ANTISPERM VACCINE FOR CONTRACEPTION IN WOMEN

用于女性避孕的抗精子疫苗

• 批准号: 6272247
• 负责人: PAUL PRIMAKOFF
• 金额: $ 16.26万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-03-01 至 1999-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6272247
• 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， 施肥是有效的，安全的和广泛接受的。PH-20，精子 在一只动物中显示出100%有效避孕的表面蛋白 模型（豚鼠），目前是我们的主要候选抗原。我们 在猴子中测试PH-20免疫原性，并预期免疫 PH-20的雌猴，在最佳条件下， 有效避孕。鉴于这一结果，我们将寻求商业 PH-20疫苗的研制 我们还建议继续研究其他精子抗原， 最终与PH-20一起用于第二代疫苗。（第二 第二代疫苗可能具有更长的持续时间，更少的剂量，更低的成本或更低的成本。 其他优势）。此外，其他精子抗原可以被开发为 PH-20的替代品，如果PH-20的发展停滞。一个替代 抗原是受精素，其在精卵结合和分裂中起作用， 有一个已知的活性部位。我们将测试避孕效果， 用受精素的活性位点区域免疫雌性猴子。其他 候选抗原，sp 56和CRISP-1（DE），将首先通过基因筛选 基因敲除以确定它们是否在受精中起作用。 如果基因敲除产生的突变雄性小鼠， 不育，蛋白质（sp 56和/或CRISP-1）将被明确地 被鉴定为避孕靶点并被开发为免疫原。因此，在本发明中， 可以获得一组抗原， 可以单独评估和组合评估。