Introduction. Cryptococcosis is a ubiquitous opportunistic fungal disease caused by Cryptococcus neoformans var. grubii. It has high global morbidity and mortality among HIV patients and non-HIV carriers with 99% and 95%, respectively. Furthermore, the increasing prevalence of undesired toxicity profile of antifungal, multidrug-resistant organisms and the scarcity of FDA-authorized vaccines were the hallmark in the present days. This study was undertaken to design a reliable epitope-based peptide vaccine through targeting highly conserved immunodominant heat shock 70 kDa protein of Cryptococcus neoformans var. grubii that covers a considerable digit of the world population through implementing a computational vaccinology approach. Materials and Methods. A total of 38 sequences of Cryptococcus neoformans var. grubii’s heat shock 70 kDa protein were retrieved from the NCBI protein database. Different prediction tools were used to analyze the aforementioned protein at the Immune Epitope Database (IEDB) to discriminate the most promising T-cell and B-cell epitopes. The proposed T-cell epitopes were subjected to the population coverage analysis tool to compute the global population’s coverage. Finally, the T-cell projected epitopes were ranked based on their binding scores and modes using AutoDock Vina software. Results and Discussion. The epitopes (ANYVQASEK, QSEKPKNVNPVI, SEKPKNVNPVI, and EKPKNVNPVI) had shown very strong binding affinity and immunogenic properties to B-cell. (FTQLVAAYL, YVYDTRGKL) and (FFGGKVLNF, FINAQLVDV, and FDYALVQHF) exhibited a very strong binding affinity to MHC-I and MHC-II, respectively, with high population coverage for each, while FYRQGAFEL has shown promising results in terms of its binding profile to MHC-II and MHC-I alleles and good strength of binding when docked with HLA-C12:03. In addition, there is massive global population coverage in the three coverage modes. Accordingly, our in silico vaccine is expected to be the future epitope-based peptide vaccine against Cryptococcus neoformans var. grubii that covers a significant figure of the entire world citizens.

中文翻译：

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基于表位的免疫信息学方法研究新型隐球菌热激 70 kDa 蛋白复合物。格鲁比


介绍。隐球菌病是由新型隐球菌引起的一种普遍存在的机会性真菌病。格鲁比。全球艾滋病毒患者和非艾滋病毒携带者的发病率和死亡率很高，分别为 99% 和 95%。此外，抗真菌、多重耐药生物体不良毒性的日益普遍以及 FDA 授权疫苗的稀缺是当今的标志。本研究旨在通过针对新生隐球菌变种的高度保守的免疫显性热休克 70 kDa 蛋白，设计一种可靠的基于表位的肽疫苗。 grubii通过实施计算疫苗学方法覆盖了相当多的世界人口。材料和方法。新型隐球菌 var.共 38 个序列grubii的热休克 70 kDa 蛋白是从 NCBI 蛋白数据库中检索到的。使用不同的预测工具分析免疫表位数据库 (IEDB) 中的上述蛋白质，以区分最有希望的 T 细胞和 B 细胞表位。所提出的 T 细胞表位经过群体覆盖率分析工具来计算全球群体的覆盖率。最后，使用 AutoDock Vina 软件根据 T 细胞投射表位的结合分数和模式对其进行排名。结果和讨论。表位（ANYVQASEK、QSEKPKNVNPVI、SEKPKNVNPVI 和 EKPKNVNPVI）对 B 细胞表现出非常强的结合亲和力和免疫原性。 (FTQLVAAYL、YVYDTRGKL) 和 (FFGGKVLNF、FINAQLVDV 和 FDYALVQHF) 分别对 MHC-I 和 MHC-II 表现出非常强的结合亲和力，且各自具有较高的群体覆盖度，而 FYRQGAFEL 在其结合谱方面显示出有希望的结果与 MHC-II 和 MHC-I 等位基因结合，与 HLA-C12:03 对接时具有良好的结合强度。此外，三种覆盖模式均覆盖全球海量人口。因此，我们的计算机疫苗预计将成为未来针对新型隐球菌变种的基于表位的肽疫苗。 grubii涵盖了全世界相当一部分公民。