Construction of a potential bivalent vaccine strain: introduction of Shigella sonnei form I antigen genes into the galE Salmonella typhi Ty21a typhoid vaccine strain

Abstract

Shigella sonnei, an intestinal pathogen, produces a characteristic form I cell surface antigen now known to be plasmid encoded. We considered that the GalE Salmonella typhi Ty21a oral vaccine strain, highly effective against typhoid, might be modified so as to be protective also against shigellosis due to S. sonnei. The plasmid responsible for form I antigen synthesis was therefore conjugally transferred to the galE S. typhi strain. Serological studies revealed that the derivative strain produces the form I antigen in addition to the normal S. typhi somatic antigens. Testing in mice demonstrated that the derivative form I galE S. typhi strain is protective against both S. sonnei and S. typhi challenges. These data suggest that the galE S. Ty21a oral vaccine strain, which presumably stimulates the local immune system in the intestine, may also serve as a useful carrier for other antigenic determinants to protect against different intestinal infections.

Determinants of the immunogenicity of live virulent and mutant Vibrio cholerae O1 in rabbit intestine

“…Results of studies in animals and volunteers suggest that live bacteria are especially efficient mucosal immunogens; one example is immunity to reinfection evoked by prior colonization or infection with Vibrio cholerae 01 (1,5,14). Such observations underlie efforts to develop oral vaccines for several enteric infections with live attenuated bacteria or avirulent genetic hybrids that produce antigens of unrelated pathogenic bacteria (3,7,10,11,15). The aim of such vaccines is to evoke mucosal immunity, including, but not necessarily restricted to, protective sIgA responses.…”

Characterization of the Shigella serotype D (S. sonnei) O polysaccharide and the enterobacterial R1 lipopolysaccharide core by use of mouse monoclonal antibodies

“…typhi TY37 is a hybrid derivative of live vaccine strain TY21a (12) bearing the entire S. sonnei virulence plasmid. TY37 is essentially equivalent to previously reported strain 5076-1C (9), with the further advantage that the virulence plasmid can be more stably maintained via selection for kanamycin resistance. Chemical analyses of the S. sonnei products expressed by strain 5076-1C suggested that the 0 antigen was present on the cell surface as a polymer of 0-disaccharide repeating units without covalent linkage to the core-lipid A region (37).…”

Oral immunization using live attenuated Salmonella spp. as carriers of foreign antigens.

“…An approach that has been proposed more recently is the use of live attenuated organisms as vectors to deliver specific target antigens to the host (55,151). The two best-characterized live vector systems are vaccinia virus and attenuated Salmonella spp.…”