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Dissertation
Characterization of immune memory responses to COVID-19 infection and vaccination
Doctor of Philosophy (Ph.D.), Drexel University
Apr 2025
DOI:
https://doi.org/10.17918/00010919
Abstract
Since the emergence of SARS-CoV-2 in late 2019, the COVID-19 pandemic has emphasized the critical need to understand the durability, quality, and variability of immune memory following infection and vaccination. Immune responses following SARS-CoV-2 infection or vaccination show significant heterogeneity in magnitude and quality of memory T and B cell responses. However, little is known about the contributing factors. Other groups have extensively characterized early immune responses to COVID-19, painting a landscape of innate immune infiltration and subsequent release of proinflammatory cytokines, chemokines and stimulatory molecules. However, little is known about how these early immune events shape memory T and B cell responses. We investigated associations between early immune responses and SARS-CoV-2 memory immunity in a cohort of individuals hospitalized with moderate and severe COVID-19 infection. We hypothesized that early immune events from cellular immunity, cytokine/chemokine release, and omic measurements altered the strength of memory T and B cell responses. We show that high levels of inflammatory proteins, and co-stimulatory molecules during the early stages of COVID-19 lead to enhanced memory T and B cell responses and improved durability. Importantly, we were able to identify early markers that are positively and negatively associated with durable antibody responses in infected participants. Additionally, the durability and effectiveness of memory immunity conferred by SARS-CoV-2 vaccination and hybrid immunity (infection and vaccination) appear to be critical for long-term protection against emerging variants. We also investigated the impact of booster doses and hybrid immunity on memory T and B cell responses over a two-year period. Notably, hybrid immunity conferred enhanced protection against multiple SARS-CoV-2 variants, particularly in individuals who were infected before vaccination. These findings underscore the importance of hybrid immunity in providing broad and durable protection, emphasizing the benefits of booster doses and combined vaccination and infection for shaping long-term immunity. Together, these findings highlight the importance of early immune signals and hybrid immunity in shaping long-lasting protective memory and provide key insights to inform future vaccine strategies against current and emerging SARS-CoV-2 pandemics.
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Details
- Title
- Characterization of immune memory responses to COVID-19 infection and vaccination
- Creators
- Kyra Woloszczuk
- Contributors
- Elias El Haddad (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xi, i, 142 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Microbiology and Immunology; College of Medicine; Drexel University
- Other Identifier
- 991022050251704721