疫苗發展作為台灣生技產業發展中主要領域中之一項 / None

全球疫苗市場85%是五大疫苗廠Sanofi Pasteur、MSD、GSK、Pfizer及Novartis所寡占。跟隨著研發技術發展、持續的疫苗政策、疾病地區化、公衛防治的提升，極大的市場需求，加速疫苗上市持續帶動疫苗產業成長。疫苗的預防接種是防治傳染病，最直接及最具經濟效益的投資，也是國家防疫能力的展現。本研究主要目的為彙整全球疫苗產業總體產業環境現況，探討影響全球疫苗產業發展之關鍵因素及我國疫苗政策發展。 本研究的主要研究方法，採用檔案分析與個案研究法，前者包括次級資料收集及彙整，後者包括疫苗政策形成、實務推動之相關人士的訪談。 本研究的結論 (1)寡占的疫苗產業及疫苗產業地區化的發展趨勢，是影響未來全球疫苗產業及我國疫苗產業發展之關鍵因素。(2)財源籌集制度會影響我國疫苗政策的擬定。(3)疫苗受害救濟機制與持續教育是疫苗政策推動必要之輔助制度。(4)提升疫苗產業成為國家經濟產業，是突破法規鴻溝及研發速度的產業扶植手段之一。 / Over 85% of vaccine market was controlled by top 5 vaccine manufactures: Sanofi Pasteur, MSD, GSK, Pfizer, and Novartis. Nowadays, research and development technology are advancing; vaccine policies are continued; diseases are regionalized; public health control and prevention are increased. Thus, an extreme market demand resulted and expedited the introduction of vaccines to the markets, driving the ongoing growth of the vaccine market. Vaccination is the most direct and cost-effective investment against infectious diseases and also the demonstration of a country’s ability to against the disease outbreak. The purpose of this study was to summarize the trend of the vaccine market and explore key factors affecting the development of the global vaccine market and vaccine policy in Taiwan. This study was carried out mainly through documentation method and in depth interview case study. Documentation method included the collection and summary of secondary data while the interview case study was to interview the experts who were involved in the formation of vaccine policy and promotion. Conclusions of this study are：(1)The top 5 vaccine manufactures and vaccine industry regionalization are the key factors affecting the development of the vaccine market across the world as well as Taiwan in the future；(2)The vaccine financing affects the formulation of vaccine policy in Taiwan；(3)The vaccine injury compensation program and continuing education as auxiliary systems are necessary mechanisms for the vaccine policy promotion；and (4)Promoting the vaccine industry to the national economic industry level is one of the ways to amend regulatory gaps and advance R&D speed for the benefit of the industry.

隨著時代進步，人們的健康意識提升，醫藥產業不斷成長，人們對藥品的消費也日益提高。許多國際大藥廠皆在近年來投入愈來愈多資源在疫苗部門的研發與製造，顯示疫苗產品在其策略版圖中佔的地位日趨重要。 本研究主要藉由文獻與理論的整理，以及實證資料的分析，探討台灣地區女性消費者不願意施打子宮頸癌疫苗的因素。主要研究內容包含: 第一，探討子宮頸癌疫苗的各種創新抵制來源(使用障礙、價值障礙、身體風險障礙、經濟風險障礙、功能風險障礙、社會風險障礙、傳統障礙、印象障礙)對女性消費者接種子宮頸癌疫苗意願的影響。第二，本研究也探討女性消費者個人的產品知識和產品涉入對其接種子宮頸癌疫苗的各種創新抵制來源以及接種意願的影響。第三，探討女性消費者擔憂罹病的程度對其接種子宮頸癌疫苗意願的影響。 實證資料的分析結果顯示，在各種創新抵制來源之中，社會風險障礙、身體風險障礙與功能風險障礙能顯著影響接種意願。而除了創新抵制因素外，消費者的產品知識、產品涉入與擔憂罹病程度皆能顯著影響接種意願。其中，產品知識對接種意願的影響完全由創新抵制來源所中介，產品涉入對接種意願的影響有部分由創新抵制來源中介，而擔憂罹病程度則為直接影響接種意願。本研究最後根據分析結果，提出整體行銷建議供相關業者參考。

