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3 results on '"Jillian Maginnis"'

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

Author

Chih-Yuan Chiang, Douglas J. Lane, Yefen Zou, Tim Hoffman, Jianfeng Pan, Janice Hampton, Jillian Maginnis, Bishnu P. Nayak, Ugo D’Oro, Nicholas Valiante, Andrew T. Miller, Michael Cooke, Tom Wu, Sina Bavari, and Rekha G. Panchal

Subjects
TLR2, agonist, Bacillus anthracis, in vivo, prophylactic, Microbiology, QR1-502
Abstract

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, Pam3CSK4 (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.

Published
2022
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2. A Novel Toll-Like Receptor 2 Agonist Protects Mice in a Prophylactic Treatment Model Against Challenge With

Author

Chih-Yuan, Chiang, Douglas J, Lane, Yefen, Zou, Tim, Hoffman, Jianfeng, Pan, Janice, Hampton, Jillian, Maginnis, Bishnu P, Nayak, Ugo, D'Oro, Nicholas, Valiante, Andrew T, Miller, Michael, Cooke, Tom, Wu, Sina, Bavari, and Rekha G, Panchal

Abstract

Current therapies for anthrax include the use of antibiotics (i.e., doxycycline, and ciprofloxacin), an anthrax vaccine (BioThrax) and

Published
2021

3. Incorporation of Phosphonate into Benzonaphthyridine Toll-like Receptor 7 Agonists for Adsorption to Aluminum Hydroxide

Author

Ugo D'Oro, Chun Li, Kathy Yue, Michael P. Cooke, Janice Hampton, Andrew T. Miller, M. Lamine Mbow, Nicholas Valiante, David A. G. Skibinski, Xiaoyue Zhang, De Shon Hall, Michael Shapiro, Derek T. O'Hagan, Manmohan Singh, Tom Y.-H. Wu, Bishnu P. Nayak, Jillian Maginnis, Yongkai Li, and Alex Cortez

Subjects
0301 basic medicine, medicine.medical_treatment, Organophosphonates, Aluminum Hydroxide, Injections, Intramuscular, Mice, Structure-Activity Relationship, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Immune system, Antigen, Adjuvanticity, Drug Discovery, medicine, Animals, Humans, Naphthyridines, Mice, Inbred BALB C, Dose-Response Relationship, Drug, Molecular Structure, Alum, Hydrogen-Ion Concentration, Phosphonate, Combinatorial chemistry, Small molecule, 030104 developmental biology, Toll-Like Receptor 7, chemistry, 030220 oncology & carcinogenesis, Immunology, Leukocytes, Mononuclear, Molecular Medicine, Hydroxide, Female, Adsorption, Adjuvant, Spleen
Abstract

Small molecule Toll-like receptor 7 (TLR7) agonists have been used as vaccine adjuvants by enhancing innate immune activation to afford better adaptive response. Localized TLR7 agonists without systemic exposure can afford good adjuvanticity, suggesting peripheral innate activation (non-antigen-specific) is not required for immune priming. To enhance colocalization of antigen and adjuvant, benzonaphthyridine (BZN) TLR7 agonists are chemically modified with phosphonates to allow adsorption onto aluminum hydroxide (alum), a formulation commonly used in vaccines for antigen stabilization and injection site deposition. The adsorption process is facilitated by enhancing aqueous solubility of BZN analogs to avoid physical mixture of two insoluble particulates. These BZN-phosphonates are highly adsorbed onto alum, which significantly reduced systemic exposure and increased local retention post injection. This report demonstrates a novel approach in vaccine adjuvant design using phosphonate modification to afford adsorption of small molecule immune potentiator (SMIP) onto alum, thereby enhancing co-delivery with antigen.

Published
2016
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