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Recombinant pseudorabies virus as a multivalent vectored vaccine platform for emerging and endemic porcine diseases


Project Description

Pseudorabies virus (PrV), the causative agent of the Aujeszky’s disease, is responsible for substantial losses to the expanding pig industry in Southeast Asia. Control and eradication of SuHV-1 in many western countries was aided by the development of highly efficacious live attenuated vaccines, including genetically modified strains capable of differentiating infected from vaccinated animals. Southeast Asian pig producers are also significantly impacted by other viral pathogens, including porcine reproductive and respiratory syndrome viruses (PRRSV). Pigs in these countries are also at risk from ‘spillover’ infection with the zoonotic Nipah virus (NiV), which devastated the Malaysian pig industry with long lasting effects. Compared to single disease vaccines, the use of bi/multi-valent vaccines in the livestock industry is more desirable, particularly in resource poor contexts. We hypothesis that live attenuated PrV may be genetically engineered to express antigens from NiV and/or PRRSV and this recombinant virus could serve as a potent bi/multi-valent vaccine.

This project aims to test this hypothesis and take the key first steps towards the development of bi/multivalent PrV vectored vaccines for NiV and PRRSV. The project will address this through the following specific objectives:

1. To genetically engineer live attenuated PrV expressing NiV and PRRSV antigens, either individually or in combination
2. To characterise recombinant PrV vectors in vitro by assessment of growth kinetics, transgene expression and antigenicity.
3. To demonstrate the immunogenicity of recombinant PrV vectors in vitro by assessing responses of porcine conventional and plasmacytoid dendritic cells.
4. To evaluate the immunogenicity/efficacy of recombinant PrV vectors in pigs (Dependent upon securing additional funding/support).

This studentship will be based primarily at The Pirbright Institute, with visits to the RVC to meet with supervisors and undertake training/complete specific project tasks as required. In addition, the student will be required to spend a period of 6-12 months at the Friedrich-Loeffler-Institute in Germany. A full range of research and transferrable skills training will be made available to the student as appropriate.

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

Funding Notes

This is a fully funded studentship open to science graduates with, or who anticipate obtaining, at least 2.1 or equivalent in relevant biological subject in undergraduate degree, or a Masters degree - subject to university regulations. Open to UK students and eligible EU students who qualify for home-rated fees - see Residential Eligibility Guidelines on website for details. Eligible students will receive minimum annual stipend of £15,009 plus cost of living top-up of £2,200; university registration fees will be paid. Students without English as first language must provide evidence of IELTS score of 7.0, no less than 6.5 in subsections.

References

1. www.pirbright.ac.uk/our-science/livestock-viral-diseases/porcine-reproductive-and-respiratory-syndrome-prrs-immunology
2. McLean RK, Graham SP. 2019. Vaccine development for Nipah virus infection in pigs. Frontiers in Veterinary Science 6:16.
3. Freuling CM, Müller TF, Mettenleiter TC. 2017. Vaccines against pseudorabies virus (PrV). Veterinary Microbiology 206:3-9.
4. Nan Y, Wu C, Gu G, Sun W, Zhang YJ, Zhou EM. 2017. Improved Vaccine against PRRSV: Current Progress and Future Perspective. Frontiers in Microbiology 8:1635.

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