Salmonella typhi attenuation

It contains the attenuated strain Ty21a of Salmonella typhi. The attenuation is due to the absence of enzyme uridine diphosphate galactose-4-epimerase which is essential for the production of the lipopolysaccharide O antigen. The absence of this enzyme makes Ty21a highly immunogenic. 

Forrest, B.D. Clinical evaluation of attenuated salmonella typhi vaccines in human subjects. In Novel Delivery Systems for Oral Vaccines O Hagan, D.T., Ed. CRC Press, Inc. Ann Arbor,, MI, 1994 59-85. 

The harvest is a very complex mixture of bacterial cells, metabolic products and exhausted medium. In the case of a live attenuated vaccine it should be innocuous, and all that is necessary is for the bacteria to be separated and resuspended under aseptic conditions in an appropriate diluent, possibly for freeze-drying. In a vaccine made from a virulent strain of pathogen the harvest may be intensely dangerous and great care is necessary in the subsequent processing. Adequate containment will be required and for class 3 pathogens such as Salmonella typhi or Yersinia pestis or bulk production of bacterial toxins, dedicated facilities that will provide complete protection for the operators and the environment are essential. 

Oral typhoid vaccine requires active replication of the attenuated Salmonella typhi strain in the ileum for the development of immunity. Mefloquine is thought to have some antibacterial effect, which may diminish the amount of S. typhi present, and therefore reduce the immune response produced by the vaccine. ... 

The other major health care products produced with the help of industrial fermentation are bacterial vaccines, therapeutic proteins, steroids, and gene therapy vectors. There are two categories of bacterial vaccines living and inactivated vaccines. Living vaccines consist of weakened, also known as attenuated, bacteria. Examples of living vaccines include those for diseases such as anthrax, which is caused by Bacillus anthracis, and typhoid fever, which is caused by Salmonella typhi. Inactivated vaccines are composed... 

Pasetti MF, Levine MM, Sztein MB. Animal models paving the way for clinical trials of attenuated Salmonella enterica serovar Typhi live oral vaccines and live vectors. Vaccine. 2003 21 401-418. 

Zhang L, Gao L, Zhao L, Guo B, Ji K, Tian Y, et al. Intratumoral delivery and suppression of prostate tumor growth by attenuated Salmonella enterica serovar typhi-murium carrying plasmid-based small interfering RNAs. Cancer Res 2007 67 5859-5864. 

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