Broadly neutralizing antibodies abrogate established hepatitis C virus infection

Ype P. De Jong, Marcus Dorner, Michiel C. Mommersteeg, Jing W. Xiao, Alejandro B. Balazs, Justin B. Robbins, Benjamin Y. Winer, Sherif Gerges, Kevin Vega, Rachael N. Labitt, Bridget M. Donovan, Erick Giang, Anuradha Krishnan, Luis Chiriboga, Michael R. Charlton, Dennis R. Burton, David Baltimore, Mansun Law, Charles M. Rice, Alexander Ploss

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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.

Original languageEnglish (US)
Article number254ra129
JournalScience translational medicine
Volume6
Issue number254
DOIs
StatePublished - Sep 17 2014

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

De Jong, Y. P., Dorner, M., Mommersteeg, M. C., Xiao, J. W., Balazs, A. B., Robbins, J. B., Winer, B. Y., Gerges, S., Vega, K., Labitt, R. N., Donovan, B. M., Giang, E., Krishnan, A., Chiriboga, L., Charlton, M. R., Burton, D. R., Baltimore, D., Law, M., Rice, C. M., & Ploss, A. (2014). Broadly neutralizing antibodies abrogate established hepatitis C virus infection. Science translational medicine, 6(254), [254ra129]. https://doi.org/10.1126/scitranslmed.3009512