The Japanese encephalitis virus (JEV) is the major cause of an acute encephalitis syndrome in many Asian countries, despite the fact that an effective vaccine has been developed. Virus-like particles (VLPs) are self-assembled multi-subunit protein structures which possess specific epitope antigenicities related to corresponding native viruses. These properties mean that VLPs are considered safe antigens that can be used in clinical applications. In this study, we developed a novel baculovirus/mosquito (BacMos) expression system which potentially enables the scalable production of JEV genotype III (GIII) VLPs (which are secreted from mosquito cells). The mosquito-cell-derived JEV VLPs comprised 30-nm spherical particles as well as precursor membrane protein (prM) and envelope (E) proteins with densities that ranged from 30% to 55% across a sucrose gradient. We used IgM antibody-capture enzyme-linked immunosorbent assays to assess the resemblance between VLPs and authentic virions and thereby characterized the epitope specific antigenicity of VLPs. VLP immunization was found to elicit a specific immune response toward a balanced IgG2a/IgG1 ratio. This response effectively neutralized both JEV GI and GIII and elicited a mixed Th1/Th2 response in mice. This study supports the development of mosquito cell-derived JEV VLPs to serve as candidate vaccines against JEV.

中文翻译：

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源自蚊细胞的日本脑炎病毒样颗粒可引起小鼠特定的体液和细胞免疫反应。

尽管已经开发出有效的疫苗，但在许多亚洲国家中，日本脑炎病毒（JEV）还是导致急性脑炎综合征的主要原因。病毒样颗粒（VLP）是自组装的多亚基蛋白质结构，具有与相应的天然病毒相关的特定表位抗原性。这些特性意味着VLP被认为是可用于临床的安全抗原。在这项研究中，我们开发了一种新型杆状病毒/蚊子（BacMos）表达系统，该系统潜在地实现了JEV基因型III（GIII）VLP（蚊子分泌）的可扩展生产。源自蚊细胞的JEV VLP包含30 nm球形颗粒以及前体膜蛋白（prM）和包膜（E）蛋白，其密度在蔗糖梯度范围内为30％至55％。我们使用IgM抗体捕获酶联免疫吸附试验来评估VLP与真实病毒颗粒之间的相似性，从而表征VLP的表位特异性抗原性。发现VLP免疫引起针对平衡的IgG2a / IgG1比例的特异性免疫反应。该反应有效中和了JEV GI和GIII，并在小鼠中引发了混合的Th1 / Th2反应。这项研究支持蚊子来源的JEV VLP的开发，以用作针对JEV的候选疫苗。我们使用IgM抗体捕获酶联免疫吸附测定法来评估VLP与真实病毒体之间的相似性，从而表征VLP的表位特异性抗原性。发现VLP免疫引起针对平衡的IgG2a / IgG1比例的特异性免疫反应。该反应有效中和了JEV GI和GIII，并在小鼠中引发了混合的Th1 / Th2反应。这项研究支持蚊子来源的JEV VLP的开发，以用作针对JEV的候选疫苗。我们使用IgM抗体捕获酶联免疫吸附试验来评估VLP与真实病毒颗粒之间的相似性，从而表征VLP的表位特异性抗原性。发现VLP免疫引起针对平衡的IgG2a / IgG1比例的特异性免疫反应。该反应有效中和了JEV GI和GIII，并在小鼠中引发了混合的Th1 / Th2反应。这项研究支持蚊子来源的JEV VLP的开发，以用作针对JEV的候选疫苗。