SALMONELLA-TYPHIMURIUM DELTA-AROA DELTA-AROD MUTANTS EXPRESSING A FOREIGN RECOMBINANT PROTEIN INDUCE SPECIFIC MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I-RESTRICTED CYTOTOXIC T-LYMPHOCYTES IN MICE

Recombinant Salmonella typhimurium aroA aroD mutants which expressed o valbumin were constructed. The two expression constructs used were bas ed on either pUC18 or pBR322. The pBR322-based construct was more stab le in vitro and in vivo than the pUC-based construct. Salmonellae cont aining the stable pBR322-based plasmid induced major histocompatibilit y complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL), in c ontrast to salmonellae containing the pUC18-based expression construct . The priming of MHC class I-restricted CTL was increased by multiple immunizations. The study described in this report suggests that S. typ himurium Delta aro mutants have the capacity to induce MHC class I-res tricted CTL against carried antigens and that MHC class I-restricted C TL responses require stable in vivo expression of the target antigen. Further, the results indicate that the Salmonella typhi Delta aro muta nts currently undergoing evaluation in studies with humans may be good carriers of viral antigens with CTL determinants.