應用蛋白質微陣列技術建立評估各式疫苗效能及篩選之平台

Using protein microarray technology as the platform for screening and evaluating efficiency of various types of vaccine

楊承育(Cheng-Yu Yang)

指導教授 ： 楊沂淵

臺北醫學大學/醫學院/醫學檢驗生物技術學研究所/碩士(2006年)

摘要

疾病能夠通過疫苗來控制。因此，篩選高效且專一性的免疫原用於疾病預防及治療非常重要，同時適當地評估疫苗的效能在疫苗的開發上扮演相當重要的角色。傳統的疫苗研發方式曠日廢時，已經無法面對新興疾病層出不窮的挑戰。隨著蛋白質體學的發展，使得快速篩檢出高效的免疫原變成可能。因此，應用蛋白質體學的研究方法如微陣列技術建立疫苗篩選及評估平台是可行的策略。本論文使用唾液酸多醣（Sialyl-Tn，STn）為抗原進行小鼠的免疫刺激，經蛋白質晶片技術進行抗體反應的測試。含有KLH的STn醣類抗原，確實能在動物體內誘導出免疫反應，產生IgM及IgG的變化。其中，官能基改變的抗原，可以得到較佳的免疫誘導反應，是為高效抗原。所以蛋白質微陣列可作為評估疫苗效能的參考。此外，我們也以市售流感疫苗進行相同的篩檢，得知流感疫苗的確會使人體的IgG效價持續上升，證實該平台亦可應用於臨床疫苗效價評估。 本論文主要目的在建立各式疫苗之效益評估及篩選的平台模式，於未來可提供疫苗研發之應用。

關鍵字

蛋白質微陣列 ； 疫苗 ； 醣類抗原

並列摘要

Vaccine was an excellent strategy of disease control. Screening of high efficiency and specificity immunogenic agents and evaluation of efficiency after vaccine injection are both important for vaccine research and development. Due to time consuming of vaccine research and development, the traditional techniques was not suitable for the condition of current pathogen changes.The issue of quickly and high-throughput screening for vaccine candidate was breakthrough after the proteomics technology, such as protein array, development.After the sailyl-Tn(STn) triggered the mice immune response, we used the microarray to detect the antibody reactivity, and found the IgM and IgG elevated in vivo. At the same way, we also found the high effectiveness vaccine agent was one of the epitope modified by specific functional group. We also using the common flu vaccine undergoing the same procedure, the efficiency were also evaluated. The protein array technique was an excellent tool for both preclinical and clinical evaluation for vaccine effectiveness. These finding was provided efficiency tool for vaccine research and development.

並列關鍵字

protein microarray ； vaccine ； glyco antigen

參考文獻

1. Burnet, F.M., The immunological significance of the thymus: an extension of the clonal selection theory of immunity. Australas Ann Med, 1962. 11: p. 79-91.

2. Farrington, C.P., Estimation of vaccine effectiveness using the screening method. Int J Epidemiol, 1993. 22(4): p. 742-6.

3. Bart, K.J. and K.F. Lin, Vaccine-preventable disease and immunization in the developing world. Pediatr Clin North Am, 1990. 37(3): p. 735-56.

5. Yu, A.S., R.C. Cheung, and E.B. Keeffe, Hepatitis B vaccines. Clin Liver Dis, 2004. 8(2): p. 283-300.

7. Vajda, S., et al., Molecular structure and vaccine design. Annu Rev Biophys Biophys Chem, 1990. 19: p. 69-82.