Development of a structural epitope mimic: an idiotypic approach to HCV vaccine design

Cowton, V. M. et al. (2021) Development of a structural epitope mimic: an idiotypic approach to HCV vaccine design. npj Vaccines, 6, 7. (doi: 10.1038/s41541-020-00269-1) (PMID:33420102) (PMCID:PMC7794244)

Abstract

HCV vaccine development is stymied by the high genetic diversity of the virus and the variability of the envelope glycoproteins. One strategy to overcome this is to identify conserved, functionally important regions—such as the epitopes of broadly neutralizing antibodies (bNAbs)—and use these as a basis for structure-based vaccine design. Here, we report an anti-idiotype approach that has generated an antibody that mimics a highly conserved neutralizing epitope on HCV E2. Crucially, a mutagenesis screen was used to identify the antibody, designated B2.1 A, whose binding characteristics to the bNAb AP33 closely resemble those of the original antigen. Protein crystallography confirmed that B2.1 A is a structural mimic of the AP33 epitope. When used as an immunogen B2.1 A induced antibodies that recognized the same epitope and E2 residues as AP33 and most importantly protected against HCV challenge in a mouse model.

• Item Type: Articles
• Additional Information: This work was supported by Medical Research Council grant MC_UU12014/2 and DPFS Grant MC_EX_G0801770 awarded to AHP, and by a studentship to VF from the Programma Master and Back, Regione Autonoma della Sardegna. This study was supported by funding from a Wellcome Trust New Investigator award to MD (104771/Z/14/Z) and a starting grant from the European Research Council to MD (ERC-StG-2015-637304).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cowton, Dr Vanessa and Di Lorenzo, Miss Caterina and Cole, Ms Sarah and Owsianka, Dr Anna and Patel, Professor Arvind
• Authors: Cowton, V. M., Owsianka, A. M., Fadda, V., Ortega-Prieto, A. M., Cole, S. J., Potter, J. A., Skelton, J. K., Jeffrey, N., Di Lorenzo, C., Dorner, M., Taylor, G. L., and Patel, A. H.
• 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: npj Vaccines
• Publisher: Nature Research
• ISSN: 2059-0105
• ISSN (Online): 2059-0105
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in npj Vaccines 6: 7
• Publisher Policy: Reproduced under a Creative Commons License
• Data DOI: 10.2210/pdb6SXI/pdb

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