Predicting the future for avian Influenza using a One Health immuno- epidemiological framework (360G-Wellcome-227041_Z_23_Z)

The pandemic potential of avian influenza considering life-long influenza infection histories, both in animal and human populations, is an unresolved question. The age distributions of influenza cases in pandemics and avian influenza spillover events suggest prior infection as an important factor. In this fellowship, I will develop an immuno-epidemiological framework to understand the interplay between life-histories of influenza infection in birds, humans and at the animal-human interface to predict pandemic conditions. Using transmission models for wild birds and humans I will investigate the hypothesis that subtype-specific infection in early life influences future susceptibility and disease dynamics of influenza A. High- throughput multiplex immunoglobulin and surrogate neutralisation assays will be developed and deployed to longitudinal birth cohorts of humans and wild birds of long-life spans. Serological profiles will be used to reconstruct subtype-specific infection histories. From this, I will calculate the frequency of influenza infections in the host population and evaluate cross- reactivity. Sero-epidemiological findings will be integrated back into mathematical models to determine conditions for pandemic potential. This work will deepen our understanding of the influenza immunity landscape for zoonotic disease control and pandemic prediction.