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Emerg Microbes Infect ; 10(1): 1574-1588, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1320287


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.

Adenoviridae/genetics , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , Spike Glycoprotein, Coronavirus/immunology , Administration, Intranasal , Animals , Antibodies, Neutralizing/blood , COVID-19 , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/genetics , Chlorocebus aethiops , Female , Genetic Vectors/genetics , HEK293 Cells , Humans , Immunogenicity, Vaccine , Injections, Intramuscular , Mice , Mice, Inbred BALB C , Pan troglodytes/virology , Protein Binding , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/administration & dosage , Spike Glycoprotein, Coronavirus/genetics , Vaccination , Vero Cells