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Title: Foot-and-mouth disease virus vaccines

item Rodriguez, Luis
item Grubman, Marvin

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/11/2009
Publication Date: 11/5/2009
Citation: Rodriguez, L.L., Grubman, M.J. 2009. Foot-and-mouth disease virus vaccines. Vaccine. 27(4):D90-4.

Interpretive Summary: Foot-and-mouth disease (FMD) is an economically devastating disease of cloven-hoofed animals. The etiologic agent, FMD virus (FMDV), is a variable virus consisting of 7 serotypes and multiple subtypes. In this review, we provide a brief overview of FMD, including pathogenesis, global economic impact, and the history of development of the current inactivated FMD vaccines including some of their limitations. As a result of these limitations researchers for the past 35 years have been attempting to develop alternative disease control approaches. We describe the novel molecular vaccines that have been developed and discuss their shortcomings. We discuss, in some detail, the development of an adenovirus vectored FMD vaccine (Ad5-FMD) which lacks the genetic information for a number of viral nonstructural proteins and thus does not contain infectious FMDV. Thus, production of this vaccine does not require expensive high-containment manufacturing facilities, can be made in the U.S., which currently prohibits work with infectious FMDV on the mainland. Animals inoculated with this marker vaccine can readily be differentiated from infected animals using blood tests that detect antibodies to non-structural viral proteins associated to FMDV infection and absent from this vaccine. We briefly describe the development and successful testing of Ad5-FMD vaccines produced against a number of FMDV serotypes and subtypes. Finally we discuss the limitations of the adenovirus vector system, possible future improvements, and the potential rational design of live-attenuated vaccines based on a more complete understanding of viral pathogenesis and virus-host interactions. The information is valuable for preventing and treating FMD.

Technical Abstract: Foot and mouth disease (FMD) is a highly infectious and economically devastating disease of livestock. Although vaccines, available since the early 1900s, have been instrumental in eradicating FMD from parts of the world, the disease still affects millions of animals around the globe and remains the main sanitary barrier to the commerce of animals and animal products. Currently available inactivated antigen vaccines applied intramuscularly to individual animals, confer serotype and subtype specific protection in 1-2 weeks but fail to induce long-term protective immunity. Among the limitations of this vaccine are potential virus escape from the production facility, short shelf life of formulated product, short duration of immunity and requirement of dozens of antigens to address viral antigenic diversity. Here we review novel vaccine approaches that address some of these limitations. Basic research and the combination of reliable animal inoculation models, reverse genetics and computational biology tools will allow the rational design of safe and effective FMD vaccines. These vaccines should address not only the needs of FMD–free countries but also allow the progressive global control and eradication of this devastating disease.