Development of recombinant COVID-19 vaccine based on CHO-produced, prefusion spike trimer and alum/CpG adjuvants

• Published in: Vaccine Vol. 39; no. 48; pp. 7001 - 7011
• Main Authors: Liu, Haitao, Zhou, Chenliang, An, Jiao, Song, Yujiao, Yu, Pin, Li, Jiadai, Gu, Chenjian, Hu, Dongdong, Jiang, Yuanxiang, Zhang, Lingli, Huang, Chuanqi, Zhang, Chao, Yang, Yunqi, Zhu, Qianjun, Wang, Dekui, Liu, Yuqiang, Miao, Chenyang, Cao, Xiayao, Ding, Longfei, Zhu, Yuanfei, Zhu, Hua, Bao, Linlin, Zhou, Lingyun, Yan, Huan, Fan, Jiang, Xu, Jianqing, Hu, Zhongyu, Xie, Youhua, Liu, Jiangning, Liu, Ge
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 26.11.2021; Elsevier Limited; Elsevier Science
• Subjects: Adjuvants; Allergy and Immunology; Alum; Aluminum; aluminum hydroxide; Antibodies; Antigens; Binding sites; CD4 antigen; China; Chromatography; Clinical trials; Coronaviruses; COVID-19; COVID-19 infection; COVID-19 vaccines; CpG islands; Cricetulus griseus; Glycoproteins; Hamsters; Immunogenicity; inflammation; Lymphocytes; Lymphocytes T; Medical research; Neutralization; Neutralizing; Pandemics; pneumonia; Proteins; Public health; recombinant vaccines; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Spike protein; Subunit vaccine; Trimeric spike protein; Trimers; Vaccines; Viral diseases; China; Trimeric spike protein; Subunit vaccine; SARS-CoV-2
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2021.10.066

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).