COMPARISON OF THE ABILITIES OF DIFFERENT ATTENUATED SALMONELLA-TYPHIMURIUM STRAINS TO ELICIT HUMORAL IMMUNE-RESPONSES AGAINST A HETEROLOGOUS ANTIGEN

We compared the abilities of different Salmonella enterica var, Typhim urium (S, typhimurium) strains harboring mutations in the genes aroA, aroAD, purA, ompR, htrA, and cya crp to present the heterologous antig en, C fragment of tetanus toxin, to the mouse immune system, Plasmid p TETtac4, encoding C fragment, was transferred into the various S, typh imurium mutants, and the levels of antigen expression were found to he equivalent, After primary oral immunization of BALB/c mice, all atten uated strains were capable of penetrating the gut epithelium and colon izing the Peyer's patches and spleens of mice, Of all strains compared , the Delta purA mutant colonized and persisted in the Peyer's patches at the lowest level, whereas the Delta htrA mutant colonized and pers isted in the spleen at the lowest level, The level of specific antibod y elicited by the different strains against either S, typhimurium lipo polysaccharide or tetanus toroid was strain dependent and did not dire ctly correlate to the mutants' ability to colonize the spleen, The lev el of immunoglobulin G1 (IgG1) and IgG2a antibody specific for tetanus toroid was determined in mice immunized with four S, typhimurium muta nts, The level of antigen-specific IgG1 and IgG2a was significantly lo wer in animals immunized with S, typhimurium Delta purA. Antigen-speci fic T-cell proliferation assays indicated a degree of variability in t he capacity of some strains to elicit T cells to the heterologous anti gen. Cytokine profiles (gamma interferon and interleukin-5) revealed t hat the four S, typhimurium mutants tested induced a Th1-type immune r esponse, Mice were challenged with a lethal dose of tetanus toxin 96 d ays after oral immunization, With the exception of the S, typhimurium Delta purA mutant, all strains elicited a protective immune response. These data indicate that the level of total Ig specific for the carrie d antigen, C fragment, does not correlate with the relative invasivene ss of the vector, but it is determined by the carrier mutation and the background of the S, typhimurium strain.