HUMAN SPERM ANTIGEN AS AN IMMUNOCONTRACEPTIVE

该研究项目的长期目标是继续解决 从免疫避孕的角度来看， 一种确定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 受精。 我们的目标是在分子和 生理水平的一组精子分子， 受精，并且其一级序列可以被工程化到一个 有效免疫避孕。 因此，分子生物学 精子生理学将引导我们更好地理解 避孕的目标。 为了继续这一调查，目前 建议的具体目标是针对研究对 用衍生自以下的构建体免疫的小鼠和猴的生育力 人Sp17（rHSp17），以及rHSp17和透明质酸的组合 (ZP)结构。 目标1：小鼠生育力试验， 在猴中对由以下组成的嵌合肽进行免疫原性测试： 混杂的T细胞表位和作为单一合成的rHSP 17肽 合成肽 目标2：小鼠生育力试验， 重组蛋白在猴中的免疫原性测试， 代表整个HSP 17序列的部分，其含有特异性的 免疫显性表位和透明质酸序列的部分 其代表精子结合位点。 目标3：生育率 15只免疫猴和15只对照猴的试验。 目标四： 通过详细研究人Sp17的生理特性， 其在真核细胞中的表达。 目标5：审查 两种不同重组蛋白免疫对小鼠生育力影响 来自精子和透明幼体的蛋白质。

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.