Ullah Hikmat, Ullah Shaukat, Li Jinze, Yang Fan, Tan Lei
Center for Energy Metabolism and Reproduction, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518000, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Biology (Basel). 2024 Aug 30;13(9):681. doi: 10.3390/biology13090681.
Dengue virus poses a significant global health challenge, particularly in tropical and subtropical regions. Despite the urgent demand for vaccines in the control of the disease, the two approved vaccines, Dengvaxia and TV003/TV005, there are current questions regarding their effectiveness due to an increased risk of antibody-dependent enhancement (ADE) and reduced protection. These challenges have underscored the need for further development of improved vaccines for Dengue Virus. This study presents a new design using an in silico approach to generate a more effective dengue vaccine. Initially, our design process began with the collection of Dengue polyprotein sequences from 10 representative countries worldwide. And then conserved fragments of viral proteins were retrieved as the bases for epitope screening. The selection of epitopes was then carried out with criteria such as antigenicity, immunogenicity, and binding affinity with MHC molecules, while the exclusion criteria were according to their allergenicity, toxicity, and potential for antibody-dependent enhancement. We then constructed a core antigen with the selected epitopes and linked the outcomes with distinct adjuvant proteins, resulting in three candidate vaccines: PSDV-1, PSDV-2, and PSDV-3. Among these, PSDV-2 was selected for further validation due to its superior physicochemical and structural properties. Extensive simulations demonstrated that PSDV-2 exhibited strong binding to pattern recognition receptors, high stability, and robust immune induction, confirming its potential as a high-quality vaccine candidate. For its recombinant expression, a plasmid was subsequently designed. Our new vaccine design offers a promising additional option for Dengue virus protection. Further experimental validations will be conducted to confirm its protective efficacy and safety.
登革病毒对全球健康构成重大挑战，在热带和亚热带地区尤为如此。尽管在控制该疾病方面对疫苗有迫切需求，但两种已获批的疫苗，即登革热疫苗（Dengvaxia）和TV003/TV005，由于抗体依赖性增强（ADE）风险增加和保护作用降低，目前关于它们的有效性存在疑问。这些挑战凸显了进一步开发改进型登革病毒疫苗的必要性。本研究提出了一种新的设计，采用计算机模拟方法来生成更有效的登革热疫苗。最初，我们的设计过程始于收集来自全球10个代表性国家的登革多聚蛋白序列。然后检索病毒蛋白的保守片段作为表位筛选的基础。随后根据抗原性、免疫原性以及与MHC分子的结合亲和力等标准进行表位选择，而排除标准则依据它们的致敏性、毒性和抗体依赖性增强的可能性。然后我们用选定的表位构建了一种核心抗原，并将结果与不同的佐剂蛋白相连，从而产生了三种候选疫苗：PSDV-1、PSDV-2和PSDV-3。其中，PSDV-2因其优异的物理化学和结构特性而被选中进行进一步验证。广泛的模拟表明，PSDV-2与模式识别受体具有强结合力、高稳定性和强大的免疫诱导能力，证实了其作为高质量疫苗候选物的潜力。为了其重组表达，随后设计了一种质粒。我们的新疫苗设计为登革病毒防护提供了一个有前景的额外选择。将进行进一步的实验验证以确认其保护效果和安全性。
