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Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 in mice

Rodney G King, Aaron Silva-Sanchez, Jessica N. Peel, Davide Botta, Selene Meza-Perez, S. Rameeza Allie, Michael D. Schultz, Mingyong Liu, John E. Bradley, Shihong Qiu, Guang Yang, Fen Zhou, Esther Zumaquero, Thomas S. Simpler, Betty Mousseau, John T. Killian Jr., Brittany Dean, Qiao Shang, Jennifer L. Tipper, Christopher Risley, Kevin S. Harrod, Ray Feng, Young Lee, Bethlehem Shiberu, Vyjayanthi Krishnan, Isabelle Peguillet, Jianfeng Zhang, J. Todd Green, Troy D. Randall, Bertrand Georges, Frances E. Lund, Scot Roberts
doi: https://doi.org/10.1101/2020.10.10.331348
Rodney G King
1Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
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Aaron Silva-Sanchez
2Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA
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Jessica N. Peel
1Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
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Davide Botta
1Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
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Selene Meza-Perez
2Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA
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S. Rameeza Allie
2Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA
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Michael D. Schultz
1Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
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Mingyong Liu
2Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA
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John E. Bradley
2Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA
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Shihong Qiu
1Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
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Guang Yang
1Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
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Fen Zhou
1Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
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Esther Zumaquero
1Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
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Thomas S. Simpler
1Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
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Betty Mousseau
1Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
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John T. Killian Jr.
1Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
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Brittany Dean
1Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
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Qiao Shang
1Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
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Jennifer L. Tipper
3Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL, USA
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Christopher Risley
1Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
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Kevin S. Harrod
3Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL, USA
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Ray Feng
4Altimmune Inc., Gaithersburg, MD, USA
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Young Lee
4Altimmune Inc., Gaithersburg, MD, USA
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Bethlehem Shiberu
4Altimmune Inc., Gaithersburg, MD, USA
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Vyjayanthi Krishnan
4Altimmune Inc., Gaithersburg, MD, USA
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Isabelle Peguillet
4Altimmune Inc., Gaithersburg, MD, USA
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Jianfeng Zhang
4Altimmune Inc., Gaithersburg, MD, USA
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J. Todd Green
1Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
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Troy D. Randall
2Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA
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Bertrand Georges
4Altimmune Inc., Gaithersburg, MD, USA
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Frances E. Lund
1Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
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  • For correspondence: flund@uab.edu sroberts@altimmune.com
Scot Roberts
4Altimmune Inc., Gaithersburg, MD, USA
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  • For correspondence: flund@uab.edu sroberts@altimmune.com
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Abstract

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective preventive vaccination to reduce burden and spread of severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) in humans. Intranasal vaccination is an attractive strategy to prevent COVID-19 as the nasal mucosa represents the first-line barrier to SARS-CoV-2 entry before viral spread to the lung. Although SARS-CoV-2 vaccine development is rapidly progressing, the current intramuscular vaccines are designed to elicit systemic immunity without conferring mucosal immunity. Here, we show that AdCOVID, an intranasal adenovirus type 5 (Ad5)-vectored vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, elicits a strong and focused immune response against RBD through the induction of mucosal IgA, serum neutralizing antibodies and CD4+ and CD8+ T cells with a Th1-like cytokine expression profile. Therefore, AdCOVID, which promotes concomitant systemic and local mucosal immunity, represents a promising COVID-19 vaccine candidate.

Competing Interest Statement

The authors have declared no competing interest.

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 October 11, 2020.
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Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 in mice
Rodney G King, Aaron Silva-Sanchez, Jessica N. Peel, Davide Botta, Selene Meza-Perez, S. Rameeza Allie, Michael D. Schultz, Mingyong Liu, John E. Bradley, Shihong Qiu, Guang Yang, Fen Zhou, Esther Zumaquero, Thomas S. Simpler, Betty Mousseau, John T. Killian Jr., Brittany Dean, Qiao Shang, Jennifer L. Tipper, Christopher Risley, Kevin S. Harrod, Ray Feng, Young Lee, Bethlehem Shiberu, Vyjayanthi Krishnan, Isabelle Peguillet, Jianfeng Zhang, J. Todd Green, Troy D. Randall, Bertrand Georges, Frances E. Lund, Scot Roberts
bioRxiv 2020.10.10.331348; doi: https://doi.org/10.1101/2020.10.10.331348
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Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 in mice
Rodney G King, Aaron Silva-Sanchez, Jessica N. Peel, Davide Botta, Selene Meza-Perez, S. Rameeza Allie, Michael D. Schultz, Mingyong Liu, John E. Bradley, Shihong Qiu, Guang Yang, Fen Zhou, Esther Zumaquero, Thomas S. Simpler, Betty Mousseau, John T. Killian Jr., Brittany Dean, Qiao Shang, Jennifer L. Tipper, Christopher Risley, Kevin S. Harrod, Ray Feng, Young Lee, Bethlehem Shiberu, Vyjayanthi Krishnan, Isabelle Peguillet, Jianfeng Zhang, J. Todd Green, Troy D. Randall, Bertrand Georges, Frances E. Lund, Scot Roberts
bioRxiv 2020.10.10.331348; doi: https://doi.org/10.1101/2020.10.10.331348

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