2011 Annual Report
1a.Objectives (from AD-416)
The objectives are: 1. to conduct feasibilty/proof-of-concept studies toward development of a reproducible Foot-and-Mouth Disease Virus (FMDV) contact challenge model in swine, 2. evaluate the ability of GenVec Ad-pIFN alpha to confer rapid onset of protection against the following FMDV serotypes: A24 Cruzeiro, 01-Manisa and A1.
Amendment 1: Additional objectives 3 through 6 to allow for the completion of the evaluation of swine interferon alpha delivered through an adenovirus replication-deficient viral vector (Ad5) as a potential biotherapeutic candidate.
3. Complete swine efficacy studies utilizing the Adt-pIFN alpha as a swine biotherapeutic candidate for FMDVAsia. 4. Complete swine efficacy studies utilizing Adt-pIFN alpha as a swine biotherapeutic candidate for FMDV for A24 Cruzeiro. 5. Identify swine innate immune cell pathways and molecules associated with Adt-pIFN alpha and Adt-pIFN gamma induced protection against FMD. 6. Identify potential new biotherapeutic candidates for FMD.
1b.Approach (from AD-416)
A reproducible model will be developed in swine leading to a contact challenge. This model will be then used to evaluate efficacy of biotherapeutics against FMDV challenge in swine. In collaboration with GenVec, Inc., novel adenovirus vectors expressing cytokines and viral antigens will be produced and tested in appropriate swine model developed above.
Amendment 1: Provides the Adt-pIFN alpha model will be utilized as a swine biotherapeutic candidate against Asia 1 and A24 Cruzeiro strains of FMDV. Dose response and delivery studies will be conducted to identify optimal biotherapeutic strategy. The swine innate immune response will be studied at the cellular level specifically focusing on the IFN alpha gene's capabilities.
Demonstrated that tissue culture cells treated with polyIC inhibit subsequent FMDV replication. Demonstrated that a combination of Ad5-pIFNalpha and polyICLC can sterilely protect swine from FMDV challenge. Demonstrated that polyICLC alone can sterilely protect swine from FMDV challenge. Preparing a manuscript concerning the above work. In tissue culture studies in both swine and bovine cell lines demonstrated that pretreatment with Venezuelan equine encephalitis (VEE) replicon (VRP) containing either porcine IFN alpha (VRP-pIFN alpha) or green fluorescent protein (VRP-GFP) can rapidly protect against subsequent infection with FMDV. Examined gene induction in tissue culture cells treated with VRP-pIFN alpha and VRP-GFP by real-time RT-PCR.