Expression of human IL-1 beta in Salmonella typhimurium. A model system for the delivery of recombinant therapeutic proteins in vivo
| Autor: | M J Carrier, S N Chatfield, G Dougan, U T Nowicka, D O'Callaghan, J E Beesley, S Milano, E Cillari, F Y Liew |
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| Rok vydání: | 1992 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 148:1176-1181 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.148.4.1176 |
| Popis: | 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-1 beta. This plasmid expresses IL-1 beta to high levels (greater than 30% total cell protein) in E. coli. In Salmonella the IL-1 beta is expressed constitutively to about 10% total cell protein, as verified by Western blotting analysis using polyclonal rabbit anti-IL-1 beta 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-1 beta as determined by a solid-phase RIA. Furthermore, mice injected with the construct were significantly protected against lethal gamma-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. |
| Databáze: | OpenAIRE |
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