Lyophilized mRNA-lipid nanoparticle vaccines with long-term stability and high antigenicity against SARS-CoV-2
Abstract Advanced mRNA vaccines play vital roles against SARS-CoV-2. However, most current mRNA delivery platforms need to be stored at −20 °C or −70 °C due to their poor stability, which severely restricts their availability. Herein, we develop a lyophilization technique to prepare SARS-CoV-2 mRNA-...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-01-01
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| Series: | Cell Discovery |
| Online Access: | https://doi.org/10.1038/s41421-022-00517-9 |
| _version_ | 1811176023290544128 |
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| author | Liangxia Ai Yafei Li Li Zhou Wenrong Yao Hao Zhang Zhaoyu Hu Jinyu Han Weijie Wang Junmiao Wu Pan Xu Ruiyue Wang Zhangyi Li Zhouwang Li Chengliang Wei Jianqun Liang Haobo Chen Zhimiao Yang Ming Guo Zhixiang Huang Xin Wang Zhen Zhang Wenjie Xiang Dazheng Sun Lianqiang Xu Meiyan Huang Bin Lv Peiqi Peng Shangfeng Zhang Xuhao Ji Huiyi Luo Nanping Chen Jianping Chen Ke Lan Yong Hu |
| author_facet | Liangxia Ai Yafei Li Li Zhou Wenrong Yao Hao Zhang Zhaoyu Hu Jinyu Han Weijie Wang Junmiao Wu Pan Xu Ruiyue Wang Zhangyi Li Zhouwang Li Chengliang Wei Jianqun Liang Haobo Chen Zhimiao Yang Ming Guo Zhixiang Huang Xin Wang Zhen Zhang Wenjie Xiang Dazheng Sun Lianqiang Xu Meiyan Huang Bin Lv Peiqi Peng Shangfeng Zhang Xuhao Ji Huiyi Luo Nanping Chen Jianping Chen Ke Lan Yong Hu |
| author_sort | Liangxia Ai |
| collection | DOAJ |
| description | Abstract Advanced mRNA vaccines play vital roles against SARS-CoV-2. However, most current mRNA delivery platforms need to be stored at −20 °C or −70 °C due to their poor stability, which severely restricts their availability. Herein, we develop a lyophilization technique to prepare SARS-CoV-2 mRNA-lipid nanoparticle vaccines with long-term thermostability. The physiochemical properties and bioactivities of lyophilized vaccines showed no change at 25 °C over 6 months, and the lyophilized SARS-CoV-2 mRNA vaccines could elicit potent humoral and cellular immunity whether in mice, rabbits, or rhesus macaques. Furthermore, in the human trial, administration of lyophilized Omicron mRNA vaccine as a booster shot also engendered strong immunity without severe adverse events, where the titers of neutralizing antibodies against Omicron BA.1/BA.2/BA.4 were increased by at least 253-fold after a booster shot following two doses of the commercial inactivated vaccine, CoronaVac. This lyophilization platform overcomes the instability of mRNA vaccines without affecting their bioactivity and significantly improves their accessibility, particularly in remote regions. |
| first_indexed | 2024-04-10T19:45:15Z |
| format | Article |
| id | doaj.art-73dae6977b1042ecb99db5da53664c88 |
| institution | Directory Open Access Journal |
| issn | 2056-5968 |
| language | English |
| last_indexed | 2024-04-10T19:45:15Z |
| publishDate | 2023-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Discovery |
| spelling | doaj.art-73dae6977b1042ecb99db5da53664c882023-01-29T12:04:10ZengNature Publishing GroupCell Discovery2056-59682023-01-019111510.1038/s41421-022-00517-9Lyophilized mRNA-lipid nanoparticle vaccines with long-term stability and high antigenicity against SARS-CoV-2Liangxia Ai0Yafei Li1Li Zhou2Wenrong Yao3Hao Zhang4Zhaoyu Hu5Jinyu Han6Weijie Wang7Junmiao Wu8Pan Xu9Ruiyue Wang10Zhangyi Li11Zhouwang Li12Chengliang Wei13Jianqun Liang14Haobo Chen15Zhimiao Yang16Ming Guo17Zhixiang Huang18Xin Wang19Zhen Zhang20Wenjie Xiang21Dazheng Sun22Lianqiang Xu23Meiyan Huang24Bin Lv25Peiqi Peng26Shangfeng Zhang27Xuhao Ji28Huiyi Luo29Nanping Chen30Jianping Chen31Ke Lan32Yong Hu33Shenzhen Rhegen Biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.State Key Laboratory of Virology, College of Life Sciences, ABSL-3 Laboratory/Institute for Vaccine Research, TaiKang Center for