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A single intranasal or intramuscular immunization with chimpanzee adenovirus vectored SARS-CoV-2 vaccine protects against pneumonia in hamsters

Traci L. Bricker, Tamarand L. Darling, Ahmed O. Hassan, Houda H. Harastani, Allison Soung, Xiaoping Jiang, Ya-Nan Dai, Haiyan Zhao, Lucas J. Adams, Michael J. Holtzman, Adam L. Bailey, James Brett Case, Daved H. Fremont, Robyn Klein, Michael S. Diamond, Adrianus C. M. Boon
doi: https://doi.org/10.1101/2020.12.02.408823
Traci L. Bricker
1Department of Internal Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
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Tamarand L. Darling
1Department of Internal Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
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Ahmed O. Hassan
1Department of Internal Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
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Houda H. Harastani
1Department of Internal Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
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Allison Soung
1Department of Internal Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
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Xiaoping Jiang
1Department of Internal Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
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Ya-Nan Dai
3Department of Pathology and Immunology, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
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Haiyan Zhao
3Department of Pathology and Immunology, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
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Lucas J. Adams
3Department of Pathology and Immunology, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
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Michael J. Holtzman
1Department of Internal Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
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Adam L. Bailey
1Department of Internal Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
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James Brett Case
1Department of Internal Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
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Daved H. Fremont
2Department of Molecular Microbiology and Microbial Pathogenesis, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
3Department of Pathology and Immunology, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
4Department of Biochemistry and Biophysics, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
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Robyn Klein
1Department of Internal Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
3Department of Pathology and Immunology, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
5Department of Neuroscience, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
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Michael S. Diamond
1Department of Internal Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
2Department of Molecular Microbiology and Microbial Pathogenesis, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
3Department of Pathology and Immunology, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
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Adrianus C. M. Boon
1Department of Internal Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
2Department of Molecular Microbiology and Microbial Pathogenesis, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
3Department of Pathology and Immunology, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA
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  • For correspondence: jboon@wustl.edu
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ABSTRACT

The development of an effective vaccine against SARS-CoV-2, the etiologic agent of COVID-19, is a global priority. Here, we compared the protective capacity of intranasal and intramuscular delivery of a chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike protein (ChAd-SARS-CoV-2-S) in Golden Syrian hamsters. While immunization with ChAd-SARS-CoV-2-S induced robust spike protein specific antibodies capable or neutralizing the virus, antibody levels in serum were higher in hamsters immunized by an intranasal compared to intramuscular route. Accordingly, ChAd-SARS-CoV-2-S immunized hamsters were protected against a challenge with a high dose of SARS-CoV-2. After challenge, ChAd-SARS-CoV-2-S-immunized hamsters had less weight loss and showed reductions in viral RNA and infectious virus titer in both nasal swabs and lungs, and reduced pathology and inflammatory gene expression in the lungs, compared to ChAd-Control immunized hamsters. Intranasal immunization with ChAd-SARS-CoV-2-S provided superior protection against SARS-CoV-2 infection and inflammation in the upper respiratory tract. These findings support intranasal administration of the ChAd-SARS-CoV-2-S candidate vaccine to prevent SARS-CoV-2 infection, disease, and possibly transmission.

Competing Interest Statement

M.S.D. is a consultant for Inbios, Vir Biotechnology, NGM Biopharmaceuticals, and Carnival Corporation 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. The Boon laboratory has received unrelated funding support in sponsored research agreements from AI Therapeutics, GreenLight Biosciences Inc., AbbVie Inc., and Nano targeting & Therapy Biopharma Inc. M.S.D. and A.O.H. have filed a disclosure with Washington University for possible commercial development of ChAd-SARS-CoV-2.

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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 December 03, 2020.
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A single intranasal or intramuscular immunization with chimpanzee adenovirus vectored SARS-CoV-2 vaccine protects against pneumonia in hamsters
Traci L. Bricker, Tamarand L. Darling, Ahmed O. Hassan, Houda H. Harastani, Allison Soung, Xiaoping Jiang, Ya-Nan Dai, Haiyan Zhao, Lucas J. Adams, Michael J. Holtzman, Adam L. Bailey, James Brett Case, Daved H. Fremont, Robyn Klein, Michael S. Diamond, Adrianus C. M. Boon
bioRxiv 2020.12.02.408823; doi: https://doi.org/10.1101/2020.12.02.408823
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A single intranasal or intramuscular immunization with chimpanzee adenovirus vectored SARS-CoV-2 vaccine protects against pneumonia in hamsters
Traci L. Bricker, Tamarand L. Darling, Ahmed O. Hassan, Houda H. Harastani, Allison Soung, Xiaoping Jiang, Ya-Nan Dai, Haiyan Zhao, Lucas J. Adams, Michael J. Holtzman, Adam L. Bailey, James Brett Case, Daved H. Fremont, Robyn Klein, Michael S. Diamond, Adrianus C. M. Boon
bioRxiv 2020.12.02.408823; doi: https://doi.org/10.1101/2020.12.02.408823

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