Development of recombinant COVID-19 vaccine based on CHO-produced, prefusion spike trimer and alum/CpG adjuvants
Haitao Liu, Chenliang Zhou, Jiao An, Yujiao Song, Pin Yu, Jiadai Li, Chenjian Gu, Dongdong Hu, Yuanxiang Jiang, Lingli Zhang, Chuanqi Huang, Chao Zhang, Yunqi Yang, Qianjun Zhu, Dekui Wang, Yuqiang Liu, Chenyang Miao, Xiayao Cao, Longfei Ding, Yuanfei Zhu, Hua Zhu, Linlin Bao, Lingyun Zhou, Huan Yan, Jiang Fan, Jianqing Xu, Zhongyu Hu, Youhua Xie, Jiangning Liu, Ge Liu, Haitao Liu, Chenliang Zhou, Jiao An, Yujiao Song, Pin Yu, Jiadai Li, Chenjian Gu, Dongdong Hu, Yuanxiang Jiang, Lingli Zhang, Chuanqi Huang, Chao Zhang, Yunqi Yang, Qianjun Zhu, Dekui Wang, Yuqiang Liu, Chenyang Miao, Xiayao Cao, Longfei Ding, Yuanfei Zhu, Hua Zhu, Linlin Bao, Lingyun Zhou, Huan Yan, Jiang Fan, Jianqing Xu, Zhongyu Hu, Youhua Xie, Jiangning Liu, Ge Liu
Abstract
COVID-19 pandemic has severely impacted the public health and social economy worldwide. A safe, effective, and affordable vaccine against SARS-CoV-2 infections/diseases is urgently needed. We have been developing a recombinant vaccine based on a prefusion-stabilized spike trimer of SARS-CoV-2 and formulated with aluminium hydroxide and CpG 7909. The spike protein was expressed in Chinese hamster ovary (CHO) cells, purified, and prepared as a stable formulation with the dual adjuvant. Immunogenicity studies showed that candidate vaccines elicited robust neutralizing antibody responses and substantial CD4+ T cell responses in both mice and non-human primates. And vaccine-induced neutralizing antibodies persisted at high level for at least 6 months. Challenge studies demonstrated that candidate vaccine reduced the viral loads and inflammation in the lungs of SARS-CoV-2 infected golden Syrian hamsters significantly. In addition, the vaccine-induced antibodies showed cross-neutralization activity against B.1.1.7 and B.1.351 variants. These data suggest candidate vaccine is efficacious in preventing SARS-CoV-2 infections and associated pneumonia, thereby justifying ongoing phase I/II clinical studies in China (NCT04982068 and NCT04990544).
Keywords: SARS-CoV-2; Subunit vaccine; Trimeric spike protein.
Conflict of interest statement
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Copyright © 2021. Published by Elsevier Ltd.
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References
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