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Intranasal immunization of mice with P. gingivalis fimbriae and recombinant cholera toxin B subunit induces strong mucosal and systemic immune responses

用牙龈卟啉单胞菌菌毛和重组霍乱毒素 B 亚基鼻内免疫小鼠可诱导强烈的粘膜和全身免疫反应

基本信息

批准号：
13671919
负责人：
KUMADA Hidefumi
金额：
$ 1.98万
依托单位：
Kanagawa Dental College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671919/
关键词：
periodontal disease mucosal vaccination Porphyromonas gingivalis fimbria rCTB IgA 粘膜ワクチン

项目摘要

This study deals with local and systemic immune responses to Porphyromonas gingivalis ATCC 33277 fimbriae after mucosal vaccination of mice via intranasal route with the fimbriae and recombinant cholira toxin B subunit (rCTB). The fimbriae by itself stimulated systemic immune responses even at a low dose (0.5 μg), and serum IgG and IgA specific to P. gingivalis fimbriae were induced in an antigen dose-dependent manner. Induction of the serum IgG and IgA was started from 10 days after the first immunization, and the levels continued to elevate until sacrifice day. rCTB co-administration did not enhance the levels of systemic responses, but the levels of serum IgA were slightly increased by rCTB-adjuvant effect when the mice was immunized with 0.5 μg of the fimbriae. The serum IgG subclass titers were revealed to be the order of IgG1 > IgG3 > IgG2b > IgG2a, suggesting that Th1 and Th2 type immune systems were stimulated by this immunization. In addition to systemic response, mucosal vacc … More ination with P. gingivalis fimbriae more than 5 μg also stimulated mucosal IgA response which was started to elevated from 18 days after the first immunization. The mucosal IgA response was significantly enhanced by rCTB co-administration, and in particular, secretory IgA specific to P. gingivalis fimbriae was induced into saliva, nosal cavity and lung at a high level even at a low dose (0.5 μg fimbriae). Thus, the mucosal vaccination with co-administration of P. gingivalis fimbriae and rCTB via intranasal route strongly stimulated not only systemic immune response but also mucosal response, indicating that this vaccination may be efficacious for the prevention of P. gingivalis-mediated periodontal disease.In addition, an approximately 80% reduction of P. gingivalis-mediated alveolar bone resorption in mice was induced by nasal administration of the fimbrial vaccine.Thus, nasal administration of the vaccine containing fimbriae and rCTB strongly stimulated both systemic and mucosal responses and may be effective for the prevention of P. gingivalis-mediated periodontitis. Less

本研究探讨了牙龈卟啉单胞菌ATCC 33277菌毛经鼻粘膜途径接种小鼠后对菌毛和重组霍乱毒素B亚单位（rCT B）的局部和全身免疫应答。即使在低剂量（0.5 μg）下，菌毛本身也刺激全身免疫应答，并且以抗原剂量依赖性方式诱导对牙龈卟啉单胞菌菌毛特异性的血清IgG和伊加。血清IgG和伊加的诱导从第一次免疫后10天开始，并且水平持续升高，直到处死日。rCTB联合给药不增强全身应答水平，但当用0.5 μg菌毛免疫小鼠时，血清伊加水平因rCTB-佐剂效应而略有增加。血清IgG亚类滴度为IgG 1> IgG 3> IgG 2b> IgG 2a，提示该免疫可激活Th 1和Th 2型免疫系统。除全身反应外，粘膜真空 ...更多信息用牙龈卟啉单胞菌菌毛5 μg以上免疫也能刺激粘膜伊加反应，从第一次免疫后18天开始升高。粘膜伊加应答通过rCTB共施用而显著增强，并且特别地，即使在低剂量（0.5 μg菌毛）下，对牙龈卟啉单胞菌菌毛特异性的分泌型伊加也以高水平被诱导到唾液、鼻腔和肺中。因此，通过鼻内途径共施用牙龈卟啉单胞菌菌毛和rCTB的粘膜接种不仅强烈刺激全身免疫应答，而且强烈刺激粘膜应答，表明这种接种可有效预防牙龈卟啉单胞菌介导的牙周病。小鼠中牙龈卟啉单胞菌介导的牙槽骨再吸收通过鼻内给予菌毛疫苗诱导约80%的减少。因此，鼻腔给药含有菌毛和rCTB的疫苗强烈刺激全身和粘膜反应，并且可能有效预防牙龈卟啉单胞菌介导的牙周炎。少