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Broadly neutralizing antibodies abrogate established hepatitis C virus infection

Author(s): de Jong, YP; Dorner, M; Mommersteeg, MC; Xiao, JW; Balazs, AB; et al

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Abstract: Hepatitis C virus (HCV) establishes a chronic infection in the majority of exposed individuals and can cause 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. Here, we demonstrate that three broadly nAbs, AR3A, AR3B and AR4A, delivered with adeno-associated viral (AAV) 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 novel therapeutic approach to interfere with HCV infection exploiting a previously unappreciated need for HCV to continuously infect new hepatocytes in order to sustain chronicity.
Publication Date: 17-Sep-2014
Electronic Publication Date: 17-Sep-2014
Citation: de Jong, YP, Dorner, M, Mommersteeg, MC, Xiao, JW, Balazs, AB, Robbins, JB, Winer, BY, Gerges, S, Vega, K, Labitt, RN, Donovan, BM, Giang, E, Krishnan, A, Chiriboga, L, Charlton, MR, Burton, DR, Baltimore, D, Law, M, Rice, CM, Ploss, A. (2014). Broadly neutralizing antibodies abrogate established hepatitis C virus infection. Science Translational Medicine, 6 (254), 254ra129 - 254ra129. doi:10.1126/scitranslmed.3009512
DOI: doi:10.1126/scitranslmed.3009512
ISSN: 1946-6234
EISSN: 1946-6242
Type of Material: Journal Article
Journal/Proceeding Title: Science Translational Medicine
Version: Author's manuscript

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