Live attenuated oral vaccine against ETEC and typhoid fever

A transgenic Salmonella typhi Ty21a comprising a heterologous enterotoxogenic Escherichia coli (ETEC) antigen biosynthetic gene region and a heterologous acid resistance biosynthetic gene system comprising one or more heterologous Shigella acid resistance enzymes, wherein:

• a. said heterologous ETEC antigen biosynthetic gene region and said heterologous acid resistance biosynthetic gene system are integrated into the Salmonella typhi Ty21a chromosome;
• b. an ETEC antigen is stably expressed from said integrated heterologous ETEC antigen biosynthetic gene region;
• c. said one or more heterologous Shigella acid resistance enzymes are stably expressed;
• d. said one or more heterologous Shigella acid resistance enzymes of the heterologous acid resistance biosynthetic gene system comprises a YbaS gene;
• and
• e. said transgenic Salmonella typhi Ty2a is more acid stable at pH 2.5 than Salmonella typhi Ty21a without the integrated heterologous acid resistance biosynthetic gene system.