Genotype I of Japanese Encephalitis Virus Virus-like Particles Elicit Sterilizing Immunity against Genotype I and III Viral Challenge in Swine

• Published in: Scientific reports Vol. 8; no. 1; pp. 7481 - 10
• Main Authors: Fan, Yi-Chin, Chen, Jo-Mei, Lin, Jen-Wei, Chen, Yi-Ying, Wu, Guan-Hong, Su, Kuan-Hsuan, Chiou, Ming-Tang, Wu, Shang-Rung, Yin, Ji-Hang, Liao, Jiunn-Wang, Chang, Gwong-Jen J., Chiou, Shyan-Song
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.05.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 101/28; 631/326/590/2294; 631/326/596/2563; 631/326/596/2564; 64/60; 82/29; 82/80; 82/83; 96; Cell fusion; Cytology; Encephalitis; Fever; Genotype & phenotype; Genotypes; Heparan sulfate; Humanities and Social Sciences; Immunity; Immunogenicity; Lymph nodes; multidisciplinary; Outbreaks; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Sulfates; Vaccines; Viremia; Virus-like particles; Viruses
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-25596-1

Swine are a critical amplifying host involved in human Japanese encephalitis (JE) outbreaks. Cross-genotypic immunogenicity and sterile protection are important for the current genotype III (GIII) virus-derived vaccines in swine, especially now that emerging genotype I (GI) JE virus (JEV) has replaced GIII virus as the dominant strain. Herein, we aimed to develop a system to generate GI JEV virus-like particles (VLPs) and evaluate the immunogenicity and protection of the GI vaccine candidate in mice and specific pathogen-free swine. A CHO-heparan sulfate-deficient (CHO-HS(-)) cell clone, named 51-10 clone, stably expressing GI-JEV VLP was selected and continually secreted GI VLPs without signs of cell fusion. 51-10 VLPs formed a homogeneously empty-particle morphology and exhibited similar antigenic activity as GI virus. GI VLP-immunized mice showed balanced cross-neutralizing antibody titers against GI to GIV viruses (50% focus-reduction micro-neutralization assay titers 71 to 240) as well as potent protection against GI or GIII virus infection. GI VLP-immunized swine challenged with GI or GIII viruses showed no fever, viremia, or viral RNA in tonsils, lymph nodes, and brains as compared with phosphate buffered saline-immunized swine. We thus conclude GI VLPs can provide sterile protection against GI and GIII viruses in swine.