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Hepatitis C virus Broadly Neutralizing Monoclonal Antibodies Isolated 25 Years after Spontaneous Clearance
Hepatitis C virus (HCV) is world-wide a major cause of liver related morbidity and mortality. No vaccine is available to prevent HCV infection. To design an effective vaccine, understanding immunity against HCV is necessary. The memory B cell repertoire was characterized from an intravenous drug use...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5077102/ https://www.ncbi.nlm.nih.gov/pubmed/27776169 http://dx.doi.org/10.1371/journal.pone.0165047 |
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author | Merat, Sabrina J. Molenkamp, Richard Wagner, Koen Koekkoek, Sylvie M. van de Berg, Dorien Yasuda, Etsuko Böhne, Martino Claassen, Yvonne B. Grady, Bart P. Prins, Maria Bakker, Arjen Q. de Jong, Menno D. Spits, Hergen Schinkel, Janke Beaumont, Tim |
author_facet | Merat, Sabrina J. Molenkamp, Richard Wagner, Koen Koekkoek, Sylvie M. van de Berg, Dorien Yasuda, Etsuko Böhne, Martino Claassen, Yvonne B. Grady, Bart P. Prins, Maria Bakker, Arjen Q. de Jong, Menno D. Spits, Hergen Schinkel, Janke Beaumont, Tim |
author_sort | Merat, Sabrina J. |
collection | PubMed |
description | Hepatitis C virus (HCV) is world-wide a major cause of liver related morbidity and mortality. No vaccine is available to prevent HCV infection. To design an effective vaccine, understanding immunity against HCV is necessary. The memory B cell repertoire was characterized from an intravenous drug user who spontaneously cleared HCV infection 25 years ago. CD27+IgG+ memory B cells were immortalized using BCL6 and Bcl-xL. These immortalized B cells were used to study antibody-mediated immunity against the HCV E1E2 glycoproteins. Five E1E2 broadly reactive antibodies were isolated: 3 antibodies showed potent neutralization of genotype 1 to 4 using HCV pseudotyped particles, whereas the other 2 antibodies neutralized genotype 1, 2 and 3 or 1 and 2 only. All antibodies recognized non-linear epitopes on E2. Finally, except for antibody AT12-011, which recognized an epitope consisting of antigenic domain C /AR2 and AR5, all other four antibodies recognized epitope II and domain B. These data show that a subject, who spontaneously cleared HCV infection 25 years ago, still has circulating memory B cells that are able to secrete broadly neutralizing antibodies. Presence of such memory B cells strengthens the argument for undertaking the development of an HCV vaccine. |
format | Online Article Text |
id | pubmed-5077102 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-50771022016-11-04 Hepatitis C virus Broadly Neutralizing Monoclonal Antibodies Isolated 25 Years after Spontaneous Clearance Merat, Sabrina J. Molenkamp, Richard Wagner, Koen Koekkoek, Sylvie M. van de Berg, Dorien Yasuda, Etsuko Böhne, Martino Claassen, Yvonne B. Grady, Bart P. Prins, Maria Bakker, Arjen Q. de Jong, Menno D. Spits, Hergen Schinkel, Janke Beaumont, Tim PLoS One Research Article Hepatitis C virus (HCV) is world-wide a major cause of liver related morbidity and mortality. No vaccine is available to prevent HCV infection. To design an effective vaccine, understanding immunity against HCV is necessary. The memory B cell repertoire was characterized from an intravenous drug user who spontaneously cleared HCV infection 25 years ago. CD27+IgG+ memory B cells were immortalized using BCL6 and Bcl-xL. These immortalized B cells were used to study antibody-mediated immunity against the HCV E1E2 glycoproteins. Five E1E2 broadly reactive antibodies were isolated: 3 antibodies showed potent neutralization of genotype 1 to 4 using HCV pseudotyped particles, whereas the other 2 antibodies neutralized genotype 1, 2 and 3 or 1 and 2 only. All antibodies recognized non-linear epitopes on E2. Finally, except for antibody AT12-011, which recognized an epitope consisting of antigenic domain C /AR2 and AR5, all other four antibodies recognized epitope II and domain B. These data show that a subject, who spontaneously cleared HCV infection 25 years ago, still has circulating memory B cells that are able to secrete broadly neutralizing antibodies. Presence of such memory B cells strengthens the argument for undertaking the development of an HCV vaccine. Public Library of Science 2016-10-24 /pmc/articles/PMC5077102/ /pubmed/27776169 http://dx.doi.org/10.1371/journal.pone.0165047 Text en © 2016 Merat et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Merat, Sabrina J. Molenkamp, Richard Wagner, Koen Koekkoek, Sylvie M. van de Berg, Dorien Yasuda, Etsuko Böhne, Martino Claassen, Yvonne B. Grady, Bart P. Prins, Maria Bakker, Arjen Q. de Jong, Menno D. Spits, Hergen Schinkel, Janke Beaumont, Tim Hepatitis C virus Broadly Neutralizing Monoclonal Antibodies Isolated 25 Years after Spontaneous Clearance |
title | Hepatitis C virus Broadly Neutralizing Monoclonal Antibodies Isolated 25 Years after Spontaneous Clearance |
title_full | Hepatitis C virus Broadly Neutralizing Monoclonal Antibodies Isolated 25 Years after Spontaneous Clearance |
title_fullStr | Hepatitis C virus Broadly Neutralizing Monoclonal Antibodies Isolated 25 Years after Spontaneous Clearance |
title_full_unstemmed | Hepatitis C virus Broadly Neutralizing Monoclonal Antibodies Isolated 25 Years after Spontaneous Clearance |
title_short | Hepatitis C virus Broadly Neutralizing Monoclonal Antibodies Isolated 25 Years after Spontaneous Clearance |
title_sort | hepatitis c virus broadly neutralizing monoclonal antibodies isolated 25 years after spontaneous clearance |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5077102/ https://www.ncbi.nlm.nih.gov/pubmed/27776169 http://dx.doi.org/10.1371/journal.pone.0165047 |
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