Chen Tsung-Hsien, Hu Chung-Chi, Liao Jia-Teh, Lee Yi-Ling, Huang Ying-Wen, Lin Na-Sheng, Lin Yi-Ling, Hsu Yau-Heiu
Graduate Institute of Biotechnology, National Chung Hsing UniversityTaichung, Taiwan.
Institute of Biomedical Sciences, Academia SinicaTaipei, Taiwan.
Front Microbiol. 2017 May 3;8:788. doi: 10.3389/fmicb.2017.00788. eCollection 2017.
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.
日本脑炎病毒(JEV)是亚洲公共卫生面临的主要威胁之一。为了疾病控制和预防,迫切需要高效生产安全有效的抗JEV疫苗。在本研究中,我们基于竹花叶病毒(BaMV)利用嵌合病毒颗粒(CVP)策略生产了一种植物源JEV候选疫苗用于表位呈递。通过将JEV包膜蛋白结构域III(EDIII)融合到BaMV外壳蛋白的N端构建嵌合病毒,命名为BJ2A,并插入口蹄疫病毒2A肽以促进未融合和表位呈递形式的产生,从而有效地组装CVP候选疫苗。该策略使融合构建体在植物中长期连续传代过程中能够稳定维持。免疫电子显微镜检查和免疫测定表明,BJ2A能够在CVP表面呈递EDIII表位,刺激小鼠产生针对JEV感染的有效中和抗体。本研究证明了基于BaMV的表位呈递系统能够在植物中高效生产有效的抗JEV CVP候选疫苗。