Location: Foreign Animal Disease Research
Project Number: 8064-32000-064-000-D
Project Type: In-House Appropriated
Start Date: Oct 11, 2021
End Date: Oct 10, 2026
OBJECTIVE 1. Develop vaccines engineered for the control and eradication of Foot-and-Mouth Disease Virus (FMDV). Sub-objective 1.A Determine the mechanisms of protective immunity to FMDV conferred by multiple Foot-and-Mouth Disease (FMD) vaccine platforms. Sub-objective 1.B Determine the mechanisms mediating duration of immunity to FMDV. Sub-objective 1.C Develop vaccine platforms that will provide cross-protective immunity against different FMDV subtypes. Sub-objective 1.D Develop vaccines that reduce the incidence and accelerate clearance of persistent FMDV infections in cattle. Sub-objective 1.E Develop vaccines that can be rapidly manufactured to respond to new FMDV outbreaks. Objective 2. Develop biotherapeutics that can rapidly control the spread of FMD. Sub-objective 2.A Develop biotherapeutic platforms that induce rapid onset of immunity as a companion to an effective FMD vaccination. Sub-objective 2.B Develop biotherapeutics that alone or in vaccine formulations can reduce or abrogate FMDV persistence. Objective 3. Elucidate the host-pathogen interactions of FMDV. Sub-objective 3.A Identify viral determinants of FMD that control virulence in susceptible hosts. Sub-objective 3.B Determine the virus/host interactions associated with FMDV persistence. Objective 4. Characterize the ecology of FMDV in endemic regions. Sub-objective 4.A Determine drivers of FMDV transmission and maintenance in endemic regions. Sub-objective 4.B Determine factors that drive viral evolution and the mechanisms that lead to the emergence and spread of new FMDV strains.
1. The development of intervention strategies to control and eradicate Foot-and-Mouth Disease Virus (FMDV) will be achieved through research on novel Foot-and-Mouth Disease (FMD) vaccine platforms including of marker modified live-attenuated FMDV vaccine candidates such as FMDV-LL3B3D, second–generation Recombinant adenovirus-5 vectored foot-and-mouth disease constructs (Ad5- FMD) vaccines, and cross-protective vaccines against multiple subtypes. 2. Combinations of vaccine and biotherapeutics / and or adjuvants will be investigated as a way to induce mucosal immunity necessary not only to prevent disease but also to decrease persistent infection. These vaccine/adjuvant formulations will be tested using alternate routes such as transdermal and by direct mucosal delivery. 3. The host-pathogen interactions of FMDV will be determined through: the identification of viral determinants of FMDV that control virulence in susceptible hosts, determining virus/host interactions associated with the FMDV life cycle, and determining the mechanisms of protective immunity to FMDV. The molecular basis for FMDV-host interactions that impact virulence and their specific contributions to virulence will be determined. In addition, the interactions of the virus with specific tissues at the primary infection sites will be studied by characterizing infected tissues at the cellular and subcellular level as well as utilizing transcriptomic analyses with micro arrays and next generation RNAsequencing. Bioinformatic analyses will be extensively applied in order to understand species specific factors mediating the establishment and maintenance of persistent infections. The withinhost FMDV genomic evolution will be characterized through an examination of sitespecific mutational pressure, genomic variation and potential adaption to the host. The immune mechanisms affecting protective immunity against FMDV will be determined through the analysis of CD4 helper and CD8 cytotoxic T cell responses to FMDV vaccination and B-cell responses to FMDV in peripheral blood and lymphoid tissue. 4.The characterization of the ecology of FMDV in endemic regions, including determining drivers of FMDV transmission and maintenance in endemic regions, characterizing factors driving FMDV emergence and spread, and the characterization of the role of the Asian buffalo in the transmission and maintenance of FMDV in the context of tolerance to infection will be analyzed. Efforts will focus on the characterization of the ecology of FMDV in endemic regions in Asia and Africa, including determining the factors driving viral transmission and maintenance. Factors driving FMDV emergence and spread of novel FMDV strains in endemic settings will be characterized. The role of Asian buffalo in maintenance and transmission of FMDV in endemic settings will be assessed.