HPV疫苗一方面是新興醫療科技產物，另一方面牽涉科學風險與社會影響力未知的議題，是當前醫療科技風險即具代表性的例子。在各利害關係人的論述競逐下，媒體如何建構此類新聞鮮少有研究關注。因此，本研究的主要目的即在探討台灣與美國媒體如何建構人類乳突病毒疫苗（簡稱HPV疫苗）爭議新聞內涵，而在地社會文化特色是否影響傳播文本的疫苗風險知識建構與定義。此外，閱聽眾對新藥的認知受媒體報導內容影響，本研究同時將疫苗風險、利益與侷限性等資訊納入分析標的，探討台灣與美國媒體HPV疫苗新聞品質。 本研究以2003年5月1日《蘋果日報》發刊為起點，至2009年6月30日為止，《聯合報》、《蘋果日報》、《紐約時報》與《今日美國》共245則HPV疫苗新聞為樣本，採用內容分析法檢視四報的HPV疫苗新聞有何特性，如何呈現HPV疫苗風險與利益資訊。 研究結果發現，HPV疫苗新聞的版面會因報紙類別、媒體屬性呈現差異，《聯合報》、《蘋果日報》、《今日美國》的HPV疫苗新聞較常出現在「生活版」或「健康」版；《紐約時報》則是以「焦點／綜合」版和「評論」版為主。且菁英報較常以硬性新聞取徑報導HPV疫苗新聞，通俗報則多以生活、消費情報處理之。在新聞形式方面，《紐約時報》與《今日美國》的「評論性文章」較其他兩報多，而通俗報出現以「專題／特寫／專訪」提供HPV疫苗爭議深度報導的趨勢。在新聞篇幅方面，《紐約時報》「1001字以上」的報導最多，《蘋果日報》以「601-1001字」為主，其於兩報多為「301-600字」的報導，但新聞篇幅不因媒體屬性而有異。 各報對HPV疫苗新聞的重要新聞主題選擇小有差異，但皆以「科學與醫學資訊」類和「政策法規」類主題的報導最多。此外，菁英報較重視政策爭議，但通俗報較聚焦科學研究成果。而台灣地區報導關注「喚醒疾病防治意識」類主題，但美國地區則企圖以「喚醒用藥安全意識」類報導提醒民眾HPV疫苗存在的未知風險。但HPV疫苗主要新聞主題呈現不受報導時間影響。 HPV疫苗新聞消息來源分布會因報導地區而出現差異。雖然「科學界人士」為各時期、各報引用傾向最高的消息來源，但台灣媒體提供「科學界人士」與「政府官員」較多的HPV疫苗議題發言權；美國媒體則是讓「使用者／民眾」有較多的發言空間，並較台灣媒體更常刊出HPV疫苗相關社論。此外，美國媒體較常註明消息來源與利害關係人的互動狀況。 至於新聞框架方面，整體而言，「科學創新框架」與「醫學藥品框架」為報導比例最高的二個新聞框架，但重要性隨時間變化遞減，然「希望框架」和「質疑科學框架」則是出現相反趨勢。此外，菁英報刊出「質疑科學框架」的比例亦高於通俗報。再者，美國媒體較常以「質疑科學框架」、「性／文化框架」建構HPV疫苗新聞；台灣媒體則偏好「希望框架」。 疫苗風險與利益資訊呈現各項目受報紙類別、媒體屬性與報導地區的影響不一。首先，《蘋果日報》提供較多關於「僅預防特定型別」、「抹片檢查」與「安全性行為」的資訊，而通俗報出現「僅預防特定型別」與「安全性行為」兩項目的比例較菁英報高。此外，美國媒體報導「疫苗利益」、「疫苗風險」、「僅預防特定型別」、「施打疫苗後仍須進行抹片檢查」的比例較台灣媒體高。

流行性感冒是一種容易快速傳染且造成地區性大流行的疾病，雖然政府宣導接種流感疫苗可以有效的防治流行性感冒的疫情，然而接種流感疫苗的人並不多，因此本研究將探討疫苗的有效性，以解決一般民眾對施打疫苗的疑慮。 我們以1998年至2012年的健保資料庫分析疫苗的有效性，分析方法以Python程式將資料分類並做運算，其中一方法以有打疫苗者和未打疫苗者的平均流感就醫次數作為判別疫苗的有效性，另一方法則是用bootstrapping來判別疫苗之有效性。 透過本研究的結果可以知道，6歲以下兒童和6歲以上65歲以下成人類別疫苗都是呈現有效的，但在65歲以上老人則是呈現疫苗無效，雖然如此，在死亡率的比較上，有打疫苗的老人死亡率則是低於沒打疫苗的老人，故仍建議民眾施打疫苗。

本研究探討以知識為基礎的產業如何形成與發展而達成產業創新。更特定言，本研究探討基於知識技術以及組織制度結構所產生之權力關係，如何透過行動者與情境條件之互動，以社群型態之集體行動使其發生轉變，進而影響產業創新之結果。 為了凸顯不同的知識特性與情境條件，本研究選擇以台灣的晶圓代工與法國的卡介苗及B型肝炎疫苗為個案，以透過其歷程的描述來瞭解知識社群與創新社群之於產業創新的關係。個案的主要觀察內容包括創新活動權力關係的源由與類型、不同階段集體行動的特性、以及與產業創新效果的關連。 本研究發現創新活動中之存在兩類權力關係，第一類是基於行動者對知識或技術本身之控制或掌握能力，是屬於知識性的權力關係；第二類是基於行動者對該項知識技術得以運用情境之影響能力，為結構性的權力關係。而行動者產生的集體行動，即分別以「知識社群」之共同語言機制轉變基於知識技術的權力關係，以「創新社群」的價值共識過程轉變基於制度結構的權力關係，而促成產業創新。 本研究亦發現社群的形成與既有的權力關係結構有關。而隨著所欲動員於產業創新的資源條件愈龐大，即待轉變的表面權力關係愈為複雜，以社群實現產業創新愈為重要。而知識與創新社群間的互動，特別是反餽的現象，特別有助於產業創新的實現。另知識和創新社群的行動者有重疊之可能，尤其特定的關鍵行動者將同時扮演知識社群與創新社群中的重要角色。 / The dissertation studies the formation and development of communities in industrial innovations of emerging technology. A community is defined as a group of actors that, strongly influenced by their contexts, voluntarily contribute to enforcement of the capability that aims at realizing their common interests. As a specific form of collective actions, the communities are critical in coordinating various actors by gradually shaping the power relations between them, thus smoothing the potential conflicts during the relatively radical innovation. In the study, two cases are chosen for observing the communitarian processes. The first case is the semiconductor foundry in Taiwan. The second one is the vaccine industry in France. The later further comprises two subcases. One is BCG innovations. The other is the vaccine anti-hepatitis B. Based on a prior case study and literature reviews, two types of communities are proposed to examine the two case studies. The first type of communities is a “knowledge community” in which innovative actors contribute voluntarily in creation and diffusion of knowledge centered at the specific technological innovation. The second type is an “innovation community” in which innovative actors from different sectors contribute together to the application of the specific technology. The study found that a technological power relation that is from the incapability of controlling an emerging technology or of controlling those who own the technology is a barrier to industrial innovation. the knowledge community is capable of transforming a technological power relation, via the formation and diffusion of a common language, for realizing the industrial innovation. It reveals that a structural power relation that is from the actors’ ignorance or resistance to the application of an emerging technology is a barrier to industrial innovation. The innovation community is capable of transforming a structural power relation, via the formation and diffusion of a common value, for realizing the industrial innovation. Moreover, the larger the distance that a surface power relation is from its realistic power relation, that is, the more the disequilibrium of a power relation has, the more efforts are required for a community to contribute in industrial innovation. On the other hand, the more the positive feedbacks between a knowledge community and an innovation community, that is, the more the outcomes of the knowledge community that enhance a common value of the innovation community, and the more the outcomes of the innovation community that enhance the diffusion and deepening of a common language of the knowledge community, the easier the realization of an industrial innovation. Finally, a key actor as a community member has a strategic meaning that the key actor reacts to deepen a common language or to increase a common value so as to facilitate the formation and development of a knowledge community or an innovation community, thus realizing the industrial innovation.

