Substitution of flagellin with hen's egg lysozyme t-cell epitopes

Abstract

Vaccines have long been one of the most effective ways in dealing with infectious diseases. Since the time of Edward Jenner, vaccines have saved countless lives and dollars. Although present day vaccines have been very effective, they do have disadvantages. Their crude preparation allows for various side effects from allergic reactions to neurological side effects. This dissertation uses the latest advances in biotechnology to study a new technique in developing more empirical vaccines which would lessen side effects and allow for easier distribution among the worid's population. The technique studied in this dissertation is the substitution of the hen's egg lysozyme T cell epitope into a flagellin protein of Salmonella. Flagellin is the protein subunit of the flagellar filament, and is a very immunogenic molecule. By substituting a known T cell epitope from hen's egg lysozyme into the Salmonella flagellin protein at various regions, valuable information about the processing and presentation of epitopes to the immune system may be obtained. If this T cell epitope can successfully stimulate an immune response from a "foreign" environment, it is likely that medically important epitopes could be expressed in this fashion. The chimeric flagellin containing medically important epitopes could then be expressed in an auxotrophic mutant of Salmonella which would express the chimeric flagellin safely and orally which would facilitate the vaccination of people who would otherwise go unvaccinated. The results of the substituted HEL T cell epitope in this work and research by other groups show that T cell epitope substitutions need to be performed on an individual basis to test each T cell epitope's effectiveness in the flagellin protein for appropriate use as a vaccine.