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.
authors.affiliation: Transplant Infectious Diseases, Alberta Transplant Institute, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.|Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Daire
authors.initials: D
authors.lastname: O'Shea
authors.affiliation: Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Law
authors.affiliation: Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Adrian
authors.initials: A
authors.lastname: Egli
authors.affiliation: Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Donna
authors.initials: D
authors.lastname: Douglas
authors.affiliation: KMT Hepatech, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Lund
authors.affiliation: Department of Food Science, Pennsylvania State University, State College, PA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Forester
authors.affiliation: Department of Food Science, Pennsylvania State University, State College, PA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Lambert
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA.
authors.forename: Mansun
authors.initials: M
authors.lastname: Law
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA.|Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.affiliation: Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: D L J
authors.initials: DL
authors.lastname: Tyrrell
authors.affiliation: Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Houghton
authors.affiliation: Toronto General Hospital, University Health Network, Multi-Organ Transplant Program, Toronto, Ontario, Canada.
authors.forename: Atul
authors.initials: A
authors.lastname: Humar
authors.affiliation: Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada.|Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Norman
authors.initials: N
authors.lastname: Kneteman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D000080908:Broadly Neutralizing Antibodies; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005838:Genotype; D006526:Hepatitis C / Q000175:diagnosis / Q000276:immunology / Q000517:prevention & control*; D006518:Hepatitis Viruses / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D016513:Mice, SCID; D013997:Time Factors
chemical_list: C000612626:AR4A cross-neutralizing monoclonal antibody; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000998:Antiviral Agents; D000080908:Broadly Neutralizing Antibodies; D002392:Catechin; C045651:epigallocatechin gallate