Delta guaBA attenuated Shigella flexneri 2a strain CVD 1204 as a Shigella vaccine and as a live mucosal delivery system for fragment C of tetanus toxin

The Delta guaBA Shigella flexneri 2a vaccine candidate, CVD 1204, was evalu ated as a delivery system for the non-toxic C-terminal of tetanus toxin (fr agment C), either as a polypeptide expressed in the bacteria or as a DNA va ccine. CVD 1204 was transformed with plasmid pTETnir15 which encodes the fr agment C gene (tetC) under the control of the inducible prokaryotic nir15 p romoter or a DNA vaccine plasmid pcDNA3tetC which encodes tetC under the eu karyotic hCMV promoter. Guinea pigs immunised intranasally (i.n.) with eith er recombinant strain mounted a secretory immune response against S. flexne ri 2a Lipopolysaccharide (LPS) and were protected against ocular challenge with wild-type S. flexneri 2a. Both strains were effective in eliciting a s erum IgG response against fragment C in guinea pigs following i.n. immunisa tion. Furthermore, serum from guinea pigs immunised with CVD 1204(pTETnir15 ) contained tetanus toxin neutralising antibodies. These results demonstrat e that this S. flexneri 2a vaccine candidate can serve as a vehicle for the delivery of foreign antigens to the systemic immune system while retaining its capacity to serve as a mucosal Shigella vaccine. (C) 2000 Elsevier Sci ence Ltd. All rights reserved.