Characterising the neutralising antibody response in chronic hepatitis C virus infection (360G-Wellcome-109162_Z_15_A)

Despite new treatment options there remains ~180 million people chronically infected with Hepatitis C virus (HCV), and, with 3-4 million new infections every year, a preventative vaccine is the greatest unmet need in tackling the HCV pandemic. A key challenge for the development of an effective vaccine is HCV’s ability to evade and disable the human immune response. This includes an array of neutralizing antibody (nAbs) evasion mechanisms. Nonetheless, nAbs contribute to the control of chronic infection and can prevent infection in various challenge models. The aim of this project will be to characterise the natural nAb response to HCV using a novel combination of computational and experimental methods. Key goals are to: characterize the nAb responses in chronically infected and acute resolving patients, including the epitope specificity of anti-HCV nAbs; understand where key epitope residues fit into the context of HCV glycoprotein structure, with potential insights into how nAbs drive viral evolution; model the impact of mutations to better understand the structural determinants of nAb evasion. This work may directly contribute to future vaccine design.