Study of the acquisition and maintenance of antibody and cellular immune responses against SARS-CoV-2 in longitudinal cohorts
[eng] The COVID-19 pandemic has underscored the importance of understanding adaptive immune responses to SARS-CoV-2 to optimize vaccination strategies and public health interventions. Adaptive immune responses generate immune memory, which is essential for preventing reinfections, facilitating rapid...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/221736 |
| Acceso en línea: | https://hdl.handle.net/2445/221736 http://hdl.handle.net/10803/694719 |
| Access Level: | acceso abierto |
| Palabra clave: | Immunologia Malalties de l'aparell respiratori Vacunes antivíriques SARS-CoV-2 COVID-19 Immunology Respiratory diseases Viral vaccines |
| Sumario: | [eng] The COVID-19 pandemic has underscored the importance of understanding adaptive immune responses to SARS-CoV-2 to optimize vaccination strategies and public health interventions. Adaptive immune responses generate immune memory, which is essential for preventing reinfections, facilitating rapid virus clearance and reducing disease severity. Neutralizing antibodies prevent viral infection and T cells support antibody production and eliminate infected cells. Despite extensive research on SARS- CoV-2 adaptive responses, evidence was scarce early in the COVID-19 pandemic, and knowledge gaps persist, such as their duration, factors influencing them, and the cross- recognition of emerging variants, key aspects to improve immunological protection. We characterized antibody and T-cell responses induced by SARS-CoV-2 infection, COVID-19 vaccination, or a combination of both against the ancestral virus and emerging variants over three years since the onset of the pandemic. Antibody levels against spike (S) and nucleocapsid (N) antigens were measured using Luminex assays, neutralizing capacity through pseudovirus assays, and T-cell responses to S, N and membrane antigens using IFN-γ/IL-2 FluoroSpot and activation induced marker assays. Antibody kinetics were modeled using linear mixed models, and determinants were analyzed with multivariable linear regression models. The results demonstrated that positive antibody and T-cell responses to S persisted for at least three years following infection during the first pandemic wave and two years after vaccination, with subsequent exposures (boosters and reinfections) supporting the maintenance. Antibody kinetics varied by isotype, antigen, and immunization type, showing greater durability in individuals with hybrid immunity and those receiving three vaccinations compared to two. These responses were heterogeneous, influenced by factors such as comorbidities and SARS-CoV-2 prior exposure. Infection as the first SARS-CoV-2 encounter was associated with weaker antibody responses against Omicron subvariants BA.1, BA.2, BA.4/5, BQ.1.1, and XBB, but with stronger T-cell responses after three years compared to vaccination as first antigen encounter. Although ancestral pre-existing antibodies showed reduced recognition of Beta, Gamma, Delta, and Omicron subvariants BA.1, BA.2, BA.4/5, BQ.1.1, XBB, with lost neutralization for BA.2.86, T cells effectively recognized BA.2.86. In conclusion, these findings contribute to a deeper knowledge of COVID-19 immunity for optimizing vaccination strategies to maximize protection against SARS-CoV-2 and future emerging variants. |
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