Understanding associations between reactogenicity, immunogenicity and genetics following vaccination

Background Vaccination is a key area for NHS policy and is vital to protect against ill health. Optimal vaccine protection against disease is achieved by delivering safe and effective vaccines to the right people at the right time at the right dose. It is not always clear how best to adapt a vaccine programme to achieve best protection and therefore vaccine programmes are regularly updated as more information becomes available. During vaccine clinical trials, data on solicited adverse reactions are collected to assess safety. The frequency and severity of adverse reactions can vary by dose and vaccine type. It is plausible that adverse reactions to earlier doses are correlated with adverse reactions to later doses. There is some research on the relationship between adverse reactions and immune responses but results are inconsistent and the area is under-researched. Genetics may affect adverse reactions following vaccination but the relationship is largely unknown. It is vital to develop our understanding of relationships with adverse reactions in order for best recommendations to be made in future vaccine campaigns, not just in terms of safety but also in terms of the best immune responses. Aims This study aims to understand the relationships between vaccine adverse reactions, immune responses, and genetics. Objectives Determine associations between adverse reactions following an initial dose and subsequent reactions following booster doses. Determine associations between reactogenicity and immunogenicity following vaccination. Determine associations between genetics and reactogenicity, and whether these associations impact on immunogenicity. Methods and timelines Objective 1: analyse associations between solicited adverse reactions following an initial vaccination and subsequent reactions following further doses (months 1-9). Objective 2: analyse associations between solicited adverse reactions and immune responses following vaccination (months 10-18). Objective 3: determine the contribution of genetic factors to the observed variation in response to vaccination through solicited adverse reactions following vaccination (months 19-30). Existing clinical trial data will be analysed. Data contains information following up to four doses across different vaccines in the NHS immunisation schedules for babies, children, adults in the NHS immunisation schedules. A project specific patient and public involvement and engagement group will be set-up. It will inform study design and dissemination of results. Members will also be invited to take-part in training and engagement events. Dissemination Results will be disseminated via publication, conferences and webinars, and via social media and news outlets to the public. Impact The results will be used by policymakers to adapt vaccine programmes. Identifying relationships between adverse reactions, immune responses, and genetics could allow for recommendations based on reactions to earlier vaccinations or their genetics. People could be offered alternative vaccines with fewer reactions and similar immune responses based on their characteristics. Fewer or less severe side effects would reduce people taking time to recover following routine vaccinations. The results would help policy makers in deciding for whom and when boosters are needed. Vaccinating at the right time will reduce vaccine-preventable communicable diseases.