Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 in mice

King, Rodney G; Silva-Sanchez, Aaron; Peel, Jessica N.; Botta, Davide; Meza-Perez, Selene; Allie, S. Rameeza; Schultz, Michael D.; Liu, Mingyong; Bradley, John E.; Qiu, Shihong; Yang, Guang; Zhou, Fen; Zumaquero, Esther; Simpler, Thomas S.; Mousseau, Betty; Killian, John T.; Dean, Brittany; Shang, Qiao; Tipper, Jennifer L.; Risley, Christopher; Harrod, Kevin S.; Feng, Ray; Lee, Young; Shiberu, Bethlehem; Krishnan, Vyjayanthi; Peguillet, Isabelle; Zhang, Jianfeng; Green, J. Todd; Randall, Troy D.; Georges, Bertrand; Lund, Frances E.; Roberts, Scot

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective preventive vaccination to reduce burden and spread of severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) in humans. Intranasal vaccination is an attractive strategy to prevent COVID-19 as the nasal mucosa represents the first-line barrier to SARS-CoV-2 entry before viral spread to the lung. Although SARS-CoV-2 vaccine development is rapidly progressing, the current intramuscular vaccines are designed to elicit systemic immunity without conferring mucosal immunity. Here, we show that AdCOVID, an intranasal adenovirus type 5 (Ad5)-vectored vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, elicits a strong and focused immune response against RBD through the induction of mucosal IgA, serum neutralizing antibodies and CD4+ and CD8+ T cells with a Th1-like cytokine expression profile. Therefore, AdCOVID, which promotes concomitant systemic and local mucosal immunity, represents a promising COVID-19 vaccine candidate.