Antigenicity of key hepatitis C virus E1E2 glycoprotein neutralizing sites is genotype independent

The development of an effective prophylactic hepatitis C virus (HCV) vaccine is a priority to achieve global elimination of the virus. Accurate assessment of the neutralizing breadth of antibodies induced by vaccines and a clear understanding of the antigenic differences between viral variants included in vaccines are both critical for vaccine development. Prior studies have indicated that HCV genotypes (gts) do not dictate the sensitivity of HCV envelope glycoprotein (E1E2) variants to neutralizing antibodies. However, most of these prior studies under-sampled variants from gts 2-6. Here, we selected a genetically diverse and representative panel of gt 2-6 E1E2 variants, used them to generate HCV pseudoparticles (HCVpp), and measured neutralization of these HCVpp by neutralizing antibodies and HCV-immune plasma from persons infected with gt 1-6 viruses. We found that neutralization results obtained with this gt 2-6 panel were remarkably similar to results obtained with a previously described, antigenically diverse, gt 1-predominant reference panel of 15 HCVpp. These data confirm that, even considering genetically diverse HCV variants across gt 1-6, E1E2 antigenicity is not dictated by gt, and that the previously published panel of 15 HCVpp represents neutralization of all HCV gts with reasonable accuracy.

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Publication Details

Journal
Journal of General Virology
Published
2026-01-13
DOI
https://doi.org/10.1099/jgv.0.002201
Primary Topic
Hepatitis C virus research
Type
article
Field-Weighted Citation Impact
0.00

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article

Antigenicity of key hepatitis C virus E1E2 glycoprotein neutralizing sites is genotype independent

Richard A. Urbanowicz, Justin R. Bailey, Mansun Law, Alexander W. Tarr et al.
Journal of General Virology
Hepatitis C virus research
article

Antigenicity of key hepatitis C virus E1E2 glycoprotein neutralizing sites is genotype independent

Richard A. Urbanowicz, Justin R. Bailey, Mansun Law, Alexander W. Tarr, Nicole Frumento, Brian G. Pierce, Arvind H. Patel, Nathaniel Felbinger, Ariadne Sinnis-Bourozikas, Jessica Mimms, Harry T. Paul, Zhenyong Keck, Jonathan K. Ball
article en

Abstract

The development of an effective prophylactic hepatitis C virus (HCV) vaccine is a priority to achieve global elimination of the virus. Accurate assessment of the neutralizing breadth of antibodies induced by vaccines and a clear understanding of the antigenic differences between viral variants included in vaccines are both critical for vaccine development. Prior studies have indicated that HCV genotypes (gts) do not dictate the sensitivity of HCV envelope glycoprotein (E1E2) variants to neutralizing antibodies. However, most of these prior studies under-sampled variants from gts 2-6. Here, we selected a genetically diverse and representative panel of gt 2-6 E1E2 variants, used them to generate HCV pseudoparticles (HCVpp), and measured neutralization of these HCVpp by neutralizing antibodies and HCV-immune plasma from persons infected with gt 1-6 viruses. We found that neutralization results obtained with this gt 2-6 panel were remarkably similar to results obtained with a previously described, antigenically diverse, gt 1-predominant reference panel of 15 HCVpp. These data confirm that, even considering genetically diverse HCV variants across gt 1-6, E1E2 antigenicity is not dictated by gt, and that the previously published panel of 15 HCVpp represents neutralization of all HCV gts with reasonable accuracy.

Journal of General VirologyVol. 107(1)
Scripps Research Institute (US), University of Maryland, Baltimore (US), National Institute of Standards and Technology (US), Nottingham University Hospitals NHS Trust (GB), University of Nottingham (GB), Johns Hopkins University (US), University of Liverpool (GB), Liverpool School of Tropical Medicine (GB), Johns Hopkins Medicine (US), University of Oxford (GB), Medawar Building for Pathogen Research (GB), MRC University of Glasgow Centre for Virus Research (GB), Nottingham Biomedical Research Centre (GB), Institute for Bioscience and Biotechnology Research, University of Maryland, College Park (US), Stanford University (US)
Johns Hopkins University, Nottingham University Hospitals NHS Trust, National Institute for Health and Care Research, University of Oxford, University of Nottingham, University of Glasgow, School of Medicine, Stanford University, Johns Hopkins Bloomberg School of Public Health, Medical Research Council, NIHR Nottingham Biomedical Research Centre, Faculty of Medicine and Health, University of Sydney
Good health and well-being
Openalex Percentile: Top 89%
Hepatitis C virus research
DOIOpen Access PDFOpenAlex
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