title: Immunogenicity difference between two hepatitis E vaccines derived from genotype 1 and 4.
abstract: We investigated the immunogenicity difference between hepatitis E vaccine p239 derived from hepatitis E virus (HEV) genotype 1 and vaccine p179 derived from HEV genotype 4; and the presence of genotype-specific neutralizing epitopes. HEV ORF2 recombinant proteins (p166W01, p166Mex, p166US and p166Chn) derived from the four HEV genotypes were used to detect anti-HEV IgGs in sera of mice and humans vaccinated with p179 or p239 and in sera of rhesus monkey challenged with HEV genotype 1 or 4 strains. Then monoclonal antibodies (mAbs) against genotype 1 or 4 ORF2 recombinant proteins were prepared and their immunoreactivity was assessed using ELISA and Western blotting; their neutralizing activity was evaluated by an in vitro PCR-based neutralization assay. The results revealed significant immunogenicity difference between the two vaccines: p239-induced IgGs reacted more strongly against p166W01 and p166Mex than against p166US and p166Chn in mice and humans. By contrast, p179-induced IgGs showed a stronger reactivity against p166US and p166Chn than against p166W01 and p166Mex. This difference has also been observed in the sera of rhesus monkeys challenged with HEV genotype 1 or 4 strains. Moreover, besides the two common neutralizing mAbs 3G1 and 5G5, two genotype-specific neutralizing mAbs, 2B1 and 4C5, were obtained. 2B1 could specifically bind to recombinant proteins derived from genotypes 1 and 2 and neutralized only genotypes 1 and 2 strains, while 4C5 immunoreacted specifically against recombinant proteins derived from genotypes 3 and 4 and neutralized only genotypes 3 and 4 strains. These findings revealed the existence of immunogenicity difference between the p179 and p239 vaccines and demonstrated that this difference could be due to the presence of HEV genotype-specific neutralization epitopes.
authors: Department of Microbiology and Immunology, Southeast University School of Medicine, Nanjing, China.
authors: Jiyue
authors: J
authors: Wen
authors: Department of Microbiology and Immunology, Southeast University School of Medicine, Nanjing, China.
authors: Nouredine
authors: N
authors: Behloul
authors: Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors: Xing
authors: X
authors: Dai
authors: Department of Microbiology and Immunology, Southeast University School of Medicine, Nanjing, China.
authors: Chen
authors: C
authors: Dong
authors: Department of Microbiology and Immunology, Southeast University School of Medicine, Nanjing, China.
authors: Jiuhong
authors: J
authors: Liang
authors: Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors: Min
authors: M
authors: Zhang
authors: Changchun Institute of Biological Products Co. Ltd, Changchun, Jilin, China.
authors: Chengbo
authors: C
authors: Shi
authors: Department of Microbiology and Immunology, Southeast University School of Medicine, Nanjing, China. Electronic address: jihongmeng@163.com.
authors: Jihong
authors: J
authors: Meng
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D016751:Hepatitis E / Q000276:immunology* / Q000628:therapy*; D016752:Hepatitis E virus / Q000235:genetics*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D014765:Viral Vaccines
keywords: Hepatitis E virus; Monoclonal antibodies; Neutralization epitopes; Vaccine