HUMAN SPERM ANTIGEN AS AN IMMUNOCONTRACEPTIVE

这项研究项目的长期目标是继续解决 从受精前免疫避孕的角度看问题 一种已定义的哺乳动物精子表面成分及其在 通过抗原特异性抗体干扰达到避孕目的 通过受精。我们的目标是在分子和 生理水平一组精子分子，它们在 受精，其主要序列可以被工程化为 有效的免疫避孕药。因此，分子生物学的混合 精子生理学将引导我们更好地理解 避孕目标。为了继续这条调查路线，目前的 提案的具体目的是针对以下影响的研究 构建物免疫小鼠和猴子的生育力 人SP17(RHSP17)以及rHSP17和透明带的组合 (ZP)构造。目标1：在小鼠和 A组嵌合肽在猴体内的免疫原性试验 杂交型T细胞表位与rHSP17单链合成 合成肽。目标2：在小鼠和 重组蛋白在猴体内的免疫原性试验 代表整个HSP17序列中包含特定序列的部分 免疫优势表位和部分透明带序列 它们代表精子结合部位(S)。目标3：生育 对15只免疫猴和15只对照猴进行试验。目标4： 人Sp17的详细检测及其生理特性 它在真核细胞中的表达。目标5：考试 两种不同重组疫苗对小鼠生育力的影响 精子和透明带中的蛋白质。

The long term goals of this research project are to continue to address the problem of prefertilization immunocontraception from the perspective of a defined mammalian sperm surface component and its role in achieving contraception by the antigen's specific antibody interfering with fertilization. It is our goal to define at the molecular and physiological level a set of sperm molecules which functions during fertilization and whose primary sequences can be engineered into an effective immunocontraceptive. Hence, a blending of molecular biology and sperm physiology will lead us to a better understanding of precise targets for contraception. To continue this line of inquiry, the current proposals's specific aims are directed toward studies on the effect on fertility of mice and monkeys immunized with constructs derived from human Sp17 (rHSp17), and a combination of rHSp17 and zona pellucida (ZP) constructs. Aim number 1: Fertility testing in mice and immunogenicity testing in monkeys of chimeric peptides consisting of a promiscuous T-cell epitope and a rHSp17 peptide synthesized as a single synthetic peptide. Aim number 2: Fertility testing in mice and immunogenicity testing in monkeys of recombinant proteins which represent portions of the entire HSp17 sequence that contain specific immunodominant epitopes and portions of the zona pellucida sequence which represent the sperm binding site(s). Aim number 3: A fertility trial of 15 immunized monkeys and 15 control monkeys. Aim number 4: the physiological characterization of human Sp17 by examining in detail its expression in a eukaryotic cell. Aim number 5: An examination of the effect on fertility in mice immunized with two different recombinant proteins from sperm and zona pellucida.