West Africa, West Indies, West London: Mechanisms driving heterogeneity in immunity to SARS-CoV-2 variants

Our proposed WWW Consortium brings together three prospective cohort studies of healthy adults in receipt of COVID-19 vaccination in West Africa, the West Indies, and West London to answer fundamental questions in the immunology of SARS-CoV-2 variants. Given the diverse outcomes of COVID-19 in our respective locations, despite many overlapping characteristics such as shared genetic ancestry and AZD1222 vaccination, we have power to make a significant contribution to understanding the mechanisms underlying the apparent heterogeneity in our cohorts. We have 3 aims: - Harmonise our studies to determine the breadth of immunity to SARS-CoV-2 variants by transferring assay and modelling capacity between sites, while also genotype participants to enable comparison across our mixed-ancestry populations; - Test four hypotheses that may contribute to breadth within and between our cohorts: exposure to prior SARS-CoV-2 variants, to other bat & human coronaviruses, to malaria, and to host immunoreactivity; and - Build models of immune responses to variants that incorporating individual-level data and are applicable in LMIC settings with limited datasets. Together, our work will provide insights into the factors that drive the complex immunology to SARS-CoV-2 variants that can also inform future pandemic response in regions currently underserved by both research and surveillance capacity.