Single-Dose Intranasal Administration of AdCOVID Elicits Systemic and Mucosal Immunity against SARS-CoV-2 and Fully Protects Mice from Lethal Challenge
R. Glenn King, Aarón Silva-Sánchez, Jessica N. Peel, Davide Botta, Alexandria M. Dickson, Amelia K. Pinto, Selene Meza‐Perez, S. Rameeza Allie, Michael D. Schultz, Mingyong Liu, John Bradley, Shihong Qiu, Guang Yang, Fen Zhou, Esther Zumaquero, Thomas S. Simpler, Betty Mousseau, John T. Killian, Brittany Dean, Qiao Shang, Jennifer L. Tipper, Christopher A. Risley, Kevin S. Harrod, Tsungwei Feng, Young Lee, Bethlehem Shiberu, Vyjayanthi Krishnan, Isabelle Péguillet, Jianfeng Zhang, Todd J. Green, Troy D. Randall, John J. Suschak, Bertrand Georges, James D. Brien, Frances E. Lund, M. Scot Roberts
Abstract
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 Th1-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.