Presentation Type

Poster

Faculty Mentor’s Full Name

David Burkhart

Faculty Mentor’s Department

Department of Biomedical and Pharmaceutical Sciences

Abstract

Purpose: Mycobacterium tuberculosis (Mtb), the causative pathogen of tuberculosis (TB), is a global pathogenic threat. In 2017, 10 million people were affected by TB infections, resulting in 1.6 million deaths worldwide. With about one-quarter of the global population infected with latent TB, tuberculosis remains one of the top ten causes of death worldwide according to a 2018 World Health Organization report. Despite the availability of a TB vaccine, new cases of multidrug-resistant TB arise yearly, threatening the efficacy of traditional treatments used to combat this disease. Recent evidence has suggested Th17 response may be protective, but no Th17 adjuvants are clinically approved. Adjuvants, substances which boost immune response to an antigen, are added to vaccines to enhance immune cross-protection, induce humoral or cell-mediated immunity, reduce reactogenicity and toxicity, reduce antigen dosing, and ameliorate side effects of vaccination for at-risk populations. Most approved vaccine adjuvants drive a Th2 or Th1 mediated immune response, which have not proven protective against Mtb. C-type lectin receptors (CLRs) show promise as targets able to drive a Th17-response upon stimulation. Agonists of this family include many glycolipids derived from trehalose 6,6’-dimycolate (TDM), the main immunostimulatory component of the Mtb cell wall. TDM is a potent Mincle agonist but remains too toxic. Therefore, we have been developing novel synthetic analogues of TDM with equivalent immunostimulatory activity but diminished toxicity and assessed their ability to modulate innate immunity in several innovative aqueous formulations.

Methods: A focused ultrasonication technique was utilized to prepare nanodispersions of the studied CLR ligands. These aqueous formulations were characterized via dynamic light scattering, transmission electron cryomicroscopy, and high-performance liquid chromatography before in vitro and in vivo testing.

Significance: In this study, immune responses were tested for an array of CLR-based adjuvant formulations to identify lead CLR adjuvant candidates for use in next-generation TB vaccines.

Category

Physical Sciences

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Apr 17th, 11:00 AM Apr 17th, 12:00 PM

Focused Ultrasonication-Assisted Preparation of Aqueous Nanodispersions for Selected Novel C-type Lectin Receptor Ligands

UC South Ballroom

Purpose: Mycobacterium tuberculosis (Mtb), the causative pathogen of tuberculosis (TB), is a global pathogenic threat. In 2017, 10 million people were affected by TB infections, resulting in 1.6 million deaths worldwide. With about one-quarter of the global population infected with latent TB, tuberculosis remains one of the top ten causes of death worldwide according to a 2018 World Health Organization report. Despite the availability of a TB vaccine, new cases of multidrug-resistant TB arise yearly, threatening the efficacy of traditional treatments used to combat this disease. Recent evidence has suggested Th17 response may be protective, but no Th17 adjuvants are clinically approved. Adjuvants, substances which boost immune response to an antigen, are added to vaccines to enhance immune cross-protection, induce humoral or cell-mediated immunity, reduce reactogenicity and toxicity, reduce antigen dosing, and ameliorate side effects of vaccination for at-risk populations. Most approved vaccine adjuvants drive a Th2 or Th1 mediated immune response, which have not proven protective against Mtb. C-type lectin receptors (CLRs) show promise as targets able to drive a Th17-response upon stimulation. Agonists of this family include many glycolipids derived from trehalose 6,6’-dimycolate (TDM), the main immunostimulatory component of the Mtb cell wall. TDM is a potent Mincle agonist but remains too toxic. Therefore, we have been developing novel synthetic analogues of TDM with equivalent immunostimulatory activity but diminished toxicity and assessed their ability to modulate innate immunity in several innovative aqueous formulations.

Methods: A focused ultrasonication technique was utilized to prepare nanodispersions of the studied CLR ligands. These aqueous formulations were characterized via dynamic light scattering, transmission electron cryomicroscopy, and high-performance liquid chromatography before in vitro and in vivo testing.

Significance: In this study, immune responses were tested for an array of CLR-based adjuvant formulations to identify lead CLR adjuvant candidates for use in next-generation TB vaccines.