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

(2011) HEPATOLOGY. 53(3). p.755-762
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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)
Keywords
INFECTION, REPLICATION, ENVELOPE PROTEIN, HUMAN LIVER, CELL-CULTURE SYSTEMS, VITRO, MICE, PSEUDOPARTICLES, CHIMPANZEES, MOUSE

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Citation

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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.
@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},
  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},
}

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