Vaccination against typhoid fever with a live oral vaccine.

A Salmonella typhi gal E mutant, designated Ty 21a, has been developed on the basis of virulence and protection studies with similar Salmonella typhimurium mutants in mice. Gal E mutants are characterized by a block in the enzyme UDP-4-galactose-epimerase. They owe their outstanding immunizing capacity when used in live oral vaccine to the fact that when galactose is supplied exogenously, as occurs in vivo, wild-type cell wall structures are synthesized. On the other hand, avirulence of these mutants is based upon the fact that when galactose is taken up it is partly accumulated as galactose-1-phosphate and UDP-galactose, which induces lysis of the bacteria. Strain S. typhi Ty 21a does not revert to wild type in vivo and in vitro. Its safety for man has been demonstrated in studies involving 137 adults and 370 children. S. typhi Ty 21a also has been shown to protect against challenge with virulent S. typhi in human volunteers.