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Title: Characterization of a hepatitis C virus-like particle vaccine produced in a human hepatocyte-derived cell line.
Austin Authors: Earnest-Silveira, L;Chua, B;Chin, R;Christiansen, D;Johnson, D;Herrmann, S;Ralph, S A;Vercauteren, K;Mesalam, A;Meuleman, P;Das, S;Boo, I;Drummer, H;Bock, C-T;Gowans, E J;Jackson, D C;Torresi, Joseph 
Affiliation: Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria 3010, Australia
Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia
The Basil Hetzel Institute and Queen Elizabeth Hospital, University of Adelaide, Australia
Center for Vaccinology, Ghent University and Hospital, De Pintelaan 189000, Ghent, Belgium
Department of Surgery, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
Department of Microbiology, Monash University, Clayton, Australia
Centre for Biomedical Research, Burnet Institute, Melbourne, Australia
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India
Department of Biochemistry and Molecular Biology, Bio2Institute of Molecular Science and Biotechnology, University of Melbourne, Australia
Issue Date: Aug-2016 2016-05-04
Publication information: The Journal of general virology 2016; 97(8): 1865-1876
Abstract: An effective immune response against hepatitis C virus (HCV) requires the early development of multi-specific class CD8+ and class II CD4+ T-cells together with broad neutralizing antibody responses. We have produced mammalian-cell-derived HCV virus-like particles (VLPs) incorporating core, Eand Eof HCV genotype 1a to produce such immune responses. Here we describe the biochemical and morphological characterization of the HCV VLPs and study HCV core-specific T-cell responses to the particles. The Eand Eglycoproteins in HCV VLPs formed non-covalent heterodimers and together with core protein assembled into VLPs with a buoyant density of 1.2to 1.2g cm-3. The HCV VLPs could be immunoprecipited with anti-ApoE and anti-ApoC. On electron microscopy, the VLPs had a heterogeneous morphology and ranged in size from 4to 8nm. The HCV VLPs demonstrated dose-dependent binding to murine-derived dendritic cells and the entry of HCV VLPs into Huhcells was blocked by anti-CD8antibody. Vaccination of BALB/c mice with HCV VLPs purified from iodixanol gradients resulted in the production of neutralizing antibody responses while vaccination of humanized MHC class I transgenic mice resulted in the prodution of HCV core-specific CD8+ T-cell responses. Furthermore, IgG purified from the sera of patients chronically infected with HCV genotypes 1a and 3a blocked the binding and entry of the HCV VLPs into Huhcells. These results show that our mammalian-cell-derived HCV VLPs induce humoral and HCV-specific CD8+ T-cell responses and will have important implications for the development of a preventative vaccine for HCV.
DOI: 10.1099/jgv.0.000493
PubMed URL: 27147296
Type: Journal Article
Appears in Collections:Journal articles

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