Mammalian expression of virus-like particles as a proof of principle for next generation polio vaccines

Abstract Global vaccination programs using live-attenuated oral and inactivated polio vaccine (OPV and IPV) have almost eradicated poliovirus (PV) but these vaccines or their production pose significant risk in a polio-free world. Recombinant PV virus-like particles (VLPs), lacking the viral genome,...

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Autores principales:	Mohammad W. Bahar, Claudine Porta, Helen Fox, Andrew J. Macadam, Elizabeth E. Fry, David I. Stuart
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/6d14a9581b7346d2a0e7c0c7fcf06ddd
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spelling	oai:doaj.org-article:6d14a9581b7346d2a0e7c0c7fcf06ddd2021-12-02T11:56:23ZMammalian expression of virus-like particles as a proof of principle for next generation polio vaccines10.1038/s41541-020-00267-32059-0105https://doaj.org/article/6d14a9581b7346d2a0e7c0c7fcf06ddd2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41541-020-00267-3https://doaj.org/toc/2059-0105Abstract Global vaccination programs using live-attenuated oral and inactivated polio vaccine (OPV and IPV) have almost eradicated poliovirus (PV) but these vaccines or their production pose significant risk in a polio-free world. Recombinant PV virus-like particles (VLPs), lacking the viral genome, represent safe next-generation vaccines, however their production requires optimisation. Here we present an efficient mammalian expression strategy producing good yields of wild-type PV VLPs for all three serotypes and a thermostabilised variant for PV3. Whilst the wild-type VLPs were predominantly in the non-native C-antigenic form, the thermostabilised PV3 VLPs adopted the native D-antigenic conformation eliciting neutralising antibody titres equivalent to the current IPV and were indistinguishable from natural empty particles by cryo-electron microscopy with a similar stabilising lipidic pocket-factor in the VP1 β-barrel. This factor may not be available in alternative expression systems, which may require synthetic pocket-binding factors. VLPs equivalent to these mammalian expressed thermostabilized particles, represent safer non-infectious vaccine candidates for the post-eradication era.Mohammad W. BaharClaudine PortaHelen FoxAndrew J. MacadamElizabeth E. FryDavid I. StuartNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-11 (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 Mohammad W. Bahar Claudine Porta Helen Fox Andrew J. Macadam Elizabeth E. Fry David I. Stuart Mammalian expression of virus-like particles as a proof of principle for next generation polio vaccines
description	Abstract Global vaccination programs using live-attenuated oral and inactivated polio vaccine (OPV and IPV) have almost eradicated poliovirus (PV) but these vaccines or their production pose significant risk in a polio-free world. Recombinant PV virus-like particles (VLPs), lacking the viral genome, represent safe next-generation vaccines, however their production requires optimisation. Here we present an efficient mammalian expression strategy producing good yields of wild-type PV VLPs for all three serotypes and a thermostabilised variant for PV3. Whilst the wild-type VLPs were predominantly in the non-native C-antigenic form, the thermostabilised PV3 VLPs adopted the native D-antigenic conformation eliciting neutralising antibody titres equivalent to the current IPV and were indistinguishable from natural empty particles by cryo-electron microscopy with a similar stabilising lipidic pocket-factor in the VP1 β-barrel. This factor may not be available in alternative expression systems, which may require synthetic pocket-binding factors. VLPs equivalent to these mammalian expressed thermostabilized particles, represent safer non-infectious vaccine candidates for the post-eradication era.
format	article
author	Mohammad W. Bahar Claudine Porta Helen Fox Andrew J. Macadam Elizabeth E. Fry David I. Stuart
author_facet	Mohammad W. Bahar Claudine Porta Helen Fox Andrew J. Macadam Elizabeth E. Fry David I. Stuart
author_sort	Mohammad W. Bahar
title	Mammalian expression of virus-like particles as a proof of principle for next generation polio vaccines
title_short	Mammalian expression of virus-like particles as a proof of principle for next generation polio vaccines
title_full	Mammalian expression of virus-like particles as a proof of principle for next generation polio vaccines
title_fullStr	Mammalian expression of virus-like particles as a proof of principle for next generation polio vaccines
title_full_unstemmed	Mammalian expression of virus-like particles as a proof of principle for next generation polio vaccines
title_sort	mammalian expression of virus-like particles as a proof of principle for next generation polio vaccines
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6d14a9581b7346d2a0e7c0c7fcf06ddd
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Mammalian expression of virus-like particles as a proof of principle for next generation polio vaccines

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