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

Xu, K.; An, Y.; Li, Q.; Huang, W.; Han, Y.; Zheng, T.; Fang, F.; Liu, H.; Liu, C.; Gao, P.; Xu, S.; Liu, W. J.; Bi, Y.; Wang, Y.; Zhou, D.; Wang, Q.; Hou, W.; Xia, Q.; Gao, G. F.; Dai, L.

doi:10.1101/2021.02.05.429860

bioRxiv · 10.1101/2021.02.05.429860

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

Xu, K.·An, Y.·Li, Q.·Huang, W.·Han, Y.·Zheng, T.·Fang, F.·Liu, H.·Liu, C.·Gao, P.·Xu, S.·Liu, W. J.·Bi, Y.·Wang, Y.·Zhou, D.·Wang, Q.·Hou, W.·Xia, Q.·Gao, G. F.·Dai, L.

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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.

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Xu, K., An, Y., Li, Q., Huang, W., Han, Y., Zheng, T., Fang, F., Liu, H., Liu, C., Gao, P., Xu, S., Liu, W. J., Bi, Y., Wang, Y., Zhou, D., Wang, Q., Hou, W., Xia, Q., Gao, G. F., Dai, L.. 2021-02-08. Recombinant chimpanzee adenovirus AdC7 expressing dimeric tandem-repeat RBD of SARS-CoV-2 spike protein protects mice against COVID-19. https://doi.org/10.1101/2021.02.05.429860

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