Foot-and-Mouth Disease Virus (FMDV) occurs as multiple serotypes causing a highly contagious disease in cloven-hoofe d animals including pigs, sheep and cattle.
In cattle, vesicular lesions on the tongue and feet can cause weight loss, and udder lesions decreasing milk production. Financial losses can be high. There are direct losses due to deaths in young animals, loss of milk, loss of meat and a decrease in productive performance. The costs associated with eradication or control can also be high and, in addition, there are indirect losses due to the imposition of trade restrictions and reduced tourism. For these reasons, FMD is one of the most economically important diseases of livestock worldwide.
Persistent infection
FMDV can also cause sub-clinical persistent infections in ruminants, which can occur following clinical or sub-clinical disease in both vaccinated and non-vaccinated ruminants. Persistently infected animals are defined as carriers if live viruses can still be isolated from the oropharynx beyond 28 days after initial infection. Cattle, for example, have been shown to maintain carrier status for up to 3.5 years. Persistently infected animals may be considered a potential risk for FMD transmission. The difficulty in identifying vaccinated animals that subsequently become persistently infected may delay the return to FMD-free status. This has deleterious economic consequences for the livestock industry of that country, in terms of reduced international livestock movement and trade.
Vaccination-to-live policy
The World Animal Health Organisation (Office International des Epizooties, OIE) has amended its Animal Health Code shortening the time frame to regain FMD-free status from twelve to six months after the completion of vaccination, provided that thorough serological surveillance is undertaken to support the absence of circulating virus. Similarly, the European Union (EU) recently adopted a revised FMD directive, which promotes a more flexible approach to different control measures and makes detailed provision for the use of a vaccinate-to-live policy. However, if current vaccines are to be used as the preferred control measure, we must broaden our understanding of and improve their effectiveness. This firmly places greater emphasis on the need to scrutinise FMD vaccines further, particularly with regard to those used in an emergency situation, and to gain a greater understanding of their effectiveness and the practicalities of how, when and where they can be usefully implemented.
Current research
Much of the research has focussed on the efficacy of emergency vaccines under different challenging conditions, including more recent studies to determine the rate at which immunity is conferred against a severe direct contact challenge. However, a number of key areas still need to be addressed on the high potency FMD vaccines that would be implemented in an emergency situation. In the past vaccines have been held by the International FMD Vaccine Bank. In a recent change of strategy, the commercial sector will be expected to both store and formulate high potency vaccines. This is another reason for national authorities to ensure that these vaccines perform as effectively as when they were stored in the International FMD Vaccine Bank. Key areas include duration of protective immunity and the capacity of the vaccines to dampen down virus excretion and prevent transmission of infection.
Reducing transmission of FMDV
Recent studies have shown the importance of antigen payload in preventing transmission of infection to vaccinated protected sheep by the aerosol route. Furthermore, using a more severe direct contact challenge, of vaccinated cattle with infected cattle, has also supported the finding that payload plays some part in reducing the level of virus transmission. However, whilst preventing transmission of infection is desirable, in part, to successfully controlling disease incursion, the reality is that full prevention is not likely to be the outcome. Therefore, a further element of importance is onward transmission of any residual sub-clinical infection to other animals, particularly those of similar vaccination status. We are obtaining quantitative data on shedding and transmission of FMDV following a challenge of fully susceptible and vaccinated cattle to determine how soon after vaccination that transmission is effectively blocked. We are also examining transmission from vaccinates to further vaccinates of similar immune status. The accumulated data would enable greater statistical interpretation, and provide a better picture not only on the vaccine’s initial ability to prevent transmission but also its capacity to influence whether ongoing infection is possible through other vaccinated animals. These results will provide accurate parameter estimates for mathematical models to design FMDV vaccination programmes [eventually a link to e.g. Simon Gubbins page]. Thus our data will have a major impact by improving models.
DNA vaccines
DNA vaccines have certain advantages, not least the ease of manipulating the DNA plasmid. This provides the ability to generate an appropriately matching vaccine strain, avoiding difficulties in adapting a suitable conventional vaccine strain to large-scale culture. Also, the vaccine can have appropriate markers to assist in the surveillance that would subsequently be required after vaccine-induced control. The ability of DNA vaccination regimes to substantially enhance so many immune parameters provides a unique opportunity to study the importance of each of these in the context of protection and local virus inhibition. DNA vaccines would also be expected to induce long lasting memory responses and if, as anticipated, they prevent persistence, comparison to conventional vaccine responses should highlight the key immune parameters. This is of paramount importance in the design of new generation vaccines and improvement of those currently available, with the potential for protecting and improving the economics of European and World agricultural sectors.
The availability of a marker vaccine for FMD could have a substantial impact on FMD control measures in both countries free of the disease and those where it is endemic. A major argument against both routine and emergency vaccination has been the inability to reliably monitor the status and extent of an outbreak, largely because there is no reliable diagnostic test to distinguish vaccinated from infected animals, and carriers.