Expression of human IL-1 beta in Salmonella typhimurium. a model system for the delivery of recombinant therapeutic proteins in vivo
Carrier, M.J.; Chatfield, S.N.; Dougan, G.; Nowicka, U.T.; O'Callaghan, D.; Beesley, J.E.; Milano, S.; Cillari, E.; Liew, F.Y.
Journal of Immunology 148(4): 1176-1181
1992
ISSN/ISBN: 0022-1767 PMID: 1737934 Document Number: 388081
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.