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