A genetically stable Zika virus vaccine candidate protects mice against virus infection and vertical transmission

Abstract Although live attenuated vaccines (LAVs) have been effective in the control of flavivirus infections, to date they have been excluded from Zika virus (ZIKV) vaccine trials due to safety concerns. We have previously reported two ZIKV mutants, each of which has a single substitution in either...

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Autores principales:	Awadalkareem Adam, Camila R. Fontes-Garfias, Vanessa V. Sarathy, Yang Liu, Huanle Luo, Emily Davis, Wenqian Li, Antonio E. Muruato, Binbin Wang, Renat Ahatov, Yoseph Mahmoud, Chao Shan, Samantha R. Osman, Steven G. Widen, Alan D. T. Barrett, Pei-Yong Shi, Tian Wang
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/f28c37c48ce34bfaad88626bc97d5974
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spelling	oai:doaj.org-article:f28c37c48ce34bfaad88626bc97d59742021-12-02T10:54:22ZA genetically stable Zika virus vaccine candidate protects mice against virus infection and vertical transmission10.1038/s41541-021-00288-62059-0105https://doaj.org/article/f28c37c48ce34bfaad88626bc97d59742021-02-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00288-6https://doaj.org/toc/2059-0105Abstract Although live attenuated vaccines (LAVs) have been effective in the control of flavivirus infections, to date they have been excluded from Zika virus (ZIKV) vaccine trials due to safety concerns. We have previously reported two ZIKV mutants, each of which has a single substitution in either envelope (E) glycosylation or nonstructural (NS) 4B P36 and displays a modest reduction in mouse neurovirulence and neuroinvasiveness, respectively. Here, we generated a ZIKV mutant, ZE4B-36, which combines mutations in both E glycosylation and NS4B P36. The ZE4B-36 mutant is stable and attenuated in viral replication. Next-generation sequence analysis showed that the attenuating mutations in the E and NS4B proteins are retained during serial cell culture passages. The mutant exhibits a significant reduction in neuroinvasiveness and neurovirulence and low infectivity in mosquitoes. It induces robust ZIKV-specific memory B cell, antibody, and T cell-mediated immune responses in type I interferon receptor (IFNR) deficient mice. ZIKV-specific T cell immunity remains strong months post-vaccination in wild-type C57BL/6 (B6) mice. Vaccination with ZE4B-36 protects mice from ZIKV-induced diseases and vertical transmission. Our results suggest that combination mutations in E glycosylation and NS4B P36 contribute to a candidate LAV with significantly increased safety but retain strong immunogenicity for prevention and control of ZIKV infection.Awadalkareem AdamCamila R. Fontes-GarfiasVanessa V. SarathyYang LiuHuanle LuoEmily DavisWenqian LiAntonio E. MuruatoBinbin WangRenat AhatovYoseph MahmoudChao ShanSamantha R. OsmanSteven G. WidenAlan D. T. BarrettPei-Yong ShiTian WangNature 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 Awadalkareem Adam Camila R. Fontes-Garfias Vanessa V. Sarathy Yang Liu Huanle Luo Emily Davis Wenqian Li Antonio E. Muruato Binbin Wang Renat Ahatov Yoseph Mahmoud Chao Shan Samantha R. Osman Steven G. Widen Alan D. T. Barrett Pei-Yong Shi Tian Wang A genetically stable Zika virus vaccine candidate protects mice against virus infection and vertical transmission
description	Abstract Although live attenuated vaccines (LAVs) have been effective in the control of flavivirus infections, to date they have been excluded from Zika virus (ZIKV) vaccine trials due to safety concerns. We have previously reported two ZIKV mutants, each of which has a single substitution in either envelope (E) glycosylation or nonstructural (NS) 4B P36 and displays a modest reduction in mouse neurovirulence and neuroinvasiveness, respectively. Here, we generated a ZIKV mutant, ZE4B-36, which combines mutations in both E glycosylation and NS4B P36. The ZE4B-36 mutant is stable and attenuated in viral replication. Next-generation sequence analysis showed that the attenuating mutations in the E and NS4B proteins are retained during serial cell culture passages. The mutant exhibits a significant reduction in neuroinvasiveness and neurovirulence and low infectivity in mosquitoes. It induces robust ZIKV-specific memory B cell, antibody, and T cell-mediated immune responses in type I interferon receptor (IFNR) deficient mice. ZIKV-specific T cell immunity remains strong months post-vaccination in wild-type C57BL/6 (B6) mice. Vaccination with ZE4B-36 protects mice from ZIKV-induced diseases and vertical transmission. Our results suggest that combination mutations in E glycosylation and NS4B P36 contribute to a candidate LAV with significantly increased safety but retain strong immunogenicity for prevention and control of ZIKV infection.
format	article
author	Awadalkareem Adam Camila R. Fontes-Garfias Vanessa V. Sarathy Yang Liu Huanle Luo Emily Davis Wenqian Li Antonio E. Muruato Binbin Wang Renat Ahatov Yoseph Mahmoud Chao Shan Samantha R. Osman Steven G. Widen Alan D. T. Barrett Pei-Yong Shi Tian Wang
author_facet	Awadalkareem Adam Camila R. Fontes-Garfias Vanessa V. Sarathy Yang Liu Huanle Luo Emily Davis Wenqian Li Antonio E. Muruato Binbin Wang Renat Ahatov Yoseph Mahmoud Chao Shan Samantha R. Osman Steven G. Widen Alan D. T. Barrett Pei-Yong Shi Tian Wang
author_sort	Awadalkareem Adam
title	A genetically stable Zika virus vaccine candidate protects mice against virus infection and vertical transmission
title_short	A genetically stable Zika virus vaccine candidate protects mice against virus infection and vertical transmission
title_full	A genetically stable Zika virus vaccine candidate protects mice against virus infection and vertical transmission
title_fullStr	A genetically stable Zika virus vaccine candidate protects mice against virus infection and vertical transmission
title_full_unstemmed	A genetically stable Zika virus vaccine candidate protects mice against virus infection and vertical transmission
title_sort	genetically stable zika virus vaccine candidate protects mice against virus infection and vertical transmission
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f28c37c48ce34bfaad88626bc97d5974
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A genetically stable Zika virus vaccine candidate protects mice against virus infection and vertical transmission

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