Date of Award
Doctor of Philosophy
Newly emerging infectious agents along with already existing ones, extended lifespan and increased population in the modern age, and the threat of biological warfare increase the demand for high amounts of pharmaceutical/diagnostic recombinant protein production. Plants are safe and cost efficient for production of recombinant pharmaceuticals for humans and livestock. This work investigated potential of corn to serve as a production and delivery vehicle for subunit vaccines and vaccine components. Highly immunogenic antigens LT-B and CT-B from enterotoxigenic strains of Escherichia coli ( E. coli) and Vibrio cholera (V. cholera ) were used in this study as vaccine/component candidates;This study indicated that corn derived LT-B is capable of inducing immune memory formation. Mice were immunized with LT-B corn through feeding when they were young. They showed a rapid immune memory response in the form of elevated levels of LT-B specific IgG and IgA antibodies upon receiving a booster dose 11 months after initial immunization. This work provided evidence that immunization through feeding with antigens produced in palatable parts of plants would be effective as conventional subunit vaccines in terms of immune memory formation;The B subunit of cholera toxin (CT-B) was expressed in transgenic corn seeds at high levels. Biochemical and immunological analysis indicated that corn derived CT-B, like the bacterial protein, is assembled into pentamers and binds to GM1 gangliosides. Although the bacterial signal peptide of CT-B appears to not cleaved in corn seed tissue, unlike its counter part LT-B, it is able to induce murine immune system to produce CT-B specific antibodies. This work also provided evidence that administration of a mixture of corn derived CT-B and LT-B together has potential to induce higher levels of specific antibodies than when they were administered alone. This finding opens the possibilities of using these two corn derived antigens in combination and may lead to more efficacious vaccines against both cholera and enderotoxigenic E. coli induced diarrhea;This work indicated that a major food and feed crop corn holds great potential to be utilized as a production and delivery vehicle for production of vaccine antigens and components which could be used for prevention of both human and animal diseases.
Digital Repository @ Iowa State University, http://lib.dr.iastate.edu
Karaman, Sule, "Production of vaccines and vaccine components in corn " (2006). Retrospective Theses and Dissertations. 1530.