本研究主要在於設計一種新式生物反應器，並應用於生產豬瘟病毒疫苗。首先根據所培養細胞的生長特性與原有生物反應器之缺點，改良成新式的生物反應器，並評估此新式生物反應器適用性、效能，以及所培養豬腎細胞之生長代謝情形與豬瘟病毒力價。整個實驗過程大致分為兩個部分，第一個部分探討細胞固定化培養之最適化培養條件與生長代謝情形，第二個部分探討豬瘟病毒培養之最適化培養條件與生長代謝情形。實驗結果發現豬腎細胞(PK-15)以批次方式培養於新式生物反應器，搭配著FIBRA-CEL®載體，成功的進行擴大培養，豬腎細胞最高的生長量達到2.29×109cells/300mL的細胞量。因此，改良之新式生物反應器可提供細胞優越的生長環境，具有擴大規模培養之潛力，可藉由此簡單設備、操作容易、成本低且低能源消耗之新式生物反應器達成細胞製品之生產基座。 / In this study, the production of PK-15 cell using immobilized animal cell culture in a novel bioreactor was investigated.We evaluated the serviceability and efficiency of a design-improved novel bioreactor for the growth and metabolic states of cultured PK-15 cells and the production of HC virus. The entire experiment includes two major stages: (1) investigation of the optimal conditions and metabolic states for the growth of immobilized cells, (2) investigation of the optimal conditions for the production of HC virus. Our results showed that immobilized PK-15 cells on the fibra-cell carries in the design-improved novel bioreactor exhibited their best growth of 2.29×109 cells/300mL.The immobilized conditions for cell culture, can provide a shearing stress of growth state, easy separation of cells from the culture mediu, and a operation of continuously feeding medium, leading to possibility growth of the high density cell and a long period of production;as a result, the efficiency of producing process is promoted. Here,our design-improved novel bioreactor is expected to provide an optimal growth environment of both the cells and viruses for the production of high-yielded, stable, and consistent cellular biological preparations. Furthermore, it will also provide the basis for the production of cell products with advantages of simple-equipped, easy-to-operate, low cost, and low energy consumption. / 致謝 i 中文摘要 ------------------------------------------------------------------------ ii 英文摘要 ------------------------------------------------------------------------ iii 目錄 ------------------------------------------------------------------------ iv 表目錄 ------------------------------------------------------------------------ vi 圖目錄 ------------------------------------------------------------------------ vii 第一章 緒論------------------------------------------------------------------ 1 第二章 文獻回顧------------------------------------------------------------ 3 2-1 豬腎傳代細胞(PK-15 cell) -------------------------------------- 3 2-2 豬瘟病毒------------------------------------------------------------ 4 2-2.1 豬瘟之歷史背景--------------------------------------------------- 4 2-2.2 豬瘟病毒之特性--------------------------------------------------- 7 2-2.3 豬瘟發生原因之探討--------------------------------------------- 11 2-3 生物反應器--------------------------------------------------------- 12 第三章 實驗材料與方法--------------------------------------------------- 21 3-1 細胞------------------------------------------------------------------ 21 3-2 細胞繼代培養------------------------------------------------------ 21 3-3 細胞冷凍保存------------------------------------------------------ 22 3-4 解凍細胞培養------------------------------------------------------ 22 3-5 病毒感染------------------------------------------------------------ 23 3-6 收集病毒------------------------------------------------------------ 24 3-7 豬瘟病毒力價測試------------------------------------------------ 24 3-8 細胞滾瓶培養------------------------------------------------------ 26 3-9 生物反應器操作--------------------------------------------------- 27 3-10 載體上細胞數的測定--------------------------------------------- 33 3-11 葡萄糖的測定------------------------------------------------------ 33 3-12 培養過程中pH值測定------------------------------------------- 34 第四章 結果與討論--------------------------------------------------------- 35 4-1 測試細胞貼附的材料--------------------------------------------- 35 4-2 細胞固定時間的比較--------------------------------------------- 36 4-3 測試不同比例的載體量培養豬腎細胞------------------------ 37 4-4 測試不同接種量--------------------------------------------------- 40 4-5 測試培養基流速對豬腎細胞生長的影響--------------------- 44 4-6 測試培養基停留於培養槽時間對豬腎細胞生長的影響--- 45 4-7 測試豬腎細胞暴露空氣時間對於生長的影響--------------- 47 4-8 測試Bellocell培養豬腎細胞(PK-15)可行性----------------- 49 4-9 測試利用新式生物反應器培樣豬瘟病毒--------------------- 50 第五章 結論與建議--------------------------------------------------------- 53 參考文獻 ------------------------------------------------------------------------ 55 表目錄 表1. 