CONSTRUCTION, EXPRESSION, AND IMMUNOGENICITY OF THE SCHISTOSOMA-MANSONI P-28 GLUTATHIONE-S-TRANSFERASE AS A GENETIC FUSION TO TETANUS TOXINFRAGMENT-C IN A LIVE ARO ATTENUATED VACCINE

A vector has been constructed to allow genetic fusions of guest antige ns via a hinge domain to the C terminus of the highly immunogenic C fr agment of tetanus toxin. A fusion has been constructed with the gene e ncoding the protective 28-kDa glutathione S-transferase (EC 2.5.1.18) from Schistosoma mansoni. The recombinant vector has been electroporat ed into the nonvirulent Salmonella typhimurium aroA live vaccine strai n SL3261. The corresponding chimeric protein is stably expressed in a soluble form in Salmonella as evaluated by Western blotting with fragm ent C and glutathione S-transferase antisera. Mice immunized intraveno usly with a single dose of the live recombinant bacteria elicit antibo dies to both fragment C and glutathione S-transferase as detected by e nzyme-linked immunosorbent assays. Furthermore, all of the mice were s olidly protected when challenged with lethal doses of either tetanus t oxin or the virulent Salmonella typhimurium strain C5. Mice have also elicited antibodies to fragment C and glutathione 5-transferase after oral immunization. It may be that a live trivalent vaccine against typ hoid, tetanus, and schistosomiasis is feasible.