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一种避孕疫苗，以阻止 施肥有效、安全且被广泛接受。 PH-20，精子 表面蛋白对一只动物具有 100% 有效的避孕效果 模型（豚鼠），是目前我们的主要候选抗原。我们是 在猴子中测试 PH-20 免疫原性并预测免疫接种 患有 PH-20 的雌性猴子在最佳条件下可以充分发挥 有效的避孕。鉴于此结果，我们将寻求商业化 开发基于 PH-20 的疫苗。 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。 （第二个 新一代疫苗可能具有更长的持续时间、更少的剂量、更低的成本或 其他优点）。此外，还可以开发其他精子抗原 如果 PH-20 的开发停滞，则可以使用 PH-20 的替代品。一种替代方案 抗原是受精素，其在精卵结合和裂变中起作用 有一个已知的活性位点。我们将测试避孕效果 用施肥素的活性位点区域对雌性猴子进行免疫。其他 首先通过基因筛选候选抗原sp56和CRISP-1（DE） 敲除以确定它们在受精中是否具有可有可无的作用。 如果基因敲除产生突变雄性小鼠 不育，蛋白质（sp56 和/或 CRISP-1）将明确 被确定为避孕目标并开发为免疫原。因此， 将提供一系列抗原，其避孕功效 可以单独评价，也可以组合评价。