Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
J Biomol Struct Dyn. 2024 Aug;42(13):7024-7036. doi: 10.1080/07391102.2023.2240059. Epub 2023 Aug 1.
Chikungunya virus (CHIKV), a type A virus borne by mosquitoes that can cause major clinical manifestations including rash, fever and debilitating arthritis, grown into a reemerging serious public health issue. Currently, there is no licensed therapy or vaccine available for CHIKV, although the most promising form of treatment appears to be immunotherapy. Neutralizing antibodies for CHIKV can provide high protection for all CHIKV strains, as well as other alphaviruses. Development of a protective vaccine may be an effective strategy to prevent the outbreak of CHIKV and provide protection for travelers. In this study, we designed a multi-epitope vaccine with a 543-amino-acid structure based on the E1, E2 and capsid proteins of CHIKV, including 6 CTL epitopes, 6 HTL epitopes, 12 linear B epitopes, along with the adjuvant β-defensin III. All T-cell epitopes were docked with their corresponding MHC alleles to validate their effect on inducing immune responses, and the vaccine's sequence was proven to have acceptable physicochemical properties. Further, the developed vaccine was docked with TLR3 and TLR8, both of which play an important role in recognizing RNA viruses. Basic analyses of the docked complexes and molecular dynamic simulations revealed that the vaccine interacted strongly with TLRs. Immunological simulations indicated that the vaccine could induce both cellular and humoral immunity. Hopefully, this proposed vaccine structure can serve as a viable candidate against CHIKV infection.Communicated by Ramaswamy H. Sarma.
基孔肯雅病毒（CHIKV）是一种由蚊子传播的 A 型病毒，可引起包括皮疹、发热和使人虚弱的关节炎在内的重大临床症状，已成为一个重新出现的严重公共卫生问题。目前，尚无针对 CHIKV 的许可疗法或疫苗，尽管最有前途的治疗形式似乎是免疫疗法。针对 CHIKV 的中和抗体可为所有 CHIKV 株以及其他甲病毒提供高度保护。开发保护性疫苗可能是预防 CHIKV 爆发和为旅行者提供保护的有效策略。在这项研究中，我们根据 CHIKV 的 E1、E2 和衣壳蛋白设计了一种具有 543 个氨基酸结构的多表位疫苗，其中包括 6 个 CTL 表位、6 个 HTL 表位、12 个线性 B 表位以及佐剂β-防御素 III。所有 T 细胞表位都与它们对应的 MHC 等位基因对接，以验证它们对诱导免疫反应的影响，并且该疫苗的序列被证明具有可接受的物理化学性质。此外，开发的疫苗与 TLR3 和 TLR8 对接，这两者在识别 RNA 病毒方面都起着重要作用。对接复合物的基本分析和分子动力学模拟表明，疫苗与 TLR 强烈相互作用。免疫模拟表明，该疫苗可以诱导细胞和体液免疫。希望这种提出的疫苗结构可以作为针对 CHIKV 感染的可行候选物。由 Ramaswamy H. Sarma 传达。
