CHARACTERIZATION OF DIFFERENCES IN THE ANTIBODY IMMUNE RESPONSE AGAINST HCV IN CHRONICALLY INFECTED INDIVIDUALS VERSUS SPONTANEOUS CLEARERS

Hepatitis C virus (HCV) is an ongoing health problem. With approximately 180 million people infected with HCV worldwide, it remains the number one cause for hepatocellular carcinoma. Although a significant progress in developing effective direct acting antivirals has been made in the last few years, the need for an effective vaccine remains high for future prevention of infection. Approximately 25% of HCV infected individuals clear the virus infection without medical interference (spontaneously cured patients - SC) while the remaining 75% develop a chronic disease (chronically infected - CI). We hypothesize that successful antibody response to HCV is dependent on the presence of neutralizing and non-neutralizing interfering antibodies and their binding to two distinct epitopes on the HCV-E2 envelope protein, epitope I and epitope II, respectively. We tested the ability of sera to bind synthetically synthesized peptides representing the important for neutralization epitope I, and the masking, interfering, epitope II. We discovered that the ratio of epitope I/epitope II bound antibodies is higher in SC than in CI patients. We also observed that changing this ratio by depleting antibodies to epitope I has a negative effect on viral neutralization in SC sera. Finally, we applied the phage display technique to discover new immunodominant epitopes of HCV. Our results revealed a high representation of an interfering epitope- HVR1, in CI patients. These findings suggest that a successful antibody response may be an important contributor to spontaneous eradication of HCV.