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Dissertation
Exploring Adenosine Deaminase 1 (ADA-1) as a Novel Molecular Vaccine Adjuvant
Doctor of Philosophy (Ph.D.), Drexel University
May 2024
DOI:
https://doi.org/10.17918/00010443
Abstract
Vaccines are the most efficient and cost-effective tool for promoting health. Some vaccine platforms such as protein subunit are often insufficiently immunogenic without adjuvants. Vaccine adjuvants allow for antigen dose sparing, the generation of rapid and durable immune responses and the increase of vaccine effectiveness. There are few adjuvants acceptable for human use and limited knowledge of their mechanisms of action highlighting the need for adjuvant development and study. SARS-CoV-2 vaccines aided in curbing the COVID-19 pandemic which is an unquestioned success in the field. However, several studies have since shown rapid waning humoral responses, decreased efficacy particularly against variants of concern, and a lack of durable immune responses that protect against mild symptomatic disease. Despite many years of attempts, there is still no immunogen or adjuvant capable of inducing robust broadly neutralizing antibodies against HIV needed for protective immunity. There is a continued need for SARS-CoV-2 and HIV vaccines and adjuvants that induce durable protective immunity. Here we evaluated a novel molecular adjuvant adenosine deaminase 1 (ADA-1) in the context of a SARS-CoV-2 and HIV DNA vaccine. ADA-1 has known immunomodulatory properties and importantly, is critical for T follicular helper (TFH) cell function. TFH cells are a necessary component of germinal center reactions needed for effective humoral immune responses. We show that ADA-1 enhances the magnitude and durability of anti-SARS-CoV-2 humoral and cellular responses in mice that translates to increased protection upon challenge. We also demonstrate that ADA-1 enhances HIV specific humoral and cellular responses in mice. Mechanistically we demonstrate that recombinant ADA-1 protein enhances IL-6 and TNFα expression in macrophages. Taken together these data demonstrate that ADA-1 effectively adjuvants several DNA vaccine antigens and provides support for further translational studies.
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Details
- Title
- Exploring Adenosine Deaminase 1 (ADA-1) as a Novel Molecular Vaccine Adjuvant
- Creators
- Gina Marie Cusimano - Drexel University, Microbiology and Immunology
- Contributors
- Michele Kutzler (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- 212 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Microbiology and Immunology; College of Medicine; Drexel University
- Other Identifier
- 991021874915504721