請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/74915
標題: | 以裝載STING促進劑之仿病毒奈米顆粒作為中東呼吸症候群冠狀病毒感染症之疫苗 A STING Agonist-loaded Viromimetic Nanoparticle for Middle East Respiratory Syndrome Coronavirus Vaccine |
作者: | Chen-Yu Huang 黃湞鈺 |
指導教授: | 陳慧文 |
關鍵字: | 中東呼吸症候群冠狀病毒感染症,PLGA,STING促進劑,RBD,奈米疫苗, MERS-CoV,PLGA,STING agonist,RBD,nanoparticle vaccine, |
出版年 : | 2018 |
學位: | 碩士 |
摘要: | II中文摘要中東呼吸症候群冠狀病毒感染症(MiddleEast respiratory syndrome coronavirus;MERS-CoV) 於2012年於中東確定首例,並且目前其疫情仍然持續在中東擴散,截至目前為止,仍未能有批准上市之疫苗可以使用,因此疫苗之研發迫在眉梢。近年來,由於奈米顆粒(Nanoparticle; NP) 具有生物可降解性、穩定性與生物可相容性,奈米顆粒成為疫苗載體研發主要方向之一,為疫苗開發提供了強而有力之遞送系統候選平台。本研究設計了以PLGA裝載有STING促進劑cd-GMP並用MERS-CoV之重組受體結合區(rRBD) 蛋白質作為MERS-CoV的抗原,進行合成仿病毒之奈米顆粒疫苗(rRBD NP) 之製備。於實驗結果中發現,以奈米顆粒形式給予STING 促進劑更容易被樹突細胞攝取、活化、進而產生免疫反應,並且比起肌肉注射給予方式,以皮下注射野生型C57BL/6小鼠給予rRBD NP能更快且持久產生特異性抗體,及有效誘導IgG2a抗體之生成;在細胞免疫方面,顯示rRBD NP能引起具抗原特異性之CD4+與CD8+ T細胞產生IFN-g,及促進記憶型T細胞的生成。進一步將rRBD NP免疫hDPP4基因轉殖小鼠,以致死劑量之MERS-CoV攻毒後,比起未免疫組別,免疫rRBD NP之hDPP4小鼠具有高力價的中和抗體、肺臟病毒含量顯著降低,並有100%的存活率。綜合以上結果表明了rRBD NP做為MERS-CoV疫苗之潛力,並且此仿病毒奈米顆粒載體亦可提供作為其餘疾病疫苗設計之參考。 The first caseofMiddle East respiratory syndrome coronavirus (MERS-CoV) was confirmed in Middle East in 2012. To date, there is a continuous outbreak ofMERS-CoV in Middle Eastand no effective prophylactic countermeasure has been developed.Facing the rising threat of MERS-CoV, vaccine development is in urgent need. Recently, nanoparticles (NPs) have become one of the key interests in vaccine development. NPscan be prepared from biodegradable andbiocompatible materials, offering a safe candidate for vaccine delivery. In this study, the synthetic virus-mimetic NPsloaded with a STING (stimulator of interferon genes) agonistwas engeneredand functionalized with recombinant receptor-binding domain (rRBD) protein as a vaccine against MERS-CoV.In contrast to free STING agonist, the STING agonist loaded in NPs is more efficient for dendritic cells uptake and immune responsestimulation.Compared with intramuscular inoculation, rRBD NPs with subcutaneous inoculationinduced strongerand sustainable specific antibody response and also enhanced production of IgG2a antibody in wildtype C57BL/6 mice. For thecellular immunity, rRBD NPs elicited IFN-gproduction which produced by specific CD4+ and CD8+ T cellsand promoted memory T cell generation. Moreover, rRBD NPs vaccination in hDPP4 transgenic mice resulted in reduced lung viral load and high titers of neutralizing antibodiesthat provided 100% protection against a MERS-CoV lethal challenge.Taken together, the rRBD NPs shown potential of MERS-CoV vaccine development and also provide a vaccine platform for other disease vaccine design. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/74915 |
DOI: | 10.6342/NTU201802369 |
全文授權: | 有償授權 |
顯示於系所單位: | 獸醫學系 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-107-1.pdf 目前未授權公開取用 | 1.88 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。