Development of Vaccines Toward the Global Control and Eradication of Foot-and-mouth Disease

Luis L Rodriguez; Cyril G Gay


Expert Rev Vaccines. 2011;10(3):377-387. 

In This Article

Abstract and Introduction


Foot-and-mouth disease (FMD) is one of the most economically and socially devastating diseases affecting animal agriculture throughout the world. Although mortality is usually low in adult animals, millions of animals have been killed in efforts to rapidly control and eradicate FMD. The causing virus, FMD virus (FMDV), is a highly variable RNA virus occurring in seven serotypes (A, O, C, Asia 1, Sat 1, Sat 2 and Sat 3) and a large number of subtypes. FMDV is one of the most infectious agents known, affecting cloven-hoofed animals with significant variations in infectivity and virus transmission. Although inactivated FMD vaccines have been available for decades, there is little or no cross-protection across serotypes and subtypes, requiring vaccines that are matched to circulating field strains. Current inactivated vaccines require growth of virulent virus, posing a threat of escape from manufacturing sites, have limited shelf life and require re-vaccination every 4–12 months. These vaccines have aided in the eradication of FMD from Europe and the control of clinical disease in many parts of the world, albeit at a very high cost. However, FMDV persists in endemic regions impacting millions of people dependent on livestock for food and their livelihood. Usually associated with developing countries that lack the resources to control it, FMD is a global problem and the World Organization for Animal Health and the United Nations' Food Agriculture Organization have called for its global control and eradication. One of the main limitations to FMDV eradication is the lack of vaccines designed for this purpose, vaccines that not only protect against clinical signs but that can actually prevent infection and effectively interrupt the natural transmission cycle. These vaccines should be safely and inexpensively produced, be easy to deliver, and also be capable of inducing lifelong immunity against multiple serotypes and subtypes. Furthermore, there is a need for better integrated strategies that fit the specific needs of endemic regions. Availability of these critical components will greatly enhance the chances for the global control and eradication of FMDV.


More than 113 years ago, Friedrich Loeffler, together with his colleague Paul Frosch from the Robert Koch's Institute of Infectious Diseases in Berlin, reported that foot-and-mouth disease (FMD) was caused by a filterable agent, and this is considered the first description of an animal disease caused by a virus.[1] The report was from the Research Commission on FMD, headed by Loeffler and Frosch, and set up the previous year by the Prussian Ministry of Culture and tasked, among other things, with developing a vaccine against the devastating disease causing "severe economic damage to the country's agriculture".[2] Inactivated FMD vaccines have been available since the early 1900s and have been instrumental in eradicating FMD from some parts of the world and repressing clinical disease in others. However, despite the use of billions of doses of inactivated FMD vaccines every year, the disease remains active, affecting millions of animals around the globe and causing economic hardship in some of the poorest regions. Today, FMD remains the main sanitary barrier to the commerce of animals and animal products. The characteristic clinical signs of FMD, which has high morbidity but low mortality, include high fever, anorexia, reduction in milk production and vesicular lesions that appear in the mouth and feet of affected animals 2–4 days after infection.[3,4] Inactivated FMD vaccines are effective in preventing clinical disease but do not necessarily prevent viral replication at the primary sites of infection, which can result in persistent infections in approximately 50% of naive and vaccinated animals exposed to FMD virus (FMDV).[5] Although the role of these persistent carrier animals on the FMD transmission cycle remains unclear, its occurrence is one of the main deterrents to using vaccination in the rapid control and eradication of disease outbreaks in FMD-free countries. Another problem with inactivated vaccines is the presence of nonstructural proteins in some vaccine formulations, which interferes with our ability to serologically distinguish infected from vaccinated animals (for details see 'differentiating infected from vaccinated animals' section to follow).

There is a clear need for a new generation of FMD vaccines with an improved profile, capable of not only preventing clinical signs but that can also prevent infection and have the necessary antigenic markers to allow differentiating infected from vaccinated animals (DIVA) testing. These new vaccines need to be fit-for-purpose to address the inadequate short duration of immunity provided by commercial inactivated FMD vaccines, and importantly, their narrow range of antigenic coverage. This is especially important for endemic areas where several FMD viral subtypes may be circulating, complicating the logistics of implementing an effective vaccination program when resources are scarce. Other attributes include the need to accelerate the onset of immunity (currently 7 days)[6] and provide negative markers to effectively distinguish infected from vaccinated animals. In this article we will provide a broad overview of existing FMD vaccines and promising new technologies in the pipeline that might become available in the coming years, and provide vaccine characteristics currently lacking in commercial FMD vaccines. Based on this knowledge, we will discuss the feasibility of global strategies for the control and, when feasible, eradication of FMDV using existing and novel vaccines.