兔化豬瘟疫苗與組織培養豬瘟疫苗的比較------------------ 6 表2. 急性、慢性與遲發型豬瘟比較---------------------------------- 10 表3. .Growth of Various cell Lines in bellocell-500----------------- 18 表4. Comparison of SF-9 cell Growth and BEV production in Various Laboratory bioreators------------------------------------ 19 表5. Comparison of HEK293 Cell growth and Receptor X production in Cell Factory®/20 roller bottles and BelloCell-500Bioreactor------------------------------------------ 20 表6. Reed-Muench Methods法計算方法----------------------------- 26 表7. 比較不同材料培養PK-15 cell所用的載體量---------------- 50 表8. 細胞固定時間的比較所接細胞量與載體量------------------ 51 圖目錄 圖1. Liau提出以潮汐生物反應器圖--------------------------------- 17 圖2. Operation principle of Bellocell system------------------------- 18 圖3. 新式生物反應器(novel reactor)-潮汐式生物反應器(tidal typereactor)之運作流程圖--------------------------------------- 30 圖4. 比較不同材料培養PK-15 cell ---------------------------------- 63 圖5. 比較不同時間細胞的貼附量------------------------------------ 64 圖6. 測試的不同比例載體量培養豬腎細胞生長曲線------------ 65 圖7. 測試的不同比例載體量培養豬腎細胞培養過程glucose消耗趨勢------------------------------------------------------------ 66 圖8. 測試的不同比例載體量培養豬腎細胞培養過程pH變化------------------------------------------------------------------------ 67 圖9. 測試不同接細胞量培養在10g carrier生長曲線------------- 68 圖10. 測試不同接細胞量培養在10g 載體glucose消耗趨勢----- 69 圖11. 測試不同接細胞量培養在10g carrier pH趨勢--------------- 70 圖12. 測試流速對豬腎細胞生長的影響------------------------------ 71 圖13. 測試流速對細胞影響的葡萄糖消耗--------------------------- 72 圖14. 測試流速對豬腎細胞生長影響pH值-------------------------- 73 圖15. 測試培養基停留時間對豬腎細胞生長影響------------------ 74 圖16. 測試培養基holding時間對豬腎細胞生長的影響之葡萄糖趨勢--------------------------------------------------------------- 75 圖17. 測試培養基holding時間對細胞的影響之pH值趨勢------- 76 圖18. 測試豬腎細胞暴露空氣時間對生長的影響------------------ 77 圖19. 測試豬腎細胞暴露空氣對生長的影響葡萄糖消耗趨勢--- 78 圖20. 測試豬腎細胞暴露空氣對細胞生長的影養pH值趨勢---- 79 圖21. Bellocell反應器培養豬腎細胞---------------------------------- 80 圖22. Bellocell培養豬腎細胞葡萄糖消耗趨勢---------------------- 81 圖23. Bellocell培養豬腎細胞pH值趨勢----------------------------- 82 圖24. 測試利用新式生物反應器培養豬瘟病------------------------ 83

生物科技為目前世界各國極力投入之新興產業，此產業無需大量天然資源及低污染的特性，同時又能解決人類的醫療問題並提昇生活水準的未來發展空間，更使得此一新興產業吸引了眾人的眼光。 　　本論文提出一個評估的模式，讓此產業之技術、產品或專利之價值能夠經系統化的分析後完整呈現，並可基於此分析結果作出策略上之判斷，並以GnRH vaccine技術為例。因為GnRH分子之序列早已發表，經本研究分析得兩種常用的專利保護策略，第一種是將GnRH與不同的載體進行結合，而新生成一個嵌合化合物，並申請此新化合物之專利；第二種是進行GnRH分子結構上之改變以取得新序列的專利保護，取得效果優於自然設計之分子，或藉以增加與免疫載體之結合率。經分析後發現，GnRH疫苗應用理論已經相當成熟，未來幾年應該會有成熟產品通過上市之審核過程；再隨著新科技的進步，可預期將會有更多的新產品會上市，而進一步地有效提昇產品功效並降低製造成本。 　　本研究最後針對GnRH未來在人用藥品及動物用藥之未來市場加以分析，並對於以重複免疫原在重組型疫苗製備法之開發提出行銷、財務、通路、價格、推廣、臨床實驗之建議，以期能經由策略規劃的角度將生物技術的價值作最大化的管理。 / Biotechnology attracts high attentions among many countries recently. New biotechnology will provide a key solution to cure diseases and potentially will be able to increase human life quality without damaging the environment and consuming massy natural resources. 　　In this thesis, we presented a possible process, which involved in academic, marketing and patent information analysis, to effectively evaluate the feasibility and potential of any novel biological technologies, so as to provide the managerial and strategic suggestions based on the analysis. GnRH repeat immunogens vaccine development was taken as an example to demonstrate if the proposed process can be executed adequately. After discretly cross examining the collected information, we concluded that many independent GnRH vaccine patents are available but will not be effective enough to stop to new competitors to get in this sector because GnRH sequence was disclosed in very early research and nobody held the patent for it and most of GnRH patents were granted to either different GnRH-Carrier chimeras or the GnRH analog sequences. Analysis results show that there is only one company closely approaching the final product approval at this moment. However, any improved technology can easily employed to provide a better product with higher effectiveness and lower cost following the first product's upcoming marketing clearance and then make the future market very complicated. 　　Based on those findings, we further analyze the Taiwanese current environment and provide a few managerial suggestions to maximize the value of a novel GnRH vaccine preparation technology.

