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

John Lok Man Law; Chao Chen; Jason Wong; Darren Hockman; Deanna M Santer; Sharon E Frey; Robert B Belshe; Takaji Wakita; Jens Bukh; Christopher T Jones; Charles M Rice; Sergio Abrignani; D Lorne Tyrrell; Michael Houghton

doi:10.1371/journal.pone.0059776

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

John Lok Man Law, Chao Chen, Jason Wong, Darren Hockman, Deanna M Santer, Sharon E Frey, Robert B Belshe, Takaji Wakita, Jens Bukh, Christopher T Jones, Charles M Rice, Sergio Abrignani, D Lorne Tyrrell, Michael Houghton

108 Citations (Scopus)

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.

Original language	English
Article number	e59776
Journal	PloS one
Volume	8
Issue number	3
Pages (from-to)	1-7
Number of pages	8
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0059776
Publication status	Published - 19 Mar 2013

Keywords

Antibodies, Neutralizing
Cell Line, Tumor
Cross Reactions
Electrophoresis, Polyacrylamide Gel
Hepacivirus
Humans
Immune Sera
Neutralization Tests
Recombinant Proteins
Rosaniline Dyes
Viral Envelope Proteins
Viral Hepatitis Vaccines

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Law, J. L. M., Chen, C., Wong, J., Hockman, D., Santer, D. M., Frey, S. E., Belshe, R. B., Wakita, T., Bukh, J., Jones, C. T., Rice, C. M., Abrignani, S., Tyrrell, D. L., & Houghton, M. (2013). A hepatitis C virus (HCV) vaccine comprising envelope glycoproteins gpE1/gpE2 derived from a single isolate elicits broad cross-genotype neutralizing antibodies in humans. PloS one, 8(3), 1-7. [e59776]. https://doi.org/10.1371/journal.pone.0059776

Law, JLM, Chen, C, Wong, J, Hockman, D, Santer, DM, Frey, SE, Belshe, RB, Wakita, T, Bukh, J, Jones, CT, Rice, CM, Abrignani, S, Tyrrell, DL & Houghton, M 2013, 'A hepatitis C virus (HCV) vaccine comprising envelope glycoproteins gpE1/gpE2 derived from a single isolate elicits broad cross-genotype neutralizing antibodies in humans', PloS one, vol. 8, no. 3, e59776, pp. 1-7. https://doi.org/10.1371/journal.pone.0059776

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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.",

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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

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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.

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KW - Cross Reactions

KW - Electrophoresis, Polyacrylamide Gel

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KW - Neutralization Tests

KW - Recombinant Proteins

KW - Rosaniline Dyes

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KW - Viral Hepatitis Vaccines

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M1 - e59776

ER -

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

Keywords

UN SDGs

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