Ai Liangxia, Li Yafei, Zhou Li, Yao Wenrong, Zhang Hao, Hu Zhaoyu, Han Jinyu, Wang Weijie, Wu Junmiao, Xu Pan, Wang Ruiyue, Li Zhangyi, Li Zhouwang, Wei Chengliang, Liang Jianqun, Chen Haobo, Yang Zhimiao, Guo Ming, Huang Zhixiang, Wang Xin, Zhang Zhen, Xiang Wenjie, Sun Dazheng, Xu Lianqiang, Huang Meiyan, Lv Bin, Peng Peiqi, Zhang Shangfeng, Ji Xuhao, Luo Huiyi, Chen Nanping, Chen Jianping, Lan Ke, Hu Yong
Shenzhen Rhegen Biotechnology Co. Ltd., Shenzhen, Guangdong, China.
State Key Laboratory of Virology, College of Life Sciences, ABSL-3 Laboratory/Institute for Vaccine Research, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, Hubei, China.
Cell Discov. 2023 Jan 23;9(1):9. doi: 10.1038/s41421-022-00517-9.
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.
先进的mRNA疫苗在对抗SARS-CoV-2方面发挥着至关重要的作用。然而，由于稳定性较差，目前大多数mRNA递送平台需要在-20°C或-70°C下储存，这严重限制了它们的可用性。在此，我们开发了一种冻干技术来制备具有长期热稳定性的SARS-CoV-2 mRNA-脂质纳米颗粒疫苗。冻干疫苗的理化性质和生物活性在25°C下6个月内无变化，冻干的SARS-CoV-2 mRNA疫苗无论在小鼠、兔子还是恒河猴中都能引发强大的体液免疫和细胞免疫。此外，在人体试验中，作为加强针接种冻干的奥密克戎mRNA疫苗也能产生强大的免疫力，且无严重不良事件，在接种两剂商用灭活疫苗科兴疫苗后再接种加强针，针对奥密克戎BA.1/BA.2/BA.4的中和抗体滴度至少提高了253倍。这种冻干平台克服了mRNA疫苗的不稳定性，同时不影响其生物活性，并显著提高了它们的可及性，特别是在偏远地区。
