HUMAN SPERM ANTIGEN AS AN IMMUNOCONTRACEPTIVE

人类精子抗原作为免疫避孕药

• 批准号: 6241159
• 负责人: MICHAEL GENE ORAND
• 金额: $ 23.3万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-14 至 1998-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6241159
• 关键词: Macaca fascicularis; active immunization; antiserum; chimeric proteins; contraceptives; epitope mapping; female; fertility immunology; fertilization; human genetic material tag; laboratory mouse; laboratory rabbit; male; northern blottings; nucleic acid sequence; protein sequence; recombinant proteins; sperm; spermicide; surface antigens; synthetic peptide; vaccine development

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.

该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 确定的哺乳动物精子表面成分及其在 通过抗原的特异性抗体干扰达到避孕的目的 与施肥。 我们的目标是在分子和 生理水平上的一组精子分子，其功能在 受精，其一级序列可以被设计成 有效的免疫避孕。 因此，分子生物学的融合 精子生理学将使我们更好地理解精确的 避孕目标。 为了继续这一调查，当前 提案的具体目标是研究对 用衍生自的构建体免疫的小鼠和猴子的生育能力 人 Sp17 (rHSp17)，以及 rHSp17 和透明带的组合 (ZP) 构造。 目标 1：小鼠生育力测试 在猴子中进行嵌合肽的免疫原性测试，所述嵌合肽由 混杂的 T 细胞表位和作为单个合成的 rHSp17 肽 合成肽。 目标 2：小鼠生育力测试 重组蛋白在猴子中的免疫原性测试 代表整个 Hsp17 序列的部分，其中包含特定的 免疫显性表位和透明带序列的部分 代表精子结合位点。 目标三：生育能力 对 15 只免疫猴子和 15 只对照猴子进行试验。 目标 4： 通过详细检查人类 Sp17 的生理特征 它在真核细胞中的表达。 目标 5：检查 两种不同重组体免疫小鼠对生育能力的影响 来自精子和透明带的蛋白质。