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

Yi Chin Fan, Jo Mei Chen, Jen Wei Lin, Yi Ying Chen, Guan Hong Wu, Kuan Hsuan Su, Ming Tang Chiou, Shang-Rung Wu, Ji Hang Yin, Jiunn Wang Liao, Gwong Jen J. Chang, Shyan Song Chiou

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Abstract

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.

Original languageEnglish
Article number7481
JournalScientific reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

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Fan, Y. C., Chen, J. M., Lin, J. W., Chen, Y. Y., Wu, G. H., Su, K. H., Chiou, M. T., Wu, S-R., Yin, J. H., Liao, J. W., Chang, G. J. J., & Chiou, S. S. (2018). Genotype I of Japanese Encephalitis Virus Virus-like Particles Elicit Sterilizing Immunity against Genotype I and III Viral Challenge in Swine. Scientific reports, 8(1), [7481]. https://doi.org/10.1038/s41598-018-25596-1