According to the World Health Organisation’s paper on Global Vector Control, vector-borne diseases are a major health threat accounting for 17% of communicable diseases worldwide. They have a major economic impact and disproportionately affect the world’s poorest regions. There is therefore a growing need for the development of cost efficient vaccine production solutions.
Vector-borne diseases include those spread by Aedes and Culex mosquitoes such as Dengue, Chikungunya and Zika virus and since 2014 there have been major outbreaks of many of these diseases with Zika virus causing serious health problems in 2016. Although there are a number of products in various stages of development to treat these diseases further work is required to tackle the growing challenges presented from them.
The WHO said of dengue fever ‘the growing global epidemic of dengue is of mounting concern, and a safe and effective vaccine is urgently needed’
Vaccines are widely recognised as an important mechanism in controlling infectious disease outbreaks. However, outbreaks of some of the world’s deadliest diseases only occur intermittently, and often in the world’s poorest countries, meaning that there may not be a strong market incentive to for the pharmaceutical industry to develop vaccines for such diseases.
There are vaccines in development aimed at Dengue fever, Zika virus and Chikungunya and new technologies including virus-like particle (VLP) based vaccines, live attenuated vaccines and Purified Inactive Virus (PIV) particles are currently under evaluation in pre-clinical and early phase clinical trials.
Development of VLPs for some of the target diseases on the WHO and Department of Health list allows some advantages over traditional vaccines. Firstly, the potential speed of preparation of a VLP means vaccines can be prepared a lot quicker than traditional routes. This was seen in the influenza pandemic of 2009 and demonstrated the inability of the established approaches for vaccine production using egg-based technology to provide sufficient vaccine in a timely fashion. It has been shown with VLP technology a potential vaccine can be prepared in around 12 weeks compared to more traditional 9 months.
Secondly, VLPs physically resemble the target virus but are non-infectious because they contain no viral genetic material. As a result, they represent an attractive option because of their safety and immunogenic characteristics. VLPs can also be produced in a variety of different cell culture systems including bacteria, mammalian cell lines, insect cell lines, yeast and plant cells. This provides a degree of flexibility and screening when a pandemic situation arises.
In the UK, the government is taking concerted and coordinated action to address the need to develop vaccines. It has committed to invest £120 million between 2016 and 2021 on the development of new vaccines for such diseases, in line with the expert advice provided by the UK Vaccines Network. This network brings together experts from industry, academia and funding bodies and its focus is to identify and shortlist targeted investment opportunities for the most promising vaccines and vaccine technologies that will help combat infectious diseases with epidemic potential.
With funding from the UK Vaccines Network, Leaf Expression Systems is at the forefront of vaccine research. The company will be using the plant based technology developed at the John Innes Centre to produce various VLPs, at scale, for further pre-clinical evaluation. Production of VLPs using plant based expression systems has a number of potential advantages over existing methods, namely around quick and rapid scale-up and reduced production costs. The method therefore, provides opportunities for rapid response to pandemics, but also for low middle income countries to access the products due to the lower cost of goods.
Leaf Expression Systems has also been awarded grant funding from SBRI and the Department of Health to develop VLPs as vaccines against emerging viral diseases. The aim is to facilitate rapid prototyping of target vaccines which can be produced cost effectively for use in low and middle income countries (LMIC).
Hypertrans® technology is a novel transient plant expression system using the non-cultivated tobacco species, N. Benthamiana. This fast-growing species can produce hundreds of plants ready for making products within as little time as a week. The flexible nature of the system enables production to be scaled from small research quantities to pilot plant scale production very quickly. The speed of the system means that it can rapidly produce large amounts of protein and so it is well suited to quickly responding to emergencies like pandemics.