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Nucleocapsid vaccine elicits spike-independent SARS-CoV-2 protective immunity

View ORCID ProfileWilliam E. Matchett, View ORCID ProfileVineet Joag, View ORCID ProfileJ. Michael Stolley, Frances K. Shepherd, Clare F. Quarnstrom, Clayton K. Mickelson, View ORCID ProfileSathi Wijeyesinghe, View ORCID ProfileAndrew G. Soerens, Samuel Becker, View ORCID ProfileJoshua M. Thiede, Eyob Weyu, Stephen O’Flanagan, Jennifer A. Walter, Michelle N. Vu, View ORCID ProfileVineet D. Menachery, View ORCID ProfileTyler D. Bold, View ORCID ProfileVaiva Vezys, View ORCID ProfileMarc K. Jenkins, View ORCID ProfileRyan A. Langlois, View ORCID ProfileDavid Masopust
doi: https://doi.org/10.1101/2021.04.26.441518
William E. Matchett
aDepartment of Microbiology and Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
bCenter for Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
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Vineet Joag
aDepartment of Microbiology and Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
bCenter for Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
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J. Michael Stolley
aDepartment of Microbiology and Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
bCenter for Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
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Frances K. Shepherd
aDepartment of Microbiology and Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
bCenter for Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
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Clare F. Quarnstrom
aDepartment of Microbiology and Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
bCenter for Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
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Clayton K. Mickelson
aDepartment of Microbiology and Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
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Sathi Wijeyesinghe
aDepartment of Microbiology and Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
bCenter for Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
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Andrew G. Soerens
aDepartment of Microbiology and Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
bCenter for Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
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Samuel Becker
aDepartment of Microbiology and Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
bCenter for Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
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Joshua M. Thiede
bCenter for Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
cDivision of Infectious Disease and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, 55455
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Eyob Weyu
aDepartment of Microbiology and Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
bCenter for Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
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Stephen O’Flanagan
aDepartment of Microbiology and Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
bCenter for Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
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Jennifer A. Walter
aDepartment of Microbiology and Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
bCenter for Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
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Michelle N. Vu
dDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA
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Vineet D. Menachery
dDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA
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Tyler D. Bold
bCenter for Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
cDivision of Infectious Disease and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, 55455
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Vaiva Vezys
aDepartment of Microbiology and Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
bCenter for Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
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Marc K. Jenkins
aDepartment of Microbiology and Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
bCenter for Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
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  • For correspondence: masopust@umn.edu langlois@umn.edu jenki002@umn.edu
Ryan A. Langlois
aDepartment of Microbiology and Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
bCenter for Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
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  • For correspondence: masopust@umn.edu langlois@umn.edu jenki002@umn.edu
David Masopust
aDepartment of Microbiology and Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
bCenter for Immunology, Department of Medicine, University of Minnesota, Minneapolis, 55455
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  • ORCID record for David Masopust
  • For correspondence: masopust@umn.edu langlois@umn.edu jenki002@umn.edu
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Abstract

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 Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 27, 2021.
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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 O’Flanagan, Jennifer A. Walter, Michelle N. Vu, Vineet D. Menachery, Tyler D. Bold, Vaiva Vezys, Marc K. Jenkins, Ryan A. Langlois, David Masopust
bioRxiv 2021.04.26.441518; doi: https://doi.org/10.1101/2021.04.26.441518
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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 O’Flanagan, Jennifer A. Walter, Michelle N. Vu, Vineet D. Menachery, Tyler D. Bold, Vaiva Vezys, Marc K. Jenkins, Ryan A. Langlois, David Masopust
bioRxiv 2021.04.26.441518; doi: https://doi.org/10.1101/2021.04.26.441518

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