Dubé Evemie, Legaré Christine, Gaudreault Christian, Sullivan Robert
Centre de Recherche en Biologie de la Reproduction and Département d'Obstétrique-Gynécologie, Faculté de Médecine, Université Laval, Québec Canada.
Contraception. 2005 Dec;72(6):459-67. doi: 10.1016/j.contraception.2005.06.062. Epub 2005 Aug 22.
A number of antigens have been characterized and proposed as potential candidates for immunocontraception. P26h, a 26-kDa hamster sperm protein located on the acrosomal cap, is known to be involved in sperm-zona pellucida interactions. Furthermore, in vivo fertilization can be blocked by active immunization of male hamsters against P26h or maltose-binding protein recombinant P26h (MBP-P26h).
The aim of this study was to investigate the immune response and reproductive function of female hamsters immunized against MBP-P26h.
Active immunization against MBP-P26h resulted in anti-P26h circulating antibodies, with enzyme-linked immunosorbent assay (ELISA) titers showing interindividual variability. The antibodies produced by the animals immunized against MBP-P26h reacted with the native P26h protein in ELISA, in Western blot analysis and in immunostaining performed on cauda epididymal spermatozoa. Mating of immunized female hamsters resulted in a significant decrease in the number of viable fetuses only in females with high titers of anti-P26h circulating antibodies.
This result is in agreement with the sperm-zona pellucida binding assay's results. Indeed, sera collected from immunized animals, and not from control animals, significantly blocked sperm-zona pellucida binding in vitro. Histological studies showed that active immunization did not cause any pathology in the reproductive tissues.
These findings suggest that P26h is a potential candidate for the development of a contraceptive vaccine in both males and females.
多种抗原已得到鉴定,并被提议作为免疫避孕的潜在候选物。P26h是一种位于顶体帽上的26 kDa仓鼠精子蛋白,已知其参与精子与透明带的相互作用。此外,对雄性仓鼠主动免疫P26h或麦芽糖结合蛋白重组P26h(MBP-P26h)可阻断体内受精。
本研究旨在调查免疫MBP-P26h的雌性仓鼠的免疫反应和生殖功能。
对MBP-P26h进行主动免疫产生了抗P26h循环抗体,酶联免疫吸附测定(ELISA)滴度显示个体间存在差异。免疫MBP-P26h的动物产生的抗体在ELISA、蛋白质印迹分析以及对附睾尾精子进行的免疫染色中与天然P26h蛋白发生反应。免疫雌性仓鼠交配后,仅在抗P26h循环抗体滴度高的雌性中,活胎数量显著减少。
这一结果与精子-透明带结合试验的结果一致。事实上,从免疫动物而非对照动物收集的血清在体外可显著阻断精子与透明带的结合。组织学研究表明,主动免疫未对生殖组织造成任何病理变化。
这些发现表明,P26h是开发用于雄性和雌性的避孕疫苗的潜在候选物。