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J Immunol . Nucleocapsid Vaccine Elicits Spike-Independent SARS-CoV-2 Protective Immunity

tetano

Editor, Senior Moderator
J Immunol


. 2021 Jun 30;ji2100421.
doi: 10.4049/jimmunol.2100421. Online ahead of print.
Nucleocapsid Vaccine Elicits Spike-Independent SARS-CoV-2 Protective Immunity


William E Matchett[SUP] 1 2 [/SUP], Vineet Joag[SUP] 1 2 [/SUP], J Michael Stolley[SUP] 1 2 [/SUP], Frances K Shepherd[SUP] 1 2 [/SUP], Clare F Quarnstrom[SUP] 1 2 [/SUP], Clayton K Mickelson[SUP] 1 [/SUP], Sathi Wijeyesinghe[SUP] 1 2 [/SUP], Andrew G Soerens[SUP] 1 2 [/SUP], Samuel Becker[SUP] 1 2 [/SUP], Joshua M Thiede[SUP] 2 3 [/SUP], Eyob Weyu[SUP] 1 2 [/SUP], Stephen D O'Flanagan[SUP] 1 2 [/SUP], Jennifer A Walter[SUP] 1 2 [/SUP], Michelle N Vu[SUP] 4 [/SUP], Vineet D Menachery[SUP] 4 [/SUP], Tyler D Bold[SUP] 2 3 [/SUP], Vaiva Vezys[SUP] 1 2 [/SUP], Marc K Jenkins[SUP] 5 2 [/SUP], Ryan A Langlois[SUP] 5 2 [/SUP], David Masopust[SUP] 5 2 [/SUP]



Affiliations

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.
 
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