Salah SH1,2*, Ghaleb HA3, Ehab H4 and EL-HARIRI HM5
1Department of Immunology, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt
2R&D Center Vaccine Immunology and Immunogen Discovery, Egypt
3Department of Pharmacology, Cairo University, Egypt
4Department of Internal Medicine, National Research Center, Egypt
5Department of Community Medicine, National Research Centre, Egypt
Despite all intensive efforts and widespread use of Direct-Acting Antivirals (DAA), that achieve a high Sustained Virological Response (SVR) rate and clearance of Hepatitis C Virus (HCV) RNA from serum, the mechanism of late relapse, is still unknown. Previous observational studies have shown the rapid onset of anti-HCV antibodies to be associated with a higher likelihood of clearance but this study introduced a controversial role of neutralizing antibodies, as it influence HCV reactivation and replication, by coating its structural and nonstructural protein particles in antigen/ neutralizing antibody immune-complex form (Ag/nAbs) comprising HCV antigen (E1, E2, C and its specific bounded neutralizing antibody as C1, C2 and C3) for a long time preventing its attacks by CD8+ cytotoxic T-cells and anti-viral drugs. A screening biomarker was designed to detect this Ag/nAbs complex in serum samples of infected patients. In a pilot study comprised 76 patients with chronic HCV Genotype 4, 22 patients were treated before with interferon/Ribavirin for 48 weeks and didn’t respond to this type of therapy as (Group I), 24 patients received Sofosbuvir 400 mg and Daclatasvir 60 mg daily for 24 weeks, as (Group II), 14 patients were diagnosed positive HCV RNA and detectable anti HCV antibody in their sera (Group III) 6 patients were negative HCV RNA and detectable anti HCV antibody as (Group IV) none of the patients in group 3, 4 had been previously treated with antiviral drugs. A total of 10 sera collected from healthy human subjects having no history of any liver complications, undetectable anti HCV antibodies and negative HCV RNA by RT-PCR in their sera were included as negative controls (Group V). Serum samples were collected 3 times at 3, 6 and 12 month intervals for quantitative measuring of (HCV RNA), circulating unbounded neutralizing (anti-E1), (anti-E2), (anti-C antigen), (E1 antigen/bounded anti E1 complex as C1), (E2 antigen/bounded anti E2 complex as C2), (C antigen/bounded anti C antibody complex as C3). We 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 the great possibility for developing a serological screening method for monitoring HCV treatment.
HCV envelope glycoproteins (E1); HCV envelope glycoproteins (E2); HCV core antigen (c); Neutralizing antibody (nAbs); Antigen/antibody complex (Ag/Abs); Type I interferon-a (IFN-a); Direct-acting antivirals (DAA)
Salah SH, Ghaleb HA, Ehab H, ELHARIRI HM. A Newly Discovered Role of the Anti HCV Neutralizing Antibody as a Potential Risk in Influencing HCV Replication and Infection Reactivation. Ann Clin Hepatol. 2019; 3(1): 1008.