Thesis
Improved HIV-specific T cell immunity following adenosine deaminase-1 co-delivery in preclinical models of vaccination
Master of Science (M.S.), Drexel University
Aug 2023
DOI:
https://doi.org/10.17918/00001811
Abstract
Human immunodeficiency virus-1 (HIV-1) impacts approximately 38.4 million people worldwide. While new treatments have improved the quality of life for infected individuals, there are no approved vaccines to prevent the spread of the virus. Most available HIV vaccines are unable to elicit protective HIV-specific responses in humans. Recent studies in non-human primates (NHP) and humans have identified significant correlations between the function of a subset of CD4+ T cells called follicular helper T cells (Tfh) and anti-HIV immunity. Indirect evidence revealed strong associations between Tfh cells and the generation of anti-HIV broadly neutralizing antibodies (bNAb). These antibodies (Abs) have demonstrated transient, but efficient, antiviral activity in humans and NHP resulting in the development of proof-of-concept vaccines aimed to generate these Abs to protect against HIV infection. We hypothesize that boosting Tfh function leads to the generation of Abs protective against HIV infection. Previous research demonstrates how the enzyme Adenosine Deaminase-1 (ADA-1) enhances the function of Tfh cells, an important subset responsible for orchestrating immune responses capable of clearing infections. Our work focuses on evaluating the performance of experimental ADA-1 adjuvanted formulations in preclinical mouse models to evaluate the T-cell characteristics that constitute a major component of HIV-1 natural immunity observed in members of the elite controller population. We anticipate inclusion of ADA-1 in vaccines will demonstrate improved performance compared to alternatively adjuvanted formulations. Analysis of immune responses to immunization indicates ADA-1 improves antibody function while T cell populations exhibit higher frequencies of activation and improved cytokine profile.
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Details
- Title
- Improved HIV-specific T cell immunity following adenosine deaminase-1 co-delivery in preclinical models of vaccination
- Creators
- David Joyner
- Contributors
- Elias El Haddad (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- viii, 71 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; College of Medicine; Drexel University
- Other Identifier
- 991021229815304721