The Biological Activity of Dual-Responsive Glycopolymers for Intracellular Codelivery of Antigen and Lipophilic Adjuvant

Author

Micaela ShieldsFollow

Date of Award

Spring 5-14-2023

Document Type

Undergraduate Thesis

Department

Chemistry and Biochemistry

First Advisor

Thomas Werfel

Second Advisor

Nikki Reinemann

Third Advisor

Glenn Walker

Relational Format

Dissertation/Thesis

Abstract

Subunit vaccines present themselves as an attractive alternative to traditional approaches to vaccines, which utilizes whole organisms to trigger an immune response. While these traditional approaches have proven themselves reliable within the history of vaccinations, they generally deliver subpar robust cellular-mediated immunity and pose many safety risks. Composed of proteins and /or peptides, subunit vaccines are safer and more precise alternatives to traditional approaches. However, the pharmacokinetic properties of the macromolecules that make up these vaccines hinder the subunit vaccine’s level of immunogenicity [d1] Examples of this hindrance include but are not limited to aggregation at the injection site and poor cellular uptake. To improve the poor immunogenicity and deliver barriers present in subunit vaccines, we developed delivery system that utilizes glycomeric nanoparticles (glycoNPs) that are composed of a dual-stimuli-responsive glycopolymer, poly [2- (diisopropylamino)ethyl methacrylate]-b-poly [(pyridyl disulfide ethyl methacrylate)-co-(methacrylamidoglucopyranose)] (p[DPAb-(PDSMA-co-MAG)]). This system boosts immunogenicity by codelivering immune-stimulating adjuvants and facilitating protein conjugation and cytosolic release, pH-responsive release of lipophilic adjuvant, and pH-dependent membrane disruption. The glycoNPs were formed through thin-film hydration of the block glycopolymers. To demonstrate the biological activity and uptake of these dual-responsive glycopolymers, DC 2.4 dendritic cells (DCs) were loaded with glycoNPs, antigen, and adjuvant. In comparison to DCs loaded with free Ovalbumin (OVA) and toll-like receptor agonist Resiquimod (R848), DCs containing glycoNPs co-loaded with OVA and R848 showed significantly more activation in addition to strong antigen presentation of the T-cell stimulating OVA epitope SIINFEKL on major histocompatibility complex I (MHC-I). The dual-stimuli-responsive glycopolymer designed and introduced overcomes barriers to immunogenicity and delivery. As such, these glycopolymers could lead to major improvements in the efficacy of subunit vaccines, or, more specifically, protein-based vaccines.

Recommended Citation

Shields, Micaela, "The Biological Activity of Dual-Responsive Glycopolymers for Intracellular Codelivery of Antigen and Lipophilic Adjuvant" (2023). Honors Theses. 3011.
https://egrove.olemiss.edu/hon_thesis/3011

Accessibility Status

Searchable text

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License