Anti-IFN-gamma-treated mice--a model for testing safety of live Salmonella vaccines.

Salmonella enterica serovars Typhimurium and Enteritidis are facultative intracellular pathogens which cause in mice a disease similar to human typhoid fever caused by serovar Typhi. An essential phase in the infection process is bacterial replication inside cells of the liver and spleen; the rate of replication is restricted by interferon-gamma (IFN-gamma) produced early in the infection. In the present study the effect of IFN-gamma was neutralized in vivo with monoclonal antibody and the fate of bacteria in the liver and spleen in these mice compared with that in control mice after intravenous challenge. The depletion of IFN-gamma remarkably sensitized the mice to Typhimurium infection. Five different Typhimurium and Enteritidis candidate vaccine strains were tested. Only one of them, the aroA mutant SL3261, was avirulent also in anti-IFN-gamma treated mice. This finding may have important implications for the safety of live attenuated Salmonella vaccines since immunosuppression is likely to cause a state of reduced production of IFN-gamma.