Expression of human IL-1β in salmonella typhimurium a model system for the delivery of recombinant therapeutic proteins in vivo

Martin J. Carrier, Steven N. Chatfield, Gordon Dougan, Urszula T A Nowicka, David O'Callaghan, Julian E. Beesley, Salvatore Milano, Enrico Cillari, F. Y. Liew

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The feasibility of using Salmonella typhimurium aroA mutant (SL3261) to deliver protein therapeutic agents was investigated in a murine model system. We have constructed an Escherichia coli expression plasmid designed to express the human protein IL-1β. This plasmid expresses IL-1β to high levels (>30% total cell protein) in E. coli. In Salmonella the IL-1β is expressed constitutively to about 10% total cell protein, as verified by Western blotting analysis using polyclonal rabbit anti-IL-1β antibody. The protein is produced in a soluble and biologically active form. BALB/c mice administered orally or i.v. with S. typhimurium aroA mutants carrying the plasmid produced highly significant antibody responses against human IL-1β as determined by a solid-phase RIA. Furthermore, mice injected with the construct were significantly protected against lethal γ-irradiation (850 rad). This study therefore demonstrates that the vaccine strain of Salmonella mutants can also be used effectively to deliver therapeutic proteins in vivo.

Original languageEnglish
Pages (from-to)1176-1181
Number of pages6
JournalJournal of Immunology
Issue number4
Publication statusPublished - 15 Feb 1992
Externally publishedYes

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