Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Bandar Sunway, 47500, Kuala Lumpur, Selangor, Malaysia.
Med Microbiol Immunol. 2021 Feb;210(1):1-11. doi: 10.1007/s00430-021-00700-x. Epub 2021 Jan 30.
Dengue virus (DENV) comprises four serotypes (DENV1-4) which cause 390 million global infections with 500,000 hospitalizations and 25,000 fatalities annually. Currently, the only FDA approved DENV vaccine is the chimeric live-attenuated vaccine, Dengvaxia®, which is based on the yellow fever virus (YFV) genome that carries the prM and E genes of the respective DENV 1, 2, 3, and 4 serotypes. However, it has lower efficacies against serotypes DENV1 (51%) and DENV2 (34%) when compared with DENV3 (75%) and DENV4 (77%). The absence of T cell epitopes from non-structural (NS) and capsid (C) proteins of the yellow fever vaccine strain might have prevented Dengvaxia® to elicit robust cellular immune responses, as CD8 T cell epitopes are mainly localized in the NS3 and NS5 regions. Multi-epitope-based peptide vaccines carrying CD4, CD8 T cell and B cell epitopes represent a novel approach to generate specific immune responses. Therefore, assessing and selecting epitopes that can induce robust B and T cell responses is a prerequisite for constructing an efficient multi-epitope peptide vaccine. Potent B and T cell epitopes can be identified by utilizing immunoinformatic analysis, but the immunogenicity of the epitopes have to be experimentally validated. In this review, we presented T cell epitopes that have been predicted by bioinformatic approaches as well as recent experimental validations of CD4 and CD8 T cell epitopes by ex-vivo stimulation of PBMCs with specific peptides. Immunoproteomic analysis could be utilized to uncover HLA-specific epitopes presented by DENV-infected cells. Based on various approaches, immunodominant epitopes capable of inducing strong immune responses could be selected and incorporated to form a universally applicable multi-epitope-based peptide dengue vaccine.
登革热病毒（DENV）由四个血清型（DENV1-4）组成，每年导致全球 3.9 亿例感染，50 万例住院和 2.5 万例死亡。目前，唯一获得 FDA 批准的 DENV 疫苗是嵌合减毒活疫苗 Dengvaxia®，它基于黄热病病毒（YFV）基因组，携带相应的 DENV 1、2、3 和 4 血清型的 prM 和 E 基因。然而，与 DENV3（75%）和 DENV4（77%）相比，它对 DENV1（51%）和 DENV2（34%）的疗效较低。黄热病疫苗株的非结构（NS）和衣壳（C）蛋白缺乏 T 细胞表位可能阻止 Dengvaxia®引发强烈的细胞免疫反应，因为 CD8+T 细胞表位主要定位于 NS3 和 NS5 区域。携带 CD4、CD8+T 细胞和 B 细胞表位的多表位肽疫苗代表了产生特异性免疫反应的新方法。因此，评估和选择能够诱导强烈 B 和 T 细胞反应的表位是构建有效多表位肽疫苗的前提。利用免疫信息学分析可以鉴定有效的 B 和 T 细胞表位，但表位的免疫原性必须通过实验验证。在本综述中，我们介绍了通过生物信息学方法预测的 T 细胞表位，以及最近通过 PBMC 与特异性肽的体外刺激对 CD4 和 CD8 T 细胞表位的实验验证。免疫蛋白质组学分析可用于揭示 DENV 感染细胞呈递的 HLA 特异性表位。基于各种方法，可以选择免疫显性表位，诱导强烈的免疫反应，并将其纳入形成普遍适用的多表位肽基登革热疫苗。
