About the Project
Novel influenza A viruses that cross the species barrier between animals and humans present a persistent threat to global public health. In 2021-2022, Europe faced the largest epizootic of avian influenza virus (AIV)1. The high pandemic potential of influenza is due to the ability of distinct subtypes to reassort either in human or porcine hosts and create novel influenza subtypes, against which there is little or no existing prior immunity in the human population. Recent increases in AIV outbreaks in Europe and America have increased concern about the risk of a novel virus emerging and heightened public health responses given mammalian spillover.

In people, it is recognised that an individual's immune history can shape susceptibility to future influenza infection and explain differences in influenza vaccine effectiveness, via phenomena known as original antigenic sin and immune imprinting2,3. In avian populations, the influence of immune history on susceptibility and incidence is less clear. Serology can provide insight into an individual’s life history of infection. However, interpretation of serological profiles is challenging due to cross-reactivity within- and between-subtypes. Investigation into how different demographies and immune histories interact will inform control strategies and pandemic preparedness.

Aims and objectives

The aim of this project is to understand the implications of influenza A immunity landscapes in wild birds to inform avian influenza control and zoonotic disease risk

Objective 1: Characterise epidemiological trends in low and high pathogenicity avian influenza in wild birds

Literature searches and data analyses using historical data will be conducted to characterise trends in AIV transmission among wild birds. Patterns of prevalent low and high pathogenicity strains of avian influenza will be identified by time, location, bird species and age. Results will inform development of serological assays and mathematical models of influenza transmission.

Objective 2: Reconstruct avian influenza infection histories in mute swans

Sera collected from a well-characterised herd of mute swans4 will be tested for the presence of antibodies to AIV using subtype specific high throughput multiplex serological assays (Luminex). A subset of samples will be assayed using gold standard techniques and pseudotyped neutralisation assays for cross-comparison. Longevity, kinetics and cross-reactivity profiles will be determined. A mechanistic model of antibody kinetics will be used to reconstruct infection histories. Outputs will inform how we can use high-throughput influenza serology for maximum epidemiological inference.

Objective 3: Modelling of immune-imprinting on age-specific subtype infection

Transmission models capturing demographic and influenza infection dynamics in a herd of mute swans will be developed. Serological insights will be used to inform model assumptions and fit. The approach of Arevalo et al. will be built on to capture the age-specific probabilities of acquiring immunity to multiple influenza A subtypes5. The hypothesis that subtype-specific infection in early life influences future susceptibility and disease dynamics of influenza A will be tested.

Funding Notes
This project is available for both home and international students. The University of Bristol Scholarship is for four years, and it includes an annual stipend set at the current UKRI recommendation of £19,237. Tuition fees and research costs are fully supported by the studentship, as well as an allowance for paid sick leave and parental leave, in addition to 5 weeks of paid leave each year.

To apply, you can submit an application via the University of Bristol application portal: Start your application | Study at Bristol | University of Bristol selecting the relevant 4-year PhD programme, e.g. “Population Health Sciences (PhD)”.

References

1. https://www.ecdc.europa.eu/en/news-events/2021-2022-data-show-largest-avian-flu-epidemic-europe-ever
2. Lessler, J. et al. Evidence for antigenic seniority in influenza A (H3N2) antibody responses in southern China. PLoS Pathog 8, 26 (2012).
3. Gostic, K. M., Ambrose, M., Worobey, M. & Lloyd-Smith, J. O. Potent protection against H5N1 and H7N9 influenza via childhood hemagglutinin imprinting. Science (2016).
4. Hill, S. C. et al. Antibody responses to avian influenza viruses in wild birds broaden with age. Proceedings of the Royal Society B: Biological Sciences 283,(2016).
5. Arevalo, P., McLean, H. Q., Belongia, E. A. & Cobey, S. Earliest infections predict the age distribution of seasonal influenza a cases. Elife(2020)