A tandem-repeat dimeric RBD protein-based covid-19 vaccine zf2001 protects mice and nonhuman primates

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) prot...

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Main Authors: 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
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Emerging Microbes and Infections
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2022.2056524
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author 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
author_facet 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
author_sort Yaling An
collection DOAJ
description 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.
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spelling doaj.art-ff8a374f442344f5abd669d7a990dd882022-12-21T19:00:40ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512022-12-011111058107110.1080/22221751.2022.2056524A tandem-repeat dimeric RBD protein-based covid-19 vaccine zf2001 protects mice and nonhuman primatesYaling An0Shihua Li1Xiyue Jin2Jian-bao Han3Kun Xu4Senyu Xu5Yuxuan Han6Chuanyu Liu7Tianyi Zheng8Mei Liu9Mi Yang10Tian-Zhang Song11Baoying Huang12Li Zhao13Wen Wang14Ruhan A15Yingjie Cheng16Changwei Wu17Enqi Huang18Shilong Yang19Gary Wong20Yuhai Bi21Changwen Ke22Wenjie Tan23Jinghua Yan24Yong-Tang Zheng25Lianpan Dai26George F. Gao27Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 101408, People’s Republic of ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of ChinaSchool of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230026, People’s Republic of ChinaKunming 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 ChinaKey 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 ChinaResearch Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of ChinaSavaid Medical School, University of Chinese Academy of Sciences, Beijing, 101408, People’s Republic of ChinaLaboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Guangxi University, Nanning, 530000, People’s Republic of ChinaResearch Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of ChinaCAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of ChinaCAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of ChinaKey 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 ChinaNHC 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 ChinaNHC 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 ChinaNHC 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 ChinaNHC 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 ChinaAnhui Zhifei Longcom Biopharmaceutical Co. Ltd, Anhui, 230088, People’s Republic of ChinaAnhui Zhifei Longcom Biopharmaceutical Co. Ltd, Anhui, 230088, People’s Republic of ChinaAnhui Zhifei Longcom Biopharmaceutical Co. Ltd, Anhui, 230088, People’s Republic of ChinaAnhui Zhifei Longcom Biopharmaceutical Co. Ltd, Anhui, 230088, People’s Republic of ChinaCAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, People’s Republic of ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of ChinaGuangdong Provincial Center for Disease Control and Prevention, Guangzhou 511430, People’s Republic of ChinaNHC 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 ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of ChinaKunming 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 ChinaSavaid Medical School, University of Chinese Academy of Sciences, Beijing, 101408, People’s Republic of ChinaSavaid Medical School, University of Chinese Academy of Sciences, Beijing, 101408, People’s Republic of ChinaSafe, 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.https://www.tandfonline.com/doi/10.1080/22221751.2022.2056524Covid-19subunit protein vaccinezf2001antibodyimmune response
spellingShingle 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
A tandem-repeat dimeric RBD protein-based covid-19 vaccine zf2001 protects mice and nonhuman primates
Emerging Microbes and Infections
Covid-19
subunit protein vaccine
zf2001
antibody
immune response
title A tandem-repeat dimeric RBD protein-based covid-19 vaccine zf2001 protects mice and nonhuman primates
title_full A tandem-repeat dimeric RBD protein-based covid-19 vaccine zf2001 protects mice and nonhuman primates
title_fullStr A tandem-repeat dimeric RBD protein-based covid-19 vaccine zf2001 protects mice and nonhuman primates
title_full_unstemmed A tandem-repeat dimeric RBD protein-based covid-19 vaccine zf2001 protects mice and nonhuman primates
title_short A tandem-repeat dimeric RBD protein-based covid-19 vaccine zf2001 protects mice and nonhuman primates
title_sort tandem repeat dimeric rbd protein based covid 19 vaccine zf2001 protects mice and nonhuman primates
topic Covid-19
subunit protein vaccine
zf2001
antibody
immune response
url https://www.tandfonline.com/doi/10.1080/22221751.2022.2056524
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