Comparative analysis of the B cell and antibody response to bluetongue virus in cattle and sheep

Introduction

Bluetongue is a haemorrhagic disease affecting ruminants, caused by the Orbivirus, bluetongue virus (BTV), and transmitted by Culicoides biting midges. BTV typically causes severe clinical disease in sheep, yet is mild/asymptomatic in cattle, the main reservoir. BTV has a huge economic impact worldwide and remains a significant threat to the UK with continued outbreaks across Europe. 

While inactivated vaccines have controlled past BTV outbreaks, vaccination only confers protection against the homologous BTV serotype, with 29 serotypes currently existing. Neutralising antibodies against BTV outer coat proteins, VP2 and VP5 (serotype determinants), are the only known correlate of protective immunity. The role of antibodies against immunodominant BTV structural protein, VP7, is unclear. This project will build on pre-existing data from the last 4 years investigating antibody responses to BTV infection/vaccination in cattle and sheep. 

Hypothesis

Comparative analysis of B cell responses and antibody repertoires to BTV vaccination/infection across susceptible hosts will confirm the immunogenic and protective potential of candidate BTV epitopes, identifying distinct immune response signatures of host clinical outcome.

Objectives

1. Develop/refine methods to study BTV-specific B cell responses and antibody repertoires in sheep and cattle. 
2. Characterise and quantify BTV-specific B cell kinetics post-infection or vaccination. 
3. Isolate and sequence BTV-specific antibodies to VP2, VP5, VP7. 
4. Analyse antibody cluster kinetics from whole repertoires of circulating B cells. 
5. Select and express antibodies, confirm binding to VP2, VP5 or VP7 and neutralisation potency. 
6. Compare immunodominance of epitopes triggering protective vs non-protective immune responses. 

Supervisors

• Dr Marie Di Placido
• Professor Christine Rollier
• Dr Kerry Newbrook
• Professor John Hammond

Open to candidates who pay UK/home rate fees. See UKCISA for further information.

This studentship is open to science graduates with, or who anticipate obtaining, at least a 2:1 or equivalent, in a relevant biological subject in their undergraduate degree, or a Masters degree - subject to university regulations. Other first degrees, e.g. veterinary science, will be considered. You should be looking for a challenging, interdisciplinary research training environment and have an active interest in the control of infectious diseases.

Students without English as a first language must provide evidence that they meet the English language requirement, e.g. with an average IELTS score of 7.0, with no lower than 7.0 in listening/reading and no lower than 6.5 in speaking/writing. 

Immunogenetics