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SUPPRESSION OF BRONCHIAL ASTHMA BY A DNA VACCINE ENCODING ALLERGEN

通过编码过敏原的 DNA 疫苗抑制支气管哮喘

基本信息

批准号：
09670485
负责人：
SATO Yukio
金额：
$ 1.73万
依托单位：
FUKUSHIMA MEDICAL UNIVERSITY, SCHOOL OF MEDICINE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670485/
关键词：
DNA vaccine bronchial asthma allergen プラスミドDNA 好酸球

项目摘要

Injection of plasmid DNA(pDNA) encoding antigen (Ag) to gastric wall caused transfection of mucosal epithelial cells and induced fecal IgA responses as well as systemic antibody. In contrast, intradermal delivery of pDNA induced systemic antibody but not mucosal IgA responses. Splenic CD4+T cells and mediastinal lymph node (MLN) cells of mice immunized via gastric mucosa with pDNA produce Th1-type cytokine, IFN-gamma, but not IL-4 or IL-5, after in vitro Ag-stimulation. The antigen-stimulated splenic CD4+ T cells from mice intradermally immunized with pDNA produced IFN-gamma, but MLN cells from these mice did not. Therefore, Th1 cells induced by gastric mucosal delivery of pDNA encoding allergen may accumulate at the lung after the inhalation of the corresponding allergen and may produce IFN-gamma that then prevent directly the accumulation of eosinophils following inhalation of various allergens. I have demonstrated using murine model of airway eosinophilia that mice immunized via gastric mucosa with pDNA were protected from airway eosinophilia following airway challenge not only with the corresponding Ag that the pDNA encodes, but also with the irrelevant Ag mixed with the corresponding Ag. In contrast mice immunized i.d. with same pDNA were protected from airway eosinophilia induced only by the corresponding Ag, but not by the irrelevant Ag mixed with the corresponding Ag. Therefore mucosal DNA immunization may be superior than systemic DNAimmunization in preventing airway eosinophilia in that mucosal delivery of pDNA encoding single allergen can protect against eosinophilic infiltration induced by multiple allergens.

将编码抗原（Ag）的质粒DNA（pDNA）注射到胃壁，引起粘膜上皮细胞转染，引起粪便IgA反应和全身抗体。相比之下，皮内递送pDNA诱导全身抗体，而不是粘膜IgA反应。pDNA经胃粘膜免疫小鼠脾CD4+T细胞和纵隔淋巴结（MLN）细胞在体外ag刺激后产生th1型细胞因子ifn - γ，但不产生IL-4和IL-5。经pDNA皮内免疫的小鼠的抗原刺激的脾CD4+ T细胞产生ifn - γ，但这些小鼠的MLN细胞不产生ifn - γ。因此，胃粘膜递送编码过敏原的pDNA诱导的Th1细胞可能在吸入相应的过敏原后在肺部积聚，并可能产生ifn - γ，从而直接阻止吸入各种过敏原后嗜酸性粒细胞的积累。我已经用小鼠气道嗜酸性粒细胞模型证明，pDNA经胃粘膜免疫的小鼠在气道攻击后，不仅受到pDNA编码的相应Ag的保护，而且受到不相关Ag与相应Ag混合的保护，从而免受气道嗜酸性粒细胞的影响。与此相反，用相同pDNA免疫的小鼠仅受相应Ag的影响，而不相关Ag与相应Ag的混合则不能引起气道嗜酸性粒细胞增多。因此，粘膜DNA免疫在预防气道嗜酸性粒细胞增多方面可能优于全身脱氧DNA免疫，因为粘膜递送编码单一过敏原的pDNA可以防止多种过敏原诱导的嗜酸性粒细胞浸润。