A Diverse Panel of Hepatitis C Virus Glycoproteins for Use in Vaccine Research Reveals Extremes of Monoclonal Antibody Neutralization Resistance.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsUrbanowicz, Richard A
McClure, C Patrick
Brown, Richard J P
Persson, Mats A A
Irving, William L
Ball, Jonathan K
Tarr, Alexander W
MetadataShow full item record
AbstractDespite significant advances in the treatment of hepatitis C virus (HCV) infection, the need to develop preventative vaccines remains. Identification of the best vaccine candidates and evaluation of their performance in preclinical and clinical development will require appropriate neutralization assays utilizing diverse HCV isolates. We aimed to generate and characterize a panel of HCV E1E2 glycoproteins suitable for subsequent use in vaccine and therapeutic antibody testing. Full-length E1E2 clones were PCR amplified from patient-derived serum samples, cloned into an expression vector, and used to generate viral pseudoparticles (HCVpp). In addition, some of these clones were used to generate cell culture infectious (HCVcc) clones. The infectivity and neutralization sensitivity of these viruses were then determined. Bioinformatic and HCVpp infectivity screening of approximately 900 E1E2 clones resulted in the assembly of a panel of 78 functional E1E2 proteins representing distinct HCV genotypes and different stages of infection. These HCV glycoproteins differed markedly in their sensitivity to neutralizing antibodies. We used this panel to predict antibody efficacy against circulating HCV strains, highlighting the likely reason why some monoclonal antibodies failed in previous clinical trials. This study provides the first objective categorization of cross-genotype patient-derived HCV E1E2 clones according to their sensitivity to antibody neutralization. It has shown that HCV isolates have clearly distinguishable neutralization-sensitive, -resistant, or -intermediate phenotypes, which are independent of genotype. The panel provides a systematic means for characterization of the neutralizing response elicited by candidate vaccines and for defining the therapeutic potential of monoclonal antibodies.
CitationA Diverse Panel of Hepatitis C Virus Glycoproteins for Use in Vaccine Research Reveals Extremes of Monoclonal Antibody Neutralization Resistance. 2015, 90 (7):3288-301 J. Virol.
AffiliationTwincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany.
JournalJournal of virology
The following license files are associated with this item:
- Hepatitis C virus resistance to broadly neutralizing antibodies measured using replication-competent virus and pseudoparticles.
- Authors: Wasilewski LN, Ray SC, Bailey JR
- Issue date: 2016 Nov
- N-glycosylation-mutated HCV envelope glycoprotein complex enhances antigen-presenting activity and cellular and neutralizing antibody responses.
- Authors: Ren Y, Min YQ, Liu M, Chi L, Zhao P, Zhang XL
- Issue date: 2016 Aug
- Native Folding of a Recombinant gpE1/gpE2 Heterodimer Vaccine Antigen from a Precursor Protein Fused with Fc IgG.
- Authors: Logan M, Law J, Wong JA, Hockman D, Landi A, Chen C, Crawford K, Kundu J, Baldwin L, Johnson J, Dahiya A, LaChance G, Marcotrigiano J, Law M, Foung S, Tyrrell L, Houghton M
- Issue date: 2017 Jan 1
- Escape of Hepatitis C Virus from Epitope I Neutralization Increases Sensitivity of Other Neutralization Epitopes.
- Authors: Gu J, Hardy J, Boo I, Vietheer P, McCaffrey K, Alhammad Y, Chopra A, Gaudieri S, Poumbourios P, Coulibaly F, Drummer HE
- Issue date: 2018 May 1
- Hepatitis C patient-derived glycoproteins exhibit marked differences in susceptibility to serum neutralizing antibodies: genetic subtype defines antigenic but not neutralization serotype.
- Authors: Tarr AW, Urbanowicz RA, Hamed MR, Albecka A, McClure CP, Brown RJ, Irving WL, Dubuisson J, Ball JK
- Issue date: 2011 May