PDF(Pubmed)
Abstract：
Yellow fever outbreaks are prevalent, particularly in endemic regions. Given the lack of an established treatment for this disease, significant attention has been directed toward managing this arbovirus. In response, we developed a multiepitope vaccine designed to elicit an immune response, utilizing advanced immunoinformatic and molecular modeling techniques. To achieve this, we predicted B- and T-cell epitopes using the sequences from all structural (E, prM, and C) and nonstructural proteins of 196 YFV strains. Through comprehensive analysis, we identified 10 cytotoxic T-lymphocyte (CTL) and 5T-helper (Th) epitopes that exhibited overlap with B-lymphocyte epitopes. These epitopes were further evaluated for their affinity to a wide range of human leukocyte antigen system alleles and were rigorously tested for antigenicity, immunogenicity, allergenicity, toxicity, and conservation. These epitopes were linked to an adjuvant ( β -defensin) and to each other using ligands, resulting in a vaccine sequence with appropriate physicochemical properties. The 3D structure of this sequence was created, improved, and quality checked; then it was anchored to the Toll-like receptor. Molecular Dynamics and Quantum Mechanics/Molecular Mechanics simulations were employed to enhance the accuracy of docking calculations, with the QM portion of the simulations carried out utilizing the density functional theory formalism. Moreover, the inoculation model was able to provide an optimal codon sequence that was inserted into the pET-28a( +) vector for in silico cloning and could even stimulate highly relevant humoral and cellular immunological responses. Overall, these results suggest that the designed multi-epitope vaccine can serve as prophylaxis against the yellow fever virus.
摘要：
黄热病流行,特别是在流行地区。鉴于这种疾病缺乏既定的治疗方法，人们对这种虫媒病毒的管理给予了极大的关注。作为回应,我们开发了一种多表位疫苗，旨在引发免疫反应，利用先进的免疫信息学和分子建模技术。为了实现这一点，我们使用来自所有结构（E，prm,和C）和196个YFV菌株的非结构蛋白。通过综合分析,我们鉴定了10个细胞毒性T淋巴细胞(CTL)和5个T辅助细胞(Th)表位,它们与B淋巴细胞表位重叠.进一步评估了这些表位对广泛的人类白细胞抗原系统等位基因的亲和力，并进行了严格的抗原性测试。免疫原性,变应原性,毒性,和保护。这些表位与佐剂（β-防御素）连接，并使用配体彼此连接，产生具有适当物理化学性质的疫苗序列。这个序列的3D结构被创建,改进,并进行质量检查；然后将其锚定在Toll样受体上。采用分子动力学和量子力学/分子力学模拟来提高对接计算的准确性，利用密度泛函理论形式主义进行了模拟的QM部分。此外，接种模型能够提供插入pET-28a（）载体的最佳密码子序列，用于计算机克隆，甚至可以刺激高度相关的体液和细胞免疫反应。总的来说,这些结果表明，设计的多表位疫苗可以预防黄热病毒。
