For future vaccination strategies to be successful, immune profiles predicting effective and non-effective immune responses in the elderly should be identified. Therefore, it is imperative to understand which factors contribute to the decreased immune responsiveness in the ageing host. Most efforts, however, concentrate on the elderly only, without considering the trajectory of immune decline during life, including the period preceding older age (so-called pre-elderly). The knowledge of this trajectory may yield important information as to whether middle-aged adults may represent an ideal target for vaccination in order to increase immune responsiveness to micro-organisms before immunosenescence begins. Furthermore, aspects other than age itself, including intrinsic and extrinsic factors, may affect the (immune) ageing process.
In this WP we aim to obtain a better insight into changes in the immune response with age, to evaluate the impact of (external) factors on vaccine performance in the aging adults and to formulate evidence-based rationale strategies for improving immunity to infections by vaccination in the ageing population such as vaccinating pre-aging adults.
Based on a prospective study design in three age groups; elderly (65 years +), pre-elderly (50-65) and adults (25-49), the proposed work will contribute to the identification of immune profiles underlying the immunosenescence process. We aim to better characterize the immune response in elderly and pre-elderly by deciphering the intrinsic immunological changes taking place during ageing including the role of inflammaging, and identifying external factors that influence immune responsiveness using samples available from unique cross-sectional and longitudinal (infection) cohorts. Furthermore, we will perform state-of-the art vaccine induced immune profiling to predict vaccine response and pinpoint the exact deficits correlated with reduced vaccine responsiveness, focusing on both innate and adaptive immunity systemically as well as at mucosal sites in the prospective clinical vaccination study. This will lead to the identification of immune signatures and of (bio)markers associated with immunosenescence which can be used to identify risk groups, select target populations for vaccination and identify ways to intervene and improve vaccinations for protecting the elderly.