Human cytomegalovirus (HCMV) poses a serious public health problem causing morbidity and mortality in transplant recipients, immunocompromised patients, and congenitally infected newborns. Considering the recent reports of emergence of Ganciclovir drug resistance, vaccine development is the need of an hour. In the present study, a multi-epitope vaccine was constructed targeting the major hotspot- the pentavalent complex of glycoproteins (H/L/UL128-UL130-UL131) of HCMV, and other important target proteins- gB and pp65. The vaccine designed was composed of series of epitopes belonging to CD4, CD8 and B cells. As an immunobooster, the CpG motifs was linked to the vaccine which severed as an adjuvant. The affinity, stability and flexibility of the vaccine construct with the immune receptor- Toll like receptor -9 (TLR-9) was investigated by molecular docking and molecular dynamics simulations. The in-silico immune simulations of the vaccine sequence were also carried out to determine its ability to stimulate different immune components. Further, an in-silico cloning of the vaccine construct was performed to analyze the feasibility of its expression and translation efficiency in pET-28a (+) vector. The overall results obtained indicated the vaccine to be immunogenic, non-allergic, had high population coverage, high affinity and stability with the immune receptor, had efficient expression in host E. coli and was effective in stimulating different immune cell types like T helper, T cytotoxic, B cells, dendritic cells, macrophages and interleukins. The proposed vaccine construct is expected to be highly efficacious and needs to be carried forward by the vaccinologists to test its efficacy in lab settings.

中文翻译：

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免疫信息学方法可设计多表位疫苗来对抗巨细胞病毒感染。

人类巨细胞病毒（HCMV）引起了严重的公共卫生问题，导致移植接受者，免疫功能低下的患者以及先天性感染的新生儿发病和死亡。考虑到更昔洛韦耐药性出现的最新报道，疫苗开发需要一个小时的时间。在本研究中，针对主要热点（HCMV糖蛋白（H / L / UL128-UL130-UL131）的五价复合物，以及其他重要的靶蛋白gB和pp65）构建了多表位疫苗。设计的疫苗由一系列属于CD4，CD8和B细胞的表位组成。作为免疫增强剂，CpG基序与作为佐剂切断的疫苗相关。亲和力 通过分子对接和分子动力学模拟研究了具有免疫受体-Toll样受体-9（TLR-9）的疫苗构建体的稳定性和柔韧性。还对疫苗序列进行了计算机模拟免疫，以确定其刺激不同免疫成分的能力。此外，进行了疫苗构建体的计算机内克隆，以分析其在pET-28a（+）载体中表达和翻译效率的可行性。获得的总体结果表明，该疫苗具有免疫原性，非过敏性，具有高种群覆盖率，对免疫受体具有高亲和力和稳定性，在宿主大肠杆菌中有效表达，并能有效刺激不同的免疫细胞类型，例如T辅助细胞， T细胞毒性，B细胞，树突状细胞，巨噬细胞和白介素。