A hepatitis C virus (HCV) vaccine comprising envelope glycoproteins gpE1/gpE2 derived from a single isolate elicits broad cross-genotype neutralizing antibodies in humans.
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 effect...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3602185?pdf=render |
| _version_ | 1819126208437157888 |
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| author | 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 |
| author_facet | 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 |
| author_sort | John Lok Man Law |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T07:52:23Z |
| format | Article |
| id | doaj.art-79f80c8f3d334a15841ec258bb18caa6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T07:52:23Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-79f80c8f3d334a15841ec258bb18caa62022-12-21T18:33:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5977610.1371/journal.pone.0059776A 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 LawChao ChenJason WongDarren HockmanDeanna M SanterSharon E FreyRobert B BelsheTakaji WakitaJens BukhChristopher T JonesCharles M RiceSergio AbrignaniD Lorne TyrrellMichael HoughtonAlthough 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.http://europepmc.org/articles/PMC3602185?pdf=render |
| spellingShingle | 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 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 |
| 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. |
| title_full | A hepatitis C virus (HCV) vaccine comprising envelope glycoproteins gpE1/gpE2 derived from a single isolate elicits broad cross-genotype neutralizing antibodies in humans. |
| title_fullStr | A hepatitis C virus (HCV) vaccine comprising envelope glycoproteins gpE1/gpE2 derived from a single isolate elicits broad cross-genotype neutralizing antibodies in humans. |
| title_full_unstemmed | A hepatitis C virus (HCV) vaccine comprising envelope glycoproteins gpE1/gpE2 derived from a single isolate elicits broad cross-genotype neutralizing antibodies in humans. |
| title_short | A hepatitis C virus (HCV) vaccine comprising envelope glycoproteins gpE1/gpE2 derived from a single isolate elicits broad cross-genotype neutralizing antibodies in humans. |
| title_sort | hepatitis c virus hcv vaccine comprising envelope glycoproteins gpe1 gpe2 derived from a single isolate elicits broad cross genotype neutralizing antibodies in humans |
| url | http://europepmc.org/articles/PMC3602185?pdf=render |
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