An antigenically diverse, representative panel of envelope glycoproteins for HCV vaccine development

Salas, J. H. et al. (2022) An antigenically diverse, representative panel of envelope glycoproteins for HCV vaccine development. Gastroenterology, 162(2), pp. 562-574. (doi: 10.1053/j.gastro.2021.10.005) (PMID:34655573) (PMCID:PMC8792218)

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Abstract

Background and Aims: Development of a prophylactic hepatitis C virus (HCV) vaccine will require accurate and reproducible measurement of neutralizing breadth of vaccine-induced antibodies. Currently available HCV panels may not adequately represent the genetic and antigenic diversity of circulating HCV strains, and the lack of standardization of these panels makes it difficult to compare neutralization results obtained in different studies. Here, we describe the selection and validation of a genetically and antigenically diverse reference panel of 15 HCV pseudoparticles (HCVpp) for neutralization assays. Methods: We chose 75 envelope (E1E2) clones to maximize representation of natural polymorphisms observed in circulating HCV isolates, and 65 of these clones generated functional HCVpp. Neutralization sensitivity of these HCVpp varied widely. HCVpp clustered into 15 distinct groups based on patterns of relative sensitivity to seven broadly neutralizing monoclonal antibodies (bNAbs). We used these data to select a final panel of 15 antigenically representative HCVpp. Results: Both the 65 and 15 HCVpp panels span four tiers of neutralization sensitivity, and neutralizing breadth measurements for seven bNAbs were nearly equivalent using either panel. Differences in neutralization sensitivity between HCVpp were independent of genetic distances between E1E2 clones. Conclusions: Neutralizing breadth of HCV antibodies should be defined using viruses spanning multiple tiers of neutralization sensitivity, rather than panels selected solely for genetic diversity. We propose that this multi-tier reference panel could be adopted as a standard for the measurement of neutralizing antibody potency and breadth, facilitating meaningful comparisons of neutralization results from vaccine studies in different laboratories.

Item Type:Articles
Additional Information:JRB is supported by NIH grants AI127469 and AI088791. ML is supported by the NIH grants AI079031 and AI123861. SF is supported by NIH grant AI123862. TRF, BGP, and SF are supported by NIH grant AI132213, and TRF and BGP are supported by NIH grant AI144083. JB, AT, and RU are supported by Medical Research Council [grant number MR/R010307/1]. AHP, VMC, and SJC are supported by the UK Medical Research Council grant MC_UU12014/2. JDG was supported by a graduate training grant (NIH T32 AI125186).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cowton, Dr Vanessa and Cole, Mrs Sarah and Patel, Professor Arvind
Authors: Salas, J. H., Urbanowicz, R. A., Guest, J. D., Frumento, N., Figueroa, A., Clark, K. E., Keck, Z., Cowton, V. M., Cole, S. J., Patel, A. H., Fuerst, T. R., Drummer, H. E., Major, M., Tarr, A. W., Ball, J. K., Law, M., Pierce, B. G., Foung, S. K.H., and Bailey, J. R.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Gastroenterology
Publisher:Elsevier
ISSN:0016-5085
ISSN (Online):1528-0012
Published Online:13 October 2021
Copyright Holders:Copyright © 2021 Elsevier
First Published:First published in Gastroenterology 162(2): 562-574
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656491Basis of the host range and tissue tropism for hepatitis C virusArvind PatelMedical Research Council (MRC)MC_UU_12014/2MVLS III - CENTRE FOR VIRUS RESEARCH