Abstract

In this study, we generated the HEV virus-like particle (VLP) vaccine expressing 239 amino acids (367–605 aa) of the HEV-3 ORF2 using the baculovirus expression system. The HEV-3-239-VLP vaccine efficacy was evaluated by dividing 12 pathogen-free pigs into four groups: negative control, positive control, 100 μg VLP-, and 200 μg VLP-vaccinated groups for 10 weeks. The pigs in either of the vaccinated groups were administered the corresponding first and booster doses on weeks 0 and 2. At week 4, the positive control and two vaccinated groups were challenged with 106 HEV-3 genomic equivalent copies; viremia and fecal shedding of the virus were identified in pigs in the positive control and 100 μg VLP-vaccinated pigs showed transient viremia and fecal viral shedding. However, no viruses were detected in the serum or fecal samples of the 200 μg VLP-vaccinated pigs. The 100 and 200 μg VLP-vaccinated pigs had significantly higher (p < 0.01) anti-HEV antibodies than the negative control pigs from weeks 6–10 with normal levels of liver enzymes. The 200 μg VLP-vaccinated pigs showed statistically less liver tissue fibrosis (p < 0.05) than that of the positive control pigs. Thus, the novel baculovirus expression system-generated VLP vaccine dose-dependently protects against HEV-3 challenge and may be useful in other animal species, including humans.

Highlights

  • Hepatitis E virus (HEV), belonging to the genus Orthohepevirus of the family Hepeviridae, is a non-enveloped virus ranging from 27–34 nm [1]

  • Western blot analysis was performed with an anti-HEV monoclonal antibody to check the molecular weight of the purified HEV-3-239-virus-like particle (VLP)

  • HEV-3-239-VLP was identified as 26 kDa-sized monomers as expected (Figure 1, lane 2)

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Summary

Introduction

Hepatitis E virus (HEV), belonging to the genus Orthohepevirus of the family Hepeviridae, is a non-enveloped virus ranging from 27–34 nm [1]. It is classified into seven genotypes and divided into at least 31 subtypes. ORF1 encodes non-structural proteins essential for the viral life cycles, ORF2 encodes a viral capsid protein, and the ORF3 protein is associated with releasing infectious viral particles [7,8,9]. The capsid protein is generally used for vaccine development [10]. Owing to the difficulty of cultivating HEV in cell culture systems, studies have focused on the virus-like particle (VLP) composed of the capsid protein for developing vaccines

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