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| 研究生： |
何立平 Ho, Li-Ping |
|---|---|
| 論文名稱： |
利用反向疫苗學開發海鱺細菌性次單位疫苗對抗發光菌 Development of bacterial subunit vaccine for cobia (Rachycentron canadum) against Photobacterium damselae ssp. piscicida by reverse vaccinology |
| 指導教授： |
楊惠郎
Yang, Huey-Lang |
| 學位類別： |
博士 Doctor |
| 系所名稱： |
生物科學與科技學院 - 生物科技研究所 Institute of Biotechnology |
| 論文出版年： | 2011 |
| 畢業學年度： | 99 |
| 語文別： | 英文 |
| 論文頁數： | 116 |
| 中文關鍵詞： | 細菌性疫苗 、次單位疫苗 、反向疫苗學 、免疫蛋白質體 、發光菌 、協同作用 |
| 外文關鍵詞： | bacterial vaccine, subunit vaccine, reverse vaccinology, immunuproteomics, Photobacterium damsela ssp. piscicida, synergetic effect |
| 相關次數： | 點閱：163 下載：1 |
| 分享至: |
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發光菌會造成魚類罹患光桿菌症，是國內水產養殖魚類最重要的致病菌，往往造成巨大的損失，過去傳統上常使用抗生素來治療，但是，會有抗生素使用過量而產生抗藥性的問題，為了有效阻止疾病的發生，疫苗已經被認為是預防疾病最有效的方法。大部分的次單位疫苗都是應用在病毒防治上，但是細菌性次單位疫苗的開發受限於基因組的長度與複雜性，仍遭遇不少困難，為有效解決此一難題，本實驗室利用反向疫苗學中的免疫蛋白質體學(Immunoproteomics)，確認出較強的抗原，經由質譜儀分析獲得胺基酸序列，利用生物資訊法預測出蛋白的身份，以重組蛋白技術進行基因選殖、表現與純化重組蛋白，將八種抗原製備成疫苗進行動物實驗，結果顯示，rHSP60, rENOLASE及rGAPDH 抗原作為疫苗注射至海鱺體內會引起較高專一性抗體，且具有較高的保護效果，此項結果可以作為日後未來次單位疫苗候選(vaccine candidates)蛋白研究的參考。經由動物實驗篩選出三個保護性較強的抗原後，為了探討三種抗原之間的關係，先以不同劑量的重組蛋白作為抗原施打於魚苗體內，決定引起免疫反應的最適合劑量，實驗結果顯示，施打不同抗原劑量所引起的免疫反應，每支魚苗施打三十毫克劑量會引起較強的免疫反應，因此，以三十毫克作為施打的總劑量，將重組蛋白以不同的組成雙價或是三價疫苗進行動物實驗評估，實驗結果顯示，施打兩種重組蛋白組成的雙價疫苗具有較好的保護效果，高 於施打單一種蛋白所提供的保護效果；三種蛋白組成的三價型疫苗保護效果最低。rHSP60在疫苗的組合中，可能扮演引起免疫的主要抗原，另外兩個抗原，則與rHSP60混合時，會有增強或是協同的作用，增加保護效果，實驗的結果，可以做為未來研發水產疫苗時的重要資訊。
Photobacterium damselae ssp. piscicida (formly Pasteurella piscicida) is the causative agent of pasteurellosis, which is the most important diseases affecting the culture of marine fishes in Taiwan. In order to protect fish from disease infection, vaccination has become achievable tool to solve problems. The development of subunit vaccines had been applied in preventing viral disease, however, the study of bacterial subunit vaccine seems to be more complicated because of large size of genome, needs lengthy assayed. A novel antigen screening system termed as “Reverse Vaccinology” that using western blotting with 2DE to identify potential antigen, LC-MS/MS to acquire amino acid sequence and recombinant technology to clone the candidate gene for the development of bacterial subunit vaccine. This approach was used to identify immune-reactive antigen candidates of P. damselae ssp. piscicida, and express these proteins such as HSP60, ENOLASE, GAPDH, MIND, GYR.B, RPSA, MREB and CDS1. These recombinant proteins were purified and used as antigen candidates in animal trial. The results indicated, we found three antigens (HSP60, ENOLASE and GAPDH ) increase of specific antibody tier after 2 weeks vaccination; after 30 days of challenge, three antigen candidates including HSP60, ENOLASE and GAPDH proteins have stronger protective efficacy might be vaccine candidates for the subunit vaccine of P. damselae ssp. piscicida. Three potent antigens (rHSP60, rENOLASE, and rGAPDH) with the ability to induce protective immunity to Photobacterium damselae ssp. piscicida in cobia fry were used to develop a subunit vaccine which was evaluated in laboratory challenge trials. Effects of varying doses and combinations of the three antigens were analyzed. The immune response increased with dose, reaching a plateau at c. 30 μg fish-1.Vaccination with 30 μg fish-1 of bivalent subunit vaccines of rHSP60 + rENOLASE, rHSP60 + rGAPDH, and rENOLASE + rGAPDH produced RPS values of 65.6, 64.0, and 48.4%, respectively, while vaccination with rHSP60, rENOLASE, or rGAPDH alone gave RPS values of 46.9, 52, and 25, respectively. The trivalent vaccine provided a RPS of 1.6%. The results indicated that a combination of two antigens rHSP60 + rEnolase or rHSP60 + rGAPDH provided the greatest protective immunity.
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校內：2012-01-01公開校外：2012-01-01公開