Single dose of a replication-defective vaccinia virus expressing Zika virus-like particles is protective in mice

Abstract Zika virus (ZIKV), a flavivirus transmitted primarily by infected mosquitos, can cause neurological symptoms such as Guillian–Barré syndrome and microcephaly. We developed several vaccinia virus (VACV) vaccine candidates for ZIKV based on replication-inducible VACVs (vINDs) expressing ZIKV...

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Autores principales:	Brittany Jasperse, Caitlin M. O’Connell, Yuxiang Wang, Paulo H. Verardi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0579b072da9c435fb3f374dfe50845f0
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spelling	oai:doaj.org-article:0579b072da9c435fb3f374dfe50845f02021-12-02T17:04:34ZSingle dose of a replication-defective vaccinia virus expressing Zika virus-like particles is protective in mice10.1038/s41598-021-85951-72045-2322https://doaj.org/article/0579b072da9c435fb3f374dfe50845f02021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85951-7https://doaj.org/toc/2045-2322Abstract Zika virus (ZIKV), a flavivirus transmitted primarily by infected mosquitos, can cause neurological symptoms such as Guillian–Barré syndrome and microcephaly. We developed several vaccinia virus (VACV) vaccine candidates for ZIKV based on replication-inducible VACVs (vINDs) expressing ZIKV pre-membrane (prM) and envelope (E) proteins (vIND-ZIKVs). These vIND-ZIKVs contain elements of the tetracycline operon and replicate only in the presence of tetracyclines. The pool of vaccine candidates was narrowed to one vIND-ZIKV containing a novel mutation in the signal peptide of prM that led to higher expression and secretion of E and production of virus-like particles, which was then tested for safety, immunogenicity, and efficacy in mice. vIND-ZIKV grows to high titers in vitro in the presence of doxycycline (DOX) but is replication-defective in vivo in the absence of DOX, causing no weight loss in mice. C57BL/6 mice vaccinated once with vIND-ZIKV in the absence of DOX (as a replication-defective virus) developed robust levels of E-peptide-specific IFN-γ-secreting splenocytes and anti-E IgG titers, with modest levels of serum-neutralizing antibodies. Vaccinated mice treated with anti-IFNAR1 antibody were completely protected from ZIKV viremia post-challenge after a single dose of vIND-ZIKV. Furthermore, mice with prior immunity to VACV developed moderate anti-E IgG titers that increased after booster vaccination, and were protected from viremia only after two vaccinations with vIND-ZIKV.Brittany JasperseCaitlin M. O’ConnellYuxiang WangPaulo H. VerardiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Brittany Jasperse Caitlin M. O’Connell Yuxiang Wang Paulo H. Verardi Single dose of a replication-defective vaccinia virus expressing Zika virus-like particles is protective in mice
description	Abstract Zika virus (ZIKV), a flavivirus transmitted primarily by infected mosquitos, can cause neurological symptoms such as Guillian–Barré syndrome and microcephaly. We developed several vaccinia virus (VACV) vaccine candidates for ZIKV based on replication-inducible VACVs (vINDs) expressing ZIKV pre-membrane (prM) and envelope (E) proteins (vIND-ZIKVs). These vIND-ZIKVs contain elements of the tetracycline operon and replicate only in the presence of tetracyclines. The pool of vaccine candidates was narrowed to one vIND-ZIKV containing a novel mutation in the signal peptide of prM that led to higher expression and secretion of E and production of virus-like particles, which was then tested for safety, immunogenicity, and efficacy in mice. vIND-ZIKV grows to high titers in vitro in the presence of doxycycline (DOX) but is replication-defective in vivo in the absence of DOX, causing no weight loss in mice. C57BL/6 mice vaccinated once with vIND-ZIKV in the absence of DOX (as a replication-defective virus) developed robust levels of E-peptide-specific IFN-γ-secreting splenocytes and anti-E IgG titers, with modest levels of serum-neutralizing antibodies. Vaccinated mice treated with anti-IFNAR1 antibody were completely protected from ZIKV viremia post-challenge after a single dose of vIND-ZIKV. Furthermore, mice with prior immunity to VACV developed moderate anti-E IgG titers that increased after booster vaccination, and were protected from viremia only after two vaccinations with vIND-ZIKV.
format	article
author	Brittany Jasperse Caitlin M. O’Connell Yuxiang Wang Paulo H. Verardi
author_facet	Brittany Jasperse Caitlin M. O’Connell Yuxiang Wang Paulo H. Verardi
author_sort	Brittany Jasperse
title	Single dose of a replication-defective vaccinia virus expressing Zika virus-like particles is protective in mice
title_short	Single dose of a replication-defective vaccinia virus expressing Zika virus-like particles is protective in mice
title_full	Single dose of a replication-defective vaccinia virus expressing Zika virus-like particles is protective in mice
title_fullStr	Single dose of a replication-defective vaccinia virus expressing Zika virus-like particles is protective in mice
title_full_unstemmed	Single dose of a replication-defective vaccinia virus expressing Zika virus-like particles is protective in mice
title_sort	single dose of a replication-defective vaccinia virus expressing zika virus-like particles is protective in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0579b072da9c435fb3f374dfe50845f0
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Single dose of a replication-defective vaccinia virus expressing Zika virus-like particles is protective in mice

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