Attenuated Delta guaBA Salmonella typhi vaccine strain CVD 915 as a live vector utilizing prokaryotic or eukaryotic expression systems to deliver foreign antigens and elicit immune responses

Attenuated Salmonella typhi strain CVD 915, harboring a deletion in guaBA t hat interrupts the biosynthesis of guanine nucleotides, was evaluated as a live vector vaccine for delivering foreign antigens utilizing prokaryotic o r eukaryotic expression systems. Plasmids pTETnir15 and pcDNA3tetC encoding fragment C (Frag C) of tetanus toxin under the control of prokaryotic or e ukaryotic promoters, respectively, were introduced into CVD 915 and adminis tered intranasally to mice. Purified pcDNA3tetC and Frag C were given intra muscularly. High titers of serum IgG1, IgG2a, and IgG2b antibodies against Frag C were elicited by CVD 915(pTETnir15) and CVD 915(pcDNA3tetC). These r esponses were significantly higher than those induced by pcDNA3tetC. Prolif erative responses and IL-2 and IFN-gamma production were observed in spleno cytes exposed to S. typhi antigens and Frag C. We conclude that CVD 915 is a highly efficient live vector to carry foreign genes under eukaryotic or p rokaryotic control and elicit potent immune responses. (C) 1999 Academic Pr ess.