Single-Dose Intranasal Administration of AdCOVID Elicits Systemic and Mucosal Immunity against SARS-CoV-2 and Fully Protects Mice from Lethal Challenge

King, R. Glenn; Silva-Sanchez, Aaron; Peel, Jessica N.; Botta, Davide; Dickson, Alexandria M.; Pinto, Amelia K.; 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 A.; Harrod, Kevin S.; Feng, Tsungwei; Lee, Young; Shiberu, Bethlehem; Krishnan, Vyjayanthi; Peguillet, Isabelle; Zhang, Jianfeng; Green, Todd J.; Randall, Troy D.; Suschak, John J.; Georges, Bertrand; Brien, James D.; Lund, Frances E.; Roberts, M. Scot

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective prophylactic vaccination to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Intranasal vaccination is an attractive strategy to prevent COVID-19 as the nasal mucosa represents the first-line barrier to SARS-CoV-2 entry. The current intramuscular vaccines elicit systemic immunity but not necessarily high-level mucosal immunity. Here, we tested a single intranasal dose of our candidate adenovirus type 5-vectored vaccine encoding the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (AdCOVID) in inbred, outbred, and transgenic mice. A single intranasal vaccination with AdCOVID elicited a strong and focused immune response against RBD through the induction of mucosal IgA in the respiratory tract, serum neutralizing antibodies, and CD4(+) and CD8(+) T cells with a T(h)1-like cytokine expression profile. A single AdCOVID dose resulted in immunity that was sustained for over six months. Moreover, a single intranasal dose completely protected K18-hACE2 mice from lethal SARS-CoV-2 challenge, preventing weight loss and mortality. These data show that AdCOVID promotes concomitant systemic and mucosal immunity and represents a promising vaccine candidate.