14 In order to validate the relevance of the mAb

D32.10 in vivo, we used the D32.10 epitope as a probe to look for the presence of anti-E1E2A,B D32.10 epitope-binding antibodies in the serum of HCV-infected patients. The prevalence of anti-E1E2 antibodies in serum was high in patients who either resolved the infection spontaneously, or who achieved a sustained viral response (SVR) after antiviral therapy. Thus, the E1E2A,B D32.10 epitope-binding antibody response appears as associated with control of HCV infection in vivo and may be predictive of the response to HCV treatment. aa, amino acid; C, cured patients; CR, complete responders; ELISA, enzyme-linked immunosorbent assay; HDL, high-density lipoprotein; HCV, hepatitis C virus; HCVcc, infectious cell culture HCV particle; HCVpp, HCV pseudotyped particle; HCVsp, serum-derived HCV particle; HVR1, hypervariable region 1; IgG, immunoglobulin Roxadustat in vivo G; mAb, monoclonal antibody; NHS, normal human serum; NPV, negative predictive value; NR, nonresponder; NT, never-treated chronic carriers; OD, optical density; PBS, phosphate-buffered saline; PBSTG, PBS–Tween–goat serum;

PEG-IFN, Protein Tyrosine Kinase inhibitor pegylated interferon; PPV, positive predictive value; SD, standard deviation; SVR, sustained viral response; Trt, treatment; ULN, upper limit of the normal range. Human serum samples positive for HCV antibody were obtained from 194 individuals, tested by third-generation enzyme-linked immunosorbent assay (ELISA; Ortho Diagnostics), and classified according to four groups. Group 1: Fifty-two samples negative for HCV RNA were from 22 patients who had spontaneously resolved symptomatic or asymptomatic acute HCV infection in the past (≥ 10 years), and from pentoxifylline 30 patients whose date of acute infection was unknown. Only 50% (26 of 52) of samples were analyzed

for genotyping, and 25 of 26 were of genotype 1 (Table 1). Group 2: Fifty serum samples were from never-treated (NT) HCV chronic carriers. Fifty-eight percent (28 of 48) were of genotype 1 (Table 1). Their median HCV viral load was 5.8 log10 IU/mL (range: 3.4-7.8 log10 IU/mL) for 44 of 47 cases (Table 1). A total of 54% (26 of 48) showed elevated aminotransferases (median = 1.4 × upper limit of the normal range [ULN], range = 1.06-4.90 × ULN) whereas 46% (22 of 48) had normal levels (median = 0.75 × ULN, range = 0.3-1 × ULN). A total of 77% (27 of 35) exhibited no or low Metavir activity score (A0-A1) and 63% (27 of 43) had a Metavir fibrosis score of F0-F1 (Table 1). Group 3: Forty serum samples were from chronically infected patients who did not respond to multiple successive antiviral therapies with standard or pegylated interferon (PEG-IFN) in association with ribavirin in the majority of cases (77%, 30 of 39; Table 1). HCV RNA levels showed a median of 5.7 log10 IU/mL (range: 4.7-6.9 log10 IU/mL) for 27 of 35 cases (Table 1).