本論文運用史學、統計與GIS繪圖法，自表至裏，自應用至體制，再至緣由，論述1895～1945年50年間臺灣預防接種史之開展、歷程與引發原因。論證臺灣人用疫苗發展歷史超過百年；日治時期臺灣住民已廣泛接種多量疫苗；臺灣諸免疫界變革不可忽視日本人事體制。 全文首先以法定之傳染病為例，論證疫苗在臺灣民間應用之普遍。首先論述最早在臺灣實施，作為全民接種開始，且採皮上切種之天花種痘，其官方制度演變、於民間推展方法、技術變革與臺日差距（少），以及從統計面所見之臺灣高接種率（社會高免疫力）、低天花感染率和死亡率，和1900年代一遇疫情風聲，即立刻實行臨時接種或擴大定期接種之防疫定制。其次論述血清型疾病預防注射。如1900年鼠疫接種，是臺灣最早由官方執行較大規模針式＼侵入性皮下預防注射之始。但1904年後因花費金額高、人體副作用大而少在臺灣實施。再如霍亂，1902年臺灣已應用霍亂血清，1916年較大規模實施＼實驗，1919～1920年國際霍亂大流行更極力推廣，兩年間，每年各有百餘萬人接種，是各地臺灣人普遍認識和接種預防注射針之始。1918～1920年流行性感冒，確切菌種和傳染原因等等均未知；但當第二波疫情較集中且嚴重時，官方已鼓勵配合副致死病因如肺炎球菌等，實施預防注射，與今日流感疫苗類似。其後，對霍亂或流感使用預防接種之防疫法，終日治結束均為常例。又如流行性腦脊髓膜炎，自1917年臺灣出現購買疫苗案例後，該疫苗自1920年代起即大量應用，1930年代後之接種人數更屢以十萬或百萬為單位。而臺灣1935年前所謂流行性腦炎或腦炎，常是指流行性腦脊髓膜炎；流行性腦炎或腦炎預防接種，實際指流行性腦脊髓膜炎接種。以上各種疫苗大量應用，至約1920年代已形成官方一遇疫情即立刻接種地積極、強力防疫定制，亦影響臺灣該等傳染病感染率和患者死亡率，以及官民對上述傳染病恐懼態度轉變。 繼應用面，本文次論人事、體制之制度面發展。首先，臺灣在1902～1905年，先後出現在臺灣設置血清藥院聲音、鼓勵細菌血清學研究、設置牛疫血清作業所、起議在臺實施全新生兒種痘和創設中央科學研究所。1916年開始製販血清疫苗，擇製本島常見菌種、強調「賣捌」非「販賣」，此後製品種類陸續增加。臺製疫苗亦供應沖繩和中國等等臺灣以外地區。1922年起，臺灣不再製造牛疫血清，改由朝鮮提供防疫之常備用品；1939年士林廠房完工，臺灣開始製造乾燥和精緻血清疫苗。另就中央衛生部人事和業績比較，細菌血清類研究和專任人力常多居各研究單位之首，1920年代達高峰；1930年代研究比重雖看似降低，然其負責人員數量、製劑內容和販賣數量，卻更深刻且快速進展，故臺灣中央一直重視免疫醫學或細菌學研究。而使臺灣於各階段發生細菌學興起、開始製販血清疫苗、研製機構體制和製品製程改變原因，首先，使細菌學、免疫學和血清研製機構在臺展開，首須歸因後藤新平和高木友枝等臺灣首長個人意識，以及其背後穩固之內務省衛生局（行政）、傳染病研究所（技術）和眾議會（審議）等人事資源和總體意向，並因人際網絡使臺灣得參酌美國作法。1916年臺灣開始製販血清疫苗，源自1914年傳研移管；擇製某類型製劑且限定專賣，則為前期人事派系延續和檢定制度便宜之計。傳承人事脈絡與社會局勢，再配合新發地政治社會需求，使1920年代後期起中央研究所人事漸變化，來自地方者再回歸地方，中央日益學術、大學化。最極致表現是1936～1939年中央研究所成為臺北帝大附屬和東大傳研化。此外，臺灣與海外各血清疫苗單位有連絡互通；臺灣是日本諸外地中最早大量製販各種血清疫苗者；也是日本國境內，極少數可以帝大附屬研究所之姿製販血清疫苗者。 / The dissertation aims to use historical data a long with GIS methods to explore the vaccination prevention to certain infectious diseases in colonial Taiwan (1895 – 1945). The smallpox vaccination was the earliest vaccination has been practiced in Taiwan. The change of polices and influstructure in cowpox manufacture revealed how the vaccination adminstration transformed and shaped local society. With the cowpox vaccine popularized, the immunity was gained as well as the low infection and mortality rate after 1910s implied its effectiveness. Secondly, the plague vaccination in 1900~1904 was the first big-scale preventive injection by the Taiwan official, but rarely injected after 1904 due to the high cost and side effects. following that, the cholera serum was often used in scale in 1916 which 3 million people received injecttion during 1919~1920, a period of cholera pandemic. One effective that cholera imunizationleft was that Taiwanese strated to accept needle injection a way of vaccinated prevention. The pandemic influenza invaded Taiwan in 1918~1921but the etiology was unknown currently. As the second wave of the epidemic occurred, the authorities began to pay attention and encouraged people to take injection from indirect causes of death