Research project
The development of a virus-free VLP polio vaccine
- Start date: 1 January 2011
- End date: 31 December 2026
- Partners and collaborators: University of Oxford, National Institute of Biological Standards and Control (now MHRA), John Innes Centre, University of Florida, University of Reading, the Pirbright Institute, Harvard University.
- Primary investigator: Professor David Rowlands
- Co-investigators: Professor Nicola Stonehouse
- Postdoctoral researchers: 01064040, 01097363, 01097437
Project title
The development of a virus-free VLP polio vaccine
Description
The Global Polio Eradication Initiative (GPEI) pledged to eradicate poliovirus (PV) from the planet. However, vaccine-derived viruses remain a major concern, as are individuals who persistently shed PV, sometimes for decades. There is an imperative to develop completely safe polio vaccines to ensure against reintroduction of the virus, following eradication.
We are developing a novel, safe vaccine based on recombinantly expressed virus-like-particles (VLPs). PV, like many other picornaviruses, produces empty capsids during its normal replication cycle. These contain no viral genome, but are antigenically indistinguishable from mature virions and can elicit similar protective immune responses.
Empty capsids can be expressed in a variety of systems while retaining characteristics of naturally produced particles. However, they are less stable than virions and readily convert to an alternative conformation, which does not elicit protective immunity.
Research overview
By selection and combination of stabilising mutations, we have generated modified versions without altering their antigenic properties for all three PV serotypes. By co-expression of the modified structural protein precursor proteins together with the viral protease, we have successfully produced stabilised VLPs in yeast, insect cells, plants and mammalian cells and in a cell-free system.
High-resolution cryoEM structure determination shows that the VLPs are essentially indistinguishable from naturally produced particles. Partial optimisation of expression in yeast (Pichia pastoris) using bioreactors has resulted in yields comparable with those obtained in current PV vaccine production, but using less expensive infrastructure and culture media.
Key findings
These VLPs can be at least as immunogenic than current vaccines in a transgenic mouse protection model and in the rat seroconversion model.
Caption: A poliovirus particle (PDB.1ASJ) super-imposed on the cartoon depiction of a liquid droplet emanating from a syringe or a vial which represent current IPV and OPV, respectively. Figure is not drawn to scale. Drawn by Oluwapelumi Adeyemi.