Browsing by Subject "vaccination"

In this thesis, I studied T cell responses to SARS-CoV-2 structural proteins in subjects who had been both vaccinated and infected (n=30), who had only been infected (n=22), and as controls, in subjects who had been neither vaccinated nor infected (n=6). In addition, I compared cellular responses between groups of subjects who had been infected with either wild-type (WT) SARS-CoV-2, Alpha (B.1.1.7), or Beta (B.1.351) variants. Before analyzing the samples to be studied, I optimized the conditions for the cell stimulations. Peripheral blood mononuclear cells (PBMCs) were collected from infected subjects six months after infection. PBMCs were stimulated with SARS-CoV-2 wild-type nucleoprotein, spike-, envelope-, and membrane protein peptide pools. I quantified cytokines and effector molecules characteristic of CD4+ and CD8+ cell responses; perforin, tumor necrosis factor alpha (TNF-a), granzyme B, interferon gamma (IFN-γ), interleukin 2 (IL-2) and interleukin 4 (IL-4) secreted by PBMCs were quantified. In this study, I found that subjects with infection, or combination of infection and vaccination had higher cellular immune responses compared to uninfected controls. Infection induced higher granzyme B, IFN-y, and IL-2 secretion, and the combination of infection and vaccination induced higher granzyme B, perforin, IFN-y, IL-2 and IL-4 secretion. I found that subjects with hybrid immunity, defined as immunity acquired from combined vaccination and infection, had on average higher IL-4 responses compared to those who had been infected only. In this study, I found that nucleoprotein, spike-, and membrane proteins stimulated T cell responses whereas envelope protein did not stimulate T cell responses. I found that WT, Alpha or Beta infection produced equally good T cell responses to WT spike peptide. In conclusion, I found that COVID-19 patients have long-lasting T cell responses. I found that T cells recognize different SARS-CoV-2 variants. Mutations present in the spike proteins of the different variants do not affect T-cell ability to recognize these antigens. Immunity based on T cells is not as susceptible to antigenic changes as the humoral immunity. T cells have a vital role in protection against variants, when new SARS-CoV-2 variants evaded antibody-based immunity.