Cutting Edge: Nucleocapsid Vaccine Elicits Spike-Independent SARS-CoV-2 Protective Immunity
William E. Matchett, Vineet Joag, J. Michael Stolley, Frances K. Shepherd, Clare F. Quarnstrom, Clayton K. Mickelson, Sathi Wijeyesinghe, Andrew G. Soerens, Samuel Becker, Joshua M. Thiede, Eyob Weyu, Stephen D. O’Flanagan, Jennifer A. Walter, Michelle N. Vu, Vineet D. Menachery, Tyler D. Bold, Vaiva Vezys, Marc K. Jenkins, Ryan A. Langlois, David Masopust
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Neutralizing Abs target the receptor binding domain of the spike (S) protein, a focus of successful vaccine efforts. Concerns have arisen that S-specific vaccine immunity may fail to neutralize emerging variants. We show that vaccination with a human adenovirus type 5 vector expressing the SARS-CoV-2 nucleocapsid (N) protein can establish protective immunity, defined by reduced weight loss and viral load, in both Syrian hamsters and K18-hACE2 mice. Challenge of vaccinated mice was associated with rapid N-specific T cell recall responses in the respiratory mucosa. This study supports the rationale for including additional viral Ags in SARS-CoV-2 vaccines, even if they are not a target of neutralizing Abs, to broaden epitope coverage and immune effector mechanisms.