LEVELS OF EXPRESSION AND IMMUNOGENICITY OF ATTENUATED SALMONELLA-ENTERICA SEROVAR TYPHIMURIUM STRAINS EXPRESSING ESCHERICHIA-COLI MUTANT HEAT-LABILE ENTEROTOXIN

The effects of heterologous gene dosage as well as Salmonella typhimur ium strain variability on immune response toward both the heterologous antigen, the nontoxic mutant of the Escherichia coli heat-labile ente rotoxin LTK63, and the carrier Salmonella strain have been analyzed, E ffects of a single integration into the host DNA and different-copy-nu mber episomal vectors were compared in S. typhimurium Delta cya Delta crp Delta asd strains of two different serotypes, UK-1 and SR-11, Expr ession of the enterotoxin in the different Salmonella isolates in vitr o was found to vary considerably and, for the episomal vectors, to cor relate with the plasmid copy number, LTK63-specific serum immunoglobul in G (IgG) and mucosal immunoglobulin A (IgA) antibodies were highest in mice immunized with the high-level-expression strain. High anti-LTK 63 IgG and IgA titers were found to correspond to higher anti-Salmonel la immunity, suggesting that LTK63 exerts an adjuvant effect on respon se to the carrier. Statistically significant differences in anti-LTK63 immune response were observed between groups of mice immunized with t he attenuated Delta cya Delta crp UK-I and SR-II derivatives producing the antigen at the same rate, These data indicate that the same atten uation in S, typhimurium strains of different genetic backgrounds can influence significantly the immune response toward the heterologous an tigen. Moreover, delivery of the LTK63 enterotoxin to the immune syste m by attenuated S. typhimurium strains is effective only when synthesi s of the antigen is very high during the initial phase of invasion, wh ile persistence of the S. typhimurium strain in deep tissues has only marginal influence.