CHARACTERIZATION OF ANTIBODY MEDIATED IMMUNITY AGAINST HEPATITIS C VIRUS

Hepatitis C virus (HCV) infects approximately 170 million people worldwide and is the leading indicator for liver transplants. While a vast progress has been made in developing HCV specific direct-acting antivirals (DAAs), the development of an efficient vaccine to prevent HCV infection remains an essential goal. We hypothesized that successful antibody response to HCV is dependent on the presence of neutralizing and non-neutralizing interfering antibodies and their binding to distinct epitopes on the HCV-E2 envelope protein. We aimed to characterize neutralization epitopes on the E2 glycoprotein to have a better insight into immunodominant epitopes that are important for antibody mediated neutralization of HCV in chronically infected patients and patients who achieved spontaneous clearance. To characterize neutralization epitopes we have generated a panel of infectious HCV containing point mutations in residues on the HCV E2 proteins, comprising neutralization epitopes. By neutralization assays with the mutant viruses and sera collected from chronically HCV- infected patients we have identified a novel neutralization epitope that was more immunodominant than previously described neutralization epitopes. In contrast, the pattern of immunodominant neutralization epitopes was different in neutralization with sera from spontaneous clearance. We also identified higher levels of neutralizing antibodies compared to non-neutralizing interfering antibodies in spontaneously cleared patients in compare to chronically infected individuals. These results suggest that successful B cell response is characterized by targeting specific neutralization epitopes and implying that not only the quantity of the B cell response plays a role in protection from infection but also its quality. This study may contribute to understanding the antibody mediated neutralization of HCV as well as the development of antibody-based therapeutic and vaccine design.