Assessing humoral immune memory after COVID-19 vaccination in healthy and immunocompromised people

COVID-19 vaccines are highly effective at preventing infection and severe disease from SARS-CoV-2. Although vaccination elicits neutralising antibodies, antibodies rapidly decline and do not correlate with protection against severe disease. Therefore, neutralising antibodies may not be informative for evaluation of immune competence in patients with a compromised immune system due to underlying disease or treatment. COVID-19 booster vaccinations have involved both monovalent and bivalent mRNA formulations. The latest monovalent vaccination contains mRNA encoding Omicron XBB.1.5 spike variant. Previous bivalent vaccines contained mRNA encoding Wuhan-1 Spike as well an Omicron Spike variant (BA.1 or BA.5). Both formulations aim to boost and broaden existing immunity to SARS-CoV-2. To assess if new formulations of COVID-19 vaccines elicit improved humoral immune responses in immunocompromised patients, this project aims to examine both SARS-CoV-2 specific B-cell memory and antibody responses in a cohort of Inflammatory bowel disease patients receiving immunosuppressive therapy. These will also be compared to a group of healthy individuals receiving COVID-19 vaccination. This project will use novel immunoassays developed in the van Zelm lab to assess B cell memory responses to existing and emerging SARS-CoV-2 variants, comparing pre- and post-vaccination samples in both patients and healthy controls. Candidates will become proficient in a wide range of immunoassays, utilising Flow Cytometry, ELISA and Western Blotting. Candidates may also learn skills in processing human peripheral blood mononuclear cells and protein production. Expected outcomes of this project will include a detailed characterisation of humoral immune memory to vaccination in immunocompromised people, to inform the design and schedule of future COVID-19 vaccination.