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mRNA Vaccines Against SARS‐CoV‐2 Variants Delivered by Lipid Nanoparticles Based on Novel Ionizable Lipids
SARS‐CoV‐2 variants are now still challenging all the approved vaccines, including mRNA vaccines. There is an urgent need to develop new generation mRNA vaccines with more powerful efficacy and better safety against SARS‐CoV‐2 variants. In this study, a new set of ionizable lipids named 4N4T are con...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349794/ https://www.ncbi.nlm.nih.gov/pubmed/35942272 http://dx.doi.org/10.1002/adfm.202204692 |
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author | Chen, Kepan Fan, Na Huang, Hai Jiang, Xin Qin, Shugang Xiao, Wen Zheng, Qian Zhang, Yupei Duan, Xing Qin, Zeyi Liu, Yongmei Zeng, Jun Wei, Yuquan Song, Xiangrong |
author_facet | Chen, Kepan Fan, Na Huang, Hai Jiang, Xin Qin, Shugang Xiao, Wen Zheng, Qian Zhang, Yupei Duan, Xing Qin, Zeyi Liu, Yongmei Zeng, Jun Wei, Yuquan Song, Xiangrong |
author_sort | Chen, Kepan |
collection | PubMed |
description | SARS‐CoV‐2 variants are now still challenging all the approved vaccines, including mRNA vaccines. There is an urgent need to develop new generation mRNA vaccines with more powerful efficacy and better safety against SARS‐CoV‐2 variants. In this study, a new set of ionizable lipids named 4N4T are constructed and applied to form novel lipid nanoparticles called 4N4T‐LNPs. Leading 4N4T‐LNPs exhibit much higher mRNA translation efficiency than the approved SM‐102‐LNPs. To test the effectiveness of the novel delivery system, the DS mRNA encoding the full‐length S protein of the SARS‐CoV‐2 variant is synthesized and loaded in 4N4T‐LNPs. The obtained 4N4T‐DS mRNA vaccines successfully trigger robust and durable humoral immune responses against SARS‐CoV‐2 and its variants including Delta and Omicron. Importantly, the novel vaccines have higher RBD‐specific IgG titers and neutralizing antibody titers than SM‐102‐based DS mRNA vaccine. Besides, for the first time, the types of mRNA vaccine‐induced neutralizing antibodies are found to be influenced by the chemical structure of ionizable lipids. 4N4T‐DS mRNA vaccines also induce strong Th1‐skewed T cell responses and have good safety. This work provides a novel vehicle for mRNA delivery that is more effective than the approved LNPs and shows its application in vaccines against SARS‐CoV‐2 variants. |
format | Online Article Text |
id | pubmed-9349794 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93497942022-08-04 mRNA Vaccines Against SARS‐CoV‐2 Variants Delivered by Lipid Nanoparticles Based on Novel Ionizable Lipids Chen, Kepan Fan, Na Huang, Hai Jiang, Xin Qin, Shugang Xiao, Wen Zheng, Qian Zhang, Yupei Duan, Xing Qin, Zeyi Liu, Yongmei Zeng, Jun Wei, Yuquan Song, Xiangrong Adv Funct Mater Research Articles SARS‐CoV‐2 variants are now still challenging all the approved vaccines, including mRNA vaccines. There is an urgent need to develop new generation mRNA vaccines with more powerful efficacy and better safety against SARS‐CoV‐2 variants. In this study, a new set of ionizable lipids named 4N4T are constructed and applied to form novel lipid nanoparticles called 4N4T‐LNPs. Leading 4N4T‐LNPs exhibit much higher mRNA translation efficiency than the approved SM‐102‐LNPs. To test the effectiveness of the novel delivery system, the DS mRNA encoding the full‐length S protein of the SARS‐CoV‐2 variant is synthesized and loaded in 4N4T‐LNPs. The obtained 4N4T‐DS mRNA vaccines successfully trigger robust and durable humoral immune responses against SARS‐CoV‐2 and its variants including Delta and Omicron. Importantly, the novel vaccines have higher RBD‐specific IgG titers and neutralizing antibody titers than SM‐102‐based DS mRNA vaccine. Besides, for the first time, the types of mRNA vaccine‐induced neutralizing antibodies are found to be influenced by the chemical structure of ionizable lipids. 4N4T‐DS mRNA vaccines also induce strong Th1‐skewed T cell responses and have good safety. This work provides a novel vehicle for mRNA delivery that is more effective than the approved LNPs and shows its application in vaccines against SARS‐CoV‐2 variants. John Wiley and Sons Inc. 2022-07-19 2022-09-26 /pmc/articles/PMC9349794/ /pubmed/35942272 http://dx.doi.org/10.1002/adfm.202204692 Text en © 2022 The Authors. Advanced Functional Materials published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Chen, Kepan Fan, Na Huang, Hai Jiang, Xin Qin, Shugang Xiao, Wen Zheng, Qian Zhang, Yupei Duan, Xing Qin, Zeyi Liu, Yongmei Zeng, Jun Wei, Yuquan Song, Xiangrong mRNA Vaccines Against SARS‐CoV‐2 Variants Delivered by Lipid Nanoparticles Based on Novel Ionizable Lipids |
title | mRNA Vaccines Against SARS‐CoV‐2 Variants Delivered by Lipid Nanoparticles Based on Novel Ionizable Lipids |
title_full | mRNA Vaccines Against SARS‐CoV‐2 Variants Delivered by Lipid Nanoparticles Based on Novel Ionizable Lipids |
title_fullStr | mRNA Vaccines Against SARS‐CoV‐2 Variants Delivered by Lipid Nanoparticles Based on Novel Ionizable Lipids |
title_full_unstemmed | mRNA Vaccines Against SARS‐CoV‐2 Variants Delivered by Lipid Nanoparticles Based on Novel Ionizable Lipids |
title_short | mRNA Vaccines Against SARS‐CoV‐2 Variants Delivered by Lipid Nanoparticles Based on Novel Ionizable Lipids |
title_sort | mrna vaccines against sars‐cov‐2 variants delivered by lipid nanoparticles based on novel ionizable lipids |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349794/ https://www.ncbi.nlm.nih.gov/pubmed/35942272 http://dx.doi.org/10.1002/adfm.202204692 |
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