TY - JOUR

T1 - A hepatitis C virus (HCV) vaccine comprising envelope glycoproteins gpE1/gpE2 derived from a single isolate elicits broad cross-genotype neutralizing antibodies in humans

AU - Law, John Lok Man

AU - Chen, Chao

AU - Wong, Jason

AU - Hockman, Darren

AU - Santer, Deanna M

AU - Frey, Sharon E

AU - Belshe, Robert B

AU - Wakita, Takaji

AU - Bukh, Jens

AU - Jones, Christopher T

AU - Rice, Charles M

AU - Abrignani, Sergio

AU - Tyrrell, D Lorne

AU - Houghton, Michael

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - Antibodies, Neutralizing

KW - Cell Line, Tumor

KW - Cross Reactions

KW - Electrophoresis, Polyacrylamide Gel

KW - Hepacivirus

KW - Humans

KW - Immune Sera

KW - Neutralization Tests

KW - Recombinant Proteins

KW - Rosaniline Dyes

KW - Viral Envelope Proteins

KW - Viral Hepatitis Vaccines

U2 - 10.1371/journal.pone.0059776

DO - 10.1371/journal.pone.0059776

M3 - Journal article

C2 - 23527266

VL - 8

SP - 1

EP - 7

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 3

M1 - e59776

ER -