Recombinant chimpanzee adenovirus AdC7 expressing dimeric tandem-repeat RBD of SARS-CoV-2 spike protein protects mice against COVID-19

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 advanced into phase 3 trials, with three approved for use. Here, we generated several recombinant chimpanzee adenovirus (AdC7)...

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Published inbioRxiv
Main Authors Xu, Kun, An, Yaling, Li, Qunlong, Huang, Weijin, Han, Yuxuan, Zheng, Tianyi, Fang, Fang, Liu, Hui, Liu, Chuanyu, Gao, Ping, Xu, Senyu, Liu, William J, Bi, Yuhai, Wang, Youchun, Zhou, Dongming, Wang, Qinghan, Hou, Wenli, Xia, Qianfeng, Gao, George F, Dai, Lianpan
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 08.02.2021
Subjects
Adenoviruses
Alveoli
Bronchus
Coronaviruses
COVID-19
COVID-19 vaccines
Immune response (humoral)
Immunogenicity
Intranasal administration
Lymphocytes T
Mucosal immunity
Pandemics
Patent applications
Severe acute respiratory syndrome coronavirus 2
Spike protein
Vaccines
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Summary: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 advanced into phase 3 trials, with three approved for use. Here, we generated several recombinant chimpanzee adenovirus (AdC7) vaccines expressing S, receptor-binding domain (RBD) or dimeric tandem-repeat RBD (RBD-tr2). We found vaccination via either intramuscular or intranasal route was highly immunogenic in mice to elicit both humoral and cellular (Th1-based) immune responses. AdC7-RBD-tr2 showed higher antibody responses compared with both AdC7-S and 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. These results support AdC7-RBD-tr2 as a promising COVID-19 vaccine candidate. Competing Interest Statement K.X., Y.A., Y.H., L.D., and G.F.G. are listed as inventors on pending patent applications for AdC7-RBD-tr2 vaccine. The pending patents for AdC7-RBD-tr2 have been licensed to Chengdu Kanghua Biological Products Co., Ltd, China. The other authors declare that they have no competing interests.
DOI:10.1101/2021.02.05.429860