Two B-cell epitope vaccines based on uPA effectively inhibit fertility in male mice
Two B-cell epitope vaccines based on uPA effectively inhibit fertility in male mice
复制标题
两种基于uPA的B细胞表位疫苗可有效抑制雄性小鼠的生育能力
作者：
Xiaofang Ding;Huimin Li;Yuanyuan Li;Donghui Huang;Chengliang Xiong
uPA是一种类似胰蛋白酶的丝氨酸蛋白酶，在雄性生殖过程中起着重要作用。我们以前的工作已经证明了其全长蛋白免疫的抗生育作用，但存在免疫耐受和其他潜在的副作用。在此我们发现了uPA的两个有效B细胞表位，分别为contraception.in生长因子样结构域和kringle结构域。这两个表位肽与载体蛋白一起免疫雄性小鼠，可诱导产生高滴度的特异性抗体。在交配试验中，两组动物的生育力均明显下降，但无明显的全身性疾病或交配行为异常。免疫雄性的附睾精子表现impaired.progressive活力和体外受精卵的能力。另一个预测epitope.in丝氨酸蛋白酶结构域的免疫组和对照组均未显示类似的阳性结果。重要的是，T细胞在这些B细胞表位本身的攻击后没有被激活，这表明这些Bvaccines.do不诱导细胞介导的自身免疫。总之，我们的研究发现了两个uPA B细胞的男性免疫避孕的新靶点，副作用最小。epitopes.as考虑到它们与人uPA蛋白的高度同源性，这两种表位疫苗具有很好的应用前景。use.in
uPA, a trypsin-like serine protease, was found to take active part in male reproduction. Our previous work.had demonstrated the antifertility effects of its full length protein immunization, but with immune tolerance.and other latent side effects. Here we discovered two effective B-cell epitopes of uPA for male contraception.in growth factor-like domain and kringle domain respectively. Together with carrier protein,.immunization of these two epitope peptides could induce high titers of specific antibodies in male mice..Significant reduction of fertility was observed in these two groups in mating trial without evident systemic.illness or abnormal mating behavior. Epididymal sperms of immunized males exhibited impaired.progressive motility and ability to fertilize eggs in vitro. The immunization of another predicted epitope.in serine protease domain and the control groups showed no similar positive results. Importantly, T cells.were not activated after the challenge of these B-cell epitopes itself, which suggests that these vaccines.do not induce cell-mediated autoimmunity. Taken together, our study discovered two uPA B-cell epitopes.as novel targets for male immunocontraception with minimum side effects. Considering their high identity.with human uPA protein, these two epitope vaccines hold great promise to be developed for man use.in the future.