小鼠避孕疫苗嵌合多表位蛋白的构建——免疫信息学和原位杂交研究

Behnam Mortazavi, N. Allahyari Fard, F. Heidari, A. Karkhaneh, Mohammad Ali Eslamizade
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引用次数: 1

摘要

背景避孕疫苗(CV)可作为预防人类和动物妊娠的一种有价值的替代方法。这些疫苗可以有几个靶点,例如表面精子蛋白。基于精子抗原的疫苗在产生避孕效果方面非常有效。然而,多表位疫苗在刺激免疫系统和产生更多抗体以降低不孕率方面更有效。材料和方法本研究旨在设计和评价含有IZUMO、SACA3和PH-20表位的嵌合融合蛋白。评估IZUMO1、SACA3和PH-20,并使用各种生物信息学工具选择合适的区域,包括IEDB、I-TASSER、ProtParam、Asa-View和Chimera软件。蛋白质表位是根据各种特性选择的,包括特异性、溶剂可及性、它们的重量和长度、抗原强度和拓扑结构。选择具有高抗原潜力的表位并通过连接体连接在一起。使用Molecular Dynamic、GROMACS 5和Chimera 1.14软件模拟设计的融合蛋白。结果新构建体的所有抗原图和表位的可用性保持不变。使用刚性连接体作为新的构建体将精子抗原结合,并显示出稳定的形成,具有适当的溶剂可及性,这通过ProSA-web和PROCHECK进行了验证。此外,将新结构与原来的结构进行比较并没有显示出任何结构变化。结论基于生物信息学结果,由三种精子抗原组成的融合蛋白具有刺激免疫系统的生产潜力,能够在循环中产生更多抗体,从而可靠地不育。
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Designing a Construct of Chimeric Multi-Epitopes Protein for Contraceptive Vaccine in Mice: An Immunoinformatics and In Silico Study
BackgroundContraceptive vaccines (CVs) can be used as a valuable and alternative method for the prevention of gestation in humans and animals. These vaccines can have several targets, such as superficial sperm proteins. Vaccines based on sperm antigens are quite efficacious to create a contraceptive effect. However, multi-epitope vaccines are more effective in stimulating the immune system and producing more antibodies to reduce the infertility rate.Materials and MethodsThis study aimed to design and evaluate a chimeric fusion protein containing IZUMO, SACA3, and PH-20 epitopes. IZUMO1, SACA3, and PH-20 were assessed, and appropriate regions were selected using various bioinformatics tools, including IEDB, I-TASSER, ProtParam, Asa-View, and Chimera software. Protein epitopes were selected based on various characters, including specificity, solvent accessibility, their weight and length, antigenic intensity, and topology. Epitopes with high antigenic potential were selected and joined together by linkers. The designed fusion protein was simulated using Molecular Dynamic, GROMACS 5, and Chimera 1.14 software.ResultsThe results demonstrated that all antigenic plots and availability of epitopes in the new construct remained constant. The spermatic antigens were combined using rigid linkers as a new construct and showed a stable formation with proper solvent accessibility validated by ProSA-web and PROCHECK. Also, comparing the new structure with its original one did not show any structural change.ConclusionBased on bioinformatics results, the fusion protein that consists of three spermatic antigens has productive potential to stimulate the immune system and capable of producing more antibodies in circulation and reliable infertility.
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