The life course of human immune responses to influenza infection and vaccination

Humans experience repeated challenges by influenza A antigens over their lifetime via natural exposure and vaccinations. The result of each challenge is dependent on the history of previous challenges up to that point. With this award, I will combine an existing highly effective serological cohort (FluScape) with state-of-the-art mathematical methods to precisely describe this lifelong interaction of humans with an evolving virus. I will conduct an additional two rounds of follow-up of the FluScape cohort to ensure that our sample collection spans multiple time points for the same individuals across two distinct antigenic clusters of H3N2. I will use conventional serological assays to measure the antibody strength in these samples against a panel of 10 historical strains of H3N2. These data will allow me to extend an existing model of antibody kinetics and to accurately describe the processes of infection and vaccination from the view point of the long-lived human host. This well-validated model will allow me and others to answer a number of key research questions related to optimal repeat vaccination schedules for different age groups. I will refine my use of traditional serological assays by also measuring the relative frequency key antigen-specific B-cells in a subset of individuals.