Title: Reducing the impact of footandmouth disease outbreaks through early detection and vaccination
Funder: Department for Environment, Food and Rural Affairs

Abstract: Description Effective control of a foot-and-mouth disease virus (FMDV) outbreak in a country normally free of the disease, such as the UK, requires the early identification of infected animals and deployment of control measures before overt disease and further spread occurs.Current methods for detecting FMDV-infected animals or farms rely on observing animals showing clinical signs of disease. However, clinical surveillance is time-consuming and delays in detection and reporting can compromise the effectiveness of control measures. Using transmission experiments we have identified a number of methods that can be used to detect infected animals before they show clinical signs: nasal and oral swabs and air and environmental sampling. These are non-invasive and quick to implement, so are practical for use in the field as means of early detection. Furthermore, mathematical modelling of within-farm transmission of FMDV suggests that sampling regimes using these preclinical tests have the potential detect infected farms quickly enough that an outbreak cannot sustain itself. These tests work well in an experimental setting and in this programme of work we propose to validate the preclinical detection methods in an FMDV-endemic setting. Practical experience of this nature will allow the development of field-relevant protocols that would form the basis for emergency response during an outbreak in the UK. In addition, we plan to extend the preclinical tests to understand how they perform with different virus strains, in different species and in vaccinated animals. We will also further develop practical surveillance and disease management tools by characterising and quantifying virus emissions from infected animals and contaminated environments.Prompt identification of infected animals needs to be tied in with rapid deployment of control measures. One arm of an effective control strategy could be to establish an immune barrier around the infected premises. To facilitate the rapid deployment of vaccine we have produced stabilised FMDV capsids (virus coat) for use as vaccines. We will develop methods that allow these capsids to be expressed in yeast, which will provide a cheap and easy means of producing them on a large scale. Empty capsids produced by yeast cultures will be tested to see how well they protect animals and, hence, assess their potential to rapidly produce vaccine in a cost-effective manner.The key impacts of the proposed research are:1. The development and validation of techniques and tools for rapid and early detection of FMDV-infected farms in the UK that are minimally invasive and which have been tested in the field. This will allow earlier interruption of the transmission cycle resulting in smaller, shorter outbreaks and with fewer animals being culled, thereby reducing the cost of an outbreak.2. An improved understanding of virus emissions will allow us to better predict airborne spread and risk of FMDV and to comment on decontamination processes that will inhibit further atmospheric spread.3. The development of surveillance and disease management tools that can be applied to other viral diseases of livestock, for example, avian and swine influenza.4. The development of a rapid, cost-effective production system for FMDV empty capsids in yeast. Objective Objective 1: Preclinical detection of foot-and-mouth disease virus (FMDV) in the field1.1 Initial testing of sampling in the field1.2 Development and testing of a protocol for samplingObjective 2: Extending preclinical detection methods2.1 Impact of emergency vaccination2.2 Other serotypesObjective 3: Validation and characteriation of aerosols3.1 Validation of aerosol retrieval3.2 Further characterisation of FMDV aerosolsObjective 4: Vaccine development4.1 To compare two common yeast strains, S. cerevisiae and P. pastoris for FMDV antigen expression from a common genetic configuration 4.2 To optimise the best performing strain by examining different promoters and growth conditions4.3 To develop an effective downstream purification method compatible with preservation of empty capsid conformation4.4 To confirm antigenicity and immunogenicity of yeast expressed empty capsids following purification


Research activity codes: 3.4 VACCINES;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION