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A Novel Toll-Like Receptor 2 Agonist Protects Mice in a Prophylactic Treatment Model Against Challenge With Bacillus anthracis

Current therapies for anthrax include the use of antibiotics (i.e., doxycycline, and ciprofloxacin), an anthrax vaccine (BioThrax) and Bacillus anthracis-specific, monoclonal antibody (mAb) (i.e., Raxibacumab and obiltoxaximab). In this study, we investigated the activity of immunomodulators, which...

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Autores principales: Chiang, Chih-Yuan, Lane, Douglas J., Zou, Yefen, Hoffman, Tim, Pan, Jianfeng, Hampton, Janice, Maginnis, Jillian, Nayak, Bishnu P., D’Oro, Ugo, Valiante, Nicholas, Miller, Andrew T., Cooke, Michael, Wu, Tom, Bavari, Sina, Panchal, Rekha G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965344/
https://www.ncbi.nlm.nih.gov/pubmed/35369443
http://dx.doi.org/10.3389/fmicb.2022.803041
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author Chiang, Chih-Yuan
Lane, Douglas J.
Zou, Yefen
Hoffman, Tim
Pan, Jianfeng
Hampton, Janice
Maginnis, Jillian
Nayak, Bishnu P.
D’Oro, Ugo
Valiante, Nicholas
Miller, Andrew T.
Cooke, Michael
Wu, Tom
Bavari, Sina
Panchal, Rekha G.
author_facet Chiang, Chih-Yuan
Lane, Douglas J.
Zou, Yefen
Hoffman, Tim
Pan, Jianfeng
Hampton, Janice
Maginnis, Jillian
Nayak, Bishnu P.
D’Oro, Ugo
Valiante, Nicholas
Miller, Andrew T.
Cooke, Michael
Wu, Tom
Bavari, Sina
Panchal, Rekha G.
author_sort Chiang, Chih-Yuan
collection PubMed
description Current therapies for anthrax include the use of antibiotics (i.e., doxycycline, and ciprofloxacin), an anthrax vaccine (BioThrax) and Bacillus anthracis-specific, monoclonal antibody (mAb) (i.e., Raxibacumab and obiltoxaximab). In this study, we investigated the activity of immunomodulators, which potentiate inflammatory responses through innate immune receptors. The rationale for the use of innate immune receptor agonists as adjunctive immunomodulators for infectious diseases is based on the concept that augmentation of host defense should promote the antimicrobial mechanism of the host. Our aim was to explore the anti-B. anthracis effector function of Toll-like receptor (TLR) agonists using a mouse model. Amongst the six TLR ligands tested, Pam(3)CSK(4) (TLR1/2 ligand) was the best at protecting mice from lethal challenge of B. anthracis. We then evaluated the activity of a novel TLR2 ligand, DA-98-WW07. DA-98-WW07 demonstrated enhanced protection in B. anthracis infected mice. The surviving mice that received DA-98-WW07 when re-challenged with B. anthracis 20 days post the first infection showed increased survival rate. Moreover, ciprofloxacin, when treated in adjunct with a suboptimal concentration of DA-98-WW07 demonstrated augmented activity in protecting mice from B. anthracis infection. Taken together, we report the prophylactic treatment potential of DA-98-WW07 for anthrax and the utility of immunomodulators in combination with an antibiotic to treat infections caused by the B. anthracis bacterium.
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spelling pubmed-89653442022-03-31 A Novel Toll-Like Receptor 2 Agonist Protects Mice in a Prophylactic Treatment Model Against Challenge With Bacillus anthracis Chiang, Chih-Yuan Lane, Douglas J. Zou, Yefen Hoffman, Tim Pan, Jianfeng Hampton, Janice Maginnis, Jillian Nayak, Bishnu P. D’Oro, Ugo Valiante, Nicholas Miller, Andrew T. Cooke, Michael Wu, Tom Bavari, Sina Panchal, Rekha G. Front Microbiol Microbiology Current therapies for anthrax include the use of antibiotics (i.e., doxycycline, and ciprofloxacin), an anthrax vaccine (BioThrax) and Bacillus anthracis-specific, monoclonal antibody (mAb) (i.e., Raxibacumab and obiltoxaximab). In this study, we investigated the activity of immunomodulators, which potentiate inflammatory responses through innate immune receptors. The rationale for the use of innate immune receptor agonists as adjunctive immunomodulators for infectious diseases is based on the concept that augmentation of host defense should promote the antimicrobial mechanism of the host. Our aim was to explore the anti-B. anthracis effector function of Toll-like receptor (TLR) agonists using a mouse model. Amongst the six TLR ligands tested, Pam(3)CSK(4) (TLR1/2 ligand) was the best at protecting mice from lethal challenge of B. anthracis. We then evaluated the activity of a novel TLR2 ligand, DA-98-WW07. DA-98-WW07 demonstrated enhanced protection in B. anthracis infected mice. The surviving mice that received DA-98-WW07 when re-challenged with B. anthracis 20 days post the first infection showed increased survival rate. Moreover, ciprofloxacin, when treated in adjunct with a suboptimal concentration of DA-98-WW07 demonstrated augmented activity in protecting mice from B. anthracis infection. Taken together, we report the prophylactic treatment potential of DA-98-WW07 for anthrax and the utility of immunomodulators in combination with an antibiotic to treat infections caused by the B. anthracis bacterium. Frontiers Media S.A. 2022-03-14 /pmc/articles/PMC8965344/ /pubmed/35369443 http://dx.doi.org/10.3389/fmicb.2022.803041 Text en Copyright © 2022 Chiang, Lane, Zou, Hoffman, Pan, Hampton, Maginnis, Nayak, D’Oro, Valiante, Miller, Cooke, Wu, Bavari and Panchal. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Chiang, Chih-Yuan
Lane, Douglas J.
Zou, Yefen
Hoffman, Tim
Pan, Jianfeng
Hampton, Janice
Maginnis, Jillian
Nayak, Bishnu P.
D’Oro, Ugo
Valiante, Nicholas
Miller, Andrew T.
Cooke, Michael
Wu, Tom
Bavari, Sina
Panchal, Rekha G.
A Novel Toll-Like Receptor 2 Agonist Protects Mice in a Prophylactic Treatment Model Against Challenge With Bacillus anthracis
title A Novel Toll-Like Receptor 2 Agonist Protects Mice in a Prophylactic Treatment Model Against Challenge With Bacillus anthracis
title_full A Novel Toll-Like Receptor 2 Agonist Protects Mice in a Prophylactic Treatment Model Against Challenge With Bacillus anthracis
title_fullStr A Novel Toll-Like Receptor 2 Agonist Protects Mice in a Prophylactic Treatment Model Against Challenge With Bacillus anthracis
title_full_unstemmed A Novel Toll-Like Receptor 2 Agonist Protects Mice in a Prophylactic Treatment Model Against Challenge With Bacillus anthracis
title_short A Novel Toll-Like Receptor 2 Agonist Protects Mice in a Prophylactic Treatment Model Against Challenge With Bacillus anthracis
title_sort novel toll-like receptor 2 agonist protects mice in a prophylactic treatment model against challenge with bacillus anthracis
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965344/
https://www.ncbi.nlm.nih.gov/pubmed/35369443
http://dx.doi.org/10.3389/fmicb.2022.803041
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