Studentship: Foot-and-mouth disease virus capsid protein VP4 as a novel target for disease control

Lead Research Organisation: The Pirbright Institute
Department Name: UNLISTED

Abstract

Foot-and-mouth disease virus (FMDV) is a member of the picornavirus family of non-enveloped viruses which comprise a single molecule of positive sense RNA inside a 30nm diameter protein capsid. FMD remains a major problem for livestock agriculture worldwide. In areas where the disease is endemic, control is by regular vaccinations. Outbreaks in areas normally free of disease are controlled by slaughter, emergency vaccination and trade restrictions. Vaccination with the current inactivated virus vaccines suffers from a delayed onset of immunity, poor duration of immunity and lack of cross-protection between virus serotypes/strains. New strategies are therefore required to improve control in areas where FMD is endemic and to improve emergency control of outbreaks in countries normally free of FMD. Emergency outbreak control by slaughter has become unpopular in recent years. An alternative strategy receiving increased interest is the use of antiviral drugs for emergency control of FMD, because treatment can act very quickly and bridge the delay until vaccine-mediated immunity is in place. The FMDV capsid protein VP4 is an attractive pan-serotype target because it is very highly conserved (the N terminus of VP4 is almost invariant across all FMDVs) and is likely to be amenable to both anti-viral and vaccination strategies.

Publications

10 25 50
 
Description 1) The membrane permeability induced by FMDV VP4 has been characterised. This has shown differences between FMDV VP4 and previous studies on HRV VP4.
2) Virus- like particles (VLP) based on the core protein of the hepatitis B virus have successfully been generated which displayed the N-terminal 15 amino acids of FMDV VP4.
3) Three different immunogens displaying the N-terminal 15 amino acids of FMDV VP4 were compared by immunizing Balb/c mice. The immune response was characterised and one construct did induce a response against the sequence. Unfortunately there was not a strong neutralising response as had been expected when considering similar published experiments using viruses from the enterovirus genus of the picornaviruses. This highlights the differences between aphthoviruses such as FMDV and enteroviruses such as human rhinovirus. Monoclonal antibodies were generated from spleens collected during the mouse work and in collaboration with The Roslin Institute.
4) Polyclonal serum against FMDV VP4 was also investigated and found to lack neutralising ability.
Exploitation Route The anti-VP4 antibodies generated in this study are being further characterised as part of additional projects. These antibodies are likely to have interesting properties and may form the basis of a model system to understand anti-viral activities of non-neutralising cross-reactive antibodies.
New funding from MRC (project grant) has been awarded to apply some of the approaches from this project to related human viruses.
Sectors Agriculture, Food and Drink,Healthcare,Pharmaceuticals and Medical Biotechnology,Other

 
Description Genomia Project Grant
Amount £174,052 (GBP)
Organisation Genomia fund 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2019 
End 01/2020
 
Description JS - 2) FEMS early career researcher travel grant for Europic 2018
Amount £307 (GBP)
Organisation Federation of European Microbiological Societies (FEMS) 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2018 
End 06/2018
 
Description JS - Annual Conference Travel Grant
Amount £233 (GBP)
Organisation Microbiology Society 
Sector Learned Society
Country United Kingdom
Start 04/2018 
End 04/2018
 
Description JS - Annual Conference Travel Grant
Amount £305 (GBP)
Funding ID SCG17/399 
Organisation Microbiology Society 
Sector Learned Society
Country United Kingdom
Start 04/2017 
End 04/2017
 
Description JS - Production of monoclonal antibodies that recognise FMDV VP4 from mouse spleens 
Organisation University of Edinburgh
Department The Roslin Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution VLPs displaying the N-terminal 15 amino acids of FMDV were designed and produced at The Pirbright Institute and then mice were immunised with them. The spleens of the immunised mice were harvested and splenocytes stored. The response to the VP4 sequence was checked by ELISA and the mouse with the best response was selected to send the splenocytes for monoclonal production.
Collaborator Contribution The collaborators took the splenocytes obtained from the mouse experiments and carried out the fusions. They then screened the supernatants for positive wells that detected the VP4 sequence.
Impact Positive wells have been identified indicating some monoclonals that are specific for VP4 have been generated. These will be further screened for ability to recognise virus and to neutralise infection.
Start Year 2017
 
Description Leeds FBS 
Organisation University of Leeds
Department Leeds Institute of Molecular Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Research
Collaborator Contribution Research and student supervision
Impact Research
Start Year 2009
 
Description Diamond (TT) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Diamond Light Source Open Day - explaining to general public the importance of structural biology and microscopy for understanding viruses and designing improved vaccines.
Year(s) Of Engagement Activity 2019
 
Description JS - Europic 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Poster presentation at the Europic 2018 conference. I presented the poster during the poster sessions and discussed my research with other picornavirus researchers.
Year(s) Of Engagement Activity 2018
 
Description JS - Microbiology Society Annual Conference 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Work was presented to a group of researchers and audience members asked questions about the work. The questions helped make plans for future work.
Year(s) Of Engagement Activity 2017
 
Description JS - Microbiology Society Annual Conference 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Poster presentation at the Microbiology Society annual conference. I presented the poster during the poster sessions and discussed my research with other researchers.
Year(s) Of Engagement Activity 2018
 
Description Microbiology Society Conference 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Microbiology Society Conference 2016
Year(s) Of Engagement Activity 2016
 
Description SinoPic TT 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 'SinoPic': Structural Biology of Picornaviruses meeting in China. Generating interest and collaborations in virus structural biology within China.
Year(s) Of Engagement Activity 2018