Studentship: Recombinant vaccines for African Horse Sickness based on baculovirus pseudotyping and transduction

Lead Research Organisation: The Pirbright Institute
Department Name: UNLISTED


The objective of this project is to determine whether protective immunity against AHSV can be achieved by baculovirus transduction and / or pseudotyping. These vaccination strategies will be based mainly on the protective antigen of AHSV, VP2, but other AHSV proteins will be explored as well. Both baculovirus approaches will be used separately or in combination. The recombinant vaccines will be tested in an appropriate mouse model for AHSV.
The construction of recombinant baculoviruses that express VP2 or sub-domains of this protein (or any other protein of AHSV or any related orbivirus) in mammalian cells upon baculovirus transduction is entirely novel. The same applies for the generation of recombinant baculoviruses displaying VP2 derived peptides on the baculovirion surface. So far, the use of baculoviruses for orbiviruses has been limited to the standard expression of recombinant proteins in insect cells. The approaches to be used in this project are completely different.
The student will explore the possibility of using these recombinant viruses (using transduction or pseudotyping or both) as novel vaccines. The student will have a wide scope for improving or modifying the expression of these antigens by deciding which domains of VP2 should be expressed or whether or not other AHSV proteins should be incorporated in the constructs. Furthermore, the student will analyse the immune responses that follow vaccination of mice with these recombinant constructs, by developing the immunological assays appropriate for these studies. Again, nobody has done this work before. Finally, testing whether a combination of both approaches (transduction and pseudotyping), which are believed to induce different effector mechanisms of immunity, is superior to either approach alone is a comparative study that has not been done with any other virus as far as we know.


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