The new methods, published in Applied and Environmental Microbiology, use a simple swabbing technique to gather samples from the environment which FMD-susceptible animals such as cattle, sheep and pigs commonly make contact with, such as water troughs.
Researchers say the technique requires very little expertise, which makes the sampling method far more accessible, allowing a higher frequency of samples to be collected and processed during an outbreak.
FMD virus is able to survive long periods of time in the environment in the right conditions (up to three months depending on environmental factors such as pH, temperature and relative humidity), so sampling areas where infected animals may have shed virus allows scientists to detect the presence of FMD even if the animals on the farm are no longer showing clinical signs.
The researchers say that novel surveillance techniques such as this can help support a robust response to outbreaks in FMD-free countries, and can also be implemented in endemic areas, such as parts of Asia, Africa and the Middle East, as part of surveillance programs to supplement current information about the spread of FMD.
Dr Claire Colenutt, who led the research at Pirbright said: "Current surveillance methods rely on the recognition of FMD infection in susceptible animals in addition to the collection of samples from the animals which requires veterinary expertise. In keeping the approach simple, samples can be taken by individuals without prior expertise, increasing the number of potential samples, and relieving pressure on veterinary services."
Photo: FMD. Dr. D. Denev
They say this approach could lead to a reduction in the number of vaccines that need to be administered to each bird.
Vaccines that target multiple diseases are in high demand due to the many viruses that can circulate simultaneously in flocks. Protecting against the most dangerous diseases with one vaccine could reduce overall vaccination costs for poultry producers and decrease the number of times that birds need to be handled.
The researchers demonstrated that a gene editing system called CRISPR/cas9 can be used to insert a gene of the IBD virus into the currently used Marek’s disease vaccine virus. The added genetic material protects poultry against IBD in addition to the protection already offered by the Marek’s disease vaccine, meaning that bird owners would only need to use one vaccine instead of two.
Other vaccines generated by conventional methods can achieve a similar result, but by using the CRISPR/cas9 system the Pirbright researchers say they have been able to insert the IBD gene far more quickly, easily and accurately than the methods that have been used before. This will significantly reduce the time needed to generate new vaccines.
Professor Venugopal Nair, joint leader of the research at Pirbright said: "The method we have created with CRISPR/cas9 really increases the scope of how we edit the Marek’s disease vaccine to include other virus components. Now we have shown that the gene-edited vaccine protects against both Marek’s disease and IBD, we are looking at inserting more genes from other viruses."
The team intend to generate a vaccine that will be able to protect against multiple avian diseases and will next target two high consequence poultry viruses - avian influenza virus and the Newcastle disease virus. The flexibility of the new method also means that as the viruses evolve, the vaccine virus can be easily edited to include new genes which protect against emerging strains.
The Pirbright Institute says there has been huge commercial interest in using this technology to develop novel vaccines, so it intends to partner vaccine manufacturing companies to bring CRISPR/cas9 edited vaccines to market.
This scientific paper can be found in the Vaccine journal and was funded by the Biotechnology and Biological Sciences Research Council (BBSRC); grant numbers BB/P016472/1 BB/L014262/1.
Photo: Cells infected with the Marek's disease vaccine virus, HVT, (green) expressing the inserted infectious bursal disease virus gene, VP2 (red). Cell nuclei are shown in blue. © Dr Na Tang, The Pirbright Institute 2018.
In the study, the Pirbright - Wageningen research team combined their expertise in both FMDV and mathematical modelling to evaluate the methods and effects of preclinical diagnosis during surveillance (as would be in place during an outbreak), in order to reduce the risk of transmission between herds of cattle on neighbouring farms.
Transmission experiments in cattle were used to collect samples taken from individual animals such as blood, saliva and nasal swabs, and at herd level such as air samples, on a daily basis during the course of infection. The sensitivity of each of these types of samples for the detection of infected cattle during different phases of infection was then quantified.
Dr. Simon Gubbins, Head of Transmission Biology at Pirbright said: "Our results were incorporated into a mathematical model for FMDV transmission in a cattle herd in order to evaluate the impact of early detection and removal of an infected herd on the reduction in the amount of infectious output which could enable transmission of the virus to cattle on a neighbouring farm.
"By using weekly surveillance, clinical inspection alone was found to be ineffective at blocking transmission. This was in contrast to the impact of weekly sampling using saliva swabs of at least ten animals per farm or daily air sampling (for housed cattle), both of which were shown to reduce the risk of transmission substantially."
Dr. José Gonzáles from Wageningen Bioveterinary Research added: "These findings provide a new approach to disease control which could be added to our emergency preparedness programmes. A potential benefit of applying this strategy is a reduction in the number of animals culled unnecessarily, which is likely to happen when traditional strategies such as pre-emptive culling are implemented."
Following these initial results, the Pirbright - Wageningen research team plan to take their approach from the controlled conditions of the laboratory and test it in field trials. If successful, they hope it will help to reduce the social and economic impact of one of the world’s most devastating livestock diseases.