such as pneumococcal. This injection strategy was applied in the whole Japanese ruled era. The epidemic cerebrospinal meningitis, since its vaccination reported in 1917, was larger implemented in the 1920s, then greatly practiced after the 1930s. Furthermore, the epidemic encephalitis or encephalitis named after Taiwan before 1935 usually referred to the epidemic cerebrospinal meningitis. Therefore, the epidemic encephalitis or encephalitis vaccination actually meant the meningococcal meningitis vaccination. In general, most implementation of vaccination appeared around 1916 progressed in 1920s and prevalently practiced after the 1930s. The police of vaccination brought down the infection and mortality rate in Taiwan a long withthe attitude of acceptance to immunization injection among people. Furthermore, Taiwan set up a professional animal serum factory and established the Central Science Institute of Taiwan Governor in 1903. In 1916, Taiwan started to make and sell serums and vaccines to the public which indicated the vaccination were already prevalent among Taiwanese. The govenemnt monopolized the sale of vaccines and the products could however offer to China and other places. In 1939, Taiwan went a step further to manufacture the dried vaccine, toxoid, and anatoxin. The phenomenon above implied various meanings. First, the promotion of bacteriology, immunology and serum in Taiwan were based on personal commitment by Gotou Shinpei (1857-1929) and Takagi Tomoe (1858-1943). With their connection to the Bureau of Sanitation of the Ministry of Interior, the Institute of Infectious Diseases (Kitazato Shibasaburou, 1853-1931), and House of Representatives, their works might link to the Rockefeller Institute which brought strong trust to the developing of bacteriology. In 1916 the attempt to produce and sell vaccine was a side-effect deriving from the domentic friction of the Institute of Infectious Diseases in 1914. It caused by the struggle of the administrative and resources, the dispute of practical and academic, and maturates of the bacteriology; lead to the essentially open to the serums and vaccines market in Japan and its foreign lands, included Taiwan. Taiwan closed to the faction of Kitazato. Soon after, the great spread of infectious diseases in 1918-1921 bright the emergency to apply and manufacture of biologics in 1920s in Japan and all of its territories. Taken the impact, the Central Research Institute of Taiwan Governor changed its infrastructure and products in the 1930s. It is worth noting that the Central Research Institute of Taiwan Governor and the Taiwan Medical Specialized School became branches of the (Taipei and Tokyo) Imperial University in 1936-1939, for the necessity of dried vaccine, toxoid, and anatoxin.