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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳俊任(Chun-Jen Chen) | |
dc.contributor.author | Wen-Juan Lin | en |
dc.contributor.author | 林文娟 | zh_TW |
dc.date.accessioned | 2021-06-08T02:20:51Z | - |
dc.date.copyright | 2015-08-25 | |
dc.date.issued | 2015 | |
dc.date.submitted | 2015-08-20 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19815 | - |
dc.description.abstract | 腸病毒在溼熱的環境下容易散播並造成感染,地處亞熱帶的台灣,每年都會出現大小不一的疫情,尤其是在夏天最為高峰。感染腸病毒 71 型 (Enterovirus 71, EV71) 後會造成手足口症,甚至導致中樞神經癱瘓及死亡,在幼童中有極高的死亡率。於 1998 年時,台灣爆發首次 EV71 大流行,但迄今仍未有疫苗可供施打。研究已證實 EV71 的主要抗原決定基位於病毒外殼蛋白中的VP1,因此在本篇研究中將發展可表現 VP1 之 DNA 疫苗,並利用 Lactobaillus casei 作為疫苗的運送載體兼免疫佐劑,以生產出 EV71 的口服 DNA 疫苗。我們使用的載體是乳酸菌穿梭載體 pMN5,其可於哺乳類細胞中表現目標基因,也可於乳酸菌中複製。目前已成功建構可分別在胞內及胞外表現 VP1 的重組質體 pMN5-VP1 及 pMN5-sVP1,並且在 HEK293T 細胞中以西方轉漬法確認 VP1 之表現。在黏膜免疫系統中,樹突細胞及巨噬細胞皆為主要的抗原呈現細胞,本研究中發現 L. casei 可被 RAW264.7 巨噬細胞及 DC2.4 樹突細胞所吞噬,同時能刺激細胞產生 TNF-α 及 IL-6,亦能使 DC2.4 細胞表面的成熟標誌 CD40、CD80、CD86 及 MHC II 之表現量上升,顯示L. casei確實具有免疫佐劑的作用。本研究已成功建構可表現 EV71 VP1 之乳酸菌穿梭載體,未來將進一步以帶有 pMN5-VP1 或 pMN5-sVP1 之 L. casei,在動物實驗中評估以其作為 EV71 口服 DNA 疫苗之潛力。 | zh_TW |
dc.description.abstract | Enteroviruses easily spread and cause infectious under hot and humid environment. In Taiwan, several enteroviruses epidemics occur throughout the year but usually peak in summer months. Enterovirus 71 (EV71) infection causes hand, foot, and mouth disease (HFMD) in infants and children, and it may also cause central nerve system collapse and even death. Since 1998, EV-71 has become an emerging infectious agent in Taiwan, but there is still no vaccine available against EV-71 so far. Previous studies have shown that the epitopes on the capsid protein VP1 can elicit the majority of neutralizing antibodies in animal models. Hence in this study, we attempt to develop an oral EV-71 DNA vaccine that expresses VP1 and is delivered by Lactobacillus casei, which functions both as a vector and an adjuvant. The Lactobacillus shuttle vector pMN5 can express target genes in mammalian cells and replicate in Lactobacillus. We have constructed pMN5-VP1 and pMN5-sVP1, which express VP1 intracellularly and extracellularly, respectively. The expression of VP1 by these constructs in HEK293T cells was confirmed by Western blotting. Dendritic cells and macrophages are major antigen-presenting cells in the mucosal immune system. Our results showed that L. casei could be phagocytosed by RAW264.7 macrophages and DC2.4 dendritic cells, and meanwhile L. casei could stimulate these cells to produce high levels of TNF-α and IL-6. Furthermore, L. casei also stimulated DC2.4 cells to express the maturation markers CD40, CD80, CD86 and MHC II, indicating that L. casei can function as an adjuvant. In this study, we have successfully constructed Lactobacillus shuttle vectors expressing EV71 VP1, and the potential of using L. casei carrying pMN5-VP1 or pMN5-sVP1 as oral DNA vaccines against EV71 will require further investigation in animals. