Naturally Acquired and Vaccine-Induced Neutralizing Humoral Responses to SARS-CoV-2
[eng] Neutralizing antibodies represent one of the major correlates of protection against viral infections. Their elicitation is one of the main goals of vaccine development. The longitudinal kinetics, the factors that determine the neutralizing activity generated by vaccination, natural infection,...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/223266 |
| Acceso en línea: | https://hdl.handle.net/2445/223266 http://hdl.handle.net/10803/695240 |
| Access Level: | acceso abierto |
| Palabra clave: | Immunoglobulines Vacunes COVID-19 Immunoglobulins Vaccines |
| Sumario: | [eng] Neutralizing antibodies represent one of the major correlates of protection against viral infections. Their elicitation is one of the main goals of vaccine development. The longitudinal kinetics, the factors that determine the neutralizing activity generated by vaccination, natural infection, or both (hybrid immunity), and their ability to neutralize different variants are key pieces of information to evaluate the immune status against SARS-CoV-2. These data would inform us to take key decision on immunization schedules and/or vaccination strategies. De- spite the plethora of published studies in this matter, at the beginning of the COVID-19 pandemic the evidence was scarce and uncertain, and today there are still gaps in our knowledge about the neutralizing response. In this thesis we evaluate in detail the anti-SARS-CoV-2 neutralizing humoral response elicited by natural infection, vaccination, or both. We report that the neutralizing response to natural SARS-CoV-2 infection is elicited early after infection and is long-lasting (beyond one year). However, it induces limited long-term variant cross-neutralization. The level and quality of neutralization is determined by disease severity, and specifically, the magnitude of the humoral response in asymptomatic or mildly symptomatic individuals is associated with duration of symptoms and age, with no apparent contribution from gender and viral load. Early vaccination schedules generated neutralizing antibodies that decay over time and poorly neutralize emerging variants. However, vaccination of convalescent individuals boosts pre-existing natural immunity and provides better variant coverage. The third dose of vaccine broadens the cross-neutralization by generating a neutralizing response that mimics hybrid immunity. Omicron breakthrough infection have a positive impact on the neutralizing response to Omicron subvariants. All these results demonstrate the complexity of the neutralizing immune response to SARS- CoV-2, and how the magnitude and quality of this response are influenced by several factors, such as the clinical course of the disease, demographic factors, and the nature and number of antigenic exposures. This information can be useful to evaluate and predict the population protective status and to guide future health strategies. |
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