Department of Vaccinology, Center for Infectious Diseases, Kobe University Graduate School of Medicine.
Microbiol Immunol. 2014 Feb;58(2):126-34. doi: 10.1111/1348-0421.12125.
Neutralizing antibodies induced by dengue virus (DENV) infection show viral infection-enhancing activities at sub-neutralizing doses. On the other hand, preimmunity against Japanese encephalitis virus (JEV), a congener of DENV, does not increase the severity of DENV infection. Several studies have demonstrated that neutralizing epitopes in the genus Flavivirus are mainly located in domain III (DIII) of the envelope (E) protein. In this study, chimeric premembrane and envelope (prM-E) gene-based expression plasmids of JEV and DENV1 with DIII substitution of each virus were constructed for use as DNA vaccines and their immunogenicity evaluated. Sera from C3H/He and ICR mice immunized with a chimeric gene containing DENV1 DIII on a JEV prM-E gene backbone showed high neutralizing antibody titers with less DENV infection-enhancing activity. Our results confirm the applicability of this approach as a new dengue vaccine development strategy.
登革病毒（DENV）感染诱导的中和抗体在亚中和剂量下显示出增强病毒感染的活性。另一方面，针对日本脑炎病毒（JEV）的预先免疫，一种 DENV 的同源物，不会增加 DENV 感染的严重程度。几项研究表明，黄病毒属中的中和表位主要位于包膜（E）蛋白的结构域 III（DIII）。在这项研究中，构建了基于嵌合前膜和包膜（prM-E）基因的 JEV 和 DENV1 表达质粒，其中每个病毒的 DIII 都被替换，用作 DNA 疫苗，并评估了它们的免疫原性。用含有 JEV prM-E 基因骨架上的 DENV1 DIII 的嵌合基因免疫的 C3H/He 和 ICR 小鼠的血清显示出高中和抗体滴度，并且 DENV 感染增强活性较低。我们的结果证实了这种方法作为一种新的登革热疫苗开发策略的适用性。
