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Intranasal ChAdOx1 nCoV-19/AZD1222 vaccination reduces shedding of SARS-CoV-2 D614G in rhesus macaques

Neeltje van Doremalen, Jyothi N. Purushotham, Jonathan E. Schulz, Myndi G. Holbrook, Trenton Bushmaker, Aaron Carmody, Julia R. Port, Claude K. Yinda, Atsushi Okumura, Greg Saturday, Fatima Amanat, Florian Krammer, Patrick W. Hanley, Brian J. Smith, Jamie Lovaglio, Sarah L. Anzick, Kent Barbian, Craig Martens, View ORCID ProfileSarah Gilbert, Teresa Lambe, View ORCID ProfileVincent J. Munster
doi: https://doi.org/10.1101/2021.01.09.426058
Neeltje van Doremalen
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Jyothi N. Purushotham
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
2The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
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Jonathan E. Schulz
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Myndi G. Holbrook
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Trenton Bushmaker
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Aaron Carmody
3Research Technologies Branch, Rocky Mountain Laboratories, National Institutes of Health, Hamilton, Montana, USA
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Julia R. Port
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Claude K. Yinda
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Atsushi Okumura
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Greg Saturday
4Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Fatima Amanat
5Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
6Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
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Florian Krammer
5Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
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Patrick W. Hanley
4Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Brian J. Smith
4Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Jamie Lovaglio
4Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Sarah L. Anzick
3Research Technologies Branch, Rocky Mountain Laboratories, National Institutes of Health, Hamilton, Montana, USA
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Kent Barbian
3Research Technologies Branch, Rocky Mountain Laboratories, National Institutes of Health, Hamilton, Montana, USA
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Craig Martens
3Research Technologies Branch, Rocky Mountain Laboratories, National Institutes of Health, Hamilton, Montana, USA
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Sarah Gilbert
2The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
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  • ORCID record for Sarah Gilbert
Teresa Lambe
2The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
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Vincent J. Munster
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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  • ORCID record for Vincent J. Munster
  • For correspondence: vincent.munster@nih.gov
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Abstract

Intramuscular vaccination with ChAdOx1 nCoV-19/AZD1222 protected rhesus macaques against pneumonia but did not reduce shedding of SARS-CoV-2. Here we investigate whether intranasally administered ChAdOx1 nCoV-19 reduces shedding, using a SARS-CoV-2 virus with the D614G mutation in the spike protein. Viral load in swabs obtained from intranasally vaccinated hamsters was significantly decreased compared to controls and no viral RNA or infectious virus was found in lung tissue, both in a direct challenge and a transmission model. Intranasal vaccination of rhesus macaques resulted in reduced shedding and a reduction in viral load in bronchoalveolar lavage and lower respiratory tract tissue. In conclusion, intranasal vaccination reduced shedding in two different SARS-CoV-2 animal models, justifying further investigation as a potential vaccination route for COVID-19 vaccines.

Competing Interest Statement

Competing interests: S.C.G. is a board member of Vaccitech and named as an inventor on a patent covering the use of ChAdOx1-vector-based vaccines and a patent application covering a SARS-CoV-2 (nCoV-19) vaccine (UK patent application no. 2003670.3). T.L. is named as an inventor on a patent application covering a SARS-CoV-2 (nCoV-19) vaccine (UK patent application no. 2003670.3). The University of Oxford and Vaccitech, having joint rights in the vaccine, entered into a partnership with AstraZeneca in April 2020 for further development, large-scale manufacture and global supply of the vaccine. Equitable access to the vaccine is a key component of the partnership. Neither Oxford University nor Vaccitech will receive any royalties during the pandemic period or from any sales of the vaccine in developing countries. All other authors declare no competing interests. Mount Sinai has licensed SARS-CoV-2 serological assays to commercial entities and has filed for patent protection for serological assays as well as SARS-CoV-2 vaccines. FA and FK are listed as inventors on the pending patent applications.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.
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Posted January 11, 2021.
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Intranasal ChAdOx1 nCoV-19/AZD1222 vaccination reduces shedding of SARS-CoV-2 D614G in rhesus macaques
Neeltje van Doremalen, Jyothi N. Purushotham, Jonathan E. Schulz, Myndi G. Holbrook, Trenton Bushmaker, Aaron Carmody, Julia R. Port, Claude K. Yinda, Atsushi Okumura, Greg Saturday, Fatima Amanat, Florian Krammer, Patrick W. Hanley, Brian J. Smith, Jamie Lovaglio, Sarah L. Anzick, Kent Barbian, Craig Martens, Sarah Gilbert, Teresa Lambe, Vincent J. Munster
bioRxiv 2021.01.09.426058; doi: https://doi.org/10.1101/2021.01.09.426058
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Intranasal ChAdOx1 nCoV-19/AZD1222 vaccination reduces shedding of SARS-CoV-2 D614G in rhesus macaques
Neeltje van Doremalen, Jyothi N. Purushotham, Jonathan E. Schulz, Myndi G. Holbrook, Trenton Bushmaker, Aaron Carmody, Julia R. Port, Claude K. Yinda, Atsushi Okumura, Greg Saturday, Fatima Amanat, Florian Krammer, Patrick W. Hanley, Brian J. Smith, Jamie Lovaglio, Sarah L. Anzick, Kent Barbian, Craig Martens, Sarah Gilbert, Teresa Lambe, Vincent J. Munster
bioRxiv 2021.01.09.426058; doi: https://doi.org/10.1101/2021.01.09.426058

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