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

The rapid emergence and global dissemination of SARS-CoV-2 that causes COVID-19 continues to cause an unprecedented global health burden resulting in nearly 7 million deaths. While multiple vaccine countermeasures have been approved for emergency use, additional treatments are still needed due to sl...

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Autores principales: Weiss, Christopher M., Liu, Hongwei, Ball, Erin E., Hoover, Ashley R., Wong, Talia S., Wong, Chun Fung, Lam, Samuel, Hode, Tomas, Keel, M. Kevin, Levenson, Richard M., Chen, Wei R., Coffey, Lark L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10409267/
https://www.ncbi.nlm.nih.gov/pubmed/37552656
http://dx.doi.org/10.1371/journal.pone.0289139
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author Weiss, Christopher M.
Liu, Hongwei
Ball, Erin E.
Hoover, Ashley R.
Wong, Talia S.
Wong, Chun Fung
Lam, Samuel
Hode, Tomas
Keel, M. Kevin
Levenson, Richard M.
Chen, Wei R.
Coffey, Lark L.
author_facet Weiss, Christopher M.
Liu, Hongwei
Ball, Erin E.
Hoover, Ashley R.
Wong, Talia S.
Wong, Chun Fung
Lam, Samuel
Hode, Tomas
Keel, M. Kevin
Levenson, Richard M.
Chen, Wei R.
Coffey, Lark L.
author_sort Weiss, Christopher M.
collection PubMed
description The rapid emergence and global dissemination of SARS-CoV-2 that causes COVID-19 continues to cause an unprecedented global health burden resulting in nearly 7 million deaths. While multiple vaccine countermeasures have been approved for emergency use, additional treatments are still needed due to sluggish vaccine rollout, vaccine hesitancy, and inefficient vaccine-mediated protection. 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 with current applications as a cancer immunotherapeutic. We tested GC as a potential countermeasure for COVID-19. GC was well-tolerated and did not produce histopathologic lesions in the mouse lung. 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. Fluorescent labeling of GC shows that it is confined to the lumen or superficial mucosa of the nasal cavity, without involvement of adjacent or deeper tissues. Our findings demonstrate a new application for soluble immunoadjuvants such as GC for preventing disease associated with SARS-CoV-2 and may be particularly attractive to persons who are needle-averse.
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spelling pubmed-104092672023-08-09 N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SARS-CoV-2 Weiss, Christopher M. Liu, Hongwei Ball, Erin E. Hoover, Ashley R. Wong, Talia S. Wong, Chun Fung Lam, Samuel Hode, Tomas Keel, M. Kevin Levenson, Richard M. Chen, Wei R. Coffey, Lark L. PLoS One Research Article The rapid emergence and global dissemination of SARS-CoV-2 that causes COVID-19 continues to cause an unprecedented global health burden resulting in nearly 7 million deaths. While multiple vaccine countermeasures have been approved for emergency use, additional treatments are still needed due to sluggish vaccine rollout, vaccine hesitancy, and inefficient vaccine-mediated protection. 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 with current applications as a cancer immunotherapeutic. We tested GC as a potential countermeasure for COVID-19. GC was well-tolerated and did not produce histopathologic lesions in the mouse lung. 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. Fluorescent labeling of GC shows that it is confined to the lumen or superficial mucosa of the nasal cavity, without involvement of adjacent or deeper tissues. Our findings demonstrate a new application for soluble immunoadjuvants such as GC for preventing disease associated with SARS-CoV-2 and may be particularly attractive to persons who are needle-averse. Public Library of Science 2023-08-08 /pmc/articles/PMC10409267/ /pubmed/37552656 http://dx.doi.org/10.1371/journal.pone.0289139 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Weiss, Christopher M.
Liu, Hongwei
Ball, Erin E.
Hoover, Ashley R.
Wong, Talia S.
Wong, Chun Fung
Lam, Samuel
Hode, Tomas
Keel, M. Kevin
Levenson, Richard M.
Chen, Wei R.
Coffey, Lark L.
N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SARS-CoV-2
title N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SARS-CoV-2
title_full N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SARS-CoV-2
title_fullStr N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SARS-CoV-2
title_full_unstemmed N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SARS-CoV-2
title_short N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SARS-CoV-2
title_sort n-dihydrogalactochitosan reduces mortality in a lethal mouse model of sars-cov-2
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10409267/
https://www.ncbi.nlm.nih.gov/pubmed/37552656
http://dx.doi.org/10.1371/journal.pone.0289139
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