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101 results on '"Burkhart, David J."'

2. Promotion of Th17 Polarized Immunity via Co-Delivery of Mincle Agonist and Tuberculosis Antigen Using Silica Nanoparticles

Author

Abdelwahab, Walid M., primary, Le-Vinh, Bao, additional, Riffey, Alexander, additional, Hicks, Linda, additional, Buhl, Cassandra, additional, Ettenger, George, additional, Jackson, Konner J., additional, Weiss, Adam M., additional, Miller, Shannon, additional, Ryter, Kendal, additional, Evans, Jay T., additional, and Burkhart, David J., additional

Published
2024
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4. Intranasal administration of a synthetic TLR4 agonist INI-2004 significantly reduces allergy symptoms following therapeutic administration in a murine model of allergic sensitization.

Author

Jackson, Konner J., Buhl, Cassandra, Miller, Shannon M., Khalaf, Juhienah K., Ward, Janine, Sands, Cherrokee, Walsh, Lois, Whitacre, Margaret, Burkhart, David J., Bazin-Lee, Hélène G., and Evans, Jay T.

Subjects
SYNTHETIC receptors, ALLERGIC rhinitis, TOLL-like receptors, INTRANASAL administration, AIRWAY resistance (Respiration)
Abstract

Introduction: Atopic diseases have been steadily increasing over the past decades and effective disease-modifying treatment options are urgently needed. These studies introduce a novel synthetic Toll-like receptor 4 (TLR4) agonist, INI-2004, with remarkable efficacy as a therapeutic intranasal treatment for seasonal allergic rhinitis. Methods: Using a murine airway allergic sensitization model, the impact of INI-2004 on allergic responses was assessed. Results: One or two intranasal doses of INI-2004 significantly reduced airway resistance, eosinophil influx, and Th2 cytokine production - providing strong evidence of allergic desensitization. Further investigations revealed that a liposomal formulation of INI-2004 exhibited better safety and efficacy profiles compared to aqueous formulations. Importantly, the liposomal formulation demonstrated a 1000-fold increase in the maximum tolerated intravenous dose in pigs. Pre-clinical GLP toxicology studies in rats and pigs confirmed the safety of liposomal INI-2004, supporting its selection for human clinical trials. Discussion: These findings lay the groundwork for the ongoing clinical evaluation of INI-2004 in allergic rhinitis as a stand-alone therapy for individuals poly-sensitized to multiple seasonal allergens. The study underscores the significance of innovative immunotherapy approaches in reshaping the landscape of allergic rhinitis management. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Co-Delivery of a Novel Lipidated TLR7/8 Agonist and Hemagglutinin-Based Influenza Antigen Using Silica Nanoparticles Promotes Enhanced Immune Responses

Author

Abdelwahab, Walid M., primary, Auclair, Sarah, additional, Borgogna, Timothy, additional, Siram, Karthik, additional, Riffey, Alexander, additional, Bazin, Hélène G., additional, Cottam, Howard B., additional, Hayashi, Tomoko, additional, Evans, Jay T., additional, and Burkhart, David J., additional

Published
2024
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7. Co-Delivery of a Novel Lipidated TLR7/8 Agonist and Hemagglutinin-based Influenza Antigen Using Silica Nanoparticles Promotes Enhanced Immune Responses

Author

Abdelwahab, Walid M., primary, Auclair, Sarah, additional, Borgogna, Timothy, additional, Siram, Karthik, additional, Riffey, Alexander, additional, Bazin, Hélène G., additional, Cottam, Howard B., additional, Hayashi, Tomoko, additional, Evans, Jay T., additional, and Burkhart, David J., additional

Published
2023
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8. Co-Delivery of Novel Synthetic TLR4 and TLR7/8 Ligands Adsorbed to Aluminum Salts Promotes Th1-Mediated Immunity against Poorly Immunogenic SARS-CoV-2 RBD.

Author

Siram, Karthik, Lathrop, Stephanie K., Abdelwahab, Walid M., Tee, Rebekah, Davison, Clara J., Partlow, Haley A., Evans, Jay T., and Burkhart, David J.

