Development of a VLP vaccine for the emerging viral pathogen Enterovirus D68

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This application concerns the development of a vaccine against EV-D68, a virus with significant pandemic potential. This virus is one of the causes of AFM, a life-threatening condition from which 90% of survivors have long-lasting muscle weakness. An outbreak in the USA in 2014 resulted in 1395 confirmed infections, and both Europe and the United States now have established EV-D68 surveillance networks. Cases of AFM have been observed across several countries, including 567 cases across 7 countries in West Africa. Cases of EV-D68 are increasing, with seasonal outbreaks occurring across much of the globe, this is of particular concern for LMIC where the ongoing medical needs place a substantial burden on healthcare, resources, and infrastructure.There are no current vaccines or licensed treatments available for EV-D68, however, studies have suggested that a virus-like particle (VLP) vaccine is likely to be effective. As part of a WHO-funded project, our team have successfully developed VLP vaccines for the closely related poliovirus. These VLP vaccines are intended to replace the current poliovirus vaccines, the current technology requires the manufacture of large quantities of poliovirus, which is a significant biosafety concern and VLP vaccines are considered an ideal replacement.VLPs consist of viral structural proteins, these assemble into a particle which resembles the virus but contains no genetic material. This means that the VLPs can be recognised by the immune system but are not capable of causing an infection, such a vaccine is a safe and effective way to provide vaccine-induced protection.This project is built on experience acquired during the successful development of VLP projects on related viruses and will progress towards pre-clinical immunisation trials to demonstrate the effectiveness of the vaccines. Production of EV-D68 VLPs will be in yeast as this is a low-cost and easily scalable process. We have already used this system to produce a poliovirus VLP vaccine candidate and have begun the process of transfer of this technology to LMIC manufacturers. As part of our polio VLP project, we have also coordinated with these partners to develop purification methods that are amenable to industrial-scale production.We have investigated a variety of vaccine formulations to assess the stability of our VLPs under a variety of storage conditions. This aspect of vaccine development is particularly significant for vaccine campaigns in regions where maintenance of cold chain may be challenging.