利用LAE 技術開發抗hCG疫苗

Development of anti-hCG vaccine by Linear Array Epitope （LAE）techology

蘇家禛(Chia-Chen Su)

指導教授 ： 黃昭蓮 ； 施子弼

臺北醫學大學/醫學院/細胞及分子生物研究所/碩士(2003年)

摘要

人類絨毛模促性腺激素（hCG）是一種糖蛋白荷爾蒙，在授精卵形成後約１０∼１２天由trophoblast分泌，人類絨毛模促性腺激素的產生，在懷孕中胚胎發育的前三個月是非常必要的，因為其會刺激卵巢上的黃體產生progesterone，促使子宮內膜增厚以維持整個胚胎發育的過程。利用免疫的方法來達到節育的效果源自於1930年間，藉由引發免疫反映所產生的抗體來阻止荷爾蒙的作用，讓受孕的機制、過程中斷，無法達到正常懷孕的環境，而達到節育的效果。未達此目的，我們利用線性重複抗體辨認區段（Linear Array Epitope, LAE）之技術，合成可轉譯重複hCG部分片段之DNA序列，並構築成包含綠膿桿菌（Pseudomonas aeruginosa）外毒素A之接收器結合區及重複hCG片段的蛋白抗原。結果在動物實驗中顯示，利用此抗原所又發出的抗體的確可以達到節育70﹪的效果。

關鍵字

人類絨毛膜促性腺激素 ； 疫苗 ； 融合蛋白抗原 ； 醣蛋白荷爾蒙 ； 抗體 ； 綠膿桿菌外毒素A ； 線性重複排列抗原 ； 節育

並列摘要

Human chorionic gonadotropin (hCG) is a glycoprotein hormone produced by trophoblastic cells of the placenta beginning 10 to 12 days after conception. Maintenance of the fetus in the first trimester of pregnancy requires the production of hCG, which binds to the corpus luteum of the ovary which is stimulated to produce progesterone which in turn maintains the secretory endometrium. In this study, I propose to develop immunogenes which can induce anti-hCG autoantibody, and hopefully they could be used as safe and efficient contraceptive vaccine. Toward this end, I used Linear-Array-Epitope（LAE）techniqes to construct DNA fragments encoding multicopies of hCG fragements, followed by subcloning it into a protein expression vector. The final immunogen is a fusion protein containg the receptor binding domain of Pseudomonas aeruginosa exotoxin A and multicopies of hCG fragements. After immunizing the mouse with individual immunogens, 70﹪immunized mouse lose reproductive ability. Our results reveaed that the immunogens are able to influence the reproductive ability.

並列關鍵字

contraception ； Human chorionic gonadotropin ； hCG ； vaccine ； fusion protein antigen ； glycoprotein hormone ； antibody ； PEIa ； linaer array epitopr ； LAE

參考文獻

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