Mosquito Cell-Derived Japanese Encephalitis Virus-Like Particles Induce Specific Humoral and Cellular Immune Responses in Mice.

Yu-Hsiu Chang,Pei-Yun Shu,Jui-Huan Chang,Szu-Cheng Kuo,Shu-Fen Chang,Chang-Chi Lin,Hsueh-Ling Wu,Yu-Lin Hsu,Der-Jiang Chiao

doi:10.3390/v12030336

Yu-Hsiu Chang, Pei-Yun Shu + Show 7 more

Open Access

https://doi.org/10.3390/v12030336

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Abstract

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.

Highlights

The Japanese encephalitis virus (JEV) is a mosquito-borne arbovirus that belongs to the genus
We developed an efficient gene delivery method to facilitate the production of JEV virus-like particles (VLPs) in mosquito cells
JEV genotype III prME genes driven by a specific promoter to deliver JEV prME genes into mosquito cells and thereby induce protein expression and the secretion of VLPs (Figure 1)

Summary

Introduction

The Japanese encephalitis virus (JEV) is a mosquito-borne arbovirus that belongs to the genusFlavivirus. The Japanese encephalitis virus (JEV) is a mosquito-borne arbovirus that belongs to the genus. An estimated 50,000–175,000 cases of JEV occur annually in Asia [1,2]. Potential outbreaks of JEV occur in Africa [3] and Europe [4,5,6]. JEV leads to death in ~20–30% cases, and ~30–50% of JEV survivors suffer serious neurologic, cognitive, or psychiatric complications for years after they recover from the initial infection [5,7]. Despite the fact that a JEV infection is responsible for an annual loss of. 709,000 disability-adjusted life years [8], no antiviral interventions to control JEV infection have yet been approved [9]. JEV GIII immunization programs have proven effective in controlling JEV [10]; subsequent JEV genotype I (GI) displacement and poor protective efficacy against JEV genotype V (GV)

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