Source The University of Nottingham;
Hepatitis C virus (HCV) is a blood-borne virus estimated to infect around 170 million people worldwide and is, therefore, a major disease burden. In some individuals the virus is spontaneously cleared during the acute phase of infection, whilst in others a persistent infection ensues. Of those persistently infected, severe liver diseases such as cirrhosis and primary liver cancer may develop, although many individuals remain asymptomatic. A range of factors shape the course of HCV infection, not least host genetic polymorphisms and host immunity. A number of studies have shown that neutralising antibodies (nAb) arise during HCV infection but that these antibodies differ in their breadth and mechanism of neutralisation. Recent studies, using both monoclonal antibodies and polyclonal sera, have provided an insight into neutralising determinants and the likely protective role of antibodies during infection. This understanding has helped to shape our knowledge of the overall structure of the HCV envelope glycoproteins - the natural target for neutralising antibodies. Most nAb identified to date target receptor binding sites within the envelope glycoprotein E2. However, there is some evidence that other viral epitopes may be targets for antibody neutralisation suggesting the need to broaden the search for neutralisation epitopes beyond E2. This review provides a comprehensive overview of our current understanding of the role played by nAb in HCV infection and disease outcome and explores the limitations in the study systems currently used. In addition, we briefly discuss the potential therapeutic benefits of nAb and efforts to develop neutralising antibody-based therapies.