title: Bacteria expressed hepatitis E virus capsid proteins maintain virion-like epitopes.
abstract: The protein encoded by ORF2 in hepatitis E virus (HEV) is the only capsid protein for this single-stranded RNA virus. It was previously shown that 148 aa (aa 459-606) was needed for dimer formation, whereas 239 aa (aa 368-606) was necessary to form virus-like particles (VLPs). The self-assembled VLPs of p239 were characterized with a series of methods including high performance size-exclusion chromatography to demonstrate the particulate nature of purified and properly refolded p239. A neutralizing and protective mouse monoclonal antibody (mAb) 8C11 was previously shown to bind three discontinuous peptide segments in the dimer. In addition to the good binding activity to recombinant dimeric form, E2s or E2, and VLP form p239, we demonstrated that 8C11 was able to capture the authentic HEV virions. The capability of virus capturing was demonstrated with a titration curve from 10(5) to 10(7) HEV genome copies, making binding activity to 8C11 a surrogate marker of virion-like epitopes on recombinant VLPs as well as vaccine efficacy in eliciting protective and neutralizing antibodies. Taken together, it was demonstrated that Escherichia coli expressed pORF2 proteins, p239 in particular, maintain the virion-like epitopes on VLP surface. This is consistent with the fact that p239 was demonstrated to be an effective prophylactic vaccine (recently licensed as Hecolin(®) in China) against HEV-induced hepatitis in a large scale clinical trial.
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361005, Fujian PR China; School of Life Sciences, Xiamen University, Xiamen 361005, Fujian, PR China.
authors.forename: Minxi
authors.initials: M
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361005, Fujian PR China; School of Public Health, Xiamen University, Xiamen 361005, Fujian PR China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361005, Fujian PR China; School of Public Health, Xiamen University, Xiamen 361005, Fujian PR China; School of Life Sciences, Xiamen University, Xiamen 361005, Fujian, PR China.
authors.forename: Hai
authors.initials: H
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361005, Fujian PR China; School of Life Sciences, Xiamen University, Xiamen 361005, Fujian, PR China.
authors.forename: Zi-Min
authors.initials: ZM
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361005, Fujian PR China; School of Life Sciences, Xiamen University, Xiamen 361005, Fujian, PR China.
authors.forename: Kaihang
authors.initials: K
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361005, Fujian PR China; School of Life Sciences, Xiamen University, Xiamen 361005, Fujian, PR China.
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361005, Fujian PR China; School of Public Health, Xiamen University, Xiamen 361005, Fujian PR China; School of Life Sciences, Xiamen University, Xiamen 361005, Fujian, PR China.
authors.forename: Zizheng
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361005, Fujian PR China; School of Public Health, Xiamen University, Xiamen 361005, Fujian PR China; School of Life Sciences, Xiamen University, Xiamen 361005, Fujian, PR China.
authors.forename: Shaowei
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361005, Fujian PR China; School of Public Health, Xiamen University, Xiamen 361005, Fujian PR China; School of Life Sciences, Xiamen University, Xiamen 361005, Fujian, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361005, Fujian PR China; School of Public Health, Xiamen University, Xiamen 361005, Fujian PR China; School of Life Sciences, Xiamen University, Xiamen 361005, Fujian, PR China. Electronic address: nsxia@xmu.edu.cn.
authors.forename: Ningshao
authors.initials: N
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361005, Fujian PR China; School of Public Health, Xiamen University, Xiamen 361005, Fujian PR China. Electronic address: qinjian_zhao@xmu.edu.cn.
authors.forename: Qinjian
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology; D036022:Capsid Proteins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D004926:Escherichia coli / Q000378:metabolism; D016752:Hepatitis E virus; D008253:Macaca mulatta; D051379:Mice; D058425:Vaccines, Virus-Like Particle / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology*; D014771:Virion / Q000276:immunology
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D057134:Antibodies, Neutralizing; D036022:Capsid Proteins; D000939:Epitopes; C400971:ORF2 protein, Hepatitis E virus; D058425:Vaccines, Virus-Like Particle; D014764:Viral Proteins
keywords: Hepatitis E virus; Prophylactic vaccine; Virion-like epitopes; Virus-capturing; Virus-like particle