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)

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, Ms Sarah
• 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
65649	1	Basis of the host range and tissue tropism for hepatitis C virus	Arvind Patel	Medical Research Council (MRC)	MC_UU_12014/2	MVLS III - CENTRE FOR VIRUS RESEARCH