Early antibody response against hypervariable region 1 is associated with acute self‐limiting infections of hepatitis C virus

Antibodies directed to hypervariable region 1 (HVR1) of hepatitis C virus (HCV) have recently been shown to neutralize the corresponding HCV isolate in vitro. We analyzed the appearance of antibodies directed to HVR1 during the course of infection in a large group of patients who have been infected by the same isolate of a HCV contaminated anti‐D immunoglobulin (HCV‐AD78). An enzyme‐linked immunosorbent assay (ELISA) was established using a synthetic peptide to detect antibodies against the main HVR1 variant of HCV‐AD78. 207 sera obtained at different time points post infection (p.i.) of 51 patients having either acute self‐ limiting (n = 28) or chronic infection (n = 23) were studied. Antibodies directed to HVR1 were found at least at one time point during the infection course in 15 of 28 patients (53%) having acute self‐limiting infections and in 17 of 23 patients (74%) with chronic disease. The time of appearance of anti‐HVR1 was significantly different between these two patient groups (P < .025) although appearance and titers of other HCV‐specific antibodies were found to be similar at early time points p.i. In acute self‐limiting infections 9 of 21 sera (43%) of respective patients with sera available within the first 6 months p.i. were anti‐HVR1 positive. The highest prevalence of anti‐HVR1 in this group of patients was within month 6 to 12 p.i. (64%). None of the sera available after 24 months p.i. had such antibodies. In contrast, only 2 of 15 sera (13%) of chronically infected patients with respective time points of sera were anti‐HVR1 positive within the first 6 months p.i. and only 5 of 18 sera (28%) were positive within month 7 to 12 p.i. Seven patients with chronic HCV infections showed at least two consecutive anti‐HVR1 negative early time points up to month 18 p.i. Prevalence of anti‐HVR1 after 24 months p.i. was high (84%) in this group of patients and most of the patients maintained high levels of anti‐HVR1 for up to 17 years p.i. Our findings suggest clearance of virus by respective neutralizing antibodies resulting in a self‐limiting infection and may have implications for prognosis of the disease and also for any future vaccine development.