The S. aureus 4-oxalocrotonate tautomerase SAR1376 enhances immune responses when fused to several antigens

Abstract A persistent goal of vaccine development is the enhancement of the immunogenicity of antigens while maintaining safety. One strategy involves alteration of the presentation of the antigen by combining antigens with a multimeric scaffold. Multi-antigen vaccines are under development, and the...

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Autores principales:	Pauline M. van Diemen, Darren B. Leneghan, Iona J. Brian, Kazutoyo Miura, Carole A. Long, Anita Milicic, Sumi Biswas, Christine S. Rollier, David H. Wyllie
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9486e757e39243498c51768ecb873839
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spelling	oai:doaj.org-article:9486e757e39243498c51768ecb8738392021-12-02T12:32:40ZThe S. aureus 4-oxalocrotonate tautomerase SAR1376 enhances immune responses when fused to several antigens10.1038/s41598-017-01421-z2045-2322https://doaj.org/article/9486e757e39243498c51768ecb8738392017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01421-zhttps://doaj.org/toc/2045-2322Abstract A persistent goal of vaccine development is the enhancement of the immunogenicity of antigens while maintaining safety. One strategy involves alteration of the presentation of the antigen by combining antigens with a multimeric scaffold. Multi-antigen vaccines are under development, and there are presently far more candidate antigens than antigen scaffolding strategies. This is potentially problematic, since prior immunity to a scaffold may inhibit immune responses to the antigen-scaffold combination. In this study, a series of domains from S. aureus which have been shown to crystallise into multimeric structures have been examined for their scaffolding potential. Of these domains, SAR1376, a 62 amino acid member of the 4-oxalocrotonate tautomerase (4-OT) family, was pro-immunogenic in mice when fused to a range of pathogen antigens from both S. aureus and P. falciparum, and delivered by either DNA vaccination, viral vector vaccines or as protein-in-adjuvant formulations. The adjuvant effect did not depend on enzymatic activity, but was abrogated by mutations disrupting the hexameric structure of the protein. We therefore propose that SAR1376, and perhaps other members of the 4-OT protein family, represent very small domains which can be fused to a wide range of antigens, enhancing immune responses against them.Pauline M. van DiemenDarren B. LeneghanIona J. BrianKazutoyo MiuraCarole A. LongAnita MilicicSumi BiswasChristine S. RollierDavid H. WyllieNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pauline M. van Diemen Darren B. Leneghan Iona J. Brian Kazutoyo Miura Carole A. Long Anita Milicic Sumi Biswas Christine S. Rollier David H. Wyllie The S. aureus 4-oxalocrotonate tautomerase SAR1376 enhances immune responses when fused to several antigens
description	Abstract A persistent goal of vaccine development is the enhancement of the immunogenicity of antigens while maintaining safety. One strategy involves alteration of the presentation of the antigen by combining antigens with a multimeric scaffold. Multi-antigen vaccines are under development, and there are presently far more candidate antigens than antigen scaffolding strategies. This is potentially problematic, since prior immunity to a scaffold may inhibit immune responses to the antigen-scaffold combination. In this study, a series of domains from S. aureus which have been shown to crystallise into multimeric structures have been examined for their scaffolding potential. Of these domains, SAR1376, a 62 amino acid member of the 4-oxalocrotonate tautomerase (4-OT) family, was pro-immunogenic in mice when fused to a range of pathogen antigens from both S. aureus and P. falciparum, and delivered by either DNA vaccination, viral vector vaccines or as protein-in-adjuvant formulations. The adjuvant effect did not depend on enzymatic activity, but was abrogated by mutations disrupting the hexameric structure of the protein. We therefore propose that SAR1376, and perhaps other members of the 4-OT protein family, represent very small domains which can be fused to a wide range of antigens, enhancing immune responses against them.
format	article
author	Pauline M. van Diemen Darren B. Leneghan Iona J. Brian Kazutoyo Miura Carole A. Long Anita Milicic Sumi Biswas Christine S. Rollier David H. Wyllie
author_facet	Pauline M. van Diemen Darren B. Leneghan Iona J. Brian Kazutoyo Miura Carole A. Long Anita Milicic Sumi Biswas Christine S. Rollier David H. Wyllie
author_sort	Pauline M. van Diemen
title	The S. aureus 4-oxalocrotonate tautomerase SAR1376 enhances immune responses when fused to several antigens
title_short	The S. aureus 4-oxalocrotonate tautomerase SAR1376 enhances immune responses when fused to several antigens
title_full	The S. aureus 4-oxalocrotonate tautomerase SAR1376 enhances immune responses when fused to several antigens
title_fullStr	The S. aureus 4-oxalocrotonate tautomerase SAR1376 enhances immune responses when fused to several antigens
title_full_unstemmed	The S. aureus 4-oxalocrotonate tautomerase SAR1376 enhances immune responses when fused to several antigens
title_sort	s. aureus 4-oxalocrotonate tautomerase sar1376 enhances immune responses when fused to several antigens
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9486e757e39243498c51768ecb873839
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The S. aureus 4-oxalocrotonate tautomerase SAR1376 enhances immune responses when fused to several antigens

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