Oral Vaccine for Immunization against Enteric Disease.

A living, attenuated, oral vaccine system and method for making oral vaccine strains is described for the immunization against enterically acquired diseases. An oval vaccine strain, according to this invention, is a genetic hybrid derivative of an attenuated galactose epimeraseless strain of S. typhi which carries at least one protective antigen other than normal S. typhi antigens. The oral vaccine can provide protection against typhoid fever andor at least one other enterically acquired disease. A bivalent oral vaccine is described wherein the non-typhoid protective antigen is the plasmid-encoded form I antigen of Shigella sonnei. A protective antigen from Shitella sonnei was transferred to a streptomycin resistant mutant of S. typhi strain Ty21a. The transconjugant S. typhi strain expressed both S. typhi and S. sonnei antigens and protected experimental animals against lethal infections with either S. typhi and S. sonnei. This strain is considered to be useful as a vaccine against typhoid fever and bacillary dysentery caused by S. sonnei. The mutated galactose epimeraseless S. typhi strain such as the S. typhi Ty21a strain can be utilized as a carrier strain for other protective antigens. Patent Applications.