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

DOI: 10.1038/s41541-020-00269-1 DOI Help

Authors: Vanessa M. Cowton (MRC-University of Glasgow Centre for Virus Research) , Ania M. Owsianka (MRC-University of Glasgow Centre for Virus Research) , Valeria Fadda (University of St. Andrews) , Ana Maria Ortega-prieto (Imperial College London) , Sarah J. Cole (MRC-University of Glasgow Centre for Virus Research) , Jane A. Potter (University of St. Andrews) , Jessica K. Skelton (Imperial College London) , Nathan Jeffrey (MRC-University of Glasgow Centre for Virus Research) , Caterina Di Lorenzo (MRC-University of Glasgow Centre for Virus Research) , Marcus Dorner (Imperial College London) , Garry L. Taylor (University of St. Andrews) , Arvind H. Patel (MRC-University of Glasgow Centre for Virus Research)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Npj Vaccines , VOL 6

State: Published (Approved)
Published: January 2021
Diamond Proposal Number(s): 10071

Open Access Open Access

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.

Journal Keywords: Diseases; Immunology; Microbiology

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I03-Macromolecular Crystallography

Documents:
s41541-020-00269-1.pdf