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A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein

Current efforts to develop Zika virus (ZIKV) subunit vaccines have been focused on pre-membrane (prM) and envelope (E) proteins, but the role of NS1 in ZIKV-specific immune response and protection is poorly understood. Here, we develop an attenuated recombinant vesicular stomatitis virus (rVSV)-base...

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Autores principales: Li, Anzhong, Yu, Jingyou, Lu, Mijia, Ma, Yuanmei, Attia, Zayed, Shan, Chao, Xue, Miaoge, Liang, Xueya, Craig, Kelsey, Makadiya, Nirajkumar, He, Jennifer J., Jennings, Ryan, Shi, Pei-Yong, Peeples, Mark E., Liu, Shan-Lu, Boyaka, Prosper N., Li, Jianrong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6076265/
https://www.ncbi.nlm.nih.gov/pubmed/30076287
http://dx.doi.org/10.1038/s41467-018-05276-4
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author Li, Anzhong
Yu, Jingyou
Lu, Mijia
Ma, Yuanmei
Attia, Zayed
Shan, Chao
Xue, Miaoge
Liang, Xueya
Craig, Kelsey
Makadiya, Nirajkumar
He, Jennifer J.
Jennings, Ryan
Shi, Pei-Yong
Peeples, Mark E.
Liu, Shan-Lu
Boyaka, Prosper N.
Li, Jianrong
author_facet Li, Anzhong
Yu, Jingyou
Lu, Mijia
Ma, Yuanmei
Attia, Zayed
Shan, Chao
Xue, Miaoge
Liang, Xueya
Craig, Kelsey
Makadiya, Nirajkumar
He, Jennifer J.
Jennings, Ryan
Shi, Pei-Yong
Peeples, Mark E.
Liu, Shan-Lu
Boyaka, Prosper N.
Li, Jianrong
author_sort Li, Anzhong
collection PubMed
description Current efforts to develop Zika virus (ZIKV) subunit vaccines have been focused on pre-membrane (prM) and envelope (E) proteins, but the role of NS1 in ZIKV-specific immune response and protection is poorly understood. Here, we develop an attenuated recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing ZIKV prM-E-NS1 as a polyprotein. This vectored vaccine candidate is attenuated in mice, where a single immunization induces ZIKV-specific antibody and T cell immune responses that provide protection against ZIKV challenge. Co-expression of prM, E, and NS1 induces significantly higher levels of Th2 and Th17 cytokine responses than prM-E. In addition, NS1 alone is capable of conferring partial protection against ZIKV infection in mice even though it does not induce neutralizing antibodies. These results demonstrate that attenuated rVSV co-expressing prM, E, and NS1 is a promising vaccine candidate for protection against ZIKV infection and highlights an important role for NS1 in ZIKV-specific cellular immune responses.
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spelling pubmed-60762652018-08-07 A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein Li, Anzhong Yu, Jingyou Lu, Mijia Ma, Yuanmei Attia, Zayed Shan, Chao Xue, Miaoge Liang, Xueya Craig, Kelsey Makadiya, Nirajkumar He, Jennifer J. Jennings, Ryan Shi, Pei-Yong Peeples, Mark E. Liu, Shan-Lu Boyaka, Prosper N. Li, Jianrong Nat Commun Article Current efforts to develop Zika virus (ZIKV) subunit vaccines have been focused on pre-membrane (prM) and envelope (E) proteins, but the role of NS1 in ZIKV-specific immune response and protection is poorly understood. Here, we develop an attenuated recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing ZIKV prM-E-NS1 as a polyprotein. This vectored vaccine candidate is attenuated in mice, where a single immunization induces ZIKV-specific antibody and T cell immune responses that provide protection against ZIKV challenge. Co-expression of prM, E, and NS1 induces significantly higher levels of Th2 and Th17 cytokine responses than prM-E. In addition, NS1 alone is capable of conferring partial protection against ZIKV infection in mice even though it does not induce neutralizing antibodies. These results demonstrate that attenuated rVSV co-expressing prM, E, and NS1 is a promising vaccine candidate for protection against ZIKV infection and highlights an important role for NS1 in ZIKV-specific cellular immune responses. Nature Publishing Group UK 2018-08-03 /pmc/articles/PMC6076265/ /pubmed/30076287 http://dx.doi.org/10.1038/s41467-018-05276-4 Text en © The Author(s) 2018 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/.
spellingShingle Article
Li, Anzhong
Yu, Jingyou
Lu, Mijia
Ma, Yuanmei
Attia, Zayed
Shan, Chao
Xue, Miaoge
Liang, Xueya
Craig, Kelsey
Makadiya, Nirajkumar
He, Jennifer J.
Jennings, Ryan
Shi, Pei-Yong
Peeples, Mark E.
Liu, Shan-Lu
Boyaka, Prosper N.
Li, Jianrong
A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein
title A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein
title_full A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein
title_fullStr A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein
title_full_unstemmed A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein
title_short A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein
title_sort zika virus vaccine expressing premembrane-envelope-ns1 polyprotein
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6076265/
https://www.ncbi.nlm.nih.gov/pubmed/30076287
http://dx.doi.org/10.1038/s41467-018-05276-4
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