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Developing a virus-like particle (VLP) Polio vaccine

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Rationale: Poliovirus is a non-enveloped RNA virus, spread via the faecal-oral route, that causes the infectious disease Poliomyelitis (Polio). In most cases poliovirus infection causes mild symptoms but in a small proportion (<1%) it can affect the central nervous system, leading to muscle weakness and paralysis. The Global Polio Eradication Initiative [1], established in 1988, has successfully eliminated circulating wildtype poliovirus in all but three countries (Nigeria, Afghanistan and Pakistan) via successful mass vaccination programmes using a combination of two Polio vaccines: a live-attenuated oral Polio vaccine (OPV) and an inactivated Polio vaccine (IPV). OPV is cheaper and easier to administer than IPV and the OPV strains replicate in the intestines and induce mucosal immunity, which helps to prevent circulation of wildtype poliovirus, making it the vaccine of choice for eradication programmes. However, in very rare cases the attenuated vaccine strain can acquire mutations and revert to a form that can cause paralysis leading to vaccine associated paralytic poliomyelitis (VAPP). Furthermore, in under vaccinated populations the OPV strains can circulate within the community (circulating vaccine derived poliovirus, cVDPV) and accumulate mutations that confer neurovirulence leading to outbreaks of paralytic Polio. The WHO have announced that OPV will no longer be used for routine vaccinations following eradication of wildtype poliovirus for these reasons [1].

Many countries that have successfully eradicated all three serotypes of wildtype poliovirus now only use IPV in their vaccination programmes. Whilst IPV prevents poliovirus from replicating within the nervous system, it does not induce mucosal immunity and it is therefore not able to prevent circulation of poliovirus within the community. IPV also requires large scale culture of live poliovirus and is costlier to manufacture, distribute and administer than OPV. A recombinant poliovirus vaccine, such as a virus-like particle (VLP) vaccine that is a structural mimic of the viral capsid without the infectious genome [2], could be manufactured without the need to culture live poliovirus. A VLP polio vaccine could potentially offer several other advantages over IPV including enhanced stability and cheaper production costs, particularly if produced in a Prokaryotic expression system such as Escherichia coli. As proof of principle, large-scale production of immunogenic VLPs has been reported for a closely related Picornavirus [3,4].

Methodology: This research will focus on development of a recombinant virus-like particle (VLP) vaccine for Polio in E. coli. Techniques used to develop the recombinant VLP vaccine will include SDS-PAGE, Western blotting, immobilised metal ion affinity chromatography (IMAC), density gradient ultracentrifugation, electron microscopy (TEM and cryo-EM) and enzyme-linked immunosorbent assays (ELISA). Stabilising mutations [5] will be introduced into the cloned constructs to test if they improve stability for long-term storage using ELISA. Immunogenicity of suitable vaccine candidates will be tested in animal models.


Funding Notes

Eligibility requirements:

Applicants should have a bachelors (at least 2.1 or equivalent) or master’s degree in a biological subject (e.g. Biology, Biochemistry, Microbiology, Genetics, Biomedicine, Biological Chemistry, Molecular Biology). Practical experience working in a microbiolgy or molecular biology laboratory is highly desired but not essential.

References

References:
1 GPEI – Global Polio Eradication Initiative. . [Online]. Available: http://polioeradication.org/. [Accessed: 07-Jun-2019]
2 Mohsen, M.O. et al. (2017) Major findings and recent advances in virus–like particle (VLP)-based vaccines. Semin. Immunol. 34, 123–132
3 Guo, H.-C. et al. (2013) Foot-and-mouth disease virus-like particles produced by a SUMO fusion protein system in Escherichia coli induce potent protective immune responses in guinea pigs, swine and cattle. Vet. Res. 44, 48
4 Xiao, Y. et al. (2016) Large-scale production of foot-and-mouth disease virus (serotype Asia1) VLP vaccine in Escherichia coli and protection potency evaluation in cattle. BMC Biotechnol. 16, 56
5 Fox, H. et al. (2017) Genetically Thermo-Stabilised, Immunogenic Poliovirus Empty Capsids; a Strategy for Non-replicating Vaccines. PLOS Pathog. 13, e1006117
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