Department of Molecular Biology, ICMR-Rajendra Memorial Research Institute of Medical Sciences, Patna, India.
J Biomol Struct Dyn. 2024 Feb-Mar;42(3):1293-1306. doi: 10.1080/07391102.2023.2201630. Epub 2023 Apr 13.
Visceral leishmaniasis (VL) is a tropical disease that causes severe public health problems in humans when untreated. As no licensed vaccine exists against VL, we aimed to formulate a potential MHC-restricted chimeric vaccine construct against this dreadful parasitic disease. Amastin-like protein derived from is considered to be stable, immunogenic and non-allergic. A comprehensive established framework was used to explore the set of immunogenic epitopes with estimated population coverage of 96.08% worldwide. The rigorous assessment revealed 6 promiscuous T-epitopes which can plausibly be presented by more than 66 diverse HLA alleles. Further docking and simulation study of peptide receptor complexes identified a strong and stable binding interaction with better structural compactness. The predicted epitopes were combined with appropriate linkers and adjuvant molecules and their translation efficiency was evaluated in pET28+(a), an bacterial expression vector using in-silico cloning. Molecular docking followed by MD simulation study revealed a stable interaction between chimeric vaccine construct with TLRs. Immune simulation of the chimeric vaccine constructs showed an elevated Th1 immune response against both B and T epitopes. With this, the detailed computational analysis suggested that the chimeric vaccine construct can evoke a robust immune response against infection. Future studies are required to validate the role of amastin as a promising vaccine target.Communicated by Ramaswamy H. Sarma.
内脏利什曼病(VL)是一种热带疾病,如果未经治疗,会给人类健康带来严重问题。由于目前尚无针对 VL 的许可疫苗,我们旨在针对这种可怕的寄生虫病制定一种潜在的 MHC 限制嵌合疫苗构建体。来自的变形蛋白被认为是稳定的、免疫原性的和非过敏性的。我们使用了一个全面的既定框架来探索一组免疫原性表位,这些表位在全球范围内估计有 96.08%的人群覆盖率。严格的评估揭示了 6 个混杂的 T 表位,这些表位可能由超过 66 种不同的 HLA 等位基因呈递。进一步对接和模拟肽受体复合物的研究确定了与更好的结构紧凑性具有强而稳定的结合相互作用。预测的表位与适当的接头和佐剂分子结合,并使用计算机克隆在 pET28+(a)细菌表达载体中评估其翻译效率。分子对接随后的 MD 模拟研究显示,嵌合疫苗构建体与 TLRs 之间存在稳定的相互作用。嵌合疫苗构建体的免疫模拟显示,针对 B 和 T 表位的 Th1 免疫反应增强。综上所述,详细的计算分析表明,嵌合疫苗构建体可以引发针对 感染的强大免疫反应。需要进一步的研究来验证变形蛋白作为一种有前途的疫苗靶标的作用。由 Ramaswamy H. Sarma 传达。