Plant-based BioProduction of Chicken IL-12 Adjuvant for Bird Flu Vaccines

The primary focus of this project is to develop new high valued health related agricultural products through the application of biotechnological research approaches. Domestic and wild fowl, as the disease reservoir for avian influenza virus, play a central role in the re-emergence of this potentially pandemic disease pathogen. The increasing threat of pandemic flu in domestic fowl and human populations has activated governments, agricultural, and medical health agencies in the US and globally to initiate multifaceted research and development efforts aimed at mitigating this threat. These efforts include monitoring global spread of pandemic strains of flu virus in bird and human populations, implementing plans to control infected domestic poultry to minimize intra and inter-species virus transmission, and accelerating research in the disease biology to develop other effective counter-measures. Although much of this effort targets human vaccines and antiviral therapeutics, new technologies for producing inexpensive high-quality agricultural vaccines to control avian flu at its source will be critical to successful intervention in the disease cycle supporting the threat of pandemic flu in both domestic poultry and humans. In order to effectively target the threat of flu to domestic poultry innovative, strategies to produce critical avian influenza research reagents and rapidly scalable vaccine components for poultry are clearly required. This project focuses on the bioproduction of avian interleukin-12 (IL-12) to address both of these needs. IL- 12 is a potent adjuvant and key modulator of cell-mediated immunity and greatly enhances the efficacy of influenza vaccines in animal studies. There are currently no sources for IL-12 from any avian species. The PIs have developed a plant-based bioproduction system for the 70 kD heterodimeric mouse IL-12 glycoprotein that provides high yields of recombinant protein with equivalent bioactivity to animal-cell derived mIL-12 in both in vitro assays and in vivo mouse vaccination trials. The goals of this SBIR are to exploit this bioproduction platform to produce chicken IL-12 (ChIL-12) and assess feasibility with respect to product yield and bioactivity. Specific aims of Phase I include developing ChIL-12 gene constructs, characterizing ChIL-12 produced in leaf material, and demonstrating the immunomodulating bioactivity of plant-derived ChIL-12. Based on a successful Phase I, Phase II would focus on process scale-up, demonstration of efficacy in avian vaccine trials, assessment of ChIL-12 activity across avian species, and tests to address efficacy with oral delivery. Co-formulation of this strong immuno-adjuvant with avian vaccines may ensure that these poultry vaccines elicit sufficient immunity to prevent avian flu transmission at the source. Plant-based bioproduction may provide the cost and scale advantages to enable these benefits to be widely integrated into avian influenza vaccine strategies for both domestic and wild bird populations.