Immunity dynamics and epidemiology of cross-reactive pathogens (360G-Wellcome-206250_Z_17_Z)

Infections such dengue fever, Zika and influenza generate a substantial public heath burden. It is therefore crucial to understand the biological mechanisms driving individual-level infection and immunity, and how these shape population-level epidemiological dynamics. However, such viruses can cross- react with antigenically similar pathogens, which makes it challenging to analyse immune responses and the implications for future outbreaks. This project aims to address this knowledge gap using a combination of novel mathematical methodology and empirical data. First, I plan to quantify the contribution of different biological mechanisms to observed antibody responses against arboviruses and influenza. In particular, I will combine a unique longitudinal study of dengue and Zika in Fiji with novel mathematical models to reconstruct individual infection histories, and examine potential interactions in immune responses to these viruses. The work will also generate statistical tools for next generation seroepidemiological study design. This will make it possible to perform power calculations when pathogen cross-react and/or assays lack sensitivity/specificity. Finally, I will investigate how herd immunity generated by prior infection history shapes the antigenic evolution of influenza and re-emergence of arbovirus strains. This will improve our understanding of pathogen invasion and potential for future outbreaks.