title: Protective vaccination with hepatitis C virus NS3 but not core antigen in a novel mouse challenge model.
abstract: BACKGROUND
  Efficient vaccines against hepatitis C virus (HCV) infection are urgently needed. Vaccine development has been hampered by the lack of suitable small animal models to reliably test the protective capacity of immmunization.
  
  
  METHODS
  We used recombinant murine gammaherpesvirus 68 (MHV-68) as a novel challenge virus in mice and tested the efficacy of heterologous candidate human vaccines based on modified vaccinia virus Ankara or adenovirus, both delivering HCV non-structural NS3 or core proteins.
  
  
  RESULTS
  Recombinant MHV-68 expressing NS3 (MHV-68-NS3) or core (MHV-68-core) were constructed and characterized in vitro and in vivo. Mice immunized with NS3-specific vector vaccines and challenged with MHV-68-NS3 were infected but showed significantly reduced viral loads in the acute and latent phase of infection. NS3-specific CD8+ T cells were amplified in immunized mice after challenge with MHV-68-NS3. By contrast, we did neither detect a reduction of viral load nor an induction of core-specific CD8+ T cells after core-specific immunization.
  
  
  CONCLUSIONS
  Our data suggest that the challenge system using recombinant MHV-68 is a highly suitable model to test the immunogenicity and protective capacity of HCV candidate vaccine antigens. Using this system, we demonstrated the usefulness of NS3-specific immunization. By contrast, our analysis rather discarded core as a vaccine antigen.
authors: Institute of Virology, Technical University München, Germany.
authors: Susanne
authors: S
authors: El-Gogo
authors: Caroline
authors: C
authors: Staib
authors: Juan José
authors: JJ
authors: Lasarte
authors: Gerd
authors: G
authors: Sutter
authors: Heiko
authors: H
authors: Adler
mesh_terms: D000818:Animals; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D018936:Hepatitis C Antigens / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D041681:NIH 3T3 Cells; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D014611:Vaccination / Q000379:methods*; D014758:Viral Core Proteins / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000276:immunology*; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000276:immunology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D018936:Hepatitis C Antigens; D014758:Viral Core Proteins; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C069130:nucleocapsid protein, Hepatitis C virus