Single dose of chimeric dengue-2/Zika vaccine candidate protects mice and non-human primates against Zika virus

The development of a safe and effective Zika virus (ZIKV) vaccine has become a global health priority since the widespread epidemic in 2015-2016. Based on previous experience in using the well-characterized and clinically proven dengue virus serotype-2 (DENV-2) PDK-53 vaccine backbone for live-atten...

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Autores principales: Baldwin, Whitney R., Giebler, Holli A., Stovall, Janae L., Young, Ginger, Bohning, Kelly J., Dean, Hansi J., Livengood, Jill A., Huang, Claire Y.-H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677809/
https://www.ncbi.nlm.nih.gov/pubmed/34916486
http://dx.doi.org/10.1038/s41467-021-27578-w
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author Baldwin, Whitney R.
Giebler, Holli A.
Stovall, Janae L.
Young, Ginger
Bohning, Kelly J.
Dean, Hansi J.
Livengood, Jill A.
Huang, Claire Y.-H.
author_facet Baldwin, Whitney R.
Giebler, Holli A.
Stovall, Janae L.
Young, Ginger
Bohning, Kelly J.
Dean, Hansi J.
Livengood, Jill A.
Huang, Claire Y.-H.
author_sort Baldwin, Whitney R.
collection PubMed
description The development of a safe and effective Zika virus (ZIKV) vaccine has become a global health priority since the widespread epidemic in 2015-2016. Based on previous experience in using the well-characterized and clinically proven dengue virus serotype-2 (DENV-2) PDK-53 vaccine backbone for live-attenuated chimeric flavivirus vaccine development, we developed chimeric DENV-2/ZIKV vaccine candidates optimized for growth and genetic stability in Vero cells. These vaccine candidates retain all previously characterized attenuation phenotypes of the PDK-53 vaccine virus, including attenuation of neurovirulence for 1-day-old CD-1 mice, absence of virulence in interferon receptor-deficient mice, and lack of transmissibility in the main mosquito vectors. A single DENV-2/ZIKV dose provides protection against ZIKV challenge in mice and rhesus macaques. Overall, these data indicate that the ZIKV live-attenuated vaccine candidates are safe, immunogenic and effective at preventing ZIKV infection in multiple animal models, warranting continued development.
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spelling pubmed-86778092022-01-04 Single dose of chimeric dengue-2/Zika vaccine candidate protects mice and non-human primates against Zika virus Baldwin, Whitney R. Giebler, Holli A. Stovall, Janae L. Young, Ginger Bohning, Kelly J. Dean, Hansi J. Livengood, Jill A. Huang, Claire Y.-H. Nat Commun Article The development of a safe and effective Zika virus (ZIKV) vaccine has become a global health priority since the widespread epidemic in 2015-2016. Based on previous experience in using the well-characterized and clinically proven dengue virus serotype-2 (DENV-2) PDK-53 vaccine backbone for live-attenuated chimeric flavivirus vaccine development, we developed chimeric DENV-2/ZIKV vaccine candidates optimized for growth and genetic stability in Vero cells. These vaccine candidates retain all previously characterized attenuation phenotypes of the PDK-53 vaccine virus, including attenuation of neurovirulence for 1-day-old CD-1 mice, absence of virulence in interferon receptor-deficient mice, and lack of transmissibility in the main mosquito vectors. A single DENV-2/ZIKV dose provides protection against ZIKV challenge in mice and rhesus macaques. Overall, these data indicate that the ZIKV live-attenuated vaccine candidates are safe, immunogenic and effective at preventing ZIKV infection in multiple animal models, warranting continued development. Nature Publishing Group UK 2021-12-16 /pmc/articles/PMC8677809/ /pubmed/34916486 http://dx.doi.org/10.1038/s41467-021-27578-w Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Baldwin, Whitney R.
Giebler, Holli A.
Stovall, Janae L.
Young, Ginger
Bohning, Kelly J.
Dean, Hansi J.
Livengood, Jill A.
Huang, Claire Y.-H.
Single dose of chimeric dengue-2/Zika vaccine candidate protects mice and non-human primates against Zika virus
title Single dose of chimeric dengue-2/Zika vaccine candidate protects mice and non-human primates against Zika virus
title_full Single dose of chimeric dengue-2/Zika vaccine candidate protects mice and non-human primates against Zika virus
title_fullStr Single dose of chimeric dengue-2/Zika vaccine candidate protects mice and non-human primates against Zika virus
title_full_unstemmed Single dose of chimeric dengue-2/Zika vaccine candidate protects mice and non-human primates against Zika virus
title_short Single dose of chimeric dengue-2/Zika vaccine candidate protects mice and non-human primates against Zika virus
title_sort single dose of chimeric dengue-2/zika vaccine candidate protects mice and non-human primates against zika virus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677809/
https://www.ncbi.nlm.nih.gov/pubmed/34916486
http://dx.doi.org/10.1038/s41467-021-27578-w
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