Intranasal administration of adenoviral vaccines expressing SARS-CoV-2 spike protein improves vaccine immunity in mouse models

Intranasal vaccines can prime or recruit to the respiratory epithelium mucosal immune cells capable of preventing transmission of SARS-CoV-2. We found that a single intranasal dose of serotype 5-based adenoviral vectors expressing either the receptor binding domain (Ad5-RBD) or the complete ectodomain (Ad5-S) of the SARS-CoV-2 spike protein was effective in inducing i) secretory and serum anti-spike IgA and IgG, ii) robust SARS-CoV-2-neutralizing activity in the serum and in respiratory secretions, iii) rigorous spike-directed T helper 1 cell/cytotoxic T cell immunity, and iv) protection of wild-type mice from a challenge with the SARS-CoV-2 beta variant. Our data confirm and extend previous studies reporting promising preclinical results on vector-based intranasal SARS-CoV-2 vaccination, and support the potential of this approach to elicit mucosal immunity for preventing reinfection and transmission of SARS-CoV-2 more effectively than the currently available vaccines. Overall design: Here we report a comprehensive series of studies to explore the intranasal vaccines using various mouse models, including HLA class II-humanized transgenic strains. To improve SARS-CoV-2 vaccine efficacy, and to better address the global demand for safe and affordable vaccines against COVID-19, we have developed two human adenovirus 5-vectored vaccines, one expressing an RBD fragment (Ad5-RBD) and the other a long version of the spike protein (Ad5-S). To test the efficacy of an Ad5-vectored, codon-optimized RBD vaccine (Ad5-RBD), we performed dose testing by single treatment via the nose (intranasal, i.n.) or muscle (intramuscular, i.m.) of wildtype Balb/c and HLA-DQB1*06:02 transgenic Ab0 NOD (HLA-DQ6) mice.