2009 - 2012
Engineered antibodies and phage products for food safety applications
Principal Investigator: Christine Szymanski, University of Alberta
Co-investigator: Roger MacKenzie and Jamshid Tanha, National Research Council; J. Christopher Hall, University of Guelph
BackgroundIn the past decade, the protein therapeutics market, led by monoclonal antibodies, has rapidly expanded to annual sales of approximately US$20 billion. Most protein therapeutics currently on the market are for the treatment of cancer, but there is huge potential for protein therapeutics to expand into other areas such as infectious diseases. Most approved protein drugs are extremely costly full-length antibodies so there is a pressing need to develop less expensive alternatives. This proposal follows a growing trend in the protein therapeutics industry away from whole antibodies and mammalian expression systems. In applications in which only the antigen binding function is required, single-domain antibodies (sdAbs) and surrogate antibodies such as the receptor binding domains of bacteriophages (PRBDs) are attractive alternatives. Plant expression of such molecules has the potential to greatly reduce cost and give high value agricultural products. The proposed work builds on preliminary data that have established proof-of-principle for the concept that oral administration of Campylobacter jejuni-specific pentameric sdAbs (pentabodies) and Salmonella enterica serovar Typhimurium-specific PRBDs, can reduce the levels of chicken colonization by these organisms. This represents a reduction-at-source approach to decreasing the incidence of food-borne illness. For C. jejuni, the specific pentabodies will be engineered for improved protease resistance and thereby lowering the dose levels required. Dr. Szymanski and colleagues have also recently obtained the first genome sequence for a C. jejuni bacteriophage. The PRBD of the phage has been identified and will be cloned, engineered and over-expressed for chicken studies to evaluate its efficacy in terms of reducing C. jejuni colonization levels.
Funding$1,324,000 (CPRC $54,000, Alberta Ingenuity Fund $1,000,000, NRC $270,000)