一种避孕免疫原的设计、合成及免疫原性研究

Study on molecular design,chemical synthesis and immunogenicity of antigenic peptides for immunocontraception

目的探讨如何将人滋养层细胞促融合表位模拟肽构建成有效的避孕免疫原。方法选择人滋养层细胞促融合表位模拟肽与一种通用辅助T细胞表位(PADRE)作为骨架,设计、合成多抗原肽(MAP)多肽和线性嵌合肽两种结构免疫原,并分别与等量弗氏佐剂混悬后免疫雌性C57BL／6小鼠,观察体液免疫反应的特点。结果在小鼠的血清和子宫黏膜冲洗液中,MAP多肽均比线性嵌合肽诱发出更高的抗体滴度；同时,经免疫组化法特异性抗体可以特异识别滋养层细胞相关抗原表位。结论辅助T细胞表位引入及增加多肽免疫原结构复杂性可提高其免疫原性,显著增强免疫反应强度。在以模拟表位肽为基础肽苗设计中,MAP结构是一种较好的结构。

Objective To explore how to arrange and construct trophoblast fusogenic epitope mimic peptide to obtain an ettective immunogen, Methods Based on fusogenic epitope mimic peptide and synthetic non-natural Pan DR T Helper Epitope（PADRE）, both of MAP and eheimeric structural antigenic peptides were designed and synthesized. After being emulified with the equivalence Freund＇s adjuvant,the antigens were used to immunize the female C57BL/6 mice to evalutate their humoral immune response in animals. Results MAP evoked antibody with higher titer than eheimerie peptide in both serum and washing of uterine mucous membrane. Through immunohistochemieal screening of immune sera with tissue sections of human placental villus, antigenic peptide conraining mimic peptide was able to elicit production of antibody specific for human trophoblastic cell. Conclusion Increased the complexity of the peptide antigen and conjoined Th cell epitope may improve its immunogenicity. MAP structure is a good candidate to design a mimic peptide-based vaccines.