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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.

本文在科研资助项目（C）的资助下，对鼻用疫苗系统的作用机制进行了新的研究（1999 - 2001）的研究结果如下。1）鼻用疫苗：用纯化的牙龈卟啉单胞菌菌毛和霍乱毒素（CT）的鼻疫苗接种是用于诱导Ag特异性Thl和Th 2细胞的有效免疫方案。产生具有抑制细菌附着于上皮细胞的能力的伊加免疫应答。2）产生IgA的粘膜B-1细胞：IgA定型的（sIgA^+）B-1细胞主要位于鼻腔固有层，而sIgA^+ B-2细胞形成于鼻腔相关淋巴组织等粘膜诱导部位。IL-5/IL-5 R信号通路对鼻腔中常见的黏膜免疫系统非依赖性sIgA^+ B-1细胞的体内发育具有重要意义。此外，IL-15也是粘膜组织中表达IL-15 R的sIgM^+、伊加-和sIgM ^-、sIgA^+ B-1细胞分化为IgA产生细胞的重要细胞因子。NALT被认为是诱导针对经鼻施用的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：当检查已知缺乏PLN和/或PP的LTα^<-/->、IL 7-R^<-/->和aly/aly小鼠时，在鼻腔中观察到NALT。此外，在用抗IL 7 R mAb和LTβR-Ig体内处理产生的PP null小鼠中也发现了NALT样结构。这些发现表明NALT器官发生独立于一组已知的淋巴组织产生细胞因子信号通路。