Salmonella enterica serovar Typhi live vector vaccines finally come of age.

Attenuated Salmonella Typhi vaccine strains hold great promise as live vectors for presentation of foreign antigens from unrelated bacterial, viral and parasitic pathogens to the immune system. Although this approach has proved quite successful in experimental animal models for eliciting antigen-specific mucosal, humoral and cellular responses, results have been disappointing for clinical trials carried out thus far. We hypothesize that the paucity of human responses to foreign antigens delivered by live vectors suggests that the strains and genetic approaches used to date have resulted in overattenuated vaccine strains with severely reduced immunogenicity. However, remarkable advances have now been made in the genetics of foreign antigen expression, understanding mechanisms of live vector immunity and refining immunization strategies. The time has now come for development of multivalent live vectors in which stable antigen expression and export is balanced with metabolic fitness to create highly immunogenic vaccines.