title: Neutralizing antibodies induced by cell culture-derived hepatitis C virus protect against infection in mice.
abstract: OBJECTIVE
  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.
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc, Kanagawa, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Akazawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Moriyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yokokawa
authors.forename: Noriaki
authors.initials: N
authors.lastname: Omi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Watanabe
authors.forename: Tomoko
authors.initials: T
authors.lastname: Date
authors.forename: Kenichi
authors.initials: K
authors.lastname: Morikawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Aizaki
authors.forename: Koji
authors.initials: K
authors.lastname: Ishii
authors.forename: Takanobu
authors.initials: T
authors.lastname: Kato
authors.forename: Hidenori
authors.initials: H
authors.lastname: Mochizuki
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakamura
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D018929:Cell Culture Techniques; D015195:Drug Design; D005260:Female; D016174:Hepacivirus; D006526:Hepatitis C / Q000517:prevention & control*; D018937:Hepatitis C Antibodies / Q000276:immunology*; D022781:Hepatocytes / Q000276:immunology; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D015164:Vaccines, Inactivated; D014759:Viral Envelope Proteins / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000276:immunology*; D014771:Virion / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D018937:Hepatitis C Antibodies; D015164:Vaccines, Inactivated; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines
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