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A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity

Although inoculation of COVID-19 vaccines has rolled out globally, there is still a critical need for safe and effective vaccines to ensure fair and equitable supply for all countries. Here, we report on the development of a highly efficacious mRNA vaccine, SW0123 that is composed of sequence-modifi...

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Autores principales: Yang, Ren, Deng, Yao, Huang, Baoying, Huang, Lei, Lin, Ang, Li, Yuhua, Wang, Wenling, Liu, Jingjing, Lu, Shuaiyao, Zhan, Zhenzhen, Wang, Yufei, A, Ruhan, Wang, Wen, Niu, Peihua, Zhao, Li, Li, Shiqiang, Ma, Xiaopin, Zhang, Luyao, Zhang, Yujian, Yao, Weiguo, Liang, Xingjie, Zhao, Jincun, Liu, Zhongmin, Peng, Xiaozhong, Li, Hangwen, Tan, Wenjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165147/
https://www.ncbi.nlm.nih.gov/pubmed/34059617
http://dx.doi.org/10.1038/s41392-021-00634-z
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author Yang, Ren
Deng, Yao
Huang, Baoying
Huang, Lei
Lin, Ang
Li, Yuhua
Wang, Wenling
Liu, Jingjing
Lu, Shuaiyao
Zhan, Zhenzhen
Wang, Yufei
A, Ruhan
Wang, Wen
Niu, Peihua
Zhao, Li
Li, Shiqiang
Ma, Xiaopin
Zhang, Luyao
Zhang, Yujian
Yao, Weiguo
Liang, Xingjie
Zhao, Jincun
Liu, Zhongmin
Peng, Xiaozhong
Li, Hangwen
Tan, Wenjie
author_facet Yang, Ren
Deng, Yao
Huang, Baoying
Huang, Lei
Lin, Ang
Li, Yuhua
Wang, Wenling
Liu, Jingjing
Lu, Shuaiyao
Zhan, Zhenzhen
Wang, Yufei
A, Ruhan
Wang, Wen
Niu, Peihua
Zhao, Li
Li, Shiqiang
Ma, Xiaopin
Zhang, Luyao
Zhang, Yujian
Yao, Weiguo
Liang, Xingjie
Zhao, Jincun
Liu, Zhongmin
Peng, Xiaozhong
Li, Hangwen
Tan, Wenjie
author_sort Yang, Ren
collection PubMed
description Although inoculation of COVID-19 vaccines has rolled out globally, there is still a critical need for safe and effective vaccines to ensure fair and equitable supply for all countries. Here, we report on the development of a highly efficacious mRNA vaccine, SW0123 that is composed of sequence-modified mRNA encoding the full-length SARS-CoV-2 Spike protein packaged in core–shell structured lipopolyplex (LPP) nanoparticles. SW0123 is easy to produce using a large-scale microfluidics-based apparatus. The unique core–shell structured nanoparticle facilitates vaccine uptake and demonstrates a high colloidal stability, and a desirable biodistribution pattern with low liver targeting effect upon intramuscular administration. Extensive evaluations in mice and nonhuman primates revealed strong immunogenicity of SW0123, represented by induction of Th1-polarized T cell responses and high levels of antibodies that were capable of neutralizing not only the wild-type SARS-CoV-2, but also a panel of variants including D614G and N501Y variants. In addition, SW0123 conferred effective protection in both mice and non-human primates upon SARS-CoV-2 challenge. Taken together, SW0123 is a promising vaccine candidate that holds prospects for further evaluation in humans.
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spelling pubmed-81651472021-06-01 A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity Yang, Ren Deng, Yao Huang, Baoying Huang, Lei Lin, Ang Li, Yuhua Wang, Wenling Liu, Jingjing Lu, Shuaiyao Zhan, Zhenzhen Wang, Yufei A, Ruhan Wang, Wen Niu, Peihua Zhao, Li Li, Shiqiang Ma, Xiaopin Zhang, Luyao Zhang, Yujian Yao, Weiguo Liang, Xingjie Zhao, Jincun Liu, Zhongmin Peng, Xiaozhong Li, Hangwen Tan, Wenjie Signal Transduct Target Ther Article Although inoculation of COVID-19 vaccines has rolled out globally, there is still a critical need for safe and effective vaccines to ensure fair and equitable supply for all countries. Here, we report on the development of a highly efficacious mRNA vaccine, SW0123 that is composed of sequence-modified mRNA encoding the full-length SARS-CoV-2 Spike protein packaged in core–shell structured lipopolyplex (LPP) nanoparticles. SW0123 is easy to produce using a large-scale microfluidics-based apparatus. The unique core–shell structured nanoparticle facilitates vaccine uptake and demonstrates a high colloidal stability, and a desirable biodistribution pattern with low liver targeting effect upon intramuscular administration. Extensive evaluations in mice and nonhuman primates revealed strong immunogenicity of SW0123, represented by induction of Th1-polarized T cell responses and high levels of antibodies that were capable of neutralizing not only the wild-type SARS-CoV-2, but also a panel of variants including D614G and N501Y variants. In addition, SW0123 conferred effective protection in both mice and non-human primates upon SARS-CoV-2 challenge. Taken together, SW0123 is a promising vaccine candidate that holds prospects for further evaluation in humans. Nature Publishing Group UK 2021-05-31 /pmc/articles/PMC8165147/ /pubmed/34059617 http://dx.doi.org/10.1038/s41392-021-00634-z Text en © The Author(s) 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
Yang, Ren
Deng, Yao
Huang, Baoying
Huang, Lei
Lin, Ang
Li, Yuhua
Wang, Wenling
Liu, Jingjing
Lu, Shuaiyao
Zhan, Zhenzhen
Wang, Yufei
A, Ruhan
Wang, Wen
Niu, Peihua
Zhao, Li
Li, Shiqiang
Ma, Xiaopin
Zhang, Luyao
Zhang, Yujian
Yao, Weiguo
Liang, Xingjie
Zhao, Jincun
Liu, Zhongmin
Peng, Xiaozhong
Li, Hangwen
Tan, Wenjie
A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity
title A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity
title_full A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity
title_fullStr A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity
title_full_unstemmed A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity
title_short A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity
title_sort core-shell structured covid-19 mrna vaccine with favorable biodistribution pattern and promising immunity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165147/
https://www.ncbi.nlm.nih.gov/pubmed/34059617
http://dx.doi.org/10.1038/s41392-021-00634-z
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