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

Autor: Weiss CM; Department of Pathology, Microbiology & Immunology, University of California, Davis, California, United States of America., Liu H; Department of Pathology, Microbiology & Immunology, University of California, Davis, California, United States of America., Ball EE; Department of Pathology, Microbiology & Immunology, University of California, Davis, California, United States of America., Hoover AR; Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, Oklahoma, United States of America., Wong TS; Department of Pathology, Microbiology & Immunology, University of California, Davis, California, United States of America., Wong CF; Immunophotonics, Inc., Saint Louis, Missouri, United States of America., Lam S; Immunophotonics, Inc., Saint Louis, Missouri, United States of America., Hode T; Immunophotonics, Inc., Saint Louis, Missouri, United States of America., Keel MK; Department of Pathology, Microbiology & Immunology, University of California, Davis, California, United States of America., Levenson RM; Department of Pathology and Laboratory Medicine, UC Davis Health, Sacramento, California, United States of America., Chen WR; Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, Oklahoma, United States of America., Coffey LL; Department of Pathology, Microbiology & Immunology, University of California, Davis, California, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2023 Aug 08; Vol. 18 (8), pp. e0289139. Date of Electronic Publication: 2023 Aug 08 (Print Publication: 2023).
DOI: 10.1371/journal.pone.0289139
Abstrakt: 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.
Competing Interests: TH, CFW, 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. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
(Copyright: 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 public domain dedication.)
Databáze: MEDLINE
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