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T02:20:51Z (GMT). No. of bitstreams: 1 ntu-104-R02b22046-1.pdf: 3471018 bytes, checksum: 61219a32393672527d9adfd02dc329c8 (MD5) Previous issue date: 2015 | en |
dc.description.tableofcontents | 誌謝 I 中文摘要 II Abstract III 目錄 V 圖表目錄 VIII Chapter 1 緒論 1 1.1 腸病毒七十一型 (Enterovirus 71, EV71) 1 1.1.1 起源 1 1.1.2 分類 1 1.1.3 病毒結構與生化特性 2 1.1.4 病毒外殼蛋白VP1 3 1.1.5 病毒生活史 3 1.1.6 病毒流行病學 4 1.1.7 EV71 疫苗的發展現況 5 1.2 DNA 疫苗 (DNA Vaccines) 6 1.2.1 DNA 疫苗的特性 6 1.2.2 作用機制 7 1.2.3 DNA 疫苗運輸系統 (deliver system) 7 1.3 以乳酸菌穿梭載體系統將 DNA 疫苗運送至腸道黏膜 8 1.3.1 黏膜免疫系統 (Mucosal immunity system) 8 1.3.2 乳酸菌 (lactic acid bacteria, LAB) 9 1.3.3 乳酸菌與腸道黏膜的交互作用 10 1.3.4 以乳酸菌做為疫苗運送系統的優點 11 1.3.5 乳酸菌穿梭載體系統 (Lactobacillus shuttle vector system) 12 Chapter 2 研究目的與架構 13 Chapter 3 實驗材料與方法 14 3.1 實驗材料 14 3.1.1 載體 14 3.1.2 細胞株 14 3.1.3 菌株 14 3.1.4 動物 14 3.1.5 反應緩衝液 15 3.2 於 HEK293T 細胞中確認 mRNA 及蛋白質表現 19 3.2.1 重組質體之建構 19 3.2.2 重組質體之 mRNA 及蛋白質表現 21 3.3 樹突細胞與巨噬細胞吞噬作用之分析 25 3.3.1 製備FITC-labeled L. casei 25 3.3.2 DC2.4 與 RAW264.7 之培養 25 3.3.3 RAW264.7 與 DC2.4 之吞噬作用分析 25 3.4 探討乳酸菌與 RAW264.7、DC2.4 及 BMDCs 之作用 26 3.4.1 以乳酸菌刺激 RAW264.7、DC2.4 及 BMDCs 26 3.4.2 培養骨髓分化之樹突細胞 (bone marrow derived dendritic cells, BMDCs) 26 3.4.3 細胞激素分泌量之測定 27 3.4.4 DC2.4 與 BMDCs 成熟標記之分析 27 3.5 統計與繪圖軟體之分析 28 Chapter 4 結果 29 4.1 重組質體之建構 29 4.2 VP1 與 sVP1 之 mRNA 及蛋白質表現 29 4.2.1 於 HEK293T 細胞確認 pMN5-VP1 及 pMN5-sVP1 的mRNA 表現 29 4.2.2 於 HEK293T 細胞確認 pMN5-VP1 及 pMN5-sVP1 的蛋白質表現 30 4.3 RAW264.7 與 DC2.4 對 L. casei 之吞噬作用分析 30 4.4 L. casei 會刺激 DC2.4 成熟 31 4.5 L. casei 刺激 RAW264.7、DC2.4 及 BMDCs 產生TNF-α 及 IL-6 31 Chapter 5 討論與結論 33 Chapter 6 圖表 37 參考文獻 51 附錄 57 | |
dc.language.iso | zh-TW | |
dc.title | 利用乳酸菌穿梭載體系統開發腸病毒 71 型 DNA 疫苗 | zh_TW |
dc.title | Development of enterovirus-71 DNA vaccine using Lactobacillus shuttle vector system | en |
dc.type | Thesis | |
dc.date.schoolyear | 103-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 張世宗(Shih-Chung Chang),朱清良(Ching-Liang Chu) | |
dc.subject.keyword | 腸病毒71型,DNA 疫苗,乳酸菌穿梭載體系統,黏膜免疫,佐劑, | zh_TW |
dc.subject.keyword | Enterovirus 71,DNA vaccine,Lactobacillus shuttle vector system,mucoal immunity,adjuvant, | en |
dc.relation.page | 61 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2015-08-20 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生化科技學系 | zh_TW |
顯示於系所單位: | 生化科技學系 |
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