以小鼠精子/睾丸特异性抗原为基础的合成肽免疫避孕效应研究

Immune-contraception of synthetic chimeric peptide

目的 研制以精子 睾丸特异性抗原为基础的多价嵌合肽避孕疫苗。方法 选择小鼠精子 睾丸特异性抗原Sp17、Cy ritestin作为对象 ,采用分子设计的方法与外源性牛核糖核酸酶非选择性T细胞表位组合合成新型嵌合肽 3 5肽 ,并对其免疫效应进行研究。结果 该嵌合肽可刺激小鼠产生较高效价的血清和阴道粘膜特异性抗体 ,诱导脾脏淋巴细胞增殖 ,促进细胞因子IL 4的分泌 ;将其与佛氏佐剂混悬 ,免疫雌性BALB c小鼠可明显降低受孕率和每胎产仔率 ,其抗血清可显著抑制体外精 卵结合和融合。结论 新型嵌合肽具有较明确的抗生育作用 ,提示以分子设计、蛋白质优化方案进行多价避孕疫苗的研究是可行的。

Objective To study a multivalent contraceptive vaccine based on sperm/testicular specific antigens Methods The immunodominant epitopes of sperm/testicular specific antigens from Sp17 and Cyritestin and promiscuous T cell epitope of bovine RNase were used to construct a chimeric peptide (35 mer) with molecular modeling technique A total of 110 female BALB/c mice were equally divided into 5 groups to receive the injections of 35 mer peptide, the other 2 constructed products, nonamer and 21 mer, saline or no injection respectively for their immune effects of contraception Results Immunization BALB/c mice with this 35 mer peptide induced a high level IgG in serum and IgA in vagina, stimulated spleen lymphocytes proliferation and excreted the cytokine IL 4 After immunization, the rate of pregnancy of mice with the 35 mer peptide injection dropped obviously, so did the average number of birth mice The antiserum can significantly inhibit the binding index and fertilization index in vitro Conclusion The new chimeric peptide with 35 amino acid residues has a stable reduction in fertility, indicating the reasonability of using the protein molecule designing method to research the multivalent contraceptive vaccine