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利用生物信息学工具分析顶膜抗原-1(AMA-1)的特性,以设计针对间日疟原虫的疫苗。

Analysis of Apical Membrane Antigen (AMA)-1 characteristics using bioinformatics tools in order to vaccine design against Plasmodium vivax.

机构信息

Department of Medical Laboratory Sciences, AJA University of Medical Sciences, Tehran, Iran.

Department of Medical Laboratory Sciences, AJA University of Medical Sciences, Tehran, Iran.

出版信息

Infect Genet Evol. 2019 Jul;71:224-231. doi: 10.1016/j.meegid.2019.04.001. Epub 2019 Apr 3.

DOI:10.1016/j.meegid.2019.04.001
PMID:30953716
Abstract

Plasmodium vivax, an intracellular protozoan, causes malaria which is characterized by fever, anemia, respiratory distress, liver and spleen enlargement. In spite of attempts to design an efficient vaccine, there is not a vaccine against P. vivax. Notable advances have recently achieved in the development of malaria vaccines targeting the surface antigens such as Apical Membrane Antigens (AMA)-1. AMA-1 is a micronemal protein synthesized during the erythrocyte-stage of Plasmodium species and plays a significant role in the invasion process of the parasite into host cells. P. vivax AMA-1 (PvAMA-1) can induce strong cellular and humoral responses, indicating that it can be an ideal candidate of vaccine against malaria. Identification and prediction of proteins characteristics increase our knowledge about them and leads to develop vaccine and diagnostic studies. In the present study several valid bioinformatics tools were applied to analyze the various characteristics of AMA-1 such as physical and chemical properties, secondary and tertiary structures, B- cell and T-cell prediction and other important features in order to introduce potential epitopes for designing a high-efficient vaccine. The results demonstrated that this protein had 57 potential PTM sites and only one transmembrane domain on its sequence. Also, multiple hydrophilic regions and classical high hydrophilic domains were predicted. Secondary structure prediction revealed that the proportions of random coil, alpha-helix and extended strand in the AMA-1 sequence were 53.74%, 27.22%, and 19.4%, respectively. Moreover, 5 disulfide bonds were predicted at positions 14-21aa, 162-192aa, 208-220aa, 247-265aa and 354-363aa. The data obtained from B-cell and T-cell epitopes prediction showed that there were several potential epitopes on AMA-1 that can be proper targets for diagnostic and vaccine studies. The current study presented interesting basic and theoretical information regarding PvAMA-1, being important for further studies in order to design a high-efficiency vaccine against malaria.

摘要

间日疟原虫是一种细胞内原生动物,可引起疟疾,其特征为发热、贫血、呼吸窘迫、肝脾肿大。尽管人们试图设计一种有效的疫苗,但目前还没有针对间日疟原虫的疫苗。最近在针对表面抗原(如顶膜抗原 1(AMA-1))的疟疾疫苗开发方面取得了显著进展。AMA-1 是一种在疟原虫属的红细胞阶段合成的微线蛋白,在寄生虫侵入宿主细胞的过程中发挥重要作用。间日疟原虫 AMA-1(PvAMA-1)可诱导强烈的细胞和体液反应,表明它可能是疟疾疫苗的理想候选物。鉴定和预测蛋白质的特征增加了我们对它们的了解,并有助于开发疫苗和诊断研究。在本研究中,应用了几种有效的生物信息学工具来分析 AMA-1 的各种特征,如物理和化学性质、二级和三级结构、B 细胞和 T 细胞预测以及其他重要特征,以鉴定潜在的表位用于设计高效疫苗。结果表明,该蛋白在其序列上有 57 个潜在的 PTM 位点和一个跨膜结构域。此外,还预测了多个亲水区域和经典的高亲水结构域。二级结构预测表明,AMA-1 序列中的无规则卷曲、α-螺旋和延伸链的比例分别为 53.74%、27.22%和 19.4%。此外,在位置 14-21aa、162-192aa、208-220aa、247-265aa 和 354-363aa 预测了 5 个二硫键。B 细胞和 T 细胞表位预测的数据表明,AMA-1 上有几个潜在的表位可以作为诊断和疫苗研究的合适靶点。本研究提供了有关 PvAMA-1 的有趣的基础和理论信息,这对于进一步的研究设计高效的疟疾疫苗非常重要。

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