The research in my laboratory is focused on the development of live, attenuated bacterial strains which can be used as vaccines delivered by the oral route. Strains of Salmonella and Shigella have been engineered with precise mutations in genes encoding critical virulence factors or biosynthetic enzymes which render the bacteria attenuated for virulence but remain immunogenic. Promising candidates have been tested in clinical trials in the CVD. Successful vaccine strains have been exploited for use as live vectors for the expression and delivery of heterologous antigens to form multivalent vaccines. Our two major projects are 1) the development of a Shigella/ETEC (enterotoxigenic E. coli) vaccine using attenuated Shigella to express critical antigens from ETEC, and 2) the development of a Salmonella based pneumococcal conserved antigen vaccine. Attenuated strains of S. Typhi, which have been shown to be safe and immunogenic in volunteer studies, have been used to express conserved protein antigens from S. penumoniae which may engender protective responses against diverse serotypes.