Japanese encephalitis virus live attenuated vaccine strains display altered immunogenicity, virulence and genetic diversity

Abstract Japanese encephalitis virus (JEV) is the etiological agent of Japanese encephalitis (JE). The most commonly used vaccine used to prevent JE is the live-attenuated strain SA14-14-2, which was generated by serial passage of the wild-type (WT) JEV strain SA14. Two other vaccine candidates, SA1...

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Autores principales:	Emily H. Davis, Andrew S. Beck, Li Li, Mellodee M. White, Marianne Banks Greenberg, Jill K. Thompson, Steven G. Widen, Alan D. T. Barrett, Nigel Bourne
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/76c97446ba9048d6a3eb3659558a8afe
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spelling	oai:doaj.org-article:76c97446ba9048d6a3eb3659558a8afe2021-12-02T15:28:51ZJapanese encephalitis virus live attenuated vaccine strains display altered immunogenicity, virulence and genetic diversity10.1038/s41541-021-00371-y2059-0105https://doaj.org/article/76c97446ba9048d6a3eb3659558a8afe2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00371-yhttps://doaj.org/toc/2059-0105Abstract Japanese encephalitis virus (JEV) is the etiological agent of Japanese encephalitis (JE). The most commonly used vaccine used to prevent JE is the live-attenuated strain SA14-14-2, which was generated by serial passage of the wild-type (WT) JEV strain SA14. Two other vaccine candidates, SA14-5-3 and SA14-2-8 were derived from SA14. Both were shown to be attenuated but lacked sufficient immunogenicity to be considered effective vaccines. To better contrast the SA14-14-2 vaccine with its less-immunogenic counterparts, genetic diversity, ribavirin sensitivity, mouse virulence and mouse immunogenicity of the three vaccines were investigated. Next generation sequencing demonstrated that SA14-14-2 was significantly more diverse than both SA14-5-3 and SA14-2-8, and was slightly less diverse than WT SA14. Notably, WT SA14 had unpredictable levels of diversity across its genome whereas SA14-14-2 is highly diverse, but genetic diversity is not random, rather the virus only tolerates variability at certain residues. Using Ribavirin sensitivity in vitro, it was found that SA14-14-2 has a lower fidelity replication complex compared to SA14-5-3 and SA14-2-8. Mouse virulence studies showed that SA14-2-8 was the most virulent of the three vaccine strains while SA14-14-2 had the most favorable combination of safety (virulence) and immunogenicity for all vaccines tested. SA14-14-2 contains genetic diversity and sensitivity to the antiviral Ribavirin similar to WT parent SA14, and this genetic diversity likely explains the (1) differences in genomic sequences reported for SA14-14-2 and (2) the encoding of major attenuation determinants by the viral E protein.Emily H. DavisAndrew S. BeckLi LiMellodee M. WhiteMarianne Banks GreenbergJill K. ThompsonSteven G. WidenAlan D. T. BarrettNigel BourneNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-14 (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 Emily H. Davis Andrew S. Beck Li Li Mellodee M. White Marianne Banks Greenberg Jill K. Thompson Steven G. Widen Alan D. T. Barrett Nigel Bourne Japanese encephalitis virus live attenuated vaccine strains display altered immunogenicity, virulence and genetic diversity
description	Abstract Japanese encephalitis virus (JEV) is the etiological agent of Japanese encephalitis (JE). The most commonly used vaccine used to prevent JE is the live-attenuated strain SA14-14-2, which was generated by serial passage of the wild-type (WT) JEV strain SA14. Two other vaccine candidates, SA14-5-3 and SA14-2-8 were derived from SA14. Both were shown to be attenuated but lacked sufficient immunogenicity to be considered effective vaccines. To better contrast the SA14-14-2 vaccine with its less-immunogenic counterparts, genetic diversity, ribavirin sensitivity, mouse virulence and mouse immunogenicity of the three vaccines were investigated. Next generation sequencing demonstrated that SA14-14-2 was significantly more diverse than both SA14-5-3 and SA14-2-8, and was slightly less diverse than WT SA14. Notably, WT SA14 had unpredictable levels of diversity across its genome whereas SA14-14-2 is highly diverse, but genetic diversity is not random, rather the virus only tolerates variability at certain residues. Using Ribavirin sensitivity in vitro, it was found that SA14-14-2 has a lower fidelity replication complex compared to SA14-5-3 and SA14-2-8. Mouse virulence studies showed that SA14-2-8 was the most virulent of the three vaccine strains while SA14-14-2 had the most favorable combination of safety (virulence) and immunogenicity for all vaccines tested. SA14-14-2 contains genetic diversity and sensitivity to the antiviral Ribavirin similar to WT parent SA14, and this genetic diversity likely explains the (1) differences in genomic sequences reported for SA14-14-2 and (2) the encoding of major attenuation determinants by the viral E protein.
format	article
author	Emily H. Davis Andrew S. Beck Li Li Mellodee M. White Marianne Banks Greenberg Jill K. Thompson Steven G. Widen Alan D. T. Barrett Nigel Bourne
author_facet	Emily H. Davis Andrew S. Beck Li Li Mellodee M. White Marianne Banks Greenberg Jill K. Thompson Steven G. Widen Alan D. T. Barrett Nigel Bourne
author_sort	Emily H. Davis
title	Japanese encephalitis virus live attenuated vaccine strains display altered immunogenicity, virulence and genetic diversity
title_short	Japanese encephalitis virus live attenuated vaccine strains display altered immunogenicity, virulence and genetic diversity
title_full	Japanese encephalitis virus live attenuated vaccine strains display altered immunogenicity, virulence and genetic diversity
title_fullStr	Japanese encephalitis virus live attenuated vaccine strains display altered immunogenicity, virulence and genetic diversity
title_full_unstemmed	Japanese encephalitis virus live attenuated vaccine strains display altered immunogenicity, virulence and genetic diversity
title_sort	japanese encephalitis virus live attenuated vaccine strains display altered immunogenicity, virulence and genetic diversity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/76c97446ba9048d6a3eb3659558a8afe
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Japanese encephalitis virus live attenuated vaccine strains display altered immunogenicity, virulence and genetic diversity

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