Typhoid, live attenuated

Salmonella typhi is the etiological agent of typhoid fever, an acute, febrile enteric disease.

Virulent strains of S. typhi upon ingestion are able to pass through the stomach acid barrier, colonize the intestinal tract, penetrate the lumen and enter the lymphatic system and blood stream, thereby causing disease. One possible mechanism by which disease may be prevented is by evoking a local immune response in the intestinal tract. Such local immunity may be induced by oral ingestion of a live attenuated strain of S. typhi undergoing an aborted infection. The ability of S. typhi to cause disease and to induce a protective immune response is dependent upon the bacteria possessing a complete lipopolysaccharide. The S. typhi Ty21a vaccine strain, by virtue of a reduction in enzymes essential for lipopolysaccharide biosynthesis, is restricted in its ability to produce complete lipopolysaccharide. However, a sufficient quantity of complete lipopolysaccharide is synthesized to evoke a protective immune response. Despite low levels of lipopolysaccharide synthesis, the cells lyse before regaining a virulent phenotype due to the intracellular build-up of intermediates during lipopolysaccharide synthesis.