Project Number: 1940-32000-057-00
Project Type: Appropriated

Start Date: Oct 11, 2011
End Date: Oct 10, 2016

Objective:
Foot-and-mouth disease virus (FMDV) causes a highly contagious, viral disease of domestic and wild cloven-hoofed animals effecting cattle, swine, sheep, goats and deer, which is characterized by fever, lameness and vesicular lesions and results in a high morbidity but low mortality in adult animals. FMD is the number one foreign animal disease threat to the United States livestock industry. Disease outbreaks result in the inhibition of trade in susceptible animals and their products. This research project will provide an understanding of virus-host interactions and disease pathogenesis that will aid in the development of alternative vaccine candidates and biotherapeutics. The objectives of this research project are: 1. Develop an understanding the mechanisms of FMDV host-pathogen interactions at the molecular and in vivo levels will aid in the development of improved disease control measures. 2. Develop new and improve current novel vaccines and biotherapeutic countermeasures that will enable rapid and effective prevention of FMDV infection in natural hosts and thereby contribute to global eradication of FMD. 3. Determine the epidemiology of FMDV in enzootic regions by biological characterization of variant FMDV strains and identifying the epidemiological importance of persistence on transmission and maintenance.

Approach:
1. To gain an understanding of the mechanisms of FMDV host-pathogen interaction, we will determine the molecular mechanisms of FMDV pathogenesis and viral-host interactions responsible for virulence, transmission and host-range specificity. Parental wild-type and attenuated viruses will be compared both in cell culture and in susceptible animals to identify virulence determinants; comparative pathogenesis studies will be conducted with multiple serotype and attenuated viruses to determine FMDV tissue distribution in susceptible hosts. The mechanisms mediating long term immunity induced by FMDV infection will be studied as well as the mechanisms of FMDV persistence and development of the carrier state. 2. The development and continued improvement of biotherapeutic countermeasures will be achieved through the discovery of biotherapeutic platforms to improve early protection against infection. Improved vaccine platforms will be identified by examining a series of vaccine approaches including inactivated vaccines derived from genetically engineered attenuated viruses with DIVA markers, live-attenuated vaccines, and adenovirus vectored FMDV. Studies will focus on the identification of the mechanisms to broaden the immune response of vaccines and to increase the duration of immunity conferred. 3. The characterization of FMDV epidemiological factors will be achieved through the collection of field samples and corresponding epidemiological information supplied by collaborating international partners from countries in which FMDV is currently circulating. Transmission, carrier state and epidemiological information will be compiled to gain a better understanding of FMD transmission and viral ecology in enzootic regions.