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Abstract：
Dengue viruses (DENVs) are re-emerging pathogens transmitted by mosquitoes mainly in tropical and subtropical regions. Each year, they are estimated to infect 390 million people globally. The major challenge confronting dengue vaccine development is the need to induce balanced, long lasting tetravalent immune responses against four co-circulating virus serotypes (DENV-I, -II, -III, -IV), because primary infection by any one of which may predispose infected individuals to more severe diseases during a heterotypic secondary infection. Another difficulty is to select representative strains in vaccine design to provide cross-protection against most circulating virus strains. In this study, aimed at developing a tetravalent subunit vaccine with a representative single protein, we designed two vaccines (named cE80(D4) and cE80(max)) based on the consensus sequences of the ectodomain of envelope protein of 3127 DENV strains, and then expressed them in the baculovirus expression system. Both vaccines were capable of eliciting specific antibodies against all four DENV serotypes, and the predominant IgG subtype elicited by the two vaccines was IgG1. Moreover, these vaccines activated both type I and type II antigen-specific helper T cells that secreted IFN-γ and IL-4, respectively. This proof-of-concept study has set foundation for further optimization of a single protein-based tetravalent DENV vaccine.
摘要：
登革热病毒（DENVs）是由主要在热带和亚热带地区的蚊子传播的重新出现的病原体。每一年,据估计，它们感染了全球3.9亿人。登革热疫苗开发面临的主要挑战是需要诱导平衡，针对四种共同循环病毒血清型(DENV-I，-II,-III,-IV),因为其中任何一种的原发性感染都可能使感染个体在异型继发性感染期间易患更严重的疾病。另一个困难是在疫苗设计中选择代表性毒株以提供针对大多数循环病毒株的交叉保护。在这项研究中,旨在开发具有代表性的单一蛋白质的四价亚单位疫苗，我们设计了两种疫苗（命名为cE80（D4）和cE80（max））基于3127个DENV株的包膜蛋白胞外域的共有序列，然后在杆状病毒表达系统中表达。两种疫苗都能够引发针对所有四种DENV血清型的特异性抗体。两种疫苗引发的主要IgG亚型为IgG1。此外，这些疫苗分别激活了分泌IFN-γ和IL-4的I型和II型抗原特异性辅助性T细胞。这项概念验证研究为进一步优化基于单一蛋白质的四价DENV疫苗奠定了基础。
