Publication Date

5-2025

Date of Final Oral Examination (Defense)

12-9-2024

Type of Culminating Activity

Dissertation

Degree Title

Doctor of Philosophy in Biomolecular Sciences

Department

Biological Sciences

Supervisory Committee Chair

Juliette Tinker, Ph.D.

Supervisory Committee Member

Allan Albig, Ph.D.

Supervisory Committee Member

Henry Charlier, Ph.D.

Supervisory Committee Member

Javier Ochoa-Repáraz, Ph.D.

Creative Commons License

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

Abstract

Vaccines have been used to prevent infectious disease for over 200 years. While they are an incredible way to prevent loss of life, they can be improved upon. Researchers around the globe are working to improve the immune response and ultimately the protection provided by existing and new vaccines. In this dissertation, I investigate three ways to improve vaccine immune responses: using an adjuvant, using a prime-boost intramammary delivery route in cows, and using microneedle delivery route. Cholera toxin (CT) is a bacterial toxin that has a non-toxic B subunit (CTB) used as a vaccine adjuvant. However, little is known about how CTB specifically activates the immune system differently than CT. I hypothesize that CTB can act as an adjuvant to induce local and systemic immunity and support alternate routes of vaccine delivery. The results in these studies indicate that CTB has a distinct immune response without causing the toxic damage seen in CT treatments, that CTB can act as a good vaccine adjuvant for a bovine vaccine, and that CTB can be incorporated successfully into microneedles. The CTB adjuvant was incorporated into a Staphylococcus aureus vaccine that was delivered by an intramammary prime with a subcutaneous boost to prevent bovine mastitis. Through a phase 1 USDA cow study, we showed that this vaccine delivered with this prime-boost method is safe and triggers an antigen-specific systemic humoral and cellular immune response when compared to an unvaccinated group. Another way to increase immune response is by delivering vaccines to the skin using microneedles. I developed a dissolvable sugar microneedle that can withstand application forces and deliver an antigen fused to a CTB adjuvant to the epidermis and dermis. Lastly, improvement to vaccines is only effective if people are willing to take them, so building trust and spreading awareness of the research process is critical. In this dissertation, I share several ways to communicate vaccine research to a variety of ages throughout the community, including, among others, elementary STEM, high school biology labs, health fairs, and news articles. In conclusion, this research substantiates and builds upon evidence that CTB is an effective adjuvant for vaccines delivered by alternative routes and advances the use of these routes to promote vaccine acceptance.

DOI

https://doi.org/10.18122/td.2322.boisestate

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