title: Immunogenicity and protective efficacy of a vaccine prepared from 53 kDa truncated hepatitis E virus capsid protein expressed in insect cells.
abstract: Hepatitis E virus (HEV) is an enterically transmitted virus that causes acute hepatitis. Expression of recombinant HEV capsid protein in insect cells results in two major proteolytically-processed products of 56 and 53kDa which consist of amino acids (aa) 112-607 and 112-578, respectively. The only neutralization epitope identified to date is located at least partially between amino acids 578 and 607 meaning it should be present only in the 56 and not in the 53kDa protein. Previously, it was shown that vaccination with the 56kDa protein greatly reduced virus shedding and protected Rhesus monkeys from hepatitis E when challenged with a high intravenous dose of homologous or heterologous HEV. To evaluate the immunogenicity and protective efficacy of the 53kDa protein, we vaccinated Rhesus monkeys with this protein and challenged them with a high or low dose of homologous virus. Vaccination with the 53kDa protein greatly reduced virus shedding but did not protect against hepatitis following the high dose challenge. Virus was not detected in the vaccinated animals following the low dose challenge, suggesting that sterilizing immunity may have been achieved.
authors.affiliation: Laboratory of Infectious Diseases, Hepatitis Viruses and Molecular Hepatitis Sections, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: S U
authors.initials: SU
authors.lastname: Emerson
authors.forename: H
authors.initials: H
authors.lastname: Nguyen
authors.forename: R E
authors.initials: RE
authors.lastname: Engle
authors.forename: S
authors.initials: S
authors.lastname: Govindarajan
authors.forename: J L
authors.initials: JL
authors.lastname: Gerin
authors.forename: R H
authors.initials: RH
authors.lastname: Purcell
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002213:Capsid / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D015870:Gene Expression; D006508:Hepatitis Antibodies / Q000097:blood; D016751:Hepatitis E / Q000276:immunology / Q000517:prevention & control*; D016752:Hepatitis E virus / Q000235:genetics / Q000276:immunology*; D007313:Insecta; D008253:Macaca mulatta; D008970:Molecular Weight; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology; D014761:Viral Hepatitis Vaccines / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D006508:Hepatitis Antibodies; D010446:Peptide Fragments; D014614:Vaccines, Synthetic; D014761:Viral Hepatitis Vaccines; D000410:Alanine Transaminase