Molecular characterization of the human neutralizing response against hepatitis C virus and its role in the prediction of the infection outcome

The hepatitis C virus (HCV) adopts several escape mechanisms and is able to evade the host immune response in the majority of patients. During primary infection, HCV is not cleared in 80% of cases resulting in chronic infection. The current treatment for HCV infection is mainly represented by the administration of a combined therapy (IFN-α, ribavirin) and by the use of new anti-viral drugs (protease inhibitors). Unfortunately, only 50% of the infected patients respond completely to these therapies. It has been demonstrated how a neutralizing antibody response is correlated with lower HCV titer in acute infection. Moreover, it is also demonstrated how a rapid induction of neutralizing antibodies can be correlated with the viral clearance. Under these purposes, results clear how neutralizing antibodies can be important for the HCV infection control. In addition, they can represent good candidates for passive immunotherapy. They also can be applied both in diagnosis, as useful tools for the evaluation of the presence of cross-neutralizing antibodies in patients sera, and in research studies to better understand the virus–host interplay, an aspect that can be crucial in predicting the infection clinical outcome. In this study, we characterized the synergistic neutralization of HCV by two broadly neutralizing human monoclonal antibodies directed against HCV/E2 glycoprotein, named e20 and e137.