Attenuated dengue viruses are genetically more diverse than their respective wild-type parents

Abstract Dengue poses a significant burden of individual health, health systems and the economy in dengue endemic regions. As such, dengue vaccine development has been an active area of research. Previous studies selected attenuated vaccine candidates based on plaque size. However, these candidates...

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Autores principales:	Amanda Makha Bifani, Milly M. Choy, Hwee Cheng Tan, Eng Eong Ooi
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/e74404e1387b4601ad89e5f5720fa7a9
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spelling	oai:doaj.org-article:e74404e1387b4601ad89e5f5720fa7a92021-12-02T15:45:20ZAttenuated dengue viruses are genetically more diverse than their respective wild-type parents10.1038/s41541-021-00340-52059-0105https://doaj.org/article/e74404e1387b4601ad89e5f5720fa7a92021-05-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00340-5https://doaj.org/toc/2059-0105Abstract Dengue poses a significant burden of individual health, health systems and the economy in dengue endemic regions. As such, dengue vaccine development has been an active area of research. Previous studies selected attenuated vaccine candidates based on plaque size. However, these candidates led to mixed safety outcome in clinical trials, suggesting it is insufficiently informative as an indicator of dengue virus (DENV) attenuation. In this study, we examined the genome diversity of wild-type DENVs and their attenuated derivatives developed by Mahidol University and tested in phase 1 clinical trials. We found that the attenuated DENVs, in particular the strain under clinical development by Takeda Vaccines, DENV2 PDK53, showed significantly higher genome diversity than its wild-type parent, DENV2 16681. The determinant of genomic diversity was intrinsic to the PDK53 genome as infectious clone of PDK53 showed greater genomic diversity after a single in vitro passage compared to 16681 infectious clone. Similar trends were observed with attenuated DENV1 and DENV4, both of which were shown to be attenuated clinically, but not DENV3 that was not adequately attenuated clinically. Taken together, evidence presented here suggests that genome diversity could be developed into a marker of DENV attenuation.Amanda Makha BifaniMilly M. ChoyHwee Cheng TanEng Eong OoiNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-8 (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 Amanda Makha Bifani Milly M. Choy Hwee Cheng Tan Eng Eong Ooi Attenuated dengue viruses are genetically more diverse than their respective wild-type parents
description	Abstract Dengue poses a significant burden of individual health, health systems and the economy in dengue endemic regions. As such, dengue vaccine development has been an active area of research. Previous studies selected attenuated vaccine candidates based on plaque size. However, these candidates led to mixed safety outcome in clinical trials, suggesting it is insufficiently informative as an indicator of dengue virus (DENV) attenuation. In this study, we examined the genome diversity of wild-type DENVs and their attenuated derivatives developed by Mahidol University and tested in phase 1 clinical trials. We found that the attenuated DENVs, in particular the strain under clinical development by Takeda Vaccines, DENV2 PDK53, showed significantly higher genome diversity than its wild-type parent, DENV2 16681. The determinant of genomic diversity was intrinsic to the PDK53 genome as infectious clone of PDK53 showed greater genomic diversity after a single in vitro passage compared to 16681 infectious clone. Similar trends were observed with attenuated DENV1 and DENV4, both of which were shown to be attenuated clinically, but not DENV3 that was not adequately attenuated clinically. Taken together, evidence presented here suggests that genome diversity could be developed into a marker of DENV attenuation.
format	article
author	Amanda Makha Bifani Milly M. Choy Hwee Cheng Tan Eng Eong Ooi
author_facet	Amanda Makha Bifani Milly M. Choy Hwee Cheng Tan Eng Eong Ooi
author_sort	Amanda Makha Bifani
title	Attenuated dengue viruses are genetically more diverse than their respective wild-type parents
title_short	Attenuated dengue viruses are genetically more diverse than their respective wild-type parents
title_full	Attenuated dengue viruses are genetically more diverse than their respective wild-type parents
title_fullStr	Attenuated dengue viruses are genetically more diverse than their respective wild-type parents
title_full_unstemmed	Attenuated dengue viruses are genetically more diverse than their respective wild-type parents
title_sort	attenuated dengue viruses are genetically more diverse than their respective wild-type parents
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e74404e1387b4601ad89e5f5720fa7a9
work_keys_str_mv	AT amandamakhabifani attenuateddenguevirusesaregeneticallymorediversethantheirrespectivewildtypeparents AT millymchoy attenuateddenguevirusesaregeneticallymorediversethantheirrespectivewildtypeparents AT hweechengtan attenuateddenguevirusesaregeneticallymorediversethantheirrespectivewildtypeparents AT engeongooi attenuateddenguevirusesaregeneticallymorediversethantheirrespectivewildtypeparents
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Attenuated dengue viruses are genetically more diverse than their respective wild-type parents

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