1. Broadly neutralizing antibodies abrogate established hepatitis C virus infection
- Author
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Charles M. Rice, Dennis R. Burton, Kevin Vega, Justin B. Robbins, Marcus Dorner, Rachael N. Labitt, Sherif Gerges, Luis Chiriboga, Mansun Law, Ype P. de Jong, Michael Charlton, Jing W. Xiao, David Baltimore, Michiel C. Mommersteeg, Alejandro B. Balazs, Benjamin Y. Winer, Anuradha Krishnan, Bridget M. Donovan, Erick Giang, and Alexander Ploss
- Subjects
Cirrhosis ,MONOCLONAL-ANTIBODY ,Genotype ,TRANSMISSION ,Hepacivirus ,Hepatitis C virus ,Research & Experimental Medicine ,medicine.disease_cause ,BLOOD MONONUCLEAR-CELLS ,Article ,Viral vector ,Mice ,medicine ,Animals ,Humans ,IN-VIVO ,Cells, Cultured ,11 Medical and Health Sciences ,Science & Technology ,biology ,VECTORED IMMUNOPROPHYLAXIS ,virus diseases ,General Medicine ,Hepatitis C ,Cell Biology ,HUMANIZED MICE ,Dependovirus ,Hepatitis C, Chronic ,06 Biological Sciences ,biology.organism_classification ,medicine.disease ,LIVER-TRANSPLANTATION ,Virology ,Antibodies, Neutralizing ,digestive system diseases ,HEPATOMA-CELLS ,Chronic infection ,HUMAN HEPATOCYTES ,Medicine, Research & Experimental ,Hepatocellular carcinoma ,Immunology ,REPLICATION ,biology.protein ,Hepatocytes ,Antibody ,Life Sciences & Biomedicine - 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.
- Published
- 2014