title: Effects of the insertion of a nonapeptide from murine IL-1beta on the immunogenicity of carrier proteins delivered by live attenuated Salmonella.
abstract: A nonapeptide from IL-1beta has been reported to be an immunostimulant and adjuvant. To investigate the possibility of enhancing the immunogenicity of recombinant antigens delivered by live-attenuated Salmonella strains, we inserted an oligonucleotide coding for the nonapeptide from murine IL-1beta into the genes of three model proteins: LamB, MalE, and flagellin. The hybrid proteins were expressed and delivered in vivo by Salmonella aroA strains, and serum antibody responses were analyzed. The results showed that the nonapeptide induced an increase in the immune response against Salmonella-delivered flagellin, measured on day 28 post-immunization. However, the adjuvant effect was lost by day 42. In no case was an adjuvant effect detected for Salmonella-delivered LamB or MalE. Thus, by comparing the immune responses raised by purified MalE with and without the peptide, we investigated whether the insertion of the peptide affected the immunogenicity of the protein itself. Also in this case, a modest adjuvant effect was shown only after primary immunization and when very low doses of antigen were used. In conclusion, the immunomodulatory properties of the IL-1beta peptide can also be detected when it is delivered in vivo by Salmonella; however, the effect is modest and antigen-dependent.
authors.affiliation: Departmento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Av. Prof. Lineu Prestes, 1374 CEP 05508-900 São Paulo, Brazil.
authors.forename: I
authors.initials: I
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Pizza
authors.forename: R
authors.initials: R
authors.lastname: Rappuoli
authors.forename: S M
authors.initials: SM
authors.lastname: Newton
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002352:Carrier Proteins / Q000276:immunology*; D005260:Female; D005408:Flagellin / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007375:Interleukin-1 / Q000494:pharmacology*; D058619:Maltose-Binding Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D010446:Peptide Fragments / Q000494:pharmacology*; D011817:Rabbits; D012475:Salmonella / Q000235:genetics*
chemical_list: