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A Novel Monoclonal Antibody 1D2 That Broadly Inhibits Clinically Important Aspergillus Species

Aspergillus fumigatus is a ubiquitous airborne fungus, is the predominant cause (>90%) of invasive aspergillosis (IA) in immunosuppressed patients and has a high mortality. New approaches to prevention and treatment are needed because of the poor efficacy, toxicity and side effects of the current...

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Autores principales: Lian, Xihua, Scott-Thomas, Amy, Lewis, John G., Bhatia, Madhav, Chambers, Stephen T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9502797/
https://www.ncbi.nlm.nih.gov/pubmed/36135685
http://dx.doi.org/10.3390/jof8090960
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author Lian, Xihua
Scott-Thomas, Amy
Lewis, John G.
Bhatia, Madhav
Chambers, Stephen T.
author_facet Lian, Xihua
Scott-Thomas, Amy
Lewis, John G.
Bhatia, Madhav
Chambers, Stephen T.
author_sort Lian, Xihua
collection PubMed
description Aspergillus fumigatus is a ubiquitous airborne fungus, is the predominant cause (>90%) of invasive aspergillosis (IA) in immunosuppressed patients and has a high mortality. New approaches to prevention and treatment are needed because of the poor efficacy, toxicity and side effects of the current anti-Aspergillus drugs on patients. Thus, we aim to explore a new avenue to combat Aspergillus infection by using a novel monoclonal antibody (mAb) 1D2 against a glycoprotein on the cell wall of Aspergillus. The ability of this mAb to inhibit attachment, germination, and growth of Aspergillus conidia and hyphae in vitro were examined. A dose-dependent growth inhibition of Aspergillus conidia in the presence of mAb 1D2 was found. The mAb 1D2 inhibited attachment of Aspergillus conidia to an untreated slide surface and fibronectin-treated surface compared to an unrelated mAb 6B10. When conidia were exposed to 1D2 concomitantly with inoculation into culture media, the mAb prevented the swelling and germination of conidia. This inhibitory ability of 1D2 was less apparent if it was added two hours after inoculation. Damage to hyphae was also observed when 1D2 was added to Aspergillus hyphae that had been incubated in media overnight. These in vitro results indicate that mAb 1D2 broadly inhibits clinically important Aspergillus species and has a promising therapeutic effect both as prophylaxis to inhibit an Aspergillus infection as well as a treatment.
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spelling pubmed-95027972022-09-24 A Novel Monoclonal Antibody 1D2 That Broadly Inhibits Clinically Important Aspergillus Species Lian, Xihua Scott-Thomas, Amy Lewis, John G. Bhatia, Madhav Chambers, Stephen T. J Fungi (Basel) Article Aspergillus fumigatus is a ubiquitous airborne fungus, is the predominant cause (>90%) of invasive aspergillosis (IA) in immunosuppressed patients and has a high mortality. New approaches to prevention and treatment are needed because of the poor efficacy, toxicity and side effects of the current anti-Aspergillus drugs on patients. Thus, we aim to explore a new avenue to combat Aspergillus infection by using a novel monoclonal antibody (mAb) 1D2 against a glycoprotein on the cell wall of Aspergillus. The ability of this mAb to inhibit attachment, germination, and growth of Aspergillus conidia and hyphae in vitro were examined. A dose-dependent growth inhibition of Aspergillus conidia in the presence of mAb 1D2 was found. The mAb 1D2 inhibited attachment of Aspergillus conidia to an untreated slide surface and fibronectin-treated surface compared to an unrelated mAb 6B10. When conidia were exposed to 1D2 concomitantly with inoculation into culture media, the mAb prevented the swelling and germination of conidia. This inhibitory ability of 1D2 was less apparent if it was added two hours after inoculation. Damage to hyphae was also observed when 1D2 was added to Aspergillus hyphae that had been incubated in media overnight. These in vitro results indicate that mAb 1D2 broadly inhibits clinically important Aspergillus species and has a promising therapeutic effect both as prophylaxis to inhibit an Aspergillus infection as well as a treatment. MDPI 2022-09-14 /pmc/articles/PMC9502797/ /pubmed/36135685 http://dx.doi.org/10.3390/jof8090960 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lian, Xihua
Scott-Thomas, Amy
Lewis, John G.
Bhatia, Madhav
Chambers, Stephen T.
A Novel Monoclonal Antibody 1D2 That Broadly Inhibits Clinically Important Aspergillus Species
title A Novel Monoclonal Antibody 1D2 That Broadly Inhibits Clinically Important Aspergillus Species
title_full A Novel Monoclonal Antibody 1D2 That Broadly Inhibits Clinically Important Aspergillus Species
title_fullStr A Novel Monoclonal Antibody 1D2 That Broadly Inhibits Clinically Important Aspergillus Species
title_full_unstemmed A Novel Monoclonal Antibody 1D2 That Broadly Inhibits Clinically Important Aspergillus Species
title_short A Novel Monoclonal Antibody 1D2 That Broadly Inhibits Clinically Important Aspergillus Species
title_sort novel monoclonal antibody 1d2 that broadly inhibits clinically important aspergillus species
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9502797/
https://www.ncbi.nlm.nih.gov/pubmed/36135685
http://dx.doi.org/10.3390/jof8090960
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