A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models

Shan, Chao; Muruato, Antonio E; Nunes, Bruno Tardelli Diniz; Luo, Huanle; Xie, Xuping; Medeiros, Daniele Barbosa de Almeida; Wakamiya, Maki; Tesh, Robert B; Barrett, Alan D; Wang, Tian; Weaver, Scott C; Vasconcelos, Pedro Fernando da Costa; Rossi, Shannan L; Shi, Pei-Yong

Artigo

A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models

Zika virus (ZIKV) infection of pregnant women can cause a wide range of congenital abnormalities, including microcephaly, in the infant, a condition now collectively known as congenital ZIKV syndrome. A vaccine to prevent or significantly attenuate viremia in pregnant women who are residents of or t...

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Autor principal:	Shan, Chao
Outros Autores:	Muruato, Antonio E, Nunes, Bruno Tardelli Diniz, Luo, Huanle, Xie, Xuping, Medeiros, Daniele Barbosa de Almeida, Wakamiya, Maki, Tesh, Robert B, Barrett, Alan D, Wang, Tian, Weaver, Scott C, Vasconcelos, Pedro Fernando da Costa, Rossi, Shannan L, Shi, Pei-Yong
Grau:	Artigo
Idioma:	eng
Publicado em:	Nature Publishing Group 2017
Assuntos:	Zika virus Vacinas Atenuadas / uso terap?utico Infec??o pelo Zika virus / preven??o & controle Experimenta??o Animal
Acesso em linha:	http://patua.iec.gov.br//handle/iec/2892

