Emerging Microbes and Infections (Dec 2022)
A tandem-repeat dimeric RBD protein-based covid-19 vaccine zf2001 protects mice and nonhuman primates
- Yaling An,
- Shihua Li,
- Xiyue Jin,
- Jian-bao Han,
- Kun Xu,
- Senyu Xu,
- Yuxuan Han,
- Chuanyu Liu,
- Tianyi Zheng,
- Mei Liu,
- Mi Yang,
- Tian-Zhang Song,
- Baoying Huang,
- Li Zhao,
- Wen Wang,
- Ruhan A,
- Yingjie Cheng,
- Changwei Wu,
- Enqi Huang,
- Shilong Yang,
- Gary Wong,
- Yuhai Bi,
- Changwen Ke,
- Wenjie Tan,
- Jinghua Yan,
- Yong-Tang Zheng,
- Lianpan Dai,
- George F. Gao
Affiliations
- Yaling An
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 101408, People’s Republic of China
- Shihua Li
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China
- Xiyue Jin
- School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230026, People’s Republic of China
- Jian-bao Han
- Kunming National High-Level Biosafety Research Center for Non-human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650107, People’s Republic of China
- Kun Xu
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Tropical Medicine and Laboratory Medicine, The First Affiliated Hospital, Hainan Medical University, Hainan, 571199, People’s Republic of China
- Senyu Xu
- Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China
- Yuxuan Han
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 101408, People’s Republic of China
- Chuanyu Liu
- Laboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Guangxi University, Nanning, 530000, People’s Republic of China
- Tianyi Zheng
- Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China
- Mei Liu
- CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China
- Mi Yang
- CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China
- Tian-Zhang Song
- Key Laboratory of Animal Models and Human Disease Mechanism of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academic of Sciences, Kunming, 650223, People’s Republic of China
- Baoying Huang
- NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China
- Li Zhao
- NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China
- Wen Wang
- NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China
- Ruhan A
- NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China
- Yingjie Cheng
- Anhui Zhifei Longcom Biopharmaceutical Co. Ltd, Anhui, 230088, People’s Republic of China
- Changwei Wu
- Anhui Zhifei Longcom Biopharmaceutical Co. Ltd, Anhui, 230088, People’s Republic of China
- Enqi Huang
- Anhui Zhifei Longcom Biopharmaceutical Co. Ltd, Anhui, 230088, People’s Republic of China
- Shilong Yang
- Anhui Zhifei Longcom Biopharmaceutical Co. Ltd, Anhui, 230088, People’s Republic of China
- Gary Wong
- CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, People’s Republic of China
- Yuhai Bi
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China
- Changwen Ke
- Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 511430, People’s Republic of China
- Wenjie Tan
- NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China
- Jinghua Yan
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China
- Yong-Tang Zheng
- Kunming National High-Level Biosafety Research Center for Non-human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650107, People’s Republic of China
- Lianpan Dai
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 101408, People’s Republic of China
- George F. Gao
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 101408, People’s Republic of China
- DOI
- https://doi.org/10.1080/22221751.2022.2056524
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1058 – 1071
Abstract
Safe, efficacious, and deployable vaccines are urgently needed to control COVID-19 in the large-scale vaccination campaigns. We report here the preclinical studies of an approved protein subunit vaccine against COVID-19, ZF2001, which contains tandem-repeat dimeric receptor-binding domain (RBD) protein with alum-based adjuvant. We assessed vaccine immunogenicity and efficacy in both mice and non-human primates (NHPs). ZF2001 induced high levels of RBD-binding and SARS-CoV-2 neutralizing antibody in both mice and non-human primates, and elicited balanced TH1/TH2 cellular responses in NHPs. Two doses of ZF2001 protected Ad-hACE2-transduced mice against SARS-CoV-2 infection, as detected by reduced viral RNA and relieved lung injuries. In NHPs, vaccination of either 25 μg or 50 μg ZF2001 prevented infection with SARS-CoV-2 in lung, trachea, and bronchi, with milder lung lesions. No evidence of disease enhancement was observed in both animal models. ZF2001 has been approved for emergency use in China, Uzbekistan, Indonesia, and Columbia. The high safety, immunogenicity, and protection efficacy in both mice and NHPs found in this preclinical study was consistent with the results in human clinical trials.
Keywords
