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

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 the...

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Autores principales:	Vanessa M. Cowton, Ania M. Owsianka, Valeria Fadda, Ana Maria Ortega-Prieto, Sarah J. Cole, Jane A. Potter, Jessica K. Skelton, Nathan Jeffrey, Caterina Di Lorenzo, Marcus Dorner, Garry L. Taylor, Arvind H. Patel
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/a3e8c908a1e3414390d0657b55f1aeda
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spelling	oai:doaj.org-article:a3e8c908a1e3414390d0657b55f1aeda2021-12-02T11:56:23ZDevelopment of a structural epitope mimic: an idiotypic approach to HCV vaccine design10.1038/s41541-020-00269-12059-0105https://doaj.org/article/a3e8c908a1e3414390d0657b55f1aeda2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41541-020-00269-1https://doaj.org/toc/2059-0105Abstract 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.Vanessa M. CowtonAnia M. OwsiankaValeria FaddaAna Maria Ortega-PrietoSarah J. ColeJane A. PotterJessica K. SkeltonNathan JeffreyCaterina Di LorenzoMarcus DornerGarry L. TaylorArvind H. PatelNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Vanessa M. Cowton Ania M. Owsianka Valeria Fadda Ana Maria Ortega-Prieto Sarah J. Cole Jane A. Potter Jessica K. Skelton Nathan Jeffrey Caterina Di Lorenzo Marcus Dorner Garry L. Taylor Arvind H. Patel Development of a structural epitope mimic: an idiotypic approach to HCV vaccine design
description	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.
format	article
author	Vanessa M. Cowton Ania M. Owsianka Valeria Fadda Ana Maria Ortega-Prieto Sarah J. Cole Jane A. Potter Jessica K. Skelton Nathan Jeffrey Caterina Di Lorenzo Marcus Dorner Garry L. Taylor Arvind H. Patel
author_facet	Vanessa M. Cowton Ania M. Owsianka Valeria Fadda Ana Maria Ortega-Prieto Sarah J. Cole Jane A. Potter Jessica K. Skelton Nathan Jeffrey Caterina Di Lorenzo Marcus Dorner Garry L. Taylor Arvind H. Patel
author_sort	Vanessa M. Cowton
title	Development of a structural epitope mimic: an idiotypic approach to HCV vaccine design
title_short	Development of a structural epitope mimic: an idiotypic approach to HCV vaccine design
title_full	Development of a structural epitope mimic: an idiotypic approach to HCV vaccine design
title_fullStr	Development of a structural epitope mimic: an idiotypic approach to HCV vaccine design
title_full_unstemmed	Development of a structural epitope mimic: an idiotypic approach to HCV vaccine design
title_sort	development of a structural epitope mimic: an idiotypic approach to hcv vaccine design
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a3e8c908a1e3414390d0657b55f1aeda
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Development of a structural epitope mimic: an idiotypic approach to HCV vaccine design

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