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

Autor: Kun Xu, Yaling An, Qunlong Li, Weijin Huang, Yuxuan Han, Tianyi Zheng, Fang Fang, Hui Liu, Chuanyu Liu, Ping Gao, Senyu Xu, Xueyuan Liu, Rong Zhang, Xin Zhao, William J. Liu, Yuhai Bi, Youchun Wang, Dongming Zhou, Qinghan Wang, Wenli Hou, Qianfeng Xia, George F. Gao, Lianpan Dai
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Emerging Microbes and Infections, Vol 10, Iss 1, Pp 1574-1588 (2021)
Druh dokumentu: article
ISSN: 22221751
2222-1751
DOI: 10.1080/22221751.2021.1959270
Popis: 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.
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