Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/20141
標題: 評估利用超音速流動力皮下遞送裸露Der p 2去氧核醣核酸疫苗抑制歐洲室塵蟎誘導之呼吸道發炎之效力
Efficacy evaluation of delivery of naked Der p 2 DNA vaccine into skin by supersonic flow for suppression of Dermatophagoides pteronyssinus-induced airway inflammation
作者: 王俊欽
Wang, Chun-Chin
關鍵字: immune
歐洲室塵蟎過敏
Der p 2
allergen
asthma
vaccine
gene gun
氣喘
疫苗
基因槍
出版社: 生物醫學研究所
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摘要: Dermatophagoides pteronyssinus group 2 (Der p 2) is a major allergen to induce allergic asthma, and is a good candidate for DNA vaccine development. Previous study suggested that intramuscular injection of plasmid DNA containing wild type Der p 2 gene induced Th1 skewed immune response. Our previous study demonstrated that novel gene gun delivering naked DNA through supersonic flow elicited similar levels of antibody and cellular response with lower dose of DNA plasmid in comparison with intramuscular injection. In addition, administration of naked DNA via novel gene gun induced a stronger Th1-skewed effect on the development of antigen-specific immune responses than traditional delivery of gold coated DNA vaccine. We focused on efficacy evaluation of naked Der p 2 DNA vaccine delivered into skin by supersonic flow for suppression of Dermatophagoides pteronyssinus- induced airway inflammation in comparison with intramuscular injection. After sensitization intraperitoneally with Der p crude extract, Balb/c mice were inoculated with naked DNA vaccine encoding Der p2 antigen by novel gene gun or intramuscular injection to protect the allergen challenges. Lung function and histological studies showed that the group of novel gene gun and intramuscular injection both reduced the airway hypersensitivity and downregulated airway inflammation. Furthermore, the vaccinated mice by gene gun showed a significant suppressed the induction of Der p and Der p2 specific immunoglobulin synthesis compared to the group of intramuscular injection. According to analysis of cell surface marker staining for intracellular cytokines, the group of gene gun had higher numbers of IFN-gamma secreting CD4 and IFN-gamma secreting CD8 T cells than intramuscular injection and significantly attenuated the numbers of IL-4 secreting CD4 T cells in spleen cells. Thus, we suggest that novel gene gun significantly increases the Der p 2-specific anti-airway inflammation Th1 immune response and has better efficacy to protect the asthmatic antigen exposures than intramuscular administration. The results also provided the immunological rationale for testing delivery of naked Der p 2 DNA vaccine into skin via novel gene gun in patients with Dermatophagoides pteronyssinus induced airway inflammation.
歐洲室塵蟎第2群抗原(Der p 2)是引起肺部氣喘的主要過敏原,因此也是作為去氧核糖核酸疫苗研製中一個好的候選抗原。而先前的研究已證實,利用肌肉注射野生型的Der p 2的DNA疫苗可在動物體內誘導第一型輔助T細胞(Th1)偏差的免疫反應。在我們之前的研究發現使用超音速流動力遞送裸露去氧核糖核酸進入皮膚層,不僅可以在較低的用量下誘導出與利用肌肉注射相似的抗體型及免疫型反應,相較於傳統金屬包裹之去氧核糖核酸疫苗,新式基因槍遞送裸露DNA疫苗的策略,可明顯誘導出非常強的抗原專一性Th1細胞型免疫反應。我們目標評估利用超音速流動力遞送裸露Der p 2去氧核糖核酸疫苗至皮下,與肌肉注射方式,比較抑制Der p誘發之呼吸道發炎之能力。在實驗設計上, Balb/c小鼠以歐洲室塵蟎粗萃物致敏後,利用基因槍施打或是肌肉注射來接種裸核DNA疫苗來抵抗過敏原的暴露。根據肺功能測試和組織染色與切片,Der p 2誘導之呼吸道發炎之小鼠肺部氣喘程度,施打新式基因槍方式和肌肉注射均降底小鼠氣喘引起的呼吸道敏感和發炎情形。進一步研究上發現,與肌肉注射作比較,利用基因槍遞送裸露Der p 2 之DNA疫苗更能顯著的抑制Der p和Der p 2特定免疫球蛋白;經由細胞內細胞素染色分析,相較於肌肉注射,施打新式基因槍方式提昇脾臟細胞內的分泌INF-gamma 的CD4及CD8之T細胞和顯著減弱分泌IL-4的CD4之T細胞數目。因此,我們的實驗證實了新式基因槍施打Der p 2 DNA疫苗顯著的增加專一性Der p 2的Th1免疫反應去抑制過敏性免疫反應,且比肌肉注射的方式有較強的效力去保護造成氣喘的過敏原暴露。實驗結果可以提供免疫上的原理,運用於新式基因槍皮下遞送裸露Der p 2之DNA疫苗治療塵螨引起之過敏病患。
URI: http://hdl.handle.net/11455/20141
其他識別: U0005-1808201012125000
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-1808201012125000
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