Review: Sperm Proteins Being Studied for Use in a Contraceptive Vaccine

Review: Sperm Proteins Being Studied for Use in a Contraceptive Vaccine
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评论:正在研究精子蛋白在避孕疫苗中的应用

DOI:
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发表时间:
1994
影响因子:
3.6
通讯作者:
P. Primakoff
P. Primakoff
中科院分区:
医学3区
文献类型:
--
作者:
P. Primakoff

文献摘要

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本文列举了研制精子蛋白免疫原避孕疫苗所需的7个基本特征,并作了简要评述。哪种精子蛋白被认为是抗原候选取决于几个关键方面。该蛋白质必须:仅针对精子;在其他哺乳动物精子中表达,如猴子,用于实验室检测;位于精子表面或非常接近精子表面;以及高度免疫原性。精子蛋白包括乳酸脱氢酶、C-4、SP-10、顶体素、FA-1、AH-20和PH-20等。然后,文章对每一种蛋白质进行了综述。乳酸脱氢酶C-4(LDH C-4)的抗体是一种细胞质酶,在动物身上测试时发现,通过抑制精子通过宫颈粘液的穿透而降低生育力。顶体SP-10蛋白最初被指定为主要的候选疫苗,但确切的作用机制尚不清楚。对狒狒体内SP-10的进一步研究正在进行中。另一种顶体蛋白是顶体酶,它也显示出免疫原性。虽然已知顶体酶在受精过程中有一定的作用,但用纯化的顶体酶免疫雌性绵羊和兔子对其生育力没有影响。任何候选疫苗都必须具备的一个至关重要的要求是,它是来自精子的表面蛋白。FA-1、AH-20和PH-20都是精子表面蛋白,其中AH-20和PH-20是质膜蛋白和精子特异性蛋白。AH-20在生育方面的作用尚不为人所知,其测试表明对雄性或雌性豚鼠的生育力没有影响。由于其具有很强的免疫原性而被研究。PH-20在受精过程中具有已知的作用。在雌性豚鼠身上进行试验,可达到100%不育。对PH-20的研究测试现在应该集中在灵长类动物身上。应继续开展以开发疫苗为重点的研究。
In this review article seven basic characteristics necessary in the development of a contraceptive vaccine from sperm protein immunogen are listed and briefly commented on. Which sperm protein (or proteins) to consider as an antigenic candidate depends on several key aspects. The protein must be: specific only to sperm; expressed in other mammalian sperm such as monkeys for laboratory testing; located on or very near the sperm surface; and highly immunogenic. Sperm proteins which have received some testing attention include lactate dehydrogenase C-4 SP-10 acrosin FA-1 AH-20 and PH-20. The article then reviews each of these proteins. Antibodies to lactate dehydrogenase C-4 (LDH C-4) a cytoplasmic enzyme when tested in animals were found to reduce fertility by inhibiting sperm penetration through the cervical mucus. The acrosomal SP-10 protein was originally designated as the primary vaccine candidate; however the exact action mechanism is unknown. Further studies of SP-10 in baboons are underway. Another acrosomal protein is acrosin and it too has showed immunogenic properties. Though acrosin is known to have a definite function during fertilization immunizations with purified acrosin in female sheep and rabbits had no effect on their fertility. One critically important requirement any vaccine candidate must have is that it is a surface protein from the sperm. FA-1 AH-20 and PH-20 are all sperm surface proteins with AH-20 and PH-20 being specifically plasma membrane proteins and sperm specific. AH-20 has no known role in fertility and its testing demonstrated no effect on male or female guinea pig fertility. It was studied for its strong immunogenic properties. PH-20 has a known function in fertilization. When tested on female guinea pigs 100% infertility was achieved. Research testing with PH-20 should now be focused on primates. Research focused on developing a vaccine should be continued.