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

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) S, receptor-binding domain (RBD), or tandem-repeat dimeric RBD (RBD-tr2). We found vaccination via either intramuscular intranasal route was highly immunogenic in mice elicit both humoral cellular immune responses. AdC7-RBD-tr2 showed higher antibody responses compared AdC7-S AdC7-RBD. Intranasal administration of additionally induced mucosal immunity with neutralizing activity bronchoalveolar lavage fluid. Either single-dose two-dose protected against SARS-CoV-2 challenge, undetectable subgenomic RNA lung relieved injury. AdC7-RBD-tr2-elicted sera preserved circulating variants, especially Delta variant. These results support as a promising candidate.