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The mechanism in the diversity and amplification of mucosal immune system -Clinical application of mucosal vaccine-

粘膜免疫系统多样性和扩增的机制-粘膜疫苗的临床应用-

基本信息

批准号：
14370548
负责人：
KURONO Yuichi
金额：
$ 8.77万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370548/
关键词：
Haemophilus influenzae Streptococcus pneumoniae Phosphorylcholine Mucosal vaccine Intra-nasal vaccination IgA IgE Type I allergy 粘膜免疫粘間ワクチン上気道感染 IgG ワクチン P6 ナノスフィアアジュバント破傷風菌トキソイド PC

项目摘要

1.Immune responses against Haemophilus influenzae(Hi) P6.Recombinant P6(rP6) and nanosphere were coupled and intra-nasally administered to mice. Although P6-specific serum IgM and IgG levels were increased, secretory IgA was not induced in external secretions, indicating the low antigenesity of rP6 as mucosal antigen.2.Mucosal immune responses against phosphorylcholine(PC).PC is contained in all Gram-positive and -negative bacteria. However, the antigenesity of PC is not yet clarified. When PC was intra-nasally administered to mice, systemic as well as mucosal immune responses were induced without using any mucosal adjuvant such as cholera toxin. Moreover, the antibodies induced by PC were cross-reactive with several different strains of Hi and Streptococcus pneumoniae. Those results suggest that PC might be a candidate of mucosal vaccine with broad spectrum.3.Inhibition of type I allergy by immunization with PC.Mucosal vaccine frequently induces type I allergy by producing IgE. However, when PC was intra-nasally or intra-peritoneally administered to mice, the production of IgE was significantly reduced. Further, splenic helper T cells isolated from immunized mice with PC produced much less IL-4 compared with the controls. Those findings suggest the efficacy and the safety of PC as a promising mucosal vaccine.

1.针对流感嗜血杆菌(Hi)P6的免疫反应。将重组P6(rP6)与纳米球偶联并给小鼠鼻内给药。虽然P6特异性血清IgM和IgG水平升高，但外分泌物中未诱导分泌型IgA，表明rP6作为粘膜抗原的抗原性较低。2.针对磷酸胆碱(PC)的粘膜免疫反应。PC存在于所有革兰氏阳性和阴性细菌中。然而，PC的抗原性尚未明确。当 PC 鼻内给予小鼠时，在不使用任何粘膜佐剂（例如霍乱毒素）的情况下，诱导了全身和粘膜免疫反应。此外，PC诱导的抗体与几种不同的Hi菌株和肺炎链球菌有交叉反应。这些结果表明PC可能是广谱粘膜疫苗的候选者。3.PC免疫抑制I型变态反应。粘膜疫苗经常通过产生IgE诱导I型变态反应。然而，当PC经鼻内或腹膜内给予小鼠时，IgE的产生显着减少。此外，与对照组相比，从接受 PC 免疫的小鼠中分离出的脾脏辅助 T 细胞产生的 IL-4 少得多。这些发现表明 PC 作为一种有前途的粘膜疫苗的有效性和安全性。