CONSTRUCTION OF A RECOMBINANT ORAL VACCINE AGAINST SALMONELLA-TYPHI AND SALMONELLA-TYPHIMURIUM

The viaB gene coding for the Vi antigen of Salmonella typhi Ty2 was subcloned into expression vector pYA248. The recombinant plasmid was termed SMM202 and transformed into Salmonella typhimurium CHI-4072, an attenuated DELTA-cya DELTA-crp mutant. Recombinant S. typhimurium Vi4072 had the ability to produce Vi capsular polysaccharide and also to invade and colonize the small intestine, mesenteric lymph nodes, and spleen of BALB/c mice. Mice orally immunized with Vi4072 developed serum and secretory antibody responses to the Vi antigen, as measured by a passive hemagglutination assay. Mice developed a delayed-type hypersensitivity following a footpad injection with Vi antigen after being sensitized orally with a suitable dose of Vi4072. Immunization of mice with Vi4072 afforded complete protection against fatal infection with virulent S. typhi Ty2. All data indicate that this route of antigen delivery is effective for stimulating antibody-mediated immunity and for inducing a cell-mediated immune response in BALB/c mice. Thus, S. typhimurium Vi4072 may serve as a vaccine for protection against typhoid fever and salmonellosis caused by S. typhimurium.