Development of the New Adjuvant Formula to Enhance Immunogenicity of JEV DNA Vaccine

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Project title

Code/計畫編號

96農科-1.2.1-牧-U1(21)

Translated Name/計畫中文名

研發疫苗新佐劑配方加強日本腦炎DNA疫苗之免疫活性

Project Coordinator/計畫主持人

Chang-Jer Wu

Funding Organization/主管機關

Council of Agriculture,Executive Yuan

Co-Investigator(s)/共同執行人

莊秀琪
鍾文彬

Department/Unit

Department of Food Science

Website

https://www.grb.gov.tw/search/planDetail?id=1481229

Year

2007

Start date/計畫起

01-01-2007

Expected Completion/計畫迄

31-12-2007

Bugetid/研究經費

1800千元

ResearchField/研究領域

畜牧獸醫
生物技術(農)

"日本腦炎病毒是一種經由蚊子傳播的病毒，每年在東亞及南亞等地區造成嚴重的疾病及畜產損害，包括人、馬及懷孕母豬等。施打疫苗是目前控制動物感染性疾病發生的最好方法。所以，發展有效的人用及畜產用疫苗技術是世界潮流的新趨勢。目前接種日本腦炎疫苗對人或畜產確實提供很好的保護效果，但現行傳統的日本腦炎死毒疫苗，不但成本高，有時會引起一些副作用，因此新疫苗的開發有其迫切性。目前開發疫苗與佐劑之新趨勢為應用生體外 (in vitro及ex vivo) 之篩選平台，快速進行各種疫苗抗原及佐劑之篩選，再以生體內 (in vivo) 試驗評估其有效性與實用性，然而，生體外篩選結果必需與生體內試驗之實際成效具有相關性。樹狀突細胞 (dendritic cell；DC) 在免疫反應之起始及維持上扮演著關鍵性的角色，且為目前所知最佳的抗原呈獻細胞 (antigen presenting cell)，其藉由TLR（Toll-like receptor）辨識抗原後，經由不同活化路徑影響免疫反應之型態，例如以TLR9辨識菌體DNA之CpG motif後，釋出細胞激素IL-12 （interleukin-12）及IL-18，可增強Th1細胞激素IFN-γ（interferon-γ）的產生，因此，經由DC的TLR辨識機制可以調節所需的免疫反應，研發出有效且安全的疫苗。本計劃擬應用已建立之生體外 (in vitro及ex vivo) 樹狀突細胞篩選平台，以日本腦炎病毒(Japanese encephalitis virus; JEV)作為抗原，以含CpG motif的oligodeoxynucleotides (ODN) 及IL-18作為佐劑，進行生體外 (in vitro及ex vivo) 及生體內 (in vivo) 之試驗，分析不同DNA佐劑於豬隻體內對日本腦炎病毒DNA疫苗之免疫調節作用，並開發出新一代DNA疫苗及佐劑。本計劃所建立之各項技術，包括應用DC進行In vitro及 In vivo之抗原及佐劑篩選試驗等，皆可作為其它疫苗研發之技術平台。" "Japanese encephalitis virus (JEV) is a mosquito-transmitted virus that causes disease in human, horses, and pregnant swine each year in southern and eastern Asia. The global trend in vaccine technology-mass vaccination in livestock has been an important thrust contributing to the control of animal infectious diseases. Vaccination has been observed to protect against JEV infection in humans and domestic animals. But, the conventional mouse brain-derived vaccine poses several adverse effects that are increasingly less tolerated. Thus, renewed interests in search of innovated technology for use in vaccine development have been a visible global phenomenon. In vitro and ex vivo screening system for quick selection of effective antigen and adjuvant components can simply the in vivo studies, which can accelerate the development of a new generation of vaccine. Dendritic cells (DC), the “professional” antigen presenting cells, are recognized as the key for the connection between the innate and adaptive immune systems. The activation of DC via Toll-like receptors (TLRs) plays a decisive role in determining the character of the immune response by secreting cytokines that drive the proliferation and differentiation of different subsets of T cells. For instance, unmethylated CpG motif recognized by the TLR9 stimulates the productions of IL-12（interleukin-12）and IL-18, which further enhance the release of IFN-gamma. Therefore, the capacity of DC to elicit distinct immune responses through TLR recognition system implicates that DC has the potential as a tool to be used in the in vitro and ex vitro systems for screening DNA vaccine adjuvant efficacy. This study will investigate the DNA adjuvant efficacy by determining the expressions of costimulatory molecules, functions, and cytokine productions of DC in the in vitro and ex vivo screening systems and further examined in the in vivo immune response studies. Different CpG motif ODN and/or IL-18 will be selected and tested as DNA adjuvants for Japanese encephalitis virus (JEV) DNA vaccine. Techniques developed in this study can also be applied to the development of other vaccines."

Keyword(s)

DNA佐劑
日本腦炎病毒
DNA疫苗
DNA Adjuvant
Japanese Encephalitis Virus
DNA Vaccine

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Development of the New Adjuvant Formula to Enhance Immunogenicity of JEV DNA Vaccine

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