Principal Investigator: Diego Diel

DESCRIPTION (provided by applicant): 

Orf virus (ORFV) has long been used in veterinary medicine as an immunotherapeutic agent due to its potent immunostimulatory properties. The goal of this study is to develop an ORFVbased vaccine delivery platform for use in livestock species. Among the biological properties that make ORFV a promising, perhaps superior alternative to current veterinary vaccine delivery vectors are the fact that: i. it does not induce neutralizing antibodies in naturally infected animals, and ii. it encodes multiple proteins with potent immunomodulatory/virulence functions.

We hypothesize that deletion of genes encoding immunomodulatory/virulence proteins from the ORFV genome will result in a vector platform with enhanced immunogenicity and safety. Indeed, recently we have shown that deletion of ORFV121 – an inhibitor of the nuclear factor kappaB (NF-κB) signaling pathway and virulence determinant of ORFV – increases the immunogenicity of the ORFV-based vectors in cattle and swine.

The objectives of this study are:
(1) to develop an ORFV-based vector platform with enhanced immunogenicity and safety; (2) to construct recombinant ORFV vectors expressing protective antigens of important pathogens of cattle and swine; and (3) to evaluate the immunogenicity and protective efficacy of ORFV-based recombinant vectors in target animal species.

These objectives are related to the program area of Animal Health and Disease. The work will significantly impact the priority areas of “disease prevention” through improved “vaccination, delivery systems and/or vaccines” for livestock. A multi-species vaccine delivery platform will allow rapid development of intervention strategies to combat endemic and/or emerging diseases that constantly threat the US livestock industry.