Production and characterization of monoclonal antibodies specific for a conserved epitope within hepatitis C virus hypervariable region 1
- PMID: 11711631
- PMCID: PMC116137
- DOI: 10.1128/JVI.75.24.12412-12420.2001
Production and characterization of monoclonal antibodies specific for a conserved epitope within hepatitis C virus hypervariable region 1
Abstract
Frequent mutations in hypervariable region 1 (HVR1) of the main envelope protein of hepatitis C virus (HCV) is a major mechanism of persistence by escaping the host immune recognition. HVR1 contains an epitope eliciting neutralizing antibodies. This study was aimed to prepare broadly cross-reacting, high-affinity, monoclonal antibodies (MAb) to the HVR1 C terminus of HCV with potential therapeutic neutralizing capacity. A conserved amino residue group of glycine (G) at position 23 and glutamic acid (Q) at position 26 in HVR1 was confirmed as a key epitope against which two MAbs were selected and characterized. MAbs 2P24 and 15H4 were immunoglobulin G1 kappa chain [IgG1(kappa)], cross-reacted with 32 and 30 of 39 random C-terminal HVR1 peptides, respectively, and did not react with other HCV peptides. The V(H) of 2P24 and 15H4 heavy chains originated from Igh germ line v gene family 1 and 8, respectively. In contrast, the V(L) kappa sequences were highly homologous. The affinity (K(d)) of 2P24 and 15H4 (10(-9) or 10(-8) M with two immunizing peptides and 10(-8) M with two nonimmunizing HVR1 peptides) paralleled the reactivity obtained with peptide enzyme immunoassay. MAbs 2P24 and 15H4 captured 25 of 31 (81%) HCV in unselected patients' plasmas. These antibodies also blocked HCV binding to Molt-4 cells in a dose-dependent fashion. The data presented suggest that broadly cross-reactive MAbs to a conserved epitope within HCV HVR1 can be produced. Clinical application for passive immunization in HCV-related chronic liver disease and after liver transplantation is considered.
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References
-
- Alberti A, Chemello L, Benvegnu L. Natural history of hepatitis C. J Hepatol. 1999;31(Suppl. 1):17–24. - PubMed
-
- Allain J P, Zhai W, Shang D, Timmers E, Alexander G J M. Hypervariable region diversity of hepatitis C virus and humoral response: comparison between patients with or without cirrhosis. J Med Virol. 1999;59:25–31. - PubMed
-
- Aswad S, Mendez R, Weingart R G, Mendez R. Expanding organ availability by using hepatitis C antibody-positive donors. Transplant Proc. 1993;25:2270–2271. - PubMed
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