The Durability of immune Responses to vaccination against SARS-CoV-2 and its Variants.

This proposal comes from a team who have been at the forefront of decoding immune parameters in COVID-19 throughout the pandemic, giving us a sharp focus on the current questions. The concern is to understand, at a qualitative and quantitative level, the details of immune response durability in 'real-life settings' of different vaccination regimens, with or without prior infection. We will study large, longitudinal, cohorts (totalling 12097 individuals) with different exposures to SARS-CoV-2 and its variants, in the UK, South Africa and Brazil, enabling us to study vaccination using diverse platforms, with or without infection by SARS-CoV-2 and the alpha, beta, gamma and delta variants of concern (VoC). These are cohorts with a high-granularity history, encompassing infection and symptom history as well as immune data. Moving forward, we wish to understand the durability and nature of immune protection, including susceptibility to reinfection and breakthrough infections. To achieve this, we will track longitudinal immunity, analysing serum antibody durability, live virus neutralisation, antibody affinity, B cell receptor repertoire and B cell memory frequency, both to wild-type and variant targets. In terms of T cell immunity, we will track durability of response frequency to wild-type and variant epitopes using a wide range of approaches. The CLARITY and CML-Co-vax Cohorts will enable us to probe vaccine response impairment and its mitigation in immunosuppressed cohorts (IBD and chronic myelogenous leukemia) after Infliximab or tyrosine kinase inhibitor (TKI) therapy respectively. Data will be modeled in relation to CoP values to extrapolate and provide guidance regarding the need / timing of boosts for different vaccine platforms in healthy adults and immunosuppressed patients to achieve protective immunity.