Virus-like particles that display Zika virus envelope protein domain III induce potent neutralizing immune responses in mice

Abstract Several Zika virus (ZIKV) vaccine candidates have recently been described which use inactivated whole virus, DNA or RNA that express the virus’ Envelope (E) glycoprotein as the antigen. These were successful in stimulating production of virus-targeted antibodies that protected animals again...

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Autores principales:	Ming Yang, Huafang Lai, Haiyan Sun, Qiang Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b021c12dcb5343079ddb8bba37280890
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spelling	oai:doaj.org-article:b021c12dcb5343079ddb8bba372808902021-12-02T15:05:59ZVirus-like particles that display Zika virus envelope protein domain III induce potent neutralizing immune responses in mice10.1038/s41598-017-08247-92045-2322https://doaj.org/article/b021c12dcb5343079ddb8bba372808902017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08247-9https://doaj.org/toc/2045-2322Abstract Several Zika virus (ZIKV) vaccine candidates have recently been described which use inactivated whole virus, DNA or RNA that express the virus’ Envelope (E) glycoprotein as the antigen. These were successful in stimulating production of virus-targeted antibodies that protected animals against ZIKV challenges, but their use potentially will predispose vaccinated individuals to infection by the related Dengue virus (DENV). We have devised a virus like particle (VLP) carrier based on the hepatitis B core antigen (HBcAg) that displays the ZIKV E protein domain III (zDIII), and shown that it can be produced quickly and easily purified in large quantities from Nicotiana benthamiana plants. HBcAg-zDIII VLPs are shown to be highly immunogenic, as two doses elicited potent humoral and cellular responses in mice that exceed the threshold correlated with protective immunity against multiple strains of Zika virus. Notably, HBcAg-zDIII VLPs-elicited antibodies did not enhance the infection of DENV in Fc gamma receptor-expressing cells, offsetting the concern of ZIKV vaccines inducing cross-reactive antibodies and sensitizing people to subsequent DENV infection. Thus, our zDIII-based vaccine offers improved safety and lower cost production than other current alternatives, with equivalent effectiveness.Ming YangHuafang LaiHaiyan SunQiang ChenNature 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 Ming Yang Huafang Lai Haiyan Sun Qiang Chen Virus-like particles that display Zika virus envelope protein domain III induce potent neutralizing immune responses in mice
description	Abstract Several Zika virus (ZIKV) vaccine candidates have recently been described which use inactivated whole virus, DNA or RNA that express the virus’ Envelope (E) glycoprotein as the antigen. These were successful in stimulating production of virus-targeted antibodies that protected animals against ZIKV challenges, but their use potentially will predispose vaccinated individuals to infection by the related Dengue virus (DENV). We have devised a virus like particle (VLP) carrier based on the hepatitis B core antigen (HBcAg) that displays the ZIKV E protein domain III (zDIII), and shown that it can be produced quickly and easily purified in large quantities from Nicotiana benthamiana plants. HBcAg-zDIII VLPs are shown to be highly immunogenic, as two doses elicited potent humoral and cellular responses in mice that exceed the threshold correlated with protective immunity against multiple strains of Zika virus. Notably, HBcAg-zDIII VLPs-elicited antibodies did not enhance the infection of DENV in Fc gamma receptor-expressing cells, offsetting the concern of ZIKV vaccines inducing cross-reactive antibodies and sensitizing people to subsequent DENV infection. Thus, our zDIII-based vaccine offers improved safety and lower cost production than other current alternatives, with equivalent effectiveness.
format	article
author	Ming Yang Huafang Lai Haiyan Sun Qiang Chen
author_facet	Ming Yang Huafang Lai Haiyan Sun Qiang Chen
author_sort	Ming Yang
title	Virus-like particles that display Zika virus envelope protein domain III induce potent neutralizing immune responses in mice
title_short	Virus-like particles that display Zika virus envelope protein domain III induce potent neutralizing immune responses in mice
title_full	Virus-like particles that display Zika virus envelope protein domain III induce potent neutralizing immune responses in mice
title_fullStr	Virus-like particles that display Zika virus envelope protein domain III induce potent neutralizing immune responses in mice
title_full_unstemmed	Virus-like particles that display Zika virus envelope protein domain III induce potent neutralizing immune responses in mice
title_sort	virus-like particles that display zika virus envelope protein domain iii induce potent neutralizing immune responses in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b021c12dcb5343079ddb8bba37280890
work_keys_str_mv	AT mingyang viruslikeparticlesthatdisplayzikavirusenvelopeproteindomainiiiinducepotentneutralizingimmuneresponsesinmice AT huafanglai viruslikeparticlesthatdisplayzikavirusenvelopeproteindomainiiiinducepotentneutralizingimmuneresponsesinmice AT haiyansun viruslikeparticlesthatdisplayzikavirusenvelopeproteindomainiiiinducepotentneutralizingimmuneresponsesinmice AT qiangchen viruslikeparticlesthatdisplayzikavirusenvelopeproteindomainiiiinducepotentneutralizingimmuneresponsesinmice
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Virus-like particles that display Zika virus envelope protein domain III induce potent neutralizing immune responses in mice

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