Design and synthesis of HCV-E2 glycoprotein epitope mimics in the molecular construction of potential as synthetic vaccines

Meuleman, T. J., Cowton, V. M., Patel, A. H. and Liskamp, R. M.J. (2021) Design and synthesis of HCV-E2 glycoprotein epitope mimics in the molecular construction of potential as synthetic vaccines. Viruses, 13(2), 326. (doi: 10.3390/v13020326) (PMID:33672697) (PMCID:PMC7924389)

Abstract

Hepatitis C virus remains a global threat, despite the availability of highly effective direct-acting antiviral (DAA) drugs. With thousands of new infections annually, the need for a prophylactic vaccine is evident. However, traditional vaccine design has been unable to provide effective vaccines so far. Therefore, alternative strategies need to be investigated. In this work, a chemistry-based approach is explored towards fully synthetic peptide-based vaccines using epitope mimicry, by focusing on highly effective and conserved amino acid sequences in HCV, which, upon antibody binding, inhibit its bio-activity. Continuous and discontinuous epitope mimics were both chemically synthesized based on the HCV-E2 glycoprotein while using designed fully synthetic cyclic peptides. These cyclic epitope mimics were assembled on an orthogonally protected scaffold. The scaffolded epitope mimics have been assessed in immunization experiments to investigate the elicitation of anti-HCV-E2 glycoprotein antibodies. The neutralizing potential of the elicited antibodies was investigated, representing a first step in employing chemically synthesized epitope mimics as a novel strategy towards vaccine design.

• Item Type: Articles
• Additional Information: This work was supported by Medical Research Council grant MC_UU12014/2 awarded to A.H.P., and by the University of Glasgow for a PhD studentship to T.J.M. and R.M.J.L.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Liskamp, Professor Robert and Cowton, Dr Vanessa and Meuleman, Theodorus and Patel, Professor Arvind
• Authors: Meuleman, T. J., Cowton, V. M., Patel, A. H., and Liskamp, R. M.J.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Science and Engineering > School of Chemistry; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Viruses
• Publisher: MDPI
• ISSN: 1999-4915
• ISSN (Online): 1999-4915
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published Viruses 13(2):326
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
				Medical Research Council (MRC)	MC_UU12014/2