St Andrews Research Repository

St Andrews University Home
View Item 
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  • Register / Login
JavaScript is disabled for your browser. Some features of this site may not work without it.

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

Thumbnail
View/Open
Cowton_2021_Development_of_a_structural_npjVaccines_7_CCBY.pdf (1.223Mb)
Date
08/01/2021
Author
Cowton, Vanessa M.
Owsianka, Ania M.
Fadda, Valeria
Ortega-Prieto, Ana Maria
Cole, Sarah J.
Potter, Jane A.
Skelton, Jessica K.
Jeffrey, Nathan
Di Lorenzo, Caterina
Dorner, Marcus
Taylor, Garry L.
Patel, Arvind H.
Keywords
QR355 Virology
RM Therapeutics. Pharmacology
DAS
SDG 3 - Good Health and Well-being
Metadata
Show full item record
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.
Citation
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 & Patel , A H 2021 , ' Development of a structural epitope mimic : an idiotypic approach to HCV vaccine design ' , npj Vaccines , vol. 6 , 7 . https://doi.org/10.1038/s41541-020-00269-1
Publication
npj Vaccines
Status
Peer reviewed
DOI
https://doi.org/10.1038/s41541-020-00269-1
ISSN
2059-0105
Type
Journal article
Rights
Copyright © The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Description
Funding: 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).
Collections
  • University of St Andrews Research
URI
http://hdl.handle.net/10023/21319

Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.

Advanced Search

Browse

All of RepositoryCommunities & CollectionsBy Issue DateNamesTitlesSubjectsClassificationTypeFunderThis CollectionBy Issue DateNamesTitlesSubjectsClassificationTypeFunder

My Account

Login

Open Access

To find out how you can benefit from open access to research, see our library web pages and Open Access blog. For open access help contact: openaccess@st-andrews.ac.uk.

Accessibility

Read our Accessibility statement.

How to submit research papers

The full text of research papers can be submitted to the repository via Pure, the University's research information system. For help see our guide: How to deposit in Pure.

Electronic thesis deposit

Help with deposit.

Repository help

For repository help contact: Digital-Repository@st-andrews.ac.uk.

Give Feedback

Cookie policy

This site may use cookies. Please see Terms and Conditions.

Usage statistics

COUNTER-compliant statistics on downloads from the repository are available from the IRUS-UK Service. Contact us for information.

© University of St Andrews Library

University of St Andrews is a charity registered in Scotland, No SC013532.

  • Facebook
  • Twitter