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Recombinant chimpanzee adenovirus AdC7 expressing dimeric tandem-repeat spike protein RBD protects mice against COVID-19.
Emerg Microbes Infect. 2021 Dec; 10(1):1574-1588.EM

Abstract

A safe and effective vaccine is urgently needed to control the unprecedented COVID-19 pandemic. Four adenovirus-vectored vaccines expressing spike (S) protein have been approved for use. Here, we generated several recombinant chimpanzee adenovirus (AdC7) vaccines expressing S, receptor-binding domain (RBD), or tandem-repeat dimeric RBD (RBD-tr2). We found vaccination via either intramuscular or intranasal route was highly immunogenic in mice to elicit both humoral and cellular immune responses. AdC7-RBD-tr2 showed higher antibody responses compared to either AdC7-S or AdC7-RBD. Intranasal administration of AdC7-RBD-tr2 additionally induced mucosal immunity with neutralizing activity in bronchoalveolar lavage fluid. Either single-dose or two-dose mucosal administration of AdC7-RBD-tr2 protected mice against SARS-CoV-2 challenge, with undetectable subgenomic RNA in lung and relieved lung injury. AdC7-RBD-tr2-elicted sera preserved the neutralizing activity against the circulating variants, especially the Delta variant. These results support AdC7-RBD-tr2 as a promising COVID-19 vaccine candidate.

Authors+Show Affiliations

Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Tropical Medicine and Laboratory Medicine, The First Affiliated Hospital, Hainan Medical University, Haikou, People's Republic of China. Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, People's Republic of China.Savaid Medical School, University of Chinese Academy of Sciences, Beijing, People's Republic of China.Chengdu Kanghua Biological Products Co., Ltd, Chengdu, People's Republic of China.Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing, People's Republic of China.Savaid Medical School, University of Chinese Academy of Sciences, Beijing, People's Republic of China.Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, People's Republic of China.Chengdu Kanghua Biological Products Co., Ltd, Chengdu, People's Republic of China.Chengdu Kanghua Biological Products Co., Ltd, Chengdu, People's Republic of China.Laboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Guangxi University, Nanning, People's Republic of China.Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, People's Republic of China.Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, People's Republic of China.School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.Laboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Guangxi University, Nanning, People's Republic of China.CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People's Republic of China. CAS Center for Influenza Research and Early-Warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing, People's Republic of China.National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People's Republic of China. CAS Center for Influenza Research and Early-Warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing, People's Republic of China.Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing, People's Republic of China.Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, People's Republic of China.Chengdu Kanghua Biological Products Co., Ltd, Chengdu, People's Republic of China.Chengdu Kanghua Biological Products Co., Ltd, Chengdu, People's Republic of China.Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Tropical Medicine and Laboratory Medicine, The First Affiliated Hospital, Hainan Medical University, Haikou, People's Republic of China.Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, People's Republic of China. CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People's Republic of China. National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Tropical Medicine and Laboratory Medicine, The First Affiliated Hospital, Hainan Medical University, Haikou, People's Republic of China. CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People's Republic of China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34289779

Citation

Xu, Kun, et al. "Recombinant Chimpanzee Adenovirus AdC7 Expressing Dimeric Tandem-repeat Spike Protein RBD Protects Mice Against COVID-19." Emerging Microbes & Infections, vol. 10, no. 1, 2021, pp. 1574-1588.
Xu K, An Y, Li Q, et al. Recombinant chimpanzee adenovirus AdC7 expressing dimeric tandem-repeat spike protein RBD protects mice against COVID-19. Emerg Microbes Infect. 2021;10(1):1574-1588.
Xu, K., An, Y., Li, Q., Huang, W., Han, Y., Zheng, T., Fang, F., Liu, H., Liu, C., Gao, P., Xu, S., Liu, X., Zhang, R., Zhao, X., Liu, W. J., Bi, Y., Wang, Y., Zhou, D., Wang, Q., ... Dai, L. (2021). Recombinant chimpanzee adenovirus AdC7 expressing dimeric tandem-repeat spike protein RBD protects mice against COVID-19. Emerging Microbes & Infections, 10(1), 1574-1588. https://doi.org/10.1080/22221751.2021.1959270
Xu K, et al. Recombinant Chimpanzee Adenovirus AdC7 Expressing Dimeric Tandem-repeat Spike Protein RBD Protects Mice Against COVID-19. Emerg Microbes Infect. 2021;10(1):1574-1588. PubMed PMID: 34289779.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recombinant chimpanzee adenovirus AdC7 expressing dimeric tandem-repeat spike protein RBD protects mice against COVID-19. AU - Xu,Kun, AU - An,Yaling, AU - Li,Qunlong, AU - Huang,Weijin, AU - Han,Yuxuan, AU - Zheng,Tianyi, AU - Fang,Fang, AU - Liu,Hui, AU - Liu,Chuanyu, AU - Gao,Ping, AU - Xu,Senyu, AU - Liu,Xueyuan, AU - Zhang,Rong, AU - Zhao,Xin, AU - Liu,William J, AU - Bi,Yuhai, AU - Wang,Youchun, AU - Zhou,Dongming, AU - Wang,Qinghan, AU - Hou,Wenli, AU - Xia,Qianfeng, AU - Gao,George F, AU - Dai,Lianpan, PY - 2021/7/23/pubmed PY - 2021/8/20/medline PY - 2021/7/22/entrez KW - COVID-19 KW - SARS-CoV-2 KW - adenovirus KW - antibody KW - immune response KW - vaccine SP - 1574 EP - 1588 JF - Emerging microbes & infections JO - Emerg Microbes Infect VL - 10 IS - 1 N2 - A safe and effective vaccine is urgently needed to control the unprecedented COVID-19 pandemic. Four adenovirus-vectored vaccines expressing spike (S) protein have been approved for use. Here, we generated several recombinant chimpanzee adenovirus (AdC7) vaccines expressing S, receptor-binding domain (RBD), or tandem-repeat dimeric RBD (RBD-tr2). We found vaccination via either intramuscular or intranasal route was highly immunogenic in mice to elicit both humoral and cellular immune responses. AdC7-RBD-tr2 showed higher antibody responses compared to either AdC7-S or AdC7-RBD. Intranasal administration of AdC7-RBD-tr2 additionally induced mucosal immunity with neutralizing activity in bronchoalveolar lavage fluid. Either single-dose or two-dose mucosal administration of AdC7-RBD-tr2 protected mice against SARS-CoV-2 challenge, with undetectable subgenomic RNA in lung and relieved lung injury. AdC7-RBD-tr2-elicted sera preserved the neutralizing activity against the circulating variants, especially the Delta variant. These results support AdC7-RBD-tr2 as a promising COVID-19 vaccine candidate. SN - 2222-1751 UR - https://www.unboundmedicine.com/medline/citation/34289779/Recombinant_chimpanzee_adenovirus_AdC7_expressing_dimeric_tandem-repeat_spike_protein_RBD_protects_mice_against_COVID-19. L2 - https://www.tandfonline.com/doi/full/10.1080/22221751.2021.1959270 DB - PRIME DP - Unbound Medicine ER -