Prevention of hepatitis C virus infection using a broad cross-neutralizing monoclonal antibody (AR4A) and epigallocatechin gallate

Daire O'Shea; John Law; Adrian Egli; Donna Douglas; Gary Lund; Sarah Forester; Joshua Lambert; Mansun Law; Dennis R. Burton; D. L.J. Tyrrell; Michael Houghton; Atul Humar; Norman Kneteman

doi:10.1002/lt.24344

Prevention of hepatitis C virus infection using a broad cross-neutralizing monoclonal antibody (AR4A) and epigallocatechin gallate

Daire O'Shea, John Law, Adrian Egli, Donna Douglas, Gary Lund, Sarah Forester, Joshua Lambert, Mansun Law, Dennis R. Burton, D. L.J. Tyrrell, Michael Houghton, Atul Humar, Norman Kneteman

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14 Scopus citations

Abstract

The anti-hepatitis C virus (HCV) activity of a novel monoclonal antibody (mAb; AR4A) and epigallocatechin gallate (EGCG) were studied in vitro using a HCV cell culture system and in vivo using a humanized liver mouse model capable of supporting HCV replication. Alone, both exhibit reliable cross-genotype HCV inhibition in vitro, and combination therapy completely prevented HCV infection. In vitro AR4A mAb (alone and combined with EGCG) robustly protects against the establishment of HCV genotype 1a infection. EGCG alone fails to reliably protect against an HCV challenge. In conclusion, AR4A mAb represents a safe and efficacious broadly neutralizing antibody against HCV applicable to strategies to safely prevent HCV reinfection following liver transplantation, and it lends further support to the concept of HCV vaccine development. The poor bioavailability of EGCG limits HCV antiviral activity in vitro. Liver Transpl 22:324-332, 2016.

Original language	English (US)
Pages (from-to)	324-332
Number of pages	9
Journal	Liver Transplantation
Volume	22
Issue number	3
DOIs	https://doi.org/10.1002/lt.24344
State	Published - Mar 1 2016

All Science Journal Classification (ASJC) codes

Surgery
Hepatology
Transplantation

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O'Shea, D., Law, J., Egli, A., Douglas, D., Lund, G., Forester, S., Lambert, J., Law, M., Burton, D. R., Tyrrell, D. L. J., Houghton, M., Humar, A., & Kneteman, N. (2016). Prevention of hepatitis C virus infection using a broad cross-neutralizing monoclonal antibody (AR4A) and epigallocatechin gallate. Liver Transplantation, 22(3), 324-332. https://doi.org/10.1002/lt.24344

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title = "Prevention of hepatitis C virus infection using a broad cross-neutralizing monoclonal antibody (AR4A) and epigallocatechin gallate",

abstract = "The anti-hepatitis C virus (HCV) activity of a novel monoclonal antibody (mAb; AR4A) and epigallocatechin gallate (EGCG) were studied in vitro using a HCV cell culture system and in vivo using a humanized liver mouse model capable of supporting HCV replication. Alone, both exhibit reliable cross-genotype HCV inhibition in vitro, and combination therapy completely prevented HCV infection. In vitro AR4A mAb (alone and combined with EGCG) robustly protects against the establishment of HCV genotype 1a infection. EGCG alone fails to reliably protect against an HCV challenge. In conclusion, AR4A mAb represents a safe and efficacious broadly neutralizing antibody against HCV applicable to strategies to safely prevent HCV reinfection following liver transplantation, and it lends further support to the concept of HCV vaccine development. The poor bioavailability of EGCG limits HCV antiviral activity in vitro. Liver Transpl 22:324-332, 2016.",

author = "Daire O'Shea and John Law and Adrian Egli and Donna Douglas and Gary Lund and Sarah Forester and Joshua Lambert and Mansun Law and Burton, {Dennis R.} and Tyrrell, {D. L.J.} and Michael Houghton and Atul Humar and Norman Kneteman",

note = "Funding Information: We thank Chelcey Dibben and Brandie Greaves for provision of expert animal care. Additional thanks to Erick Giang of The Scripps Research Institute for antibody production. Publisher Copyright: {\textcopyright} 2015 American Association for the Study of Liver Diseases.",

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doi = "10.1002/lt.24344",

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AU - O'Shea, Daire

AU - Law, John

AU - Egli, Adrian

AU - Douglas, Donna

AU - Lund, Gary

AU - Forester, Sarah

AU - Lambert, Joshua

AU - Law, Mansun

AU - Burton, Dennis R.

AU - Tyrrell, D. L.J.

AU - Houghton, Michael

AU - Humar, Atul

AU - Kneteman, Norman

N1 - Funding Information: We thank Chelcey Dibben and Brandie Greaves for provision of expert animal care. Additional thanks to Erick Giang of The Scripps Research Institute for antibody production. Publisher Copyright: © 2015 American Association for the Study of Liver Diseases.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - The anti-hepatitis C virus (HCV) activity of a novel monoclonal antibody (mAb; AR4A) and epigallocatechin gallate (EGCG) were studied in vitro using a HCV cell culture system and in vivo using a humanized liver mouse model capable of supporting HCV replication. Alone, both exhibit reliable cross-genotype HCV inhibition in vitro, and combination therapy completely prevented HCV infection. In vitro AR4A mAb (alone and combined with EGCG) robustly protects against the establishment of HCV genotype 1a infection. EGCG alone fails to reliably protect against an HCV challenge. In conclusion, AR4A mAb represents a safe and efficacious broadly neutralizing antibody against HCV applicable to strategies to safely prevent HCV reinfection following liver transplantation, and it lends further support to the concept of HCV vaccine development. The poor bioavailability of EGCG limits HCV antiviral activity in vitro. Liver Transpl 22:324-332, 2016.

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Prevention of hepatitis C virus infection using a broad cross-neutralizing monoclonal antibody (AR4A) and epigallocatechin gallate

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