title: Broadly neutralizing antibodies abrogate established hepatitis C virus infection.
abstract: In most exposed individuals, hepatitis C virus (HCV) establishes a chronic infection; this long-term infection in turn contributes to the development of liver diseases such as cirrhosis and hepatocellular carcinoma. The role of antibodies directed against HCV in disease progression is poorly understood. Neutralizing antibodies (nAbs) can prevent HCV infection in vitro and in animal models. However, the effects of nAbs on an established HCV infection are unclear. We demonstrate that three broadly nAbs-AR3A, AR3B, and AR4A-delivered with adeno-associated viral vectors can confer protection against viral challenge in humanized mice. Furthermore, we provide evidence that nAbs can abrogate an ongoing HCV infection in primary hepatocyte cultures and in a human liver chimeric mouse model. These results showcase a therapeutic approach to interfere with HCV infection by exploiting a previously unappreciated need for HCV to continuously infect new hepatocytes to sustain a chronic infection.
authors.affiliation: Center for the Study of Hepatitis C, Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY 10065, USA. Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA. ydj2001@med.cornell.edu aploss@princeton.edu.
authors.forename: Ype P
authors.initials: YP
authors.lastname: de Jong
authors.affiliation: Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Marcus
authors.initials: M
authors.lastname: Dorner
authors.affiliation: Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Michiel C
authors.initials: MC
authors.lastname: Mommersteeg
authors.affiliation: Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Jing W
authors.initials: JW
authors.lastname: Xiao
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
authors.forename: Alejandro B
authors.initials: AB
authors.lastname: Balazs
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Justin B
authors.initials: JB
authors.lastname: Robbins
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Benjamin Y
authors.initials: BY
authors.lastname: Winer
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Sherif
authors.initials: S
authors.lastname: Gerges
authors.affiliation: Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Vega
authors.affiliation: Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Rachael N
authors.initials: RN
authors.lastname: Labitt
authors.affiliation: Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Bridget M
authors.initials: BM
authors.lastname: Donovan
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Erick
authors.initials: E
authors.lastname: Giang
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Krishnan
authors.affiliation: Department of Pathology, New York University Medical Center, New York, NY 10016, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Chiriboga
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Charlton
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA. Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: David
authors.initials: D
authors.lastname: Baltimore
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Mansun
authors.initials: M
authors.lastname: Law
authors.affiliation: Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rice
authors.affiliation: Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA. Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. ydj2001@med.cornell.edu aploss@princeton.edu.
authors.forename: Alexander
authors.initials: A
authors.lastname: Ploss
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000627:therapeutic use; D002478:Cells, Cultured; D000229:Dependovirus / Q000235:genetics; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000628:therapy; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D051379:Mice
chemical_list: D057134:Antibodies, Neutralizing