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 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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)376-379
Number of pages4
JournalJournal of Immunology
Volume207
Issue number2
Early online dateJun 30 2021
DOIs
StatePublished - Jul 15 2021

Bibliographical note

Funding Information:
This work was supported by the Office of the Dean of the University of Minnesota Medical School and University of Minnesota–Mayo Clinic Partnership for Biotechnology and Medical Genomics. W.E.M., V.J., J.M.S., S.W., and J.M.T. were supported by National Institutes of Health (NIH) T32 HL007741, a Canadian Institutes of Health Research Fellowship, NIH T90 DE022732, NIH F30 DK114942 and NIH T32 AI055433, respectively.

Funding Information:
This work was supported by the Office of the Dean of the University of Minnesota Medical School and University of Minnesota-Mayo Clinic Partnership for Biotechnology and Medical Genomics. W.E.M., V.J., J.M.S., S.W., and J.M.T. were supported by National Institutes of Health (NIH) T32 HL007741, a Canadian Institutes of Health Research Fellowship, NIH T90 DE022732, NIH F30 DK114942 and NIH T32 AI055433, respectively.

Publisher Copyright:
Copyright © 2021 by The American Association of Immunologists, Inc.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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