Life and Medical Sciences, Wuhan UniversityJiangsu Rec-biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.State Key Laboratory of Virology, College of Life Sciences, ABSL-3 Laboratory/Institute for Vaccine Research, TaiKang Center for Life and Medical Sciences, Wuhan UniversityState Key Laboratory of Virology, College of Life Sciences, ABSL-3 Laboratory/Institute for Vaccine Research, TaiKang Center for Life and Medical Sciences, Wuhan UniversityState Key Laboratory of Virology, College of Life Sciences, ABSL-3 Laboratory/Institute for Vaccine Research, TaiKang Center for Life and Medical Sciences, Wuhan UniversityState Key Laboratory of Virology, College of Life Sciences, ABSL-3 Laboratory/Institute for Vaccine Research, TaiKang Center for Life and Medical Sciences, Wuhan UniversityState Key Laboratory of Virology, College of Life Sciences, ABSL-3 Laboratory/Institute for Vaccine Research, TaiKang Center for Life and Medical Sciences, Wuhan UniversityShenzhen Rhegen Biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.Shenzhen Rhegen Biotechnology Co. Ltd.Jiangsu Rec-biotechnology Co. Ltd.State Key Laboratory of Virology, College of Life Sciences, ABSL-3 Laboratory/Institute for Vaccine Research, TaiKang Center for Life and Medical Sciences, Wuhan UniversityShenzhen Rhegen Biotechnology Co. Ltd.Abstract Advanced mRNA vaccines play vital roles against SARS-CoV-2. However, most current mRNA delivery platforms need to be stored at −20 °C or −70 °C due to their poor stability, which severely restricts their availability. Herein, we develop a lyophilization technique to prepare SARS-CoV-2 mRNA-lipid nanoparticle vaccines with long-term thermostability. The physiochemical properties and bioactivities of lyophilized vaccines showed no change at 25 °C over 6 months, and the lyophilized SARS-CoV-2 mRNA vaccines could elicit potent humoral and cellular immunity whether in mice, rabbits, or rhesus macaques. Furthermore, in the human trial, administration of lyophilized Omicron mRNA vaccine as a booster shot also engendered strong immunity without severe adverse events, where the titers of neutralizing antibodies against Omicron BA.1/BA.2/BA.4 were increased by at least 253-fold after a booster shot following two doses of the commercial inactivated vaccine, CoronaVac. This lyophilization platform overcomes the instability of mRNA vaccines without affecting their bioactivity and significantly improves their accessibility, particularly in remote regions.https://doi.org/10.1038/s41421-022-00517-9 |
| spellingShingle | Liangxia Ai Yafei Li Li Zhou Wenrong Yao Hao Zhang Zhaoyu Hu Jinyu Han Weijie Wang Junmiao Wu Pan Xu Ruiyue Wang Zhangyi Li Zhouwang Li Chengliang Wei Jianqun Liang Haobo Chen Zhimiao Yang Ming Guo Zhixiang Huang Xin Wang Zhen Zhang Wenjie Xiang Dazheng Sun Lianqiang Xu Meiyan Huang Bin Lv Peiqi Peng Shangfeng Zhang Xuhao Ji Huiyi Luo Nanping Chen Jianping Chen Ke Lan Yong Hu Lyophilized mRNA-lipid nanoparticle vaccines with long-term stability and high antigenicity against SARS-CoV-2 Cell Discovery |
| title | Lyophilized mRNA-lipid nanoparticle vaccines with long-term stability and high antigenicity against SARS-CoV-2 |
| title_full | Lyophilized mRNA-lipid nanoparticle vaccines with long-term stability and high antigenicity against SARS-CoV-2 |
| title_fullStr | Lyophilized mRNA-lipid nanoparticle vaccines with long-term stability and high antigenicity against SARS-CoV-2 |
| title_full_unstemmed | Lyophilized mRNA-lipid nanoparticle vaccines with long-term stability and high antigenicity against SARS-CoV-2 |
| title_short | Lyophilized mRNA-lipid nanoparticle vaccines with long-term stability and high antigenicity against SARS-CoV-2 |
| title_sort | lyophilized mrna lipid nanoparticle vaccines with long term stability and high antigenicity against sars cov 2 |
| url | https://doi.org/10.1038/s41421-022-00517-9 |
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