title: A hepatitis C virus (HCV) vaccine comprising envelope glycoproteins gpE1/gpE2 derived from a single isolate elicits broad cross-genotype neutralizing antibodies in humans.
abstract: Although a cure for HCV is on the near horizon, emerging drug cocktails will be expensive, associated with side-effects and resistance making a global vaccine an urgent priority given the estimated high incidence of infection around the world. Due to the highly heterogeneous nature of HCV, an effective HCV vaccine which could elicit broadly cross-neutralizing antibodies has represented a major challenge. In this study, we tested for the presence of cross-neutralizing antibodies in human volunteers who were immunized with recombinant glycoproteins gpE1/gpE2 derived from a single HCV strain (HCV1 of genotype 1a). Cross neutralization was tested in Huh-7.5 human hepatoma cell cultures using infectious recombinant HCV (HCVcc) expressing structural proteins of heterologous HCV strains from all known major genotypes, 1-7. Vaccination induced significant neutralizing antibodies against heterologous HCV genotype 1a virus which represents the most common genotype in North America. Of the 16 vaccinees tested, 3 were selected on the basis of strong 1a virus neutralization for testing of broad cross-neutralizing responses. At least 1 vaccinee was shown to elicit broad cross-neutralization against all HCV genotypes. Although observed in only a minority of vaccinees, our results prove the key concept that a vaccine derived from a single strain of HCV can elicit broad cross-neutralizing antibodies against all known major genotypes of HCV and provide considerable encouragement for the further development of a human vaccine against this common, global pathogen.
authors.affiliation: Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.
authors.forename: John Lok Man
authors.initials: JL
authors.lastname: Law
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.forename: Jason
authors.initials: J
authors.lastname: Wong
authors.forename: Darren
authors.initials: D
authors.lastname: Hockman
authors.forename: Deanna M
authors.initials: DM
authors.lastname: Santer
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Frey
authors.forename: Robert B
authors.initials: RB
authors.lastname: Belshe
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.forename: Jens
authors.initials: J
authors.lastname: Bukh
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Jones
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rice
authors.forename: Sergio
authors.initials: S
authors.lastname: Abrignani
authors.forename: D Lorne
authors.initials: DL
authors.lastname: Tyrrell
authors.forename: Michael
authors.initials: M
authors.lastname: Houghton
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D045744:Cell Line, Tumor; D003429:Cross Reactions; D004591:Electrophoresis, Polyacrylamide Gel; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000378:metabolism*; D012394:Rosaniline Dyes; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014761:Viral Hepatitis Vaccines / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D007106:Immune Sera; D011994:Recombinant Proteins; D012394:Rosaniline Dyes; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines; C048139:Coomassie blue