ANTISPERM VACCINE FOR CONTRACEPTION IN WOMEN

用于女性避孕的抗精子疫苗

• 批准号: 6314111
• 负责人: PAUL PRIMAKOFF
• 金额: $ 16.49万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6314111
• 关键词: Macaca fascicularis; active immunization; antigens; contraceptives; cooperative study; drug screening /evaluation; female; female antifertility drug; fertility immunology; gene targeting; guinea pigs; histopathology; laboratory mouse; protein purification; sperm; vaccine development; vaccines; zona pellucida glycoproteins

We propose to develop a birth control vaccine for women that blocks fertilization and is effective, safe and widely acceptable. PH-20, a sperm surface protein shown to give 100% effective contraception in one animal model (guinea pig), is currently our primary candidate antigen. We are testing PH-20 immunogenicity in monkeys and anticipate that immunization of female monkeys with PH-20, under optimal conditions, could give fully effective contraception. Given this result, we will pursue commercial development of a PH-20 based vaccine. We also propose to continue to study other sperm antigens that might eventually be used with PH-20 in a second generation vaccine. (A second generation vaccine might have longer duration, fewer doses, lower cost or other advantages). Also, other sperm antigens can be developed as alternatives to PH-20, if PH-20's development stalls. One alternative antigen is fertilin which functions in sperm-egg binding and fission and has a known- active site. We will test contraceptive efficacy of immunizing female monkeys with the active site region of fertilin. Other candidate antigens, sp56 and CRISP-1 (DE), will first be screened by gene knockout to determine if they have an dispensable role in fertilization. If the gene knockout produces mutant male mice that are completely infertile, the protein (sp56 and/or CRISP-1) will be definitively identified as a contraceptive target and developed as an immunogen. Thus, a collection of antigens will be available whose contraceptive efficacy can be evaluated singly and combined.

我们建议开发一种节育疫苗，用于阻止 这是一种有效、安全和被广泛接受的方法。PH-20，一种精子 表面蛋白在一只动物身上显示出100%有效的避孕效果 模型(豚鼠)，目前是我们的首要候选抗原。我们是 在猴子身上检测PH-20的免疫原性，并预计免疫 在最佳条件下，携带PH-20的雌性猴子可以充分给予 有效的避孕措施。鉴于这一结果，我们将继续进行商业 基于PH-20的疫苗的开发。 我们还建议继续研究其他可能的精子抗原 最终与PH-20一起用于第二代疫苗。(一秒钟 新一代疫苗可能持续时间更长、剂量更少、成本更低或 其他优势)。此外，其他精子抗原也可以发展为 PH-20的替代品，如果PH-20‘S发展停滞。一种替代方案 抗原是在精子-卵子结合和分裂中起作用的受精素 有一个已知的活跃站点。我们将测试避孕药的效果 用受精素的活性部位区域免疫雌性猴子。其他 候选抗原sp56和CRISP-1(DE)将首先通过基因筛选 以确定它们在受精过程中是否具有可有可无的作用。 如果基因敲除产生的突变雄性小鼠完全是 不育，蛋白质(sp56和/或CRISP-1)将被确定为 被确定为避孕目标，并被开发为免疫原。因此， 将有一系列具有避孕效果的抗原问世 可以单独评估也可以组合评估。