Rational engineering of recombinant picornavirus capsids to produce safe, protective vaccine antigen.

Foot-and-mouth disease remains a major plague of livestock and outbreaks are often economically catastrophic. Current inactivated virus vaccines require expensive high containment facilities for their production and maintenance of a cold-chain for their activity. We have addressed both of these majo...

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Autores principales:	Claudine Porta, Abhay Kotecha, Alison Burman, Terry Jackson, Jingshan Ren, Silvia Loureiro, Ian M Jones, Elizabeth E Fry, David I Stuart, Bryan Charleston
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/fc4b6b80395249348ee566851c53b6d1
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spelling	oai:doaj.org-article:fc4b6b80395249348ee566851c53b6d12021-11-18T06:05:52ZRational engineering of recombinant picornavirus capsids to produce safe, protective vaccine antigen.1553-73661553-737410.1371/journal.ppat.1003255https://doaj.org/article/fc4b6b80395249348ee566851c53b6d12013-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23544011/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Foot-and-mouth disease remains a major plague of livestock and outbreaks are often economically catastrophic. Current inactivated virus vaccines require expensive high containment facilities for their production and maintenance of a cold-chain for their activity. We have addressed both of these major drawbacks. Firstly we have developed methods to efficiently express recombinant empty capsids. Expression constructs aimed at lowering the levels and activity of the viral protease required for the cleavage of the capsid protein precursor were used; this enabled the synthesis of empty A-serotype capsids in eukaryotic cells at levels potentially attractive to industry using both vaccinia virus and baculovirus driven expression. Secondly we have enhanced capsid stability by incorporating a rationally designed mutation, and shown by X-ray crystallography that stabilised and wild-type empty capsids have essentially the same structure as intact virus. Cattle vaccinated with recombinant capsids showed sustained virus neutralisation titres and protection from challenge 34 weeks after immunization. This approach to vaccine antigen production has several potential advantages over current technologies by reducing production costs, eliminating the risk of infectivity and enhancing the temperature stability of the product. Similar strategies that will optimize host cell viability during expression of a foreign toxic gene and/or improve capsid stability could allow the production of safe vaccines for other pathogenic picornaviruses of humans and animals.Claudine PortaAbhay KotechaAlison BurmanTerry JacksonJingshan RenSilvia LoureiroIan M JonesElizabeth E FryDavid I StuartBryan CharlestonPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 3, p e1003255 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Claudine Porta Abhay Kotecha Alison Burman Terry Jackson Jingshan Ren Silvia Loureiro Ian M Jones Elizabeth E Fry David I Stuart Bryan Charleston Rational engineering of recombinant picornavirus capsids to produce safe, protective vaccine antigen.
description	Foot-and-mouth disease remains a major plague of livestock and outbreaks are often economically catastrophic. Current inactivated virus vaccines require expensive high containment facilities for their production and maintenance of a cold-chain for their activity. We have addressed both of these major drawbacks. Firstly we have developed methods to efficiently express recombinant empty capsids. Expression constructs aimed at lowering the levels and activity of the viral protease required for the cleavage of the capsid protein precursor were used; this enabled the synthesis of empty A-serotype capsids in eukaryotic cells at levels potentially attractive to industry using both vaccinia virus and baculovirus driven expression. Secondly we have enhanced capsid stability by incorporating a rationally designed mutation, and shown by X-ray crystallography that stabilised and wild-type empty capsids have essentially the same structure as intact virus. Cattle vaccinated with recombinant capsids showed sustained virus neutralisation titres and protection from challenge 34 weeks after immunization. This approach to vaccine antigen production has several potential advantages over current technologies by reducing production costs, eliminating the risk of infectivity and enhancing the temperature stability of the product. Similar strategies that will optimize host cell viability during expression of a foreign toxic gene and/or improve capsid stability could allow the production of safe vaccines for other pathogenic picornaviruses of humans and animals.
format	article
author	Claudine Porta Abhay Kotecha Alison Burman Terry Jackson Jingshan Ren Silvia Loureiro Ian M Jones Elizabeth E Fry David I Stuart Bryan Charleston
author_facet	Claudine Porta Abhay Kotecha Alison Burman Terry Jackson Jingshan Ren Silvia Loureiro Ian M Jones Elizabeth E Fry David I Stuart Bryan Charleston
author_sort	Claudine Porta
title	Rational engineering of recombinant picornavirus capsids to produce safe, protective vaccine antigen.
title_short	Rational engineering of recombinant picornavirus capsids to produce safe, protective vaccine antigen.
title_full	Rational engineering of recombinant picornavirus capsids to produce safe, protective vaccine antigen.
title_fullStr	Rational engineering of recombinant picornavirus capsids to produce safe, protective vaccine antigen.
title_full_unstemmed	Rational engineering of recombinant picornavirus capsids to produce safe, protective vaccine antigen.
title_sort	rational engineering of recombinant picornavirus capsids to produce safe, protective vaccine antigen.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/fc4b6b80395249348ee566851c53b6d1
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Rational engineering of recombinant picornavirus capsids to produce safe, protective vaccine antigen.

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