Characterization of a hepatitis C virus-like particle vaccine produced in a human hepatocyte-derived cell line

Earnest-Silveira, L and Chua, B and Chin, R and Christiansen, D and Johnson, D and Herrmann, S and Ralph, SA and Vercauteren, K and Mesalam, A and Meuleman, P and Das, S and Boo, I and Drummer, H and Bock, CT and Gowans, EJ and Jackson, DC and Torresi, Joseph (2016) Characterization of a hepatitis C virus-like particle vaccine produced in a human hepatocyte-derived cell line. In: JOURNAL OF GENERAL VIROLOGY, 97 (8). pp. 1865-1876.

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Abstract

An effective immune response against hepatitis C virus (HCV) requires the early development of multi-specific class 1 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, E1 and E2 of 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 E1 and E2 glycoproteins in HCV VLPs formed non-covalent heterodimers and together with core protein assembled into VLPs with a buoyant density of 1.22 to 1.28 g 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 40 to 80 nm. The HCV VLPs demonstrated dose-dependent binding to murine-derived dendritic cells and the entry of HCV VLPs into Huh7 cells was blocked by anti-CD81 antibody. 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 Huh7 cells. 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.

Item Type:	Journal Article
Publication:	JOURNAL OF GENERAL VIROLOGY
Additional Information:	Copy right for this article belongs to the MICROBIOLOGY SOC, CHARLES DARWIN HOUSE, 12 ROGER ST, LONDON WC1N 2JU, ERKS, ENGLAND
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	21 Dec 2016 07:16
Last Modified:	21 Dec 2016 07:16
URI:	http://eprints.iisc.ac.in/id/eprint/55359

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