Understanding the Host-Pathogen interaction of Hepatitis E virus in pigs

Hepatitis E virus (HEV) is the causative agent of hepatitis E, a human liver disease with worldwide occurrence. Of particular interest is HEV genotype 3 (HEV-3) which is zoonotic, infecting a diverse range of hosts, including pigs. In contrast to the human infection, the infection of pigs with HEV remains always subclinical. However, the level of HEV replication post infection is highly variable between pigs, the reasons for which are unclear, as is the infection cycle within pigs. Investigations in other human viral infections have revealed differences in gut microbiota to be associated with levels of immunity and viral load. No comparative data are available for HEV in pigs, nor is there a vaccine available.  

This project will comprehensively test different vaccine approaches against HEV in pigs, applying a range of methods from measuring Abs to the protective signature in the liver. The hypothesis is that the vaccines may not be able to prevent infection, but to reduce HEV replication to an extend that onward transmission between pigs would no longer be possible. To that extent the approaches to investigate the above concept are as follows: 

• Use of an oral vaccine, a parantal vaccine, and the combination of the above – as prime/boost approach.
• In all cases the project will analyse the levels and quality of Abs generated. 
• The project will further analyse the induction of T cells by the vaccine – such analysis will be undertaken via liver and gut samples (locally) as well as systemically (in blood). The project can use flow cytometry, RNASeq or scRNASeq to demonstrate the full spectrum of functional T cells induced. 

The most promising candidate approach will then also be used for a challenge study.

You will need to meet the minimum entry requirements for our Veterinary Medicine and Science PhD programme. 

Open to UK nationals and those who pay UK/home rate fees. See UKCISA for further information

In addition, you will have to be resident in the UK for at least two, ideally 3 years (at the time of application) to meet the requirement for additional security clearances required to carry out work as part of this project.