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 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.
【저자키워드】 COVID-19, SARS-CoV-2, Vaccine, immune response, antibody, Adenovirus, 【초록키워드】 COVID-19 vaccine, vaccination, Immunity, COVID-19 pandemic, Antibody Response, lung, Lung injury, delta variant, RNA, Protein, Neutralizing activity, Bronchoalveolar lavage fluid, mice, RBD, sera, Adenovirus-vectored vaccine, intramuscular, mucosal, administration, Safe, humoral, Support, domain, immunogenic, cellular immune responses, circulating variants, effective, approved, elicit, expressing, dimeric, intranasal route, preserved, recombinant chimpanzee adenovirus, undetectable, 【제목키워드】 mice, recombinant, spike protein RBD, PROTECT, expressing, dimeric,