title: Clearance of genotype 1b hepatitis C virus in chimpanzees in the presence of vaccine-induced E1-neutralizing antibodies.
abstract: Accumulating evidence indicates that neutralizing antibodies play an important role in protection from chronic hepatitis C virus (HCV) infection. Efforts to elicit such responses by immunization with intact heterodimeric E1E2 envelope proteins have met with limited success. To determine whether antigenic sites, which are not exposed by the combined E1E2 heterodimer structure, are capable of eliciting neutralizing antibody responses, we expressed and purified each as separate recombinant proteins E1 and E2, from which the immunodominant hypervariable region (HVR-1) was deleted. Immunization of chimpanzees with either E1 or E2 alone induced antigen-specific T-helper cytokines of similar magnitude. Unexpectedly, the capacity to neutralize HCV was observed in E1 but not in animals immunized with E2 devoid of HVR-1. Furthermore, in vivo only E1-vaccinated animals exposed to the heterologous HCV-1b inoculum cleared HCV infection.
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Babs E
authors.initials: BE
authors.lastname: Verstrepen
authors.forename: Erik
authors.initials: E
authors.lastname: Depla
authors.forename: Christine S
authors.initials: CS
authors.lastname: Rollier
authors.forename: Gwenny
authors.initials: G
authors.lastname: Mares
authors.forename: Joost A R
authors.initials: JA
authors.lastname: Drexhage
authors.forename: Sofie
authors.initials: S
authors.lastname: Priem
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Verschoor
authors.forename: Gerrit
authors.initials: G
authors.lastname: Koopman
authors.forename: Christelle
authors.initials: C
authors.lastname: Granier
authors.forename: Marlène
authors.initials: M
authors.lastname: Dreux
authors.forename: François L
authors.initials: FL
authors.lastname: Cosset
authors.forename: Geert
authors.initials: G
authors.lastname: Maertens
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Heeney
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D004195:Disease Models, Animal; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000628:therapy*; D002679:Pan troglodytes; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; C087035:E1 protein, Hepatitis C virus; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines