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In vivo evaluation of the cross-genotype neutralizing activity of polyclonal antibodies against hepatitis C virus

Philip Meuleman UGent, Jens Bukh, Lieven Verhoye UGent, Aliasghar Farhoudi Moghadam UGent, THOMAS VANWOLLEGHEM UGent, Richard Y Wang, Isabelle Desombere UGent, Harvey Alter, Robert H Purcell and Geert Leroux-Roels UGent (2011) HEPATOLOGY. 53(3). p.755-762
abstract
Control of hepatitis C virus (HCV) infection remains a huge challenge of global medical importance. Using a variety of in vitro approaches, neutralizing antibodies (nAbs) have been identified in patients with acute and chronic hepatitis C. The exact role these nAbs play in the resolution of acute HCV infection still remains elusive. We have previously shown that purified polyclonal antibodies isolated from plasma obtained in 2003 from a chronic HCV patient (Patient H) can protect human liver chimeric mice from a subsequent challenge with the autologous HCV strain isolated from Patient H in 1977 (H77). In this study we investigated whether polyclonal antibodies isolated from Patient H in 2006 (H06), which display high cross-genotype neutralizing activity in both the HCV pseudoparticle (HCVpp) and HCV cell culture (HCVcc) systems, were also able to prevent HCV infection of different genotypes (gt) in vivo. Following passive immunization with H06-antibodies, chimeric mice were challenged with the consensus strains H77C (gt1a), ED43 (gt4a), or HK6a (gt6a). In accordance with previous results, H06-antibodies prevented infection of chimeric mice with the autologous virus. However, the outcome of a homologous challenge is highly influenced by the amount of challenge virus injected. Depending on the viral genotype used, H06-antibodies were able to protect up to 50% of chimeric mice from a heterologous challenge. Animals in which the antibody pretreatment failed displayed a clear delay in the kinetics of viral infection. Sequence analysis of the recovered viruses did not suggest antibody-induced viral escape. Conclusion: Polyclonal anti-HCV antibodies isolated from a chronic HCV patient can protect against an in vivo challenge with different HCV genotypes. However, the in vivo protective efficacy of cross-genotype neutralizing antibodies was less than predicted by cell culture experiments. (HEPATOLOGY 2011;53:755-762)
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
INFECTION, REPLICATION, ENVELOPE PROTEIN, HUMAN LIVER, CELL-CULTURE SYSTEMS, VITRO, MICE, PSEUDOPARTICLES, CHIMPANZEES, MOUSE
journal title
HEPATOLOGY
Hepatology
volume
53
issue
3
pages
755 - 762
Web of Science type
Article
Web of Science id
000288211200006
JCR category
GASTROENTEROLOGY & HEPATOLOGY
JCR impact factor
11.665 (2011)
JCR rank
2/73 (2011)
JCR quartile
1 (2011)
ISSN
0270-9139
DOI
10.1002/hep.24171
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1231085
handle
http://hdl.handle.net/1854/LU-1231085
date created
2011-05-23 16:56:50
date last changed
2011-06-01 12:55:53
@article{1231085,
  abstract     = {Control of hepatitis C virus (HCV) infection remains a huge challenge of global medical importance. Using a variety of in vitro approaches, neutralizing antibodies (nAbs) have been identified in patients with acute and chronic hepatitis C. The exact role these nAbs play in the resolution of acute HCV infection still remains elusive. We have previously shown that purified polyclonal antibodies isolated from plasma obtained in 2003 from a chronic HCV patient (Patient H) can protect human liver chimeric mice from a subsequent challenge with the autologous HCV strain isolated from Patient H in 1977 (H77). In this study we investigated whether polyclonal antibodies isolated from Patient H in 2006 (H06), which display high cross-genotype neutralizing activity in both the HCV pseudoparticle (HCVpp) and HCV cell culture (HCVcc) systems, were also able to prevent HCV infection of different genotypes (gt) in vivo. Following passive immunization with H06-antibodies, chimeric mice were challenged with the consensus strains H77C (gt1a), ED43 (gt4a), or HK6a (gt6a). In accordance with previous results, H06-antibodies prevented infection of chimeric mice with the autologous virus. However, the outcome of a homologous challenge is highly influenced by the amount of challenge virus injected. Depending on the viral genotype used, H06-antibodies were able to protect up to 50\% of chimeric mice from a heterologous challenge. Animals in which the antibody pretreatment failed displayed a clear delay in the kinetics of viral infection. Sequence analysis of the recovered viruses did not suggest antibody-induced viral escape. Conclusion: Polyclonal anti-HCV antibodies isolated from a chronic HCV patient can protect against an in vivo challenge with different HCV genotypes. However, the in vivo protective efficacy of cross-genotype neutralizing antibodies was less than predicted by cell culture experiments. (HEPATOLOGY 2011;53:755-762)},
  author       = {Meuleman, Philip and Bukh, Jens and Verhoye, Lieven and Farhoudi Moghadam, Aliasghar and VANWOLLEGHEM, THOMAS and Wang, Richard Y and Desombere, Isabelle and Alter, Harvey and Purcell, Robert H and Leroux-Roels, Geert},
  issn         = {0270-9139},
  journal      = {HEPATOLOGY},
  keyword      = {INFECTION,REPLICATION,ENVELOPE PROTEIN,HUMAN LIVER,CELL-CULTURE SYSTEMS,VITRO,MICE,PSEUDOPARTICLES,CHIMPANZEES,MOUSE},
  language     = {eng},
  number       = {3},
  pages        = {755--762},
  title        = {In vivo evaluation of the cross-genotype neutralizing activity of polyclonal antibodies against hepatitis C virus},
  url          = {http://dx.doi.org/10.1002/hep.24171},
  volume       = {53},
  year         = {2011},
}

Chicago
Meuleman, Philip, Jens Bukh, Lieven Verhoye, Aliasghar Farhoudi Moghadam, THOMAS VANWOLLEGHEM, Richard Y Wang, Isabelle Desombere, Harvey Alter, Robert H Purcell, and Geert Leroux-Roels. 2011. “In Vivo Evaluation of the Cross-genotype Neutralizing Activity of Polyclonal Antibodies Against Hepatitis C Virus.” Hepatology 53 (3): 755–762.
APA
Meuleman, P., Bukh, J., Verhoye, L., Farhoudi Moghadam, A., VANWOLLEGHEM, T., Wang, R. Y., Desombere, I., et al. (2011). In vivo evaluation of the cross-genotype neutralizing activity of polyclonal antibodies against hepatitis C virus. HEPATOLOGY, 53(3), 755–762.
Vancouver
1.
Meuleman P, Bukh J, Verhoye L, Farhoudi Moghadam A, VANWOLLEGHEM T, Wang RY, et al. In vivo evaluation of the cross-genotype neutralizing activity of polyclonal antibodies against hepatitis C virus. HEPATOLOGY. 2011;53(3):755–62.
MLA
Meuleman, Philip, Jens Bukh, Lieven Verhoye, et al. “In Vivo Evaluation of the Cross-genotype Neutralizing Activity of Polyclonal Antibodies Against Hepatitis C Virus.” HEPATOLOGY 53.3 (2011): 755–762. Print.