The COVID-19 pandemic saw the rapid development and deployment of a range of vaccine platforms. While essential to protect against severe disease, these vaccine platforms need further optimisation to provide long-term and local protection against infection including future variants. This vaccine optimisation requires an improved understanding of how a protective immune response is induced, how it is maintained, and the role of immunity in the nose and the lungs. Building on the experience our consortium amassed during the COVID-19 pandemic, we will answer some of the key outstanding questions in the field: 1.MEMORY We will delineate the mechanisms which influence the duration of protective immune responses. Improving understanding of immune memory is critical for the development and deployment of future vaccines with long-lasting protection against both pandemic and endemic pathogens. 2. LOCATION We will determine the role of the immune response in the airways, as the entry route for virus, in protection against infection. The aim is to understand if nasally administered vaccines can stop infection and onward transmission, as well as protect against severe disease. 3. PROTECTION We will define which aspects of the immune response protect against disease and how to maximise these responses. This will enable vaccine developers to focus on new vaccines that deliver improved protection. 4. DATA There exist large datasets from clinical trials and real-world studies that, if combined with the data from this programme, would generate a unique resource for understanding how vaccines work. To achieve this, we will develop an integrated data structure and open-source computational tools to integrate disparate data and maximise data usefulness. 5.IMPACT We will bolster pandemic preparedness by the training and empowerment of future leaders in vaccine development and engaging public understanding of the need for vaccines. Targeting these questions will lead to increased capability for rational, immunologically-driven vaccine development and uptake.