id	ir-iec-2892
recordtype	dspace
spelling	ir-iec-28922019-02-26T16:45:22Z A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models Shan, Chao Muruato, Antonio E Nunes, Bruno Tardelli Diniz Luo, Huanle Xie, Xuping Medeiros, Daniele Barbosa de Almeida Wakamiya, Maki Tesh, Robert B Barrett, Alan D Wang, Tian Weaver, Scott C Vasconcelos, Pedro Fernando da Costa Rossi, Shannan L Shi, Pei-Yong Zika virus Vacinas Atenuadas / uso terap?utico Infec??o pelo Zika virus / preven??o & controle Experimenta??o Animal Zika virus (ZIKV) infection of pregnant women can cause a wide range of congenital abnormalities, including microcephaly, in the infant, a condition now collectively known as congenital ZIKV syndrome. A vaccine to prevent or significantly attenuate viremia in pregnant women who are residents of or travelers to epidemic or endemic regions is needed to avert congenital ZIKV syndrome, and might also help to suppress epidemic transmission. Here we report on a live-attenuated vaccine candidate that contains a 10-nucleotide deletion in the 3' untranslated region of the ZIKV genome (10-del ZIKV). The 10-del ZIKV is highly attenuated, immunogenic, and protective in type 1 interferon receptor-deficient A129 mice. Crucially, a single dose of 10-del ZIKV induced sterilizing immunity with a saturated neutralizing antibody titer, which no longer increased after challenge with an epidemic ZIKV, and completely prevented viremia. The immunized mice also developed a robust T cell response. Intracranial inoculation of 1-d-old immunocompetent CD-1 mice with 1 ? 104 infectious focus units (IFU) of 10-del ZIKV caused no mortality, whereas infections with 10 IFU of wild-type ZIKV were lethal. Mechanistically, the attenuated virulence of 10-del ZIKV may be due to decreased viral RNA synthesis and increased sensitivity to type-1-interferon inhibition. The attenuated 10-del ZIKV was incapable of infecting mosquitoes after oral feeding of spiked-blood meals, representing an additional safety feature. Collectively, the safety and efficacy results suggest that further development of this promising, live-attenuated ZIKV vaccine candidate is warranted. P.-Y.S. was supported by a University of Texas Medical Branch (UTMB) start-up award, UTMB Innovation and Commercialization award, University of Texas STARs Award, CDC grant for the Western Gulf Center of Excellence for Vector-Borne Diseases, Pan American Health Organization grant SCON2016- 01353, and UTMB CTSA UL1TR-001439. This research was also partially supported by a US National Institutes of Health grant AI120942 to S.C.W. 2017-11-29T11:43:26Z 2017-11-29T11:43:26Z 2017 Artigo SHAN, Chao et al. A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models. Nature Medicine, v. 23, n. 6, p. 763-767, June 2017. 1078-8956 http://patua.iec.gov.br//handle/iec/2892 10.1038/nm.4322 eng Acesso Aberto application/pdf Nature Publishing Group
institution	Instituto Evandro Chagas (IEC)
collection	PATUA
language	eng
topic	Zika virus Vacinas Atenuadas / uso terap?utico Infec??o pelo Zika virus / preven??o & controle Experimenta??o Animal
spellingShingle	Zika virus Vacinas Atenuadas / uso terap?utico Infec??o pelo Zika virus / preven??o & controle Experimenta??o Animal Shan, Chao A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models
topic_facet	Zika virus Vacinas Atenuadas / uso terap?utico Infec??o pelo Zika virus / preven??o & controle Experimenta??o Animal
description	Zika virus (ZIKV) infection of pregnant women can cause a wide range of congenital abnormalities, including microcephaly, in the infant, a condition now collectively known as congenital ZIKV syndrome. A vaccine to prevent or significantly attenuate viremia in pregnant women who are residents of or travelers to epidemic or endemic regions is needed to avert congenital ZIKV syndrome, and might also help to suppress epidemic transmission. Here we report on a live-attenuated vaccine candidate that contains a 10-nucleotide deletion in the 3' untranslated region of the ZIKV genome (10-del ZIKV). The 10-del ZIKV is highly attenuated, immunogenic, and protective in type 1 interferon receptor-deficient A129 mice. Crucially, a single dose of 10-del ZIKV induced sterilizing immunity with a saturated neutralizing antibody titer, which no longer increased after challenge with an epidemic ZIKV, and completely prevented viremia. The immunized mice also developed a robust T cell response. Intracranial inoculation of 1-d-old immunocompetent CD-1 mice with 1 ? 104 infectious focus units (IFU) of 10-del ZIKV caused no mortality, whereas infections with 10 IFU of wild-type ZIKV were lethal. Mechanistically, the attenuated virulence of 10-del ZIKV may be due to decreased viral RNA synthesis and increased sensitivity to type-1-interferon inhibition. The attenuated 10-del ZIKV was incapable of infecting mosquitoes after oral feeding of spiked-blood meals, representing an additional safety feature. Collectively, the safety and efficacy results suggest that further development of this promising, live-attenuated ZIKV vaccine candidate is warranted.
format	Artigo
author	Shan, Chao
author2	Muruato, Antonio E Nunes, Bruno Tardelli Diniz Luo, Huanle Xie, Xuping Medeiros, Daniele Barbosa de Almeida Wakamiya, Maki Tesh, Robert B Barrett, Alan D Wang, Tian Weaver, Scott C Vasconcelos, Pedro Fernando da Costa Rossi, Shannan L Shi, Pei-Yong
author2Str	Muruato, Antonio E Nunes, Bruno Tardelli Diniz Luo, Huanle Xie, Xuping Medeiros, Daniele Barbosa de Almeida Wakamiya, Maki Tesh, Robert B Barrett, Alan D Wang, Tian Weaver, Scott C Vasconcelos, Pedro Fernando da Costa Rossi, Shannan L Shi, Pei-Yong
title	A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models
title_short	A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models
title_full	A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models
title_fullStr	A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models
title_full_unstemmed	A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models
title_sort	live-attenuated zika virus vaccine candidate induces sterilizing immunity in mouse models
publisher	Nature Publishing Group
publishDate	2017
url	http://patua.iec.gov.br//handle/iec/2892
_version_	1717584530620022784
score	11.755432

A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models

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