Scientists at The Pirbright Institute, led by Gareth Shimmon, have found a new way of diagnosing foot-and-mouth disease (FMD) which is more cost effective and relies less on the use of small animals.
FMD is a highly contagious viral disease that infects cloven-hoofed (two-toed) mammals such as cattle, sheep, goats, pigs and various wildlife species. The disease occurs in parts of Africa, the Middle East, Asia and parts of South America and causes huge economic losses annually.
There are seven types (serotypes) of FMD virus (FMDV) that have high mutation rates which constantly generate new FMDV variants. This makes rapid diagnosis essential for vaccinating against the correct type of FMDV and ensuring control policies are put in place quickly.
Previously, diagnostic tests known as ELISA’s have required small animals such as rabbits and guinea pigs to produce proteins called antibodies. These antibodies bind to FMDV enabling the disease to be detected in samples. Each strain of FMDV requires highly specific antibodies which means new antibodies are regularly required to keep up with emerging new strains.
Instead of using animal antibodies, previous research has shown that a protein called integrin αvβ6 can be used to detect the presence of FMDV. This works because integrin αvβ6 is a receptor that universally binds to field strain FMD viruses in order to gain entry into cells. The group therefore used a truncated bovine integrin αvβ6 (a shorter, modified cow version of the protein) in their ELISA tests that all FMDV types would bind to.
The researchers have been able to create large amounts of bovine integrin αvβ6 in the lab using a rapid technique called ‘transient cell transfection’. This could make diagnosis of FMD strains cheaper and easier, as only one integrin would be needed to identify all strains of FMDV, compared to the many antibodies that were needed previously.
Gareth Shimmon said “The ability to rapidly produce a cost-effective universal diagnostic reagent for FMD is an important step forward in simplifying lab-based diagnostics and making these techniques more accessible to the many countries struggling to control this devastating disease.”
Another major benefit is that animals are not needed to produce bovine integrin αvβ6. This is a huge step towards supporting the 3Rs agenda (Refine, Replace and Reduce) in science regarding the use of animals, to which the Institute is strongly committed.
Further experiments are needed to optimise and validate the test for routine FMDV diagnosis, but it is hoped that bovine integrin αvβ6 could eventually be used in the FMDV diagnostic kits that the Institute distributes all over the world.
The researchers also set out to find an alternative to using inactivated FMD virus as a positive control for the integrin diagnostic tests, which is used to confirm the test is working. Previously this required the production of live FMD virus, which is costly since this infectious virus must be produced in a high containment laboratory.
Pirbright Institute scientists successfully demonstrated that modified empty shells of FMD virus (capsids) without any genetic material, can be used instead of the inactivated live virus, as these capsids have the ability to bind to integrin and can be produced without the need for high containment. This could lower the cost for positive control production and make the process faster and more efficient.
FMD surveillance and early detection is essential for successful control of the disease, especially for countries that do not use routine vaccination as a control measure. New developments in diagnostics such as these are vital for providing such countries with fast and cost effective detection methods.
This study was published in the PLOS One journal and was jointly funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Department for Environment, Food and Rural Affairs (Defra).