TY - JOUR T1 - Nucleocapsid vaccine elicits spike-independent SARS-CoV-2 protective immunity JF - bioRxiv DO - 10.1101/2021.04.26.441518 SP - 2021.04.26.441518 AU - William E. Matchett AU - Vineet Joag AU - J. Michael Stolley AU - Frances K. Shepherd AU - Clare F. Quarnstrom AU - Clayton K. Mickelson AU - Sathi Wijeyesinghe AU - Andrew G. Soerens AU - Samuel Becker AU - Joshua M. Thiede AU - Eyob Weyu AU - Stephen O’Flanagan AU - Jennifer A. Walter AU - Michelle N. Vu AU - Vineet D. Menachery AU - Tyler D. Bold AU - Vaiva Vezys AU - Marc K. Jenkins AU - Ryan A. Langlois AU - David Masopust Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/04/27/2021.04.26.441518.abstract N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Neutralizing antibodies 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 HAd5 expressing the 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 antigens, even if they are not a target of neutralizing antibodies, to broaden epitope coverage and immune effector mechanisms.Competing Interest StatementThe authors have declared no competing interest. ER -