Public Funding for Leaf Expression Systems Limited

"Development of Virus-Like Particles as vaccines against emerging viral diseases" Recent decades have seen changes in the mobility of arthropod vectors, driven by global warming. This has resulted in the spread of several diseases from their previously restricted ranges into larger naïve human and animal populations, resulting in severe epidemics. In addition, modern global transport networks has led to highly mobile human populations, who could transport a virulent infection around the globe within days. Recent outbreaks such as Zika and Ebola have highlighted this potential threat. To cope with new outbreaks, effective vaccines are required that are cheap to produce and can be deployed in regions of low technological sophistication and financial resources. However, the limited occurrence and geographic distribution of such diseases on a day-to-day basis have thus far precluded the development of such vaccines, on the basis of simple economics. Many of the viral agents of these emerging diseases share common characteristics in their structures and lifecycles, notably the production of complex capsid and envelope structures that house the viral genomes. Virus-like particles (VLPs) are biological structures that comprise the outer shell of a virus but without the viral genome. In certain circumstances, VLPs can be produced in high quantities by expressing the structural components of a virus in a suitable host cell, where they can assemble into a form that closely mimics the native virus. Such VLPs can be highly immunogenic and very effective vaccines as they present all the antigenic components of the virus to the immune system, in a form that is identical to the real virus. Unlike killed or attenuated virus preparations, there is no risk of live virus contaminating the material or of genetic reversions giving rise to virulent virus de novo. Many expression systems struggle to fold and assemble the viral proteins or to provide the required post-translational processing and maturation functions that are necessary to assemble a fully mature VLP. Even in expression systems where the processing is performed correctly, yields are often very low. Plant cells are highly competent at expressing, folding and assembling VLPs and often with high efficiency. This group have successfully produced VLPs of several significant pathogens, including Bluetongue virus and poliovirus. In the commercial sector, Medicago Inc. (Quebec, Canada) and Caliber Biotherapeutics (Austin, US) have been able to produce influenza VLPs, at scale, in very short timescales (12M doses in 30 days; 50M doses in 90 days, respectively) from genome sequence alone using transient plant expressions systems. Plant transient expression (PTE) facilities are reported to be less costly to build and operate than traditional fermentation or cell culture facilities, making them ideal to deploy in low-income economies or in quick-response, surge manufacturing situations. This project aims to develop new VLP vaccine constructs from two of the most challenging viral targets that are considered a high-priority, namely Chikungunya virus (CHIKV) and Rift Valley Fever virus (RVFV). The construct(s) will be configured for PTE and the ultimate aim is to deliver VLP vaccine products, that are both inexpensive to manufacture and capable of rapid surge production.