Broadly neutralizing antibodies abrogate established hepatitis C virus infection

YP De Jong, M Dorner, MC Mommersteeg… - Science translational …, 2014 - science.org
YP De Jong, M Dorner, MC Mommersteeg, JW Xiao, AB Balazs, JB Robbins, BY Winer
Science translational medicine, 2014science.org
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 …
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.
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