Subjects
SARS-CoV-2, TOLL-like receptors
Abstract

Despite the availability of effective vaccines against COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide, pressing the need for new vaccines with improved breadth and durability. We developed an adjuvanted subunit vaccine against SARS-CoV-2 using the recombinant receptor–binding domain (RBD) of spikes with synthetic adjuvants targeting TLR7/8 (INI-4001) and TLR4 (INI-2002), co-delivered with aluminum hydroxide (AH) or aluminum phosphate (AP). The formulations were characterized for the quantities of RBD, INI-4001, and INI-2002 adsorbed onto the respective aluminum salts. Results indicated that at pH 6, the uncharged RBD (5.73 ± 4.2 mV) did not efficiently adsorb to the positively charged AH (22.68 ± 7.01 mV), whereas it adsorbed efficiently to the negatively charged AP (−31.87 ± 0.33 mV). Alternatively, pre-adsorption of the TLR ligands to AH converted it to a negatively charged particle, allowing for the efficient adsorption of RBD. RBD could also be directly adsorbed to AH at a pH of 8.1, which changed the charge of the RBD to negative. INI-4001 and INI-2002 efficiently to AH. Following vaccination in C57BL/6 mice, both aluminum salts promoted Th2-mediated immunity when used as the sole adjuvant. Co-delivery with TLR4 and/or TLR7/8 ligands efficiently promoted a switch to Th1-mediated immunity instead. Measurements of viral neutralization by serum antibodies demonstrated that the addition of TLR ligands to alum also greatly improved the neutralizing antibody response. These results indicate that the addition of a TLR7/8 and/or TLR4 agonist to a subunit vaccine containing RBD antigen and alum is a promising strategy for driving a Th1 response and neutralizing antibody titers targeting SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Using Dual Toll-like Receptor Agonism to Drive Th1-Biased Response in a Squalene- and α-Tocopherol-Containing Emulsion for a More Effective SARS-CoV-2 Vaccine

Author

Short, Kristopher K., primary, Lathrop, Stephanie K., additional, Davison, Clara J., additional, Partlow, Haley A., additional, Kaiser, Johnathan A., additional, Tee, Rebekah D., additional, Lorentz, Elizabeth B., additional, Evans, Jay T., additional, and Burkhart, David J., additional

Published
2022
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13. Development of a TLR7/8 agonist adjuvant formulation to overcome early life hyporesponsiveness to DTaP vaccination

Author

Dowling, David, primary, Barman, Soumik, additional, Smith, Alyson J., additional, Borriello, Francesco, additional, Chaney, Danielle, additional, Brightman, Spencer E., additional, Malhem, Gandolina, additional, Brook, Byron, additional, Menon, Manisha, additional, Soni, Dheeraj, additional, Schüller, Simone, additional, Siram, Karthik, additional, Nanishi, Etsuro, additional, Bazin, Hélène G., additional, Burkhart, David J., additional, Levy, Ofer, additional, and Evans, Jay T., additional

Published
2022
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27. Identification and Characterization of Stimulator of Interferon Genes As a Robust Adjuvant Target for Early Life Immunization

Author

Borriello, Francesco, primary, Pietrasanta, Carlo, additional, Lai, Jacqueline C. Y., additional, Walsh, Lois M., additional, Sharma, Pankaj, additional, O’Driscoll, David N., additional, Ramirez, Juan, additional, Brightman, Spencer, additional, Pugni, Lorenza, additional, Mosca, Fabio, additional, Burkhart, David J., additional, Dowling, David J., additional, and Levy, Ofer, additional

Published
2017
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29. Structural basis for glutamate recognition: can small molecules which bind selectively be developed?

Author

Natale, Nicholas R., Nelson, Jared K., Burkhart, David J., Magnusson, Kathy R., Zhao, Xue, and Bridges, Richard J.

Subjects
Ligand binding (Biochemistry) -- Research -- Physiological aspects -- Chemical properties, Glutamate -- Chemical properties -- Research -- Physiological aspects, Neural transmission -- Physiological aspects -- Chemical properties -- Research, Science and technology, Chemical properties, Physiological aspects, Research
Abstract

Glutamate is a major neurotransmitter in the mammalian central nervous system. In a key event during nerve impulse transmission glutamate is released from vesicles in the presynaptic neuron, and travels [...]

Published
2005

33. Isoxazole analogues bind the System xc- transporter: Structure–activity relationship and pharmacophore model

Author

Patel, Sarjubhai A., primary, Rajale, Trideep, additional, O’Brien, Erin, additional, Burkhart, David J., additional, Nelson, Jared K., additional, Twamley, Brendan, additional, Blumenfeld, Alex, additional, Szabon-Watola, Monika I., additional, Gerdes, John M., additional, Bridges, Richard J., additional, and Natale, Nicholas R., additional

Published
2010
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41. Modifying AMPA to increase Glutamate Receptor Ligand-Binding. (Chemistry Paper Abstracts)

Author

Grieser, Matthew J., Burkhart, David J., and Natale, N.R.

Subjects
Ligand binding (Biochemistry) -- Research, Glutamate -- Research, Amino compounds -- Research, Science and technology, Research
Abstract

Matthew J. Grieser* 2-Amino-3-(3-carboxyl-5-methyl-4-isoxazoyl) propionic acid (ACPA) was modified by double activation at the three position with amino alcohols using SmCl3 and N-Butyl Lithium. These molecules were Snthesized for Glutamate [...]

Published
2001

44. Preparation of chiral isoxazole carbinols via catalytic asymmetric Corey-Bakshi-Shibata reduction.

Author

Rider, Kevin C., Burkhart, David J., Chun Li, McKenzie, Andrew R., Nelson, Jared K., and Natale, Nicholas R.

Subjects
*ASYMMETRIC synthesis, *CATALYSIS, *CHEMICAL reduction, *METHYL ether, *PHARMACOKINETICS, *METHANOL, *ENANTIOSELECTIVE catalysis, *ORGANIC compounds, *ORGANIC chemistry
Abstract

A diverse set of isoxazoles, with activity in three different disease categories, was reduced asymmetrically from pro-chiral ketones to chiral alcohols using the Corey-Bakshi-Shibata methodology at the α, β, and γ positions relative to the C-5-methyl of the isoxazole. The experiments described provide an easy route to hydroxylated isoxazoles that represent the common CYP-450 3A4 metabolic site. [ABSTRACT FROM AUTHOR]

Published
2010

46. Combinations of alum and synthetic toll-like receptor agonists as adjuvants for CoVID-19 vaccines

Author

Davison, Clara J., Partlow, Haley A., Lathrop, Stephanie K., Karthik Siram, Abdelwahab, Walid, Burkhart, David J., and Evans, Jay

Subjects
Immunology, Immunology and Allergy
Abstract

Aluminum-based adjuvants (“alum”) are the most widely-used adjuvants for human vaccines, with an extensive history of safety and efficacy. Alum is known to elicit high antibody titers by driving a Th2-based immune response, which may not be optimal for many viral infections, such as SARS-CoV-2. Therefore, combining the strong safety and efficacy attributes of alum with a Th1-polarizing adjuvant could improve immunity against viral antigens. Here we test the combination of alum with synthetic TLR4- and TLR7/8 -ligands in vaccines against SARS-CoV-2. The combination of alum and TLR agonists resulted in efficient adjuvantation of both humoral and cell-mediated immunity. Alum adsorption studies showed low association between the small, positively-charged receptor binding domain (RBD) antigen and aluminum hydroxide (Alhydrogel) and high adsorption to negatively charged aluminum phosphate (Adju-phos). However, Adju-phos and Alhydrogel both enhanced immunity to the SARS-CoV-2 RBD antigen, suggesting antigen adsorption may not be required for the immune enhancing effects of alum. These data demonstrated that adjuvants combining alum with a TLR agonist result in an improved anti-viral immune response. However, the ability of alum to adsorb to an antigen may not predict its ability to effectively adjuvant.

48. Code review: Fire protection systems need heating up.

Author

Burkhart, David J.

Subjects
BUILDING protection, FIRE prevention
Abstract

Discusses the need for a design and code review for fire protection systems before construction begins. Fire code drills; Need for changes in the traditional way of reviewing fire protection systems; Historical perspective; Building setbacks.

Published
1997

49. The heat is on for better fire protection guidelines.

Author

Burkhart, David J. and Loftin, Rahe E.

Subjects
FIRE prevention
Abstract

Reports that everyone can agree on the need for tougher fire prevention requirements and specific codes but what no one can agree on is who is responsible for them. List of departments who deny responsibility; Early 1900 process of creating buildings; Lack of fire protection in growing cities; Fire departments.

Published
1995

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