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

Autor: Qunlong Li, Kun Xu, Youchun Wang, Dongming Zhou, Senyu Xu, Yuhai Bi, Hui Liu, Ping Gao, George F. Gao, Weijin Huang, Chuanyu Liu, Fang Fang, Tianyi Zheng, Lianpan Dai, Wenli Hou, Qinghan Wang, William J. Liu, Yuxuan Han, Yaling An, Qianfeng Xia
Rok vydání: 2021
Předmět:
DOI: 10.1101/2021.02.05.429860
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 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.
Databáze: OpenAIRE