Japan Society for the Promotion of Science as following.1) Nasal Vaccine: Nasal vaccination with purified P. gingivalis fimbriae and cholera toxin (CT) is an effective immunization regimen for the induction of Ag-specific Thl and Th2 cell-derive IgA immune responses that possess the ability to inhibit bacterial attachment to epithelial cells. In addition, nasal recombinant BCG vector-based vaccine can secrete the V3 principal neutralizing epitope of HIV in serum, but not mucosal secreted IgA.2) IgA producing mucosal B-l cell: IgA-committed (sIgA^+) B-l cells mainly resided in the lamina propria in the nasal cavity, while sIgA^+ B-2 cell formed in mucosal inductive site such as nasal associated lymphoid tissue. IL-5/IL-5R signaling pathway is important for the development of common mucosal immune system independent sIgA^+ B-l cell in nasal cavity in vivo. Further, IL-15 is also important cytokine for the differentiation of both sIgM^+, IgA- and slgM^-, sIgA^+ B-1 cells expressing IL-15R into IgA-producing cells in mucosal tissues. NALT is considered to be an important inductive site for the induction of antigen-specific mucosal and systemic immunity against nasally-administered vaccine antigen.3) Organization of NALT: When LTα^<-/->, IL7-R^<-/-> and aly/aly mice were examined, known to lacking PLN and/or PP, NALT was observed in nasal cavity. Further, NALT like structure was also found in PP null mice generated by in vivo treatments with anti-IL7R mAb and LTβR-Ig. These findings suggested that NALT organogenesis is independently operated from a group of known lymphoid tissue generation cytokine signaling pathway.

我在日本学术振兴会科学研究大援助（C）（1999 - 2001）支持的这份报告中展示了鼻疫苗系统机制的新开发成果如下。1）鼻疫苗：用纯化的牙龈卟啉单胞菌菌毛和霍乱毒素 (CT) 进行鼻疫苗接种是一种有效的免疫方案，用于诱导 Ag 特异性 Th1 和 Th2 细胞衍生的 IgA 免疫应答，该免疫应答具有此外，基于鼻重组 BCG 载体的疫苗可以分泌血清中 HIV 的 V3 主要中和表位，但不能分泌粘膜分泌的 IgA。2) 产生 IgA 的粘膜 B-1 细胞：IgA 定向（IgA-commited）（ sIgA^+) B-1 细胞主要存在于鼻腔固有层，而 sIgA^+ B-2 细胞则形成于鼻腔固有层。鼻相关淋巴组织等粘膜诱导位点对于体内鼻腔中常见粘膜免疫系统独立的sIgA^+B-1细胞的发育很重要。此外，IL-15也是重要的细胞因子。用于将表达 IL-15R 的 sIgM^+、IgA- 和 slgM^-、sIgA^+ B-1 细胞分化为产生 IgA 的细胞NALT被认为是诱导针对鼻内疫苗抗原的抗原特异性粘膜和全身免疫的重要诱导位点。3) NALT的组织：当LTα^<-/->、IL7-R^<时。 -/-> 对 aly/aly 小鼠进行了检查，已知其缺乏 PLN 和/或 PP，在鼻腔中观察到 NALT。此外，在通过体内治疗产生的 PP 缺失小鼠中也发现了 NALT 样结构。这些研究结果表明，NALT 器官发生独立于一组已知的淋巴组织生成细胞因子信号通路。