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Lipid nanoparticle-encapsulated mRNA antibody provides long-term protection against SARS-CoV-2 in mice and hamsters
Monoclonal antibodies represent important weapons in our arsenal to against the COVID-19 pandemic. However, this potential is severely limited by the time-consuming process of developing effective antibodies and the relative high cost of manufacturing. Herein, we present a rapid and cost-effective l...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Singapore
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866932/ https://www.ncbi.nlm.nih.gov/pubmed/35210606 http://dx.doi.org/10.1038/s41422-022-00630-0 |
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author | Deng, Yong-Qiang Zhang, Na-Na Zhang, Yi-Fei Zhong, Xia Xu, Sue Qiu, Hong-Ying Wang, Tie-Cheng Zhao, Hui Zhou, Chao Zu, Shu-Long Chen, Qi Cao, Tian-Shu Ye, Qing Chi, Hang Duan, Xiang-Hui Lin, Dan-Dan Zhang, Xiao-Jing Xie, Liang-Zhi Gao, Yu-Wei Ying, Bo Qin, Cheng-Feng |
author_facet | Deng, Yong-Qiang Zhang, Na-Na Zhang, Yi-Fei Zhong, Xia Xu, Sue Qiu, Hong-Ying Wang, Tie-Cheng Zhao, Hui Zhou, Chao Zu, Shu-Long Chen, Qi Cao, Tian-Shu Ye, Qing Chi, Hang Duan, Xiang-Hui Lin, Dan-Dan Zhang, Xiao-Jing Xie, Liang-Zhi Gao, Yu-Wei Ying, Bo Qin, Cheng-Feng |
author_sort | Deng, Yong-Qiang |
collection | PubMed |
description | Monoclonal antibodies represent important weapons in our arsenal to against the COVID-19 pandemic. However, this potential is severely limited by the time-consuming process of developing effective antibodies and the relative high cost of manufacturing. Herein, we present a rapid and cost-effective lipid nanoparticle (LNP) encapsulated-mRNA platform for in vivo delivery of SARS-CoV-2 neutralization antibodies. Two mRNAs encoding the light and heavy chains of a potent SARS-CoV-2 neutralizing antibody HB27, which is currently being evaluated in clinical trials, were encapsulated into clinical grade LNP formulations (named as mRNA-HB27-LNP). In vivo characterization demonstrated that intravenous administration of mRNA-HB27-LNP in mice resulted in a longer circulating half-life compared with the original HB27 antibody in protein format. More importantly, a single prophylactic administration of mRNA-HB27-LNP provided protection against SARS-CoV-2 challenge in mice at 1, 7 and even 63 days post administration. In a close contact transmission model, prophylactic administration of mRNA-HB27-LNP prevented SARS-CoV-2 infection between hamsters in a dose-dependent manner. Overall, our results demonstrate a superior long-term protection against SARS-CoV-2 conferred by a single administration of this unique mRNA antibody, highlighting the potential of this universal platform for antibody-based disease prevention and therapy against COVID-19 as well as a variety of other infectious diseases. |
format | Online Article Text |
id | pubmed-8866932 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Singapore |
record_format | MEDLINE/PubMed |
spelling | pubmed-88669322022-02-24 Lipid nanoparticle-encapsulated mRNA antibody provides long-term protection against SARS-CoV-2 in mice and hamsters Deng, Yong-Qiang Zhang, Na-Na Zhang, Yi-Fei Zhong, Xia Xu, Sue Qiu, Hong-Ying Wang, Tie-Cheng Zhao, Hui Zhou, Chao Zu, Shu-Long Chen, Qi Cao, Tian-Shu Ye, Qing Chi, Hang Duan, Xiang-Hui Lin, Dan-Dan Zhang, Xiao-Jing Xie, Liang-Zhi Gao, Yu-Wei Ying, Bo Qin, Cheng-Feng Cell Res Article Monoclonal antibodies represent important weapons in our arsenal to against the COVID-19 pandemic. However, this potential is severely limited by the time-consuming process of developing effective antibodies and the relative high cost of manufacturing. Herein, we present a rapid and cost-effective lipid nanoparticle (LNP) encapsulated-mRNA platform for in vivo delivery of SARS-CoV-2 neutralization antibodies. Two mRNAs encoding the light and heavy chains of a potent SARS-CoV-2 neutralizing antibody HB27, which is currently being evaluated in clinical trials, were encapsulated into clinical grade LNP formulations (named as mRNA-HB27-LNP). In vivo characterization demonstrated that intravenous administration of mRNA-HB27-LNP in mice resulted in a longer circulating half-life compared with the original HB27 antibody in protein format. More importantly, a single prophylactic administration of mRNA-HB27-LNP provided protection against SARS-CoV-2 challenge in mice at 1, 7 and even 63 days post administration. In a close contact transmission model, prophylactic administration of mRNA-HB27-LNP prevented SARS-CoV-2 infection between hamsters in a dose-dependent manner. Overall, our results demonstrate a superior long-term protection against SARS-CoV-2 conferred by a single administration of this unique mRNA antibody, highlighting the potential of this universal platform for antibody-based disease prevention and therapy against COVID-19 as well as a variety of other infectious diseases. Springer Singapore 2022-02-24 2022-04 /pmc/articles/PMC8866932/ /pubmed/35210606 http://dx.doi.org/10.1038/s41422-022-00630-0 Text en © The Author(s) 2022 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 Deng, Yong-Qiang Zhang, Na-Na Zhang, Yi-Fei Zhong, Xia Xu, Sue Qiu, Hong-Ying Wang, Tie-Cheng Zhao, Hui Zhou, Chao Zu, Shu-Long Chen, Qi Cao, Tian-Shu Ye, Qing Chi, Hang Duan, Xiang-Hui Lin, Dan-Dan Zhang, Xiao-Jing Xie, Liang-Zhi Gao, Yu-Wei Ying, Bo Qin, Cheng-Feng Lipid nanoparticle-encapsulated mRNA antibody provides long-term protection against SARS-CoV-2 in mice and hamsters |
title | Lipid nanoparticle-encapsulated mRNA antibody provides long-term protection against SARS-CoV-2 in mice and hamsters |
title_full | Lipid nanoparticle-encapsulated mRNA antibody provides long-term protection against SARS-CoV-2 in mice and hamsters |
title_fullStr | Lipid nanoparticle-encapsulated mRNA antibody provides long-term protection against SARS-CoV-2 in mice and hamsters |
title_full_unstemmed | Lipid nanoparticle-encapsulated mRNA antibody provides long-term protection against SARS-CoV-2 in mice and hamsters |
title_short | Lipid nanoparticle-encapsulated mRNA antibody provides long-term protection against SARS-CoV-2 in mice and hamsters |
title_sort | lipid nanoparticle-encapsulated mrna antibody provides long-term protection against sars-cov-2 in mice and hamsters |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866932/ https://www.ncbi.nlm.nih.gov/pubmed/35210606 http://dx.doi.org/10.1038/s41422-022-00630-0 |
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