Polymer-based vaccine delivery for enhancing immunity
Abstract/Contents
- Abstract
- Vaccines remain one of the most effective medical treatments to prevent infectious diseases. In modern vaccine design, the co-delivery of a subunit vaccine's antigen and adjuvant is essential for inducing an optimal immune response and the subsequent adaptive immunity that is acquired. Small-molecule Toll-like receptor agonists (TLRa) have been increasingly recognized as promising adjuvants due to their targeted pathways, allowing for specific immune signatures and response. However, the pharmacokinetics/pharmacodynamics (PK/PD) profiles of small adjuvants are often mismatched from large protein antigens due to vast differences in molecular weight. Polymeric-based delivery platforms offer a highly tunable approach for antigen/ adjuvant co-delivery. By conjugating adjuvants to a polymeric nanoparticle, PK/PD can be favorably altered to improve retention and trafficking into lymphoid tissues, while also reducing systemic toxicity. Simultaneous release of vaccine components prolongs the cytokine response profile for higher antibody titers and isotype switching. Further, augmenting the co-delivery platform for sustained release elicits a more robust humoral immunity and improved antibody longevity and breadth. Sustained release, as compared to a traditional bolus delivery, more closely mimics a natural pathogen infection, and as a result of the extended antigen presentation and germinal center lifetime, enables an increased quality and magnitude of antibody response. In this work, we mixed biopolymers with nanoparticles to create dynamically cross-linked polymer nanoparticle (PNP) hydrogels. These PNP hydrogels are supramoleculary crosslinked networks that transiently form and break, simultaneously releasing protein antigens and small-molecule adjuvants in a slow-release manner. Although vaccines are commonly thought of as prophylactic in nature, they can also be utilized in a therapeutic setting. Cancer immunotherapy with vaccines is a promising strategy to overcome the immunosuppressive tumor microenviroment to stage a potent anti-tumor response. Potentiating the immune response with PNP hydrogel delivery increases the short-lived effector T cell populations compared to a bolus-delivered vaccine. Additionally, supplementing the vaccine with a novel immune checkpoint blockade therapy further enhances the increased T cell populations for a robust immune response. In this dissertation, I will discuss polymeric strategies for spatiotemporal control in vaccine design, enabling improved co-delivery of antigen and adjuvant. Extending the co-delivery into sustained delivery further improves humoral immunity for disease protection and cellular immunity for anti-cancer response.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Liong, Celine Sao Yeng |
|---|---|
| Degree supervisor | Appel, Eric (Eric Andrew) |
| Thesis advisor | Appel, Eric (Eric Andrew) |
| Thesis advisor | DeSimone, Joseph M |
| Thesis advisor | Heilshorn, Sarah |
| Degree committee member | DeSimone, Joseph M |
| Degree committee member | Heilshorn, Sarah |
| Associated with | Stanford University, Department of Bioengineering |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Celine Sao Yeng Liong. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/fr390wb0855 |
Access conditions
- Copyright
- © 2022 by Celine Sao Yeng Liong
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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