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Title
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COVID-19 and SARS-CoV-2 vaccination related T-cell immune response in diverse populations
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Author
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Abstract
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| Immune dysregulation has been established as a key feature of COVID-19. Both vaccination against COVID-19 and infection by SARS-CoV-2 induce adaptive immune responses. However, much of the focus in vaccine development and immunity surveillance has been on the role of serology and neutralizing antibodies, with less emphasis on understanding the role of T cells, especially in immunocompromised hosts. Mounting evidence suggests T cell contributions to the host immune response are required for early, broad, and durable protection from the SARS-CoV-2 virus, especially in the setting of new variants of concern (VOCs). The main objective of this thesis was to expand our understanding of cellular immune responses against SARS-CoV-2 and COVID-19 vaccinations with a focus on CD4+ and CD8+ compartments in diverse populations. In the first chapters, I describe the current literature on key immunocompromised groups – concentrating on people living with human immunodeficiency virus (PLWH), solid organ transplant (SOT) recipients, and patients with solid and haematological malignancies – and the unique T cell phenotypes observed in different fragile hosts in response to SARS-CoV-2 antigens. After describing the framework of the T cell analysis in Chapter 2, I focus on investigating longitudinal T cell responses among PLWH after BNT162b2 vaccination in Chapter 3. Our results suggest that the durable serological and CD4+ T-cell responses developing in vaccinated PLWH are associated with IL-2-mediated CD4+ T-cell activation that likely compensates for CD4+ T-cell depletion in PLWH. In Chapter 4 I assess monoclonal antibody (mAb) therapy for the treatment of COVID-19 and the effect of host immune factors on Spike mutation development. We hypothesise that the de novo mutations identified in the SARS-CoV-2 spike protein are escape mutants that evade mAb neutralisation and facilitate a more natural progression of disease, thereby resulting in a more robust T cell immune response. We further demonstrate that host-driven immune and non-immune responses are essential for the development of mutant SARS-CoV-2 and support informed decision-making in reducing the risk of mAb treatment failure. Finally, in Chapter 5, I discuss the overall results with a focus on future considerations for our workgroup and the direction towards which this research can be expanded. This thesis forms the basis for future research in the development of effective vaccination strategies and provides advice for developing best practice policies in terms of COVID-19 therapeutics. |
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Language
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English
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Publication
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Antwerp
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University of Antwerp, Faculty of Medicine and Health Sciences
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2025
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DOI
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10.63028/10067/2115380151162165141
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Volume/pages
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173 p.
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Note
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Kumar Singh, Samir [Supervisor]
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Malhotra-Kumar, Surbhi [Supervisor]
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Hotterbeekx, An [Supervisor]
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Berkell, Matilda [Supervisor]
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Full text (open access)
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