Invasive non-typhoidal Salmonella (iNTS) disease is a leading cause of bloodstream infection and death in young children across sub-Saharan Africa, and the World Health Organization (WHO) ranks an iNTS vaccine among its top-ten vaccine priorities for the continent. A critical gap identified in the WHO iNTS vaccine R&D Roadmap is the absence of a validated correlate of protection (CoP); a measurable immune marker that predicts who is protected against invasive disease. Without a CoP, the development, licensure and deployment of candidate iNTS vaccines is slow and costly.

The Protection Against iNTS (PAINTS) project is an international, multidisciplinary vaccinology consortium funded by the Wellcome Trust and led by the University of Edinburgh, established to derive an evidence-based, functionally validated and internationally standardised CoP for iNTS disease. The consortium includes 5 UK academic partners as well as 3 LMIC partners in Malawi and DR Congo, and an industrial global health partner (GSK Vaccines for Global Health). The Work Package in which this studentship is embedded characterises endemic paediatric populations with natural exposure to NTS at two African field sites; in Malawi (Malawi-Liverpool-Wellcome Programme) and the Democratic Republic of Congo (Institut National pour la Recherche Biomedicale), linking age-stratified serological immunity to detailed epidemiological metadata.

This project is focused on the mathematical modelling, statistical analysis and integration of data generated across both field sites. The central premise is that invasive disease declines after the first year of life despite continued enteric exposure, implying that protection is driven by naturally acquired O-antigen IgG, rather than by waning exposure. By jointly modelling age-stratified antibody titres, the force of enteric exposure (faecal NTS carriage) and the established age-specific incidence of invasive disease, the protective effect of antibody can be separated from changing exposure and a putative antibody threshold of protection derived.

The successful candidate will build and fit these models, integrate immunological and epidemiological datasets from Malawi and DRC, and quantify how risk factors such as malaria, anaemia and malnutrition modify the immune response and the protective threshold across settings. This work will define the “protective immunity gap” that a vaccine must fill in different epidemiological contexts and generate policy-relevant evidence to accelerate iNTS vaccine licensure and deployment. The exact objectives will be refined jointly by the student and the supervisory team, but may include:

• Integrating and harmonising serological and epidemiological datasets across the Malawi and DRC field sites.
• Developing and fitting mathematical and statistical models to age-stratified data on O-antigen IgG, enteric NTS infection and invasive disease incidence to derive putative protective thresholds.
• Exploring and quantifying the effect of force of infection and host risk factors (malaria, anaemia, malnutrition, sickle cell disease) on acquired immunity and the protective threshold across both sites
• Comparing exposure and the acquisition of immunity between sites to characterise how the protective immunity gap varies geographically.
• Validating the candidate correlate against additional serological or functional measures generated by consortium partners.
• Contributing to reports, publications and consortium outputs

This position brings the opportunity to work in an area of high global health priority and impact, as part of a large Wellcome-funded international consortium. It is possible that the candidate may have opportunity to travel for national and/or international collaborations within the PAiNTS consortium.

Informal enquiries are encouraged to Melita Gordon (mgordon5@ed.ac.uk)