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) 包括四种血清型 (DENV1-4)，每年在全球造成 3.9 亿人感染、500,000 人住院和 25,000 人死亡。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，该基因组携带各自 DENV 1、2、3 和 4 的 prM 和 E 基因血清型。然而，与 DENV3 (75%) 和 DENV4 (77%) 相比，它对血清型 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 细胞表位可能会阻止 Dengvaxia® 引发强大的细胞免疫反应，因为 CD8 ⁺ T 细胞表位主要位于 NS3 和 NS5 区域。携带 CD4 ⁺、CD8 ⁺  T 细胞和 B 细胞表位的基于多表位的肽疫苗代表了一种产生特异性免疫反应的新方法。因此，评估和选择可以诱导强大的 B 和 T 细胞反应的表位是构建有效的多表位肽疫苗的先决条件。可以利用免疫信息学分析鉴定有效的 B 和 T 细胞表位，但必须通过实验验证表位的免疫原性。在这篇综述中，我们介绍了通过生物信息学方法预测的 T 细胞表位以及最近对 CD4 ⁺和 CD8 ^{+ 的}实验验证。通过用特定肽对 PBMC 进行离体刺激，形成 T 细胞表位。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，可以选择并整合能够诱导强免疫反应的免疫优势表位，以形成普遍适用的基于多表位的肽登革热疫苗。