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Evaluation of multi-epitope recombinant protein as a candidate for a contraceptive vaccine
Journal of Reproductive Immunology ( IF 2.9 ) Pub Date : 2021-04-15 , DOI: 10.1016/j.jri.2021.103325
Behnam Mortazavi 1 , Najaf Allahyari Fard 2 , Ali Asghar Karkhane 2 , Sara Shokrpoor 3 , Farid Heidari 1
Affiliation  

Contraceptive vaccine (CV) is a valuable, non-invasive, and alternative method for purposeful contraception. Sperm antigens are useful targets for producing CVs due to their specialized expression in sperm. In this study, a recombinant protein containing three main sperm epitopes (IZUMO1, SACA3, and PH-20) was designed and evaluated as CV to control fertility in male mice. The chimeric recombinant protein was expressed and purified in E. coli. Male mice were immunized by 100 μg purified protein and sera were collected to assess IgG antibodies. Evaluating the reproductive performance, immunized male mice mated with normal-fertile female mice and mating rate and the number of newborns was studied. Immunized mice were sacrificed and necropsy and histopathology studies were conducted. The results revealed that the designed chimeric protein stimulated the immune system of the mice effectively. The level of IgG antibody was significantly higher in vaccinated mouse rather than control mouse. Eighty percent of the vaccinated mice became infertile and in the remaining ones, the number of children decreased to 4-6 offspring instead of 10–12 in normal mice. Histopathological studies showed that no organs including heart, brain, lung, liver, kidney and intestine were damaged. However, Normal spermatogenesis has been disrupted and necrotic spermatogonia cells were reported in Seminiferous tubules. We concluded that the designed chimeric protein containing IZUMO1, SACA3, and PH-20 epitopes can stimulate the immune system and cause male contraception without any side effects.



中文翻译:

多表位重组蛋白作为避孕疫苗候选物的评价

避孕疫苗 (CV) 是一种有价值的、非侵入性的、可替代的有目的的避孕方法。精子抗原是产生 CV 的有用目标,因为它们在精子中专门表达。在这项研究中,设计了一种包含三个主要精子表位(IZUMO1、SACA3 和 PH-20)的重组蛋白,并将其作为 CV 进行评估,以控制雄性小鼠的生育能力。嵌合重组蛋白在大肠杆菌中表达纯化. 雄性小鼠用 100 μg 纯化蛋白免疫,收集血清以评估 IgG 抗体。评估繁殖性能,研究了免疫雄性小鼠与正常可育雌性小鼠的交配率和新生儿数量。处死免疫小鼠并进行尸体剖检和组织病理学研究。结果表明,设计的嵌合蛋白有效地刺激了小鼠的免疫系统。接种疫苗的小鼠的 IgG 抗体水平明显高于对照小鼠。80% 的接种疫苗的老鼠变得不育,而在其余老鼠中,孩子的数量减少到 4-6 个,而不是正常老鼠的 10-12 个。组织病理学研究表明,心、脑、肺、肝、肾和肠等器官均未受损。然而,正常的精子发生已被破坏,并且在生精小管中报告了坏死的精原细胞。我们得出的结论是,设计的包含 IZUMO1、SACA3 和 PH-20 表位的嵌合蛋白可以刺激免疫系统并导致男性避孕,而且没有任何副作用。

更新日期:2021-04-27
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