Functional and immunogenic characterization of diverse HCV glycoprotein E2 variants.
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
Brown, Richard J P
Ghafoor Khan, Abdul
Wong, Jason Alexander Ji-Xhin
Tarr, Alexander W
Manns, Michael P
Guzman, Carlos A
MetadataShow full item record
AbstractInduction of cross-reactive antibodies targeting conserved epitopes of the envelope proteins E1E2 is a key requirement for an HCV vaccine. Conserved epitopes like the viral CD81-binding site are targeted by rare broadly neutralizing antibodies. However, these viral segments are occluded by variable regions and glycans. We aimed to identify antigens exposing conserved epitopes and to characterize their immunogenicity. We created HCV variants with mutated glycosylation sites and/or hypervariable region 1 (HVR1). Exposure of the CD81 binding site and conserved epitopes was quantified by soluble CD81 and antibody interaction and neutralization assays. E2 or E1-E2 heterodimers with mutations causing epitope exposure were used to immunize mice. Vaccine-induced antibodies were examined and compared with patient-derived antibodies. Mutant viruses bound soluble CD81 and antibodies targeting the CD81 binding site with enhanced efficacy. Mice immunized with E2 or E1E2 heterodimers incorporating these modifications mounted strong, cross-binding, and non-interfering antibodies. E2-induced antibodies neutralized the autologous virus but they were not cross-neutralizing. Viruses lacking the HVR1 and selected glycosylation sites expose the CD81 binding site and cross-neutralization antibody epitopes. Recombinant E2 proteins carrying these modifications induce strong cross-binding but not cross-neutralizing antibodies.
AffiliationTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany; HZI, Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7 38124 Braunschweig, Germany.
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Fine mapping of murine antibody responses to immunization with a novel soluble form of hepatitis C virus envelope glycoprotein complex.
- Authors: Ruwona TB, Giang E, Nieusma T, Law M
- Issue date: 2014 Sep
- Antigenicity and Immunogenicity of Differentially Glycosylated Hepatitis C Virus E2 Envelope Proteins Expressed in Mammalian and Insect Cells.
- Authors: Urbanowicz RA, Wang R, Schiel JE, Keck ZY, Kerzic MC, Lau P, Rangarajan S, Garagusi KJ, Tan L, Guest JD, Ball JK, Pierce BG, Mariuzza RA, Foung SKH, Fuerst TR
- Issue date: 2019 Apr 1
- Structure-Based Design of Hepatitis C Virus E2 Glycoprotein Improves Serum Binding and Cross-Neutralization.
- Authors: Pierce BG, Keck ZY, Wang R, Lau P, Garagusi K, Elkholy K, Toth EA, Urbanowicz RA, Guest JD, Agnihotri P, Kerzic MC, Marin A, Andrianov AK, Ball JK, Mariuzza RA, Fuerst TR, Foung SKH
- Issue date: 2020 Oct 27
- Role of the E2 Hypervariable Region (HVR1) in the Immunogenicity of a Recombinant Hepatitis C Virus Vaccine.
- Authors: Law JLM, Logan M, Wong J, Kundu J, Hockman D, Landi A, Chen C, Crawford K, Wininger M, Johnson J, Mesa Prince C, Dudek E, Mehta N, Tyrrell DL, Houghton M
- Issue date: 2018 Jun 1
- Native Folding of a Recombinant gpE1/gpE2 Heterodimer Vaccine Antigen from a Precursor Protein Fused with Fc IgG.
- Authors: Logan M, Law J, Wong JAJ, 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