A newly discovered controversial role of the neutralizing HCV antibodies in the relapse of hepatitis C virus

Despite all intensive efforts and widespread use of direct-acting antivirals (DAA), and their high sustained virological responses (SVR) rate and the clearance of hepatitis C virus (HCV) RNA from serum, the mechanism of late relapse is still unclear. This study introduces a controversial role of neutralizing antibodies, and their influence in HCV protection and reactivation, by coating the virus's structural and nonstructural protein particles and protects it from CD8+ cytotoxic T cells and antiviral drugs. A new ELISA screening assay was designed to detect this Ag/ nAbs complex in serum samples. In a pilot study comprised of 76 subjects, 66 of them were diagnosed with chronic HCV genotype 4, patients were divided into 5 groups, group l patients were treated with interferon, group ll patients received Sofo/dacla, group lll patients did not receive any antiviral drugs, as for group lV patients were negative for HCV RNA, group V included sera samples collected from healthy individuals. Samples were collected after 3, 6, 12 months and the results we obtained concluded that there is a marked association between the increase levels of circulating immune complex C1, C2, C3 and the clearance of HCV RNA from blood, also we identified significant correlation between the relapse of HCV RNA after achieving SVR for a long time and the diminish in levels of these immune complex. These results have important implications for the development of real therapeutic and prophylactic vaccine and also raise a great possibility for developing a serological screening method for monitoring HCV treatment.