Production of Japanese Encephalitis Virus Antigens in Plants Using Bamboo Mosaic Virus-Based Vector.

Tsung-Hsien Chen,Yau-Heiu Hsu,Chung-Chi Hu,Jia-Teh Liao,Ying-Wen Huang,Yi-Ling Lee,Yi-Ling Lin,Na-Sheng Lin

doi:10.3389/fmicb.2017.00788

Abstract

Japanese encephalitis virus (JEV) is among the major threats to public health in Asia. For disease control and prevention, the efficient production of safe and effective vaccines against JEV is in urgent need. In this study, we produced a plant-made JEV vaccine candidate using a chimeric virus particle (CVP) strategy based on bamboo mosaic virus (BaMV) for epitope presentation. The chimeric virus, designated BJ2A, was constructed by fusing JEV envelope protein domain III (EDIII) at the N-terminus of BaMV coat protein, with an insertion of the foot-and-mouth disease virus 2A peptide to facilitate the production of both unfused and epitope-presenting for efficient assembly of the CVP vaccine candidate. The strategy allowed stable maintenance of the fusion construct over long-term serial passages in plants. Immuno-electron microscopy examination and immunization assays revealed that BJ2A is able to present the EDIII epitope on the surface of the CVPs, which stimulated effective neutralizing antibodies against JEV infection in mice. This study demonstrates the efficient production of an effective CVP vaccine candidate against JEV in plants by the BaMV-based epitope presentation system.

Highlights

Japanese encephalitis virus (JEV), the causal agent of Japanese encephalitis (JE), is a plus-strand RNA virus of the family Flaviviridae (Vaughn and Hoke, 1992; Unni et al, 2011)
We have reported the use of a bamboo mosaic virus (BaMV)-based vector as an effective epitope presentation system, and demonstrated that the foot-and-mouth disease virus (FMDV) VP1 epitopes expressed on BaMV chimeric virus particle (CVP) can effectively induce humoral and cell-mediated immune responses in swine and provide full protection against FMDV challenges in that host (Yang et al, 2007)
We have resolved the atomic model of the BaMV virion structure by using cryoelectron microscopy recently (DiMaio et al, 2015). This model provides the theoretical basis for the modeling of more candidate epitopes to be presented on BaMV-based vector system by using convenient in silico analyses. This is the first report describing the production of a vaccine candidate of JEV envelope protein domain III (EDIII) using plant virus-based vector system

Summary

Introduction

Japanese encephalitis virus (JEV), the causal agent of Japanese encephalitis (JE), is a plus-strand RNA virus of the family Flaviviridae (Vaughn and Hoke, 1992; Unni et al, 2011). With the lack of specific antiviral treatment, vaccination against JEV is crucial for prevention (Li et al, 2014), and is recommended by the World Health Organization (WHO) for the at-risk populations (WHO, 2015). The successful implementation of vaccination programs in such areas may depend largely on the cost-effectiveness and safety concerns of the vaccines, similar to the cases for a close relative of JEV, the West Nile virus (Zohrabian et al, 2006; Martina et al, 2010; Chen, 2015). The use of inactivated JEV vaccine does not confer sufficient long-term immunity to provide

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