Association of anti-E1E2 antibodies with spontaneous recovery or sustained viral response to therapy in patients infected with hepatitis C virus.
The monoclonal antibody (mAb) D32.10 recognizes a discontinuous epitope encompassing three regions E1 (amino acids 297-306), E2A (amino acids 480-494), and E2B (amino acids 613-621) juxtaposed on the surface of serum-derived hepatitis C virus (HCV) particles (HCVsp). The mAb D32.10 inhibits efficiently and specifically the binding of HCVsp to human hepatocytes. Therefore, we investigated the clinical relevance of anti-E1E2A,B response in the serum of patients infected with HCV. To this end, an enzyme-linked immunosorbent assay (ELISA) using synthetic E1-, E2A-, and E2B-derived peptides was used. The ELISA was validated in terms of sensitivity, specificity, and test efficiency. The detection of the anti-E1E2 D32.10 epitope-binding antibodies during natural HCV infection in more than 300 HCV-positive sera demonstrated significantly (P < 0.001) higher prevalence of these antibodies: (1) in patients who spontaneously cured HCV infection (46 of 52, 88.5%) showing high titers (70% ≥ 1/1000) compared to never-treated patients with chronic hepatitis C (7 of 50, 14%) who actively replicated the virus, and (2) in complete responders (20 of 52, 38.5%) who cleared virus following treatment and achieved a sustained viral response compared to nonresponders (4 of 40, 10%). Serum anti-E1E2 antibodies were monitored before, during, and after the current standard-of-care therapy (pegylated interferon plus ribavirin) in responder and nonresponder patients. Optimal cutoff values were assessed by receiver operating characteristic curve analysis. One month prior to therapy initiation, the threshold of 1131 (optical density × 1000) gave 100% and 86% positive and negative predictive values, respectively, for achieving or not achieving a sustained viral response.


CONCLUSIONS
The anti-E1E2 D32.10 epitope-binding antibodies are associated with control of HCV infection and may represent a new relevant prognostic marker in serum. This unique D32.10 mAb may also have immunotherapeutic potential.
Ndongo
Ndiémé
N
Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 871, Molecular Physiopathology and New Therapies in Viral Hepatitis, Lyon, France.
Berthillon
Pascale
P
Pradat
Pierre
P
Vieux
Claude
C
Bordes
Isabelle
I
Berby
Françoise
F
Maynard
Marianne
M
Zoulim
Fabien
F
Trépo
Christian
C
Petit
Marie-Anne
MA
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000276:immunology / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D000939:Epitopes / Q000276:immunology / Q000627:therapeutic use; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000276:immunology; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D008137:Longitudinal Studies; D010455:Peptides / Q000276:immunology; D015203:Reproducibility of Results; D016036:Seroepidemiologic Studies; D016896:Treatment Outcome
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000998:Antiviral Agents; C116123:E1E2 peptide; D000939:Epitopes; D007136:Immunoglobulins; D010455:Peptides