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Developing improved methods to quantify transmission of foot-and-mouth disease virus - SE2815

Description
Effective control of an outbreak of foot-and-mouth disease virus (FMDV) in a country free of the disease, for example the UK, requires the early identification of infected animals and deployment of control measures before overt disease and further spread occurs.
In this programme of work we will study in detail the early stages of FMDV infection in cattle to identify which specific samples can be used to detect virus production before the onset of clinical signs and transmission occurs. Specifically, we aim to develop methods to sample large numbers of animals quickly and efficiently to detect virus as early as possible. Our previous studies have shown virus can be detected in the throat and in the breath of animals before clinical signs are seen and transmission is likely to occur. We will continue these studies with an emphasis on developing practical sampling methods. We will liaise closely with the diagnostics group to utilize the most sensitive methods to detect virus or viral genome in the samples collected.
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 plan to produce vaccines that can be stored as formulated products and which provide enhanced protection compared to current vaccines. Specifically, we have developed a baculovirus (insect cell) expression system that can incorporate sequences from different FMDV isolates to produce empty FMDV capsids. Proof of principle experiments have demonstrated that the use of recombinant technology to produce FMDV empty capsids with improved physical stability results in a vaccine that induces potent protective immune responses. We will now focus, with a commercial partner, on providing evidence to support applications for market authorization of these vaccines so they can be used in a FMDV outbreak. Capsids will be expressed from all of the viruses identified as high priority for an emergency vaccine bank by Defra and the FMD World reference laboratory. The immunogenicity of the resulting capsids will be tested in guinea pigs and cattle to ensure rapid induction of protective immune responses. We will also continue to optimize the expression, purification and storage characteristics of the FMDV capsids to produce stockpiles of vaccines to control the spread of FMDV.
Objective
The project involves two independent components. The first relates to early detection of FMD (objective 1) and quantifying indirect transmission route probabilities (objective 2). The second component will focus on producing a stockpile of FMDV empty capsids for use as an emergency vaccine bank (objective 3).

Objective 1. To address the identification of early biomarkers of FMD infection requires a series of experiments to infect cattle under controlled conditions and to take samples at different stages of the infection process. The outputs of these experiments will be:

1.1. Evaluation of the diagnostic efficacy (Sensitivity and Specificity) of the tests used to detect FMDV early biomarkers (time post infection becomes a very important component of this evaluation).

1.2. Development of a model for early detection during post-outbreak surveillance. This will determine sample size and frequency of sampling. This will apply mainly to swab or direct sampling or aerosol sampling directly from the animals. In case of herd sampling (air samples), it will help determine sampling frequency.

Objective 2. Quantifying the rate of FMD transmission by indirect routes also requires a series of experimental infections, but including exposure of naïve animals to fomites and to aerosols. The outputs of these experiments will be:

2.1. An estimate of the tranmsission rate for indirect FMD spread between calves via environmental fomite contamination.
2.2. An estimate of the transmission rate for indirect FMD spread between calves via short-distance aerosol spread.

Objective 3. Produce a FMDV emergency vaccine bank based on empty capsids produced using baculovirus expression systems. The outputs of these experiments will be:

3.1. Express FMDV capsids using baculovirus expression for high priority vaccine bank strains.
3.2. Further development of methods to quantify whole capsids in baculovirus infected cell cultures.
3.3. Development of baculovirus culture methods in collaboration with industry to optimise yield and downstream processing.
3.4 Evaluate the immunogenicity of capsids in guinea pigs and cattle.
Time-Scale and Cost
From: 2013

To: 2016

Cost: £2,409,257
Contractor / Funded Organisations
IAH - Institute for Animal Health
Keywords
Animals              
Foot and Mouth              
Plants and Animals              
Vaccines              
Fields of Study
Animal Health