Salmonella as carrier
Salmonella enterica is an important pathogen of animals and humans causing a variety of infectious diseases. The large number of cases of typhoid fever due to S. enterica serovar Typhi infections gives rise to the continuous need for improved vaccines against this life-threatening infection. However, S. enterica is also an interesting organism to act as a live attenuated carrier for the presentation of recombinant heterologous antigens. Comprehensive experimental studies have been performed and a detailed knowledge of the molecular mechanisms of important virulence factors is available. This allows the rational design of improved
Salmonella carrier strains and the development of novel strategies for the expression and presentation of recombinant antigens.
We use the SPI2-encoded T3SS and promoters of SPI2-T3SS effector proteins to construct Salmonella strains that translocate heterologous recombinant antigens for presentation by antigen-presenting cells such as dendritic cells. This strategy allowed the efficient induction of protective immune responses against pathogens as well as anti-tumor immunity.
We aim to
- optimize the safety of attenuated Salmonella carrier strains
- find optimized combinations of effector proteins and intracellular activated promoters of highly efficient stimulation of immune responses
- develop new strategies to utilize Salmonella for therapeutic anti-cancer therapy
The project is currently funded by the DAAD through a PhD fellowship
- Prof. Dr. Leonid Metelitsa, Baylor College, Houston, Texas, USA
- Dr. Mohamed Husseiny, City of Hope, Duarte, California, USA
Xu, X., Husseiny, M. I., Goldwich, A., and Hensel, M. (2010).
Efficacy of intracellular activated promoters for generation of Salmonella-based vaccines. Infect. Immun. in press.
Xu, X., and Hensel, M. (2010). Systematic analysis of the SsrAB virulon of Salmonella enterica. Infect Immun 78, 49-58.
Xiong, G., Husseiny, M.I., Song, L., Erdreich-Epstein, A., Shackleford, G.M., Seeger, R.C., Jäckel, D., Hensel, M., and Metelitsa, L.S. (2009). Novel cancer vaccine based on genes of Salmonella pathogenicity Island 2. Int J Cancer, in press.
Husseiny, M.I., and Hensel, M. (2009). Evaluation of Salmonella live vaccines with chromosomal expression cassettes for translocated fusion proteins. Vaccine 27, 3780-3787.
Husseiny, M.I., Wartha, F., and Hensel, M. (2007). Recombinant vaccines based on translocated effector proteins of Salmonella Pathogenicity Island 2. Vaccine 25, 185-193.
Cheminay, C., and Hensel, M. (2008). Rational design of Salmonella recombinant vaccines. Int J Med Microbiol 298, 87-98.