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N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SARS-CoV-2

View ORCID ProfileChristopher M. Weiss, View ORCID ProfileHongwei Liu, View ORCID ProfileErin E. Ball, Samuel Lam, Tomas Hode, M. Kevin Keel, View ORCID ProfileRichard M. Levenson, View ORCID ProfileLark L. Coffey
doi: https://doi.org/10.1101/2021.08.10.455872
Christopher M. Weiss
1Department of Pathology, Microbiology & Immunology, University of California, Davis, CA
4Meissa Vaccines, Inc., Redwood City, CA
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  • ORCID record for Christopher M. Weiss
Hongwei Liu
1Department of Pathology, Microbiology & Immunology, University of California, Davis, CA
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Erin E. Ball
1Department of Pathology, Microbiology & Immunology, University of California, Davis, CA
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Samuel Lam
2Immunophotonics, Inc., Saint Louis, MO
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Tomas Hode
2Immunophotonics, Inc., Saint Louis, MO
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M. Kevin Keel
1Department of Pathology, Microbiology & Immunology, University of California, Davis, CA
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Richard M. Levenson
3Department of Pathology and Laboratory Medicine, UC Davis Health, Sacramento, CA
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Lark L. Coffey
1Department of Pathology, Microbiology & Immunology, University of California, Davis, CA
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  • For correspondence: lcoffey@ucdavis.edu
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ABSTRACT

The rapid emergence and global dissemination of SARS-CoV-2 that causes COVID-19 continues to cause an unprecedented global health burden resulting in more than 4 million deaths in the 20 months since the virus was discovered. While multiple vaccine countermeasures have been approved for emergency use, additional treatments are still needed due to sluggish vaccine rollout and vaccine hesitancy. Immunoadjuvant compounds delivered intranasally can guide non-specific innate immune responses during the critical early stages of viral replication, reducing morbidity and mortality. N-dihydrogalactochitosan (GC) is a novel mucoadhesive immunostimulatory polymer of β-0-4-linked N-acetylglucosamine that is solubilized by the conjugation of galactose glycans. We tested GC as a potential countermeasure for COVID-19. GC administered intranasally before and after SARS-CoV-2 exposure diminished morbidity and mortality in humanized ACE2 receptor expressing mice by up to 75% and reduced infectious virus levels in the upper airway and lungs. Our findings demonstrate a new application for soluble immunoadjuvants like GC for preventing severe disease associated with SARS-CoV-2.

Single Sentence Summary The immunoadjuvant N-dihydrogalactochitosan diminishes SARS-CoV-2 disease in humanized ACE2 mice representing a new countermeasure against COVID-19.

Competing Interest Statement

TH and SSKL declare a conflict of interest as employees with minority ownership stakes of Immunophotonics, Inc., the manufacturer of the proprietary immune stimulant GC. RML declares a conflict of interest as an advisor with minority ownership stake in Immunophotonics.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted August 13, 2021.
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N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SARS-CoV-2
Christopher M. Weiss, Hongwei Liu, Erin E. Ball, Samuel Lam, Tomas Hode, M. Kevin Keel, Richard M. Levenson, Lark L. Coffey
bioRxiv 2021.08.10.455872; doi: https://doi.org/10.1101/2021.08.10.455872
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N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SARS-CoV-2
Christopher M. Weiss, Hongwei Liu, Erin E. Ball, Samuel Lam, Tomas Hode, M. Kevin Keel, Richard M. Levenson, Lark L. Coffey
bioRxiv 2021.08.10.455872; doi: https://doi.org/10.1101/2021.08.10.455872

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