Location: Foreign Animal Disease Research
Project Number: 8064-32000-057-38
Start Date: May 01, 2012
End Date: May 01, 2013
1. Test the virulence in swine of FHA mutant FMDV. In vivo studies will be conducted in swine to test the virulence of an available mutant FMDV strain containing mutations in a conserved domain (FHA) of the virus leader coding region. 2. Construction and in vitro characterization of FMDV strains with mutations in the CTE domain and/or the SAP and/or FHA domains. Several mutant FMDV strains will be constructed by using the infectious clone and targeting conserved residues contained in the CTE region of the leader coding region with the goal of obtaining new stable attenuated phenotypes that have a low probability of reversion to virulent wild type phenotype. 3. Test the virulence in swine of FMDV strains containing multiple mutations in the leader coding region (SAP and/or FHA and/or CTE mutations). In vivo studies will be conducted in swine with newly constructed FMDV containing multiple attenuating mutations in the leader coding region. 4. Test the efficacy of vaccination with attenuated FMDV SAP mutant of serotype A against infection with wild type FMDV of different subtypes and serotypes. Heterologus subypes/serotype specific cross-protection will be assayed by vaccination of swine with FMDV SAP mutant of serotype A followed by challenging with wild type FMDV of serotype A24 or O and/or Asia. The role of induction of protective innate immunity such as the interferon response will be evaluated.