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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Japanese Encephalitis Virus
Virion
Immunity
Swine
Genotype
Viruses

All Science Journal Classification (ASJC) codes

  • General

Cite this

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. / Genotype I of Japanese Encephalitis Virus Virus-like Particles Elicit Sterilizing Immunity against Genotype I and III Viral Challenge in Swine. In: Scientific reports. 2018 ; Vol. 8, No. 1.
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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.",
author = "Fan, {Yi Chin} and Chen, {Jo Mei} and Lin, {Jen Wei} and Chen, {Yi Ying} and Wu, {Guan Hong} and Su, {Kuan Hsuan} and Chiou, {Ming Tang} and Shang-Rung Wu and Yin, {Ji Hang} and Liao, {Jiunn Wang} and Chang, {Gwong Jen J.} and Chiou, {Shyan Song}",
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Genotype I of Japanese Encephalitis Virus Virus-like Particles Elicit Sterilizing Immunity against Genotype I and III Viral Challenge in Swine. / 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.

In: Scientific reports, Vol. 8, No. 1, 7481, 01.12.2018.

Research output: Contribution to journalArticle

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AU - Chang, Gwong Jen J.

AU - Chiou, Shyan Song

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