Oral vaccination of mice against tetanus by use of a live attenuated Salmonella carrier

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Abstract
A Salmonella typhimurium aroA mutant has been used as a live carrier to immunize mice against tetanus. Plasmid pTETtac4, which expresses a 50-kilodalton fragment of tetanus toxin (fragment C) under the control of the tac promoter, was introduced into SL3261 aroA. When used as a live vaccine and administered orally or intravenously, this strain was able to induce protective immunity in mice against a lethal tetanus toxin challenge. When plasmid pTETtac2, which contains the lacI gene, was used, no immunity was obtained, indicating that the expression of fragment C was repressed in vivo. We believe that this is the first example of a successful oral vaccination that uses an attenuated bacterial carrier to deliver a protective antigen derived from tetanus toxin.