ANTISPERM VACCINE FOR CONTRACEPTION IN WOMEN

用于女性避孕的抗精子疫苗

• 批准号: 6577258
• 负责人: PAUL PRIMAKOFF
• 金额: $ 16.56万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6577258
• 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.

我们建议为女性开发避孕疫苗 受精并且有效，安全且广泛接受。 PH-20，精子 表面蛋白显示可在一只动物中100％有效避孕 模型（豚鼠）目前是我们的主要候选抗原。我们是 测试猴子中的pH-20免疫原性，并预测免疫 在最佳条件下，具有pH-20的雌猴可以完全给予 有效的避孕。鉴于此结果，我们将追求商业 开发基于PH-20的疫苗。 我们还建议继续研究其他可能 最终在第二代疫苗中与PH-20一起使用。 （第二 发电疫苗的持续时间可能更长，剂量较少，成本较低或 其他优势）。另外，其他精子抗原可以开发为 ph-20的替代方案，如果PH-20的开发失速。一种选择 抗原是受精蛋白，在精子结合和裂变中起作用， 有一个已知的活性站点。我们将测试的避孕功效 用受精蛋白的活性部位区域免疫雌猴。其他 候选抗原Sp56和Crisp-1（DE）将首先通过基因筛选 敲除确定他们在受精中是否具有可分配作用。 如果基因敲除产生完全是完全的雄性小鼠 不育，蛋白质（SP56和/或Crisp-1）将是确定的 被鉴定为避孕靶标，并发展为免疫原。因此， 将提供一系列抗原的避孕功效 可以单独评估并组合。