ABSTRACT
Vaccination against S. typhi, the causative agent of typhoid fever in humans, has a long history. Initial attempts to vaccinate used parenterally delivered heat-killed whole S. typhi organisms. Live attenuated typhoid vaccines have a number of potential advantages over killed vaccines. One of the first attempts to produce a live attenuated S. typhi vaccine involved using a mutant of S. typhi which required streptomycin for growth in vitro. A number of different S. typhi and S. typhimurium strains have been used as carriers of heterologous antigens from nonsalmonellae species for the purpose of studying virulence or for vaccine development. The effect of the location of foreign antigens in the vaccine strain cells on immune response needs to be studied in relation to protective immune responses. Some antigens which are expressed well inside Salmonella cells are not recognized by the humoral immune response during experimental infections, and the reasons for this need to be determined.
