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B cell responses in protection against African swine fever virus


Pirbright Laboratory, Surrey, Outer London

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Dr C Netherton , Prof N Locker , Prof S Graham No more applications being accepted Funded PhD Project (UK Students Only)
Woking United Kingdom Bioinformatics Cell Biology Genetics Immunology Microbiology Molecular Biology Veterinary Sciences Structural Biology Virology

About the Project

TO APPLY: Full details of how to apply can be found on our website: How to apply | The Pirbright Institute

African swine fever is a viral disease of domestic pigs and wild boar that has resulted in the deaths of millions animals across Europe and Asia since its introduction into Georgia in 2007. The virus is now endemic in 4 continents of the world and presents a constant threat to farmers as well as to wild populations of animals in South East Asia and Oceania. An effective and affordable vaccine would make a significant contribution to our ability to control the disease and improve animal welfare.

Vaccine development is hindered due to the complexity of the virus and a lack of understanding of the protective immune response. Subunit vaccines induce antibody responses that recognise virally infected cells, but antibody function as well as the importance of the individual components of the vaccine is unknown. Antibodies capable of neutralisation, infection inhibition and antibody dependent cellular cytotoxicity have been described in pigs immunised with live attenuated viruses therefore the initial focus of the project will be to refine assays to study these effector functions and then test if our vaccine induces them. A major research goal of the group is understand the contribution of the response to individual viral proteins to the overall protective immune response. Pairing the project with the Livestock Antibody Hub will enable the student to take advantage of cutting-edge techniques and their associated reagents, as well as world class expertise, for the study of B-cells and antibodies in pigs domesticated animals. The project will develop along the following themes.

1)    Functional antibody responses against whole ASFV and ASFV infected cells.

2)    Target-function correlation of ASFV specific antibody responses.

3)    Comparative analysis of the antibody response between live attenuated and subunit vaccines.

As the project develops the student may choose to focus on specific effector functions or to focus on the mechanism by which these activities act on virus or infected cells, alternatively they be more interested in the specific viral proteins or domains within those proteins that are the targets of these activities. We have observed enhancement of disease in one groups of pigs, therefore as well as looking at protective immunity there may also be the opportunity to study antibody dependent enhancement in disease. The pig has been used extensively at the Pirbright Institute as a model to study human disease and therefore the techniques and knowledge the student will develop during their PhD will have broad applicability.

The PhD student will be supervised at Pirbright by Dr Chris Netherton who has expertise in ASF vaccinology and immunology and Prof Simon Graham who leads the Livestock Antibody Hub work programme that aims to link Fc and Fc-receptor function in livestock species and has developed many of the techniques to study porcine B-cell immunology. University supervision will be provided by Prof Nicolas Locker and the student will be able to benefit from a suite of training in transferable skills available at the University of Surrey. 

TO APPLY: Full details of how to apply can be found on our website How to apply | The Pirbright Institute

For informal enquiries regarding this project please contact the project supervisors noted above.

For enquiries regarding eligibility and the application process please email [Email Address Removed]

For Home student eligibility guidelines, please refer to the UKRI Full Eligibility Criteria (Annex One): UKRI-030221-Guidance-International-Eligibility-Implementation-training-grant-holders-V2.pdf


Funding Notes

This is a fully funded studentship open to UK nationals. Eligible students will receive a minimum stipend of £15,609 pa plus a cost of living allowance £2,200 pa. University tuition fees will be paid at the Home rate. EU and international applicants are welcome to apply, however from 1st August 2021, EU and International students will be liable for tuition fees at the international rate and must be able to fund the difference between Home and Overseas tuition fees themselves. For Home student eligibility guidelines, please refer to UKRI Full Eligibility Criteria (Annex One) - link below.

References

• A Pool of Eight Virally Vectored African Swine Fever Antigens Protect Pigs Against Fatal Disease (2020) Goatley et al., Vaccines (Basel) 8:234. doi: 10.3390/vaccines8020234 https://pubmed.ncbi.nlm.nih.gov/32443536/
• Identification and Immunogenicity of African Swine Fever Virus Antigens (2019) Netherton et al., Frontiers in Immunology 10:1318. doi: 10.3389/fimmu.2019.01318 https://pubmed.ncbi.nlm.nih.gov/31275307/
• Establishment of Systems to Enable Isolation of Porcine Monoclonal Antibodies Broadly Neutralizing the Porcine Reproductive and Respiratory Syndrome Virus (2019) Goldeck et al., Frontiers in Immunology 10:572. doi: 10.3389/fimmu.2019.00572 https://pubmed.ncbi.nlm.nih.gov/30972067/
• Association of the Host Immune Response with Protection Using a Live Attenuated African Swine Fever Virus Model (2016) Carlson et al., Viruses 8:291 doi: 10.3390/v8100291. https://pubmed.ncbi.nlm.nih.gov/27782090/
• Antibody-mediated neutralization of African swine fever virus: myths and facts (2013) Escribano et al., Virus Research 173:101-109 doi: 10.1016/j.virusres.2012.10.012. https://pubmed.ncbi.nlm.nih.gov/23159730/


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