抗疟疾疫苗的开发在疟疾控制方面具有广阔的前景。称为传播阻断疫苗(TBV)的抗疟疾疫苗策略之一是通过靶向寄生虫配子体来抑制人和蚊子之间的寄生虫传播。以前,我们发现P48/45包含在疟原虫共有的6-半胱氨酸蛋白家族中。我们还检测到所有感染人类的疟原虫所具有的疫苗特性,可以用作跨物种的抗疟疾疫苗。在这项研究中,我们通过祖先和共识重建方法研究了P48/45的疗效.通过RAXML和BEAST2进行P48/45系统发育和时间树分析。使用GRASP服务器和Ugene软件重建祖先和共有序列,分别。通过使用psipred和Rosetta程序进行蛋白质结构预测。通过评估疏水性和翻译后修饰位点来分析P48/45的每种蛋白质特征。同时,B细胞的表位序列,T细胞,使用免疫信息学方法确定HLA。最后,进行分子对接模拟以确定P48/45-P230的天然结合相互作用。结果显示祖先和共有序列具有明显的蛋白质特征。免疫原性分析显示祖先序列中表位的数量大于共有序列。该研究还发现了位于结合位点中的保守表位,由特定的翻译后修饰位点组成。因此,我们的研究为跨物种抗疟疾疫苗的祖先和共识P48/45功效提供了详细的见解.
The development of the anti-malaria vaccine holds a promising future in malaria control. One of the anti-malaria vaccine strategies known as the transmission-blocking vaccine (TBV) is to inhibit the parasite transmission between humans and mosquitoes by targeting the parasite gametocyte. Previously, we found that P48/45 included in the 6-Cysteine protein family shared by Plasmodium sp. We also detected vaccine properties possessed by all human-infecting Plasmodium and could be used as a cross-species anti-malaria vaccine. In this study, we investigated the efficacy of P48/45 through the ancestral and
consensus reconstruction approach. P48/45 phylogenetic and time tree analysis was done by RAXML and BEAST2. GRASP server and Ugene software were used to reconstruct ancestral and
consensus sequences, respectively. The protein structural prediction was made by using a psipred and Rosetta program. Each protein characteristic of P48/45 was analyzed by assessing hydrophobicity and Post-Translational Modification sites. Meanwhile, the Epitope sequence for B-cell, T-cell, and HLA was determined using an immunoinformatics approach. Lastly, molecular docking simulation was done to determine native binding interactions of P48/45-P230. The result showed a distinct protein characteristic of ancestral and
consensus sequences. The immunogenicity analysis revealed the number of epitopes in the ancestral sequence is greater than the
consensus sequence. The study also found a conserved epitope located in the binding site and consists of specific Post-Translational Modification sites. Hence, our research provides detailed insight into ancestral and
consensus P48/45 efficacy for the cross-species anti-malaria vaccine.