Neutralizing antibodies in patients with chronic hepatitis C, genotype 1, against a panel of genotype 1 culture viruses: lack of correlation to treatment outcome.

The correlation of neutralizing antibodies to treatment outcome in patients with chronic hepatitis C virus (HCV) infection has not been established. The aim of this study was to determine whether neutralizing antibodies could be used as an outcome predictor in patients with chronic HCV, genotype 1,...

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Autores principales:	Jannie Pedersen, Tanja B Jensen, Thomas H R Carlsen, Kristian Schønning, Peer Brehm Christensen, Alex Lund Laursen, Henrik Krarup, Jens Bukh, Nina Weis
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/07e65dcbfd714cfdb93daf9844005c81
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spelling	oai:doaj.org-article:07e65dcbfd714cfdb93daf9844005c812021-11-18T07:46:40ZNeutralizing antibodies in patients with chronic hepatitis C, genotype 1, against a panel of genotype 1 culture viruses: lack of correlation to treatment outcome.1932-620310.1371/journal.pone.0062674https://doaj.org/article/07e65dcbfd714cfdb93daf9844005c812013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23667506/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The correlation of neutralizing antibodies to treatment outcome in patients with chronic hepatitis C virus (HCV) infection has not been established. The aim of this study was to determine whether neutralizing antibodies could be used as an outcome predictor in patients with chronic HCV, genotype 1, infection treated with pegylated interferon-α and ribavirin. Thirty-nine patients with chronic hepatitis C, genotype 1a or 1b, with either sustained virologic response (n = 23) or non-sustained virologic response (n = 16) were enrolled. Samples taken prior to treatment were tested for their ability to neutralize 6 different HCV genotype 1 cell culture recombinants (1a: H77/JFH1, TN/JFH1, DH6/JFH1; 1b: J4/JFH1, DH1/JFH1, DH5/JFH1). The results were expressed as the highest dilution yielding 50% neutralization (NAb50-titer). We observed no genotype or subtype specific differences in NAb50-titers between patients with chronic HCV infection with and without sustained virologic response when tested against any of the included culture viruses. However, NAb50-titers varied significantly with a mean reciprocal NAb50-titer of 800 (range: 100-6400) against DH6/JFH1 compared to a mean NAb50-titer of 50 (range: <50-400) against all other included isolates. Subsequent studies demonstrated that the efficient neutralization of DH6/JFH1 could be linked to engineered adaptive mutations in the envelope-2 protein. In analysis of envelope 1 and 2 sequences of HCV, recovered from a subset of patients, we observed no apparent link between relatedness of patient sequences with culture viruses used and the corresponding neutralization results. In conclusion, pre-treatment levels of neutralizing antibodies against HCV genotype 1 isolates could not predict treatment outcome in patients with chronic HCV infection. High neutralization susceptibility of DH6/JFH1 could be correlated with adaptive envelope mutations previously highlighted as important for neutralization. Our study emphasizes the importance of using multiple culture viruses for neutralization studies and contributes to the current knowledge about neutralizing epitopes, important for future therapeutic- and vaccine-studies.Jannie PedersenTanja B JensenThomas H R CarlsenKristian SchønningPeer Brehm ChristensenAlex Lund LaursenHenrik KrarupJens BukhNina WeisPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e62674 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jannie Pedersen Tanja B Jensen Thomas H R Carlsen Kristian Schønning Peer Brehm Christensen Alex Lund Laursen Henrik Krarup Jens Bukh Nina Weis Neutralizing antibodies in patients with chronic hepatitis C, genotype 1, against a panel of genotype 1 culture viruses: lack of correlation to treatment outcome.
description	The correlation of neutralizing antibodies to treatment outcome in patients with chronic hepatitis C virus (HCV) infection has not been established. The aim of this study was to determine whether neutralizing antibodies could be used as an outcome predictor in patients with chronic HCV, genotype 1, infection treated with pegylated interferon-α and ribavirin. Thirty-nine patients with chronic hepatitis C, genotype 1a or 1b, with either sustained virologic response (n = 23) or non-sustained virologic response (n = 16) were enrolled. Samples taken prior to treatment were tested for their ability to neutralize 6 different HCV genotype 1 cell culture recombinants (1a: H77/JFH1, TN/JFH1, DH6/JFH1; 1b: J4/JFH1, DH1/JFH1, DH5/JFH1). The results were expressed as the highest dilution yielding 50% neutralization (NAb50-titer). We observed no genotype or subtype specific differences in NAb50-titers between patients with chronic HCV infection with and without sustained virologic response when tested against any of the included culture viruses. However, NAb50-titers varied significantly with a mean reciprocal NAb50-titer of 800 (range: 100-6400) against DH6/JFH1 compared to a mean NAb50-titer of 50 (range: <50-400) against all other included isolates. Subsequent studies demonstrated that the efficient neutralization of DH6/JFH1 could be linked to engineered adaptive mutations in the envelope-2 protein. In analysis of envelope 1 and 2 sequences of HCV, recovered from a subset of patients, we observed no apparent link between relatedness of patient sequences with culture viruses used and the corresponding neutralization results. In conclusion, pre-treatment levels of neutralizing antibodies against HCV genotype 1 isolates could not predict treatment outcome in patients with chronic HCV infection. High neutralization susceptibility of DH6/JFH1 could be correlated with adaptive envelope mutations previously highlighted as important for neutralization. Our study emphasizes the importance of using multiple culture viruses for neutralization studies and contributes to the current knowledge about neutralizing epitopes, important for future therapeutic- and vaccine-studies.
format	article
author	Jannie Pedersen Tanja B Jensen Thomas H R Carlsen Kristian Schønning Peer Brehm Christensen Alex Lund Laursen Henrik Krarup Jens Bukh Nina Weis
author_facet	Jannie Pedersen Tanja B Jensen Thomas H R Carlsen Kristian Schønning Peer Brehm Christensen Alex Lund Laursen Henrik Krarup Jens Bukh Nina Weis
author_sort	Jannie Pedersen
title	Neutralizing antibodies in patients with chronic hepatitis C, genotype 1, against a panel of genotype 1 culture viruses: lack of correlation to treatment outcome.
title_short	Neutralizing antibodies in patients with chronic hepatitis C, genotype 1, against a panel of genotype 1 culture viruses: lack of correlation to treatment outcome.
title_full	Neutralizing antibodies in patients with chronic hepatitis C, genotype 1, against a panel of genotype 1 culture viruses: lack of correlation to treatment outcome.
title_fullStr	Neutralizing antibodies in patients with chronic hepatitis C, genotype 1, against a panel of genotype 1 culture viruses: lack of correlation to treatment outcome.
title_full_unstemmed	Neutralizing antibodies in patients with chronic hepatitis C, genotype 1, against a panel of genotype 1 culture viruses: lack of correlation to treatment outcome.
title_sort	neutralizing antibodies in patients with chronic hepatitis c, genotype 1, against a panel of genotype 1 culture viruses: lack of correlation to treatment outcome.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/07e65dcbfd714cfdb93daf9844005c81
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Neutralizing antibodies in patients with chronic hepatitis C, genotype 1, against a panel of genotype 1 culture viruses: lack of correlation to treatment outcome.

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