Research and Development of the Influenza Vaccine 羅筱芳、楊博文
E-mail: [email protected]
ABSTRACT
Today's influenza vaccines are prepared in fertilized chicken eggs, a traditional method that has been used for nearly 50 years. The chicken egg-based system is still considered the most reliance and well-established production process so far. However, this
production cannot provide immediately supply of vaccines, as a new strain of influenza virus is break out. Thus, many researchers have studied in the relevant field to increase the vaccine production in terms of effectiveness, safety and an acceptance of
medical/pharmaceutical market. The current production of flu vaccine approach is the use of influenza viruses that are injected into the chicken embryo and replicated. The infected embryo is then go through the process of incubation, concentration, purification, inactivation and formulation, and finally the bulk of vaccines are produced. The method has demonstrated both matured
vaccine-production process and cost-effective. However, egg protein allergy, availability of embryo supply, time-consuming production and limitation of biotechnology development are its disadvantages. In recent years, there are some improvement and development in vaccine manufacturing, including cell culture, DNA vaccine, and an immune adjuvant. They all have common characteristics such as shortening of preparation time, suitable against widespread viruses and more flexible schedule of production.
However, it still remains some technical difficulties that needed to be overcome when mass productions of vaccines are scale up into manufacture. In the future, there are some concepts in manufacturing technique of influenza vaccine, including reverse genetic techniques, universal vaccine, food-based vaccine and the vaccine mired in tape, which are expected that will improve the method of vaccination, pared-down and shortening of manufacturing process, and increase the protency after vaccination. Hopes of the influenza vaccine will be applied more economically, widely and safely in the countries that need the vaccination. Key Words:
Influenza vaccine, Embryo egg, Cell culture.
Keywords : Influenza vaccine, Embryo egg, Cell culture.
Table of Contents
封面內頁 簽名頁 授權書iii 中文摘要iv 英文摘要V 誌謝vi 目錄vii 圖目錄xi 表目錄xii 1. 緒言1 2. 免疫系統簡介4 2.1 非特異性 免疫系統5 2.1.1 防禦組織5 2.1.2 巨噬細胞及顆粒細胞的殺菌作用6 2.2 特異性免疫系統6 2.2.1 B細胞7 2.2.2 T細胞8 2.2.3 NK 細胞9 2.2.4 抗原加工呈現細胞12 2.2.4.1 巨噬細胞12 2.2.4.2 樹突細胞13 2.2.4.3 B細胞14 2.2.5 體液性免疫14 2.2.6 細胞性免 疫17 2.2.7 抗原19 2.2.8 抗體20 2.2.9 主要組織相容性複合體27 2.2.10 動物免疫的防禦機制28 2.2.10.1 被動免疫29 2.2.10.2 主 動免疫30 2.3 疫苗引發之免疫反應31 3. 疫苗之介紹33 3.1 疫苗之發展史33 3.2 疫苗的分類37 3.2.1 細菌或病毒之整個致病病 原體37 3.2.1.1 減毒疫苗37 3.2.1.2 不活化疫苗38 3.2.2 純化的次單位抗原42 3.2.3 基因重組表現的抗原42 3.2.4 合成胜?43 3.2.5 基因重組載體44 3.2.6 基因疫苗45 3.3 疫苗的安全性49 4. 流行性感冒疫苗之歷史背景及功能機制50 4.1 流行性感冒的 歷史背景50 4.1.1 1918年50 4.1.2 1957年52 4.1.3 1968年52 4.2 流行性感冒的流行病學56 4.2.1 流行性感冒之季節性56 4.2.2 流 行病和大流行病傳播56 4.3 流行性感冒病毒之分類及命名58 4.4 流行性感冒病毒之結構59 4.4.1 紅血球凝集素62 4.4.2 神經 胺酸酵素65 4.4.3 間質蛋白65 4.4.4 非結構性蛋白66 4.5 流行性感冒病毒致病與免疫機制67 4.6 流行性感冒疫苗之製作68 5.
結論73 5.1 現階段流感疫苗製造技術73 5.1.1 細胞培養73 5.1.2 DNA疫苗74 5.1.3 佐劑75 5.1.4 Virosome疫苗75 5.1.5 鼻腔噴 霧疫苗76 5.2 未來流感疫苗製造技術之展望76 5.2.1 反向遺傳技術76 5.2.2 通用型疫苗77 5.2.3 食物疫苗77 5.2.4 貼布疫苗77 5.3 建議78 參考文獻79 圖目錄 圖1. NK細胞之作用機制11 圖2. 體液性免疫反應16 圖3. 流感病毒感染所引發之體液及細胞性 免疫反應18 圖4. Ig的五種抗體結構22 圖5. 抗體分子結構24 圖6. A型流行性感冒病毒之結構61 圖7. 流感病毒的抗原飄變64 圖8. 流感疫苗製造流程圖72 表目錄 表1. 人用疫苗的發展史36 表2. 不活化疫苗與減毒疫苗特性比較表40 表3. 減毒疫苗與不 活化疫苗的優點表41 表4. 不同疫苗的比較48 表5. 主要的流感大流行54 表6. 西班牙流行性感冒期間死亡人數統計55 表7. 上 市流感疫苗種類69
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