Virus-like particles with FLAG-tagged envelope protein as a tetravalent dengue vaccine candidate

Abstract The global incidence of dengue, which is caused by dengue virus (DENV) infection, has grown dramatically in recent decades and secondary infection with heterologous serotype of the virus may cause severe symptoms. Efficacious dengue vaccines should be able to provide long-lasting immunity a...

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Autores principales:	Toshifumi Imagawa, Masahiko Ito, Mami Matsuda, Kenji Nakashima, Yuhei Tokunaga, Isao Ohta, Tian-Cheng Li, Ryosuke Suzuki, Tetsuro Suzuki
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0567ac1e974b4525bd4bf3c91772a513
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spelling	oai:doaj.org-article:0567ac1e974b4525bd4bf3c91772a5132021-12-02T16:38:49ZVirus-like particles with FLAG-tagged envelope protein as a tetravalent dengue vaccine candidate10.1038/s41598-021-97038-42045-2322https://doaj.org/article/0567ac1e974b4525bd4bf3c91772a5132021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97038-4https://doaj.org/toc/2045-2322Abstract The global incidence of dengue, which is caused by dengue virus (DENV) infection, has grown dramatically in recent decades and secondary infection with heterologous serotype of the virus may cause severe symptoms. Efficacious dengue vaccines should be able to provide long-lasting immunity against all four DENV serotypes simultaneously. In this study, we constructed a novel vaccine platform based on tetravalent dengue virus-like particles (DENV-LPs) in which envelope (E) protein carried a FLAG tag sequence at the position located not only in the exterior loop on the protruding domain but outside of dimerization interface of the protein. We demonstrated an effective strategy to produce the DENV-LPs by transient transfection with expression plasmids for pre-membrane and E proteins of DENV-1 to DENV-4 in mammalian cells and to concentrate and purify them with one-step affinity chromatography. Characteristic features of VLPs such as particle size, shape and density were comparable to flavivirus-like particles reported. The neutralizing activity against all four DENV serotypes was successfully induced by immunization with the purified tetravalent VLPs in mice. Simple, one-step purification systems for VLP vaccine platforms using epitope-tagging strategy should be advantageous for vaccine development not only for dengue but for emerging pandemics in the future.Toshifumi ImagawaMasahiko ItoMami MatsudaKenji NakashimaYuhei TokunagaIsao OhtaTian-Cheng LiRyosuke SuzukiTetsuro SuzukiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Toshifumi Imagawa Masahiko Ito Mami Matsuda Kenji Nakashima Yuhei Tokunaga Isao Ohta Tian-Cheng Li Ryosuke Suzuki Tetsuro Suzuki Virus-like particles with FLAG-tagged envelope protein as a tetravalent dengue vaccine candidate
description	Abstract The global incidence of dengue, which is caused by dengue virus (DENV) infection, has grown dramatically in recent decades and secondary infection with heterologous serotype of the virus may cause severe symptoms. Efficacious dengue vaccines should be able to provide long-lasting immunity against all four DENV serotypes simultaneously. In this study, we constructed a novel vaccine platform based on tetravalent dengue virus-like particles (DENV-LPs) in which envelope (E) protein carried a FLAG tag sequence at the position located not only in the exterior loop on the protruding domain but outside of dimerization interface of the protein. We demonstrated an effective strategy to produce the DENV-LPs by transient transfection with expression plasmids for pre-membrane and E proteins of DENV-1 to DENV-4 in mammalian cells and to concentrate and purify them with one-step affinity chromatography. Characteristic features of VLPs such as particle size, shape and density were comparable to flavivirus-like particles reported. The neutralizing activity against all four DENV serotypes was successfully induced by immunization with the purified tetravalent VLPs in mice. Simple, one-step purification systems for VLP vaccine platforms using epitope-tagging strategy should be advantageous for vaccine development not only for dengue but for emerging pandemics in the future.
format	article
author	Toshifumi Imagawa Masahiko Ito Mami Matsuda Kenji Nakashima Yuhei Tokunaga Isao Ohta Tian-Cheng Li Ryosuke Suzuki Tetsuro Suzuki
author_facet	Toshifumi Imagawa Masahiko Ito Mami Matsuda Kenji Nakashima Yuhei Tokunaga Isao Ohta Tian-Cheng Li Ryosuke Suzuki Tetsuro Suzuki
author_sort	Toshifumi Imagawa
title	Virus-like particles with FLAG-tagged envelope protein as a tetravalent dengue vaccine candidate
title_short	Virus-like particles with FLAG-tagged envelope protein as a tetravalent dengue vaccine candidate
title_full	Virus-like particles with FLAG-tagged envelope protein as a tetravalent dengue vaccine candidate
title_fullStr	Virus-like particles with FLAG-tagged envelope protein as a tetravalent dengue vaccine candidate
title_full_unstemmed	Virus-like particles with FLAG-tagged envelope protein as a tetravalent dengue vaccine candidate
title_sort	virus-like particles with flag-tagged envelope protein as a tetravalent dengue vaccine candidate
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0567ac1e974b4525bd4bf3c91772a513
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Virus-like particles with FLAG-tagged envelope protein as a tetravalent dengue vaccine candidate

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