口服劑型微脂粒豬放線桿菌胸膜肺炎(APP)疫苗之研究與開發

中文摘要動物接受疫苗接種，刺激免疫系統活化而產生相應抗體，是目前對於疾病防治的有效方法之一。疫苗接種的途徑不一，有注射、口服、塗抹方式…等等，且各有其優缺點。若是以使用方便性而言，就當屬「口服劑型」。如何以口服方式將疫苗順利保護運送到腸道集合淋巴結(GALT)中的Peyer’s patches，引發免疫反應是本篇研究的主要目的。本研究以豬放線桿菌胸膜肺炎 (Actinobacillus pleuropneumoniae , APP)為對象，用微脂粒包覆其產生的毒素Apx Ⅰ與菌苗，同時在微脂粒疫苗載體表面修飾上Chitosan形成「立體式微脂粒疫苗」，期許能夠克服胃腸道當中的各種理化性與生物性破壞。實驗結果發現，0.2~0.4%是Chitosan建議修飾添加濃度；模擬胃酸pH 2~3、Bile salt、Lipase皆會對「立體式微脂粒疫苗」產生明顯的影響；模擬胃酸pH 7時有助於Chitoan去吸附現象，這是進行控制釋放的有利指標；包覆率方面，磷脂質與膽固醇(4:1)時包覆效率較佳。最後新劑型經過動物實驗證實，在「傳統式微脂粒」與「立體式微脂粒」兩實驗組皆見到強度不一的抗體反應；腸道組織切片也未見到新劑型對免疫對象產生傷害，因此若能廣泛詳盡持續研究，相信口服疫苗是值得推廣應用的免疫方式。

關鍵字

微脂粒；立體式(隱藏式)微脂粒；幾丁聚醣；豬放線桿菌胸膜肺炎疫苗；口服劑型；胃腸道派氏淋巴結；藥物控制釋放；生物醫學材料

並列摘要

Abstract Animals receive vaccination to activate immune system and produce relevant antibody, nowadays is one useful way to prevent disease. Vaccination gets many ways injection , oral , skin ,…ect. Each way has it’s advantage and disadvantage, but the most convenient means is oral route. The purpose of this research is how to protect vaccine reach the peyer’s patches of GALT to activate immune system by the way of oral. In this research we use liposome to encapsulate APX I and bacteria that APP engendered and modify liposomal vaccine carrier with chitosan, through that we get stealth liposomal vaccine. We expect this kind of vaccine can surmount the physical , chemical and biological ruin of GI tract. The result of experiment tells that the perfect consistency for modifying liposome is 0.2~0.4% chitosan; gastric juice pH 2~3, bile salt and lipase are influential for stealth liposome vaccine obviously. Imitative gastric juice pH 7 can help chitosan to deadsorb on liposome and it is also important point for control release. We can get best encapsulation ratio when DPPC and cholesterol at 4:1. In animal experiment , we set two compare groups, traditional liposomal vaccine and stealth liposomal vaccine, in two groups we found antibody response. In tissue slices of GI trace, we haven’t found destructive circumstance that liposomal vaccine caused. We regard through the advanced study and further research, in near future the oral vaccine will be a useful form and main stream of vaccine industry.

並列關鍵字

Liposome ； Stealth Liposome ； Chitosan ； APP Vaccine ； Oral Administration Dosage ； Peyer''''s Patches in GI Tract ； Drug Control Release ； Biomedical Materials

參考文獻

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國際替代計量

口服劑型微脂粒豬放線桿菌胸膜肺炎(APP)疫苗之研究與開發

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