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An intranasal vaccine durably protects against SARS-CoV-2 variants in mice

Ahmed O. Hassan, Swathi Shrihari, Matthew J. Gorman, Baoling Ying, Dansu Yuan, Saravanan Raju, Rita E. Chen, Igor P. Dmitriev, Elena Kashentseva, Lucas J. Adams, Pei-Yong Shi, Daved H. Fremont, David T. Curiel, Galit Alter, View ORCID ProfileMichael S. Diamond
doi: https://doi.org/10.1101/2021.05.08.443267
Ahmed O. Hassan
1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
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Swathi Shrihari
1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
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Matthew J. Gorman
2Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology, and Harvard University, Cambridge, MA, USA
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Baoling Ying
1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
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Dansu Yuan
2Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology, and Harvard University, Cambridge, MA, USA
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Saravanan Raju
1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
3Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
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Rita E. Chen
1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
3Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
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Igor P. Dmitriev
4Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA
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Elena Kashentseva
4Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA
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Lucas J. Adams
4Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA
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Pei-Yong Shi
5Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston TX
6Departments of Microbiology and Immunology, University of Texas Medical Branch, Galveston TX
7Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX
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Daved H. Fremont
3Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
8Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA
9Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA
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David T. Curiel
4Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA
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Galit Alter
2Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology, and Harvard University, Cambridge, MA, USA
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Michael S. Diamond
1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
8Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA
9Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA
10The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine. St. Louis, MO 63110, USA
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  • ORCID record for Michael S. Diamond
  • For correspondence: diamond@wusm.wustl.edu
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ABSTRACT

SARS-CoV-2 variants that attenuate antibody neutralization could jeopardize vaccine efficacy and the end of the COVID-19 pandemic. We recently reported the protective activity of a single-dose intranasally-administered spike protein-based chimpanzee adenovirus-vectored vaccine (ChAd-SARS-CoV-2-S) in animals, which has advanced to human trials. Here, we assessed its durability, dose-response, and cross-protective activity in mice. A single intranasal dose of ChAd-SARS-CoV-2-S induced durably high neutralizing and Fc effector antibody responses in serum and S-specific IgG and IgA secreting long-lived plasma cells in the bone marrow. Protection against a historical SARS-CoV-2 strain was observed across a 100-fold vaccine dose range and over a 200-day period. At 6 weeks or 9 months after vaccination, serum antibodies neutralized SARS-CoV-2 strains with B.1.351 and B.1.1.28 spike proteins and conferred almost complete protection in the upper and lower respiratory tracts after challenge. Thus, in mice, intranasal immunization with ChAd-SARS-CoV-2-S provides durable protection against historical and emerging SARS-CoV-2 strains.

Competing Interest Statement

MSD is a consultant for Inbios, Vir Biotechnology, and Fortress Biotech, and on the Scientific Advisory Board of Moderna and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. MSD, AOH, IPD, and DTC have filed a disclosure with Washington University for possible commercial development of the vaccine described in this paper. DTC is an equity holder in Precision Virologics, which has optioned the vaccine.

Copyright 
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 May 09, 2021.
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An intranasal vaccine durably protects against SARS-CoV-2 variants in mice
Ahmed O. Hassan, Swathi Shrihari, Matthew J. Gorman, Baoling Ying, Dansu Yuan, Saravanan Raju, Rita E. Chen, Igor P. Dmitriev, Elena Kashentseva, Lucas J. Adams, Pei-Yong Shi, Daved H. Fremont, David T. Curiel, Galit Alter, Michael S. Diamond
bioRxiv 2021.05.08.443267; doi: https://doi.org/10.1101/2021.05.08.443267
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An intranasal vaccine durably protects against SARS-CoV-2 variants in mice
Ahmed O. Hassan, Swathi Shrihari, Matthew J. Gorman, Baoling Ying, Dansu Yuan, Saravanan Raju, Rita E. Chen, Igor P. Dmitriev, Elena Kashentseva, Lucas J. Adams, Pei-Yong Shi, Daved H. Fremont, David T. Curiel, Galit Alter, Michael S. Diamond
bioRxiv 2021.05.08.443267; doi: https://doi.org/10.1101/2021.05.08.443267

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