Neutralizing antibodies induced by cell culture-derived hepatitis C virus protect against infection in mice

Abstract

Background & aims: Hepatitis C virus (HCV) infection is a major cause of liver cancer, so strategies to prevent infection are needed. A system for cell culture of infectious HCV particles (HCVcc) has recently been established; the inactivated HCVcc particles might be used as antigens in vaccine development. We aimed to confirm the potential of HCVcc as an HCV particle vaccine.

Methods: HCVcc derived from the J6/JFH-1 chimeric genome was purified from cultured cells by ultrafiltration and ultracentrifugation purification steps. Purified HCV particles were inactivated and injected into female BALB/c mice with adjuvant. Sera from immunized mice were collected and their ability to neutralize HCV was examined in naive Huh7.5.1 cells and urokinase-type plasminogen activator-severe combined immunodeficiency mice (uPA(+/+)-SCID mice) given transplants of human hepatocytes (humanized livers).

Results: Antibodies against HCV envelope proteins were detected in the sera of immunized mice; these sera inhibited infection of cultured cells with HCV genotypes 1a, 1b, and 2a. Immunoglobulin G purified from the sera of HCV-particle-immunized mice (iHCV-IgG) inhibited HCV infection of cultured cells. Injection of IgG from the immunized mice into uPA(+/+)-SCID mice with humanized livers prevented infection with the minimum infectious dose of HCV.

Conclusions: Inactivated HCV particles derived from cultured cells protect chimeric liver uPA(+/+)-SCID mice against HCV infection, and might be used in the development of a prophylactic vaccine.

Keywords: 50% inhibitory concentration; Cont; DMEM; Dulbecco's modified Eagle medium; Frac; HCV; HCV Particle; HCV Vaccine; HCVcc; HCVpp; IC50; Immunization; RTD-PCR; SCID; Virology; albumin enhancer/promoter urokinase plasminogen activator; cell-cultured hepatitis C virus; control; fraction; hepatitis C virus; hepatitis C virus pseudoparticle; iHCV; rE1; rE2; real-time detection reverse-transcription polymerase chain reaction; recombinant E1; recombinant E2; severe combined immunodeficiency; uPA; vaccine immunized hepatitis C virus.