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El-Gogo, S.* ; Staib, C. ; Lasarte, J.J.* ; Sutter, G.* ; Adler, H.

Protective vaccination with hepatitis C virus NS3 but not core antigen in a novel mouse challenge model.

J. Gene Med. 10, 177-186 (2008)
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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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter hepatitis C virus; immunization; recombinant adenovirus; recombinant MVA; recombinant MHV-68; vaccine
ISSN (print) / ISBN 1099-498X
e-ISSN 1521-2254
Quellenangaben Band: 10, Heft: 2, Seiten: 177-186 Artikelnummer: , Supplement: ,
Verlag Wiley
Begutachtungsstatus Peer reviewed
Institut(e) CCG Hematopoetic Cell Transplants (IMI-KHZ)
Institute of Virology (VIRO)