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Sci Transl Med. 2014 Sep 17;6(254):254ra129. doi: 10.1126/scitranslmed.3009512.

Broadly neutralizing antibodies abrogate established hepatitis C virus infection.

Author information

1
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.
2
Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
3
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
4
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
5
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
6
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
7
Department of Pathology, New York University Medical Center, New York, NY 10016, USA.
8
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.
9
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
10
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.

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.

PMID:
25232181
PMCID:
PMC4312107
DOI:
10.1126/scitranslmed.3009512
[Indexed for MEDLINE]
Free PMC Article

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