Understanding T cell immunity to SARS-CoV-2 natural infection and vaccination in healthy and immunocompromised individuals

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The emergent virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic and has had a huge impact on global health and society. Infection with SARS-CoV-2 leads to a diverse range of disease outcomes, from asymptomatic infection to severe disease which may require hospitalisation or may even lead to death. A key player in deciding the outcome for infection is the immune system - the body's natural defence mechanism against infection. Since 2019, much work has been done to begin to understand the role of the immune system in COVID-19 outcomes and to investigate what parts of the immune response are important for proper protection against infection. So far, the central role of two specific compartments of the immune system: B cells and the antibody response, and T cells, has been shown. T cells seem to be particularly interesting in their role in clearing infection - however, because of the relative difficulty in exploring these responses experimentally (compared to other immune responses such as antibodies), there remains much to be understood about their role in immune protection. Viewing these responses in specific contexts - such as looking at the effect of pre-existing immunity, potentially caused by previous infection with very similar coronaviruses which cause the common cold, is therefore potentially very interesting and important in our understanding of COVID-19 outcomes. Another very important aspect of SARS-CoV-2 immunity which remains poorly understood is the outcome of infection in the large population of people that are on medication or have underlying conditions (such as cancer, chronic liver disease and more) which suppress their immune system. Key in this group of people is understanding their ability to respond to SARS-CoV-2 vaccines and see if their response is sufficient to protect them against infection. By looking at different groups of immunosuppressed people, we can begin to understand the effect of certain diseases or medication on vaccine response which will be key in guiding policy and treatment options for these people. The aim and objectives of my project therefore are to:1.) Investigate T cell immunity in natural SARS-CoV-2 infection and against the SARS-CoV-2 vaccines.2.) Explore the impact of compromised immunity on responses to SARS-CoV-2 vaccines and to determine the role that T cells play in these responses. 3.) Investigate the potential role of pre-existing T cell immunity to SARS-CoV-2 on responses to infection.ImportanceAs an emergent virus that has been hugely detrimental not only to human health but to global society and economy, building more detailed understanding of the role of the immune system in SARS-CoV-2 is key. Comprehensive knowledge of T cells in the immune response to SARS-CoV-2 is key in building this understanding. Exploring the role of potentially hugely important factors such as pre-existing immunity to SARS-CoV-2 on disease outcomes is key and may have a great impact on our understanding immunity to SARS-CoV-2 infections which may have cross-over to other families of viruses. As well as this, investigating immunity in immunocompromised people is hugely important, as this is a large knowledge gap which is integral to the protection of a very large global population of highly clinically vulnerable people. As these people are immunosuppressed, it is likely that their response to vaccines will be worse than those with healthy immune systems and therefore protection in these people may be decreased. So far however, there is very little definitive information on the effect of specific diseases and medications on responses to SARS-CoV-2 infection or vaccination. By gathering evidence of the responses that immunocompromised people make to vaccines, we can guide the development of policy and clinical advice which will protect patients in the future and develop understanding of vaccine responses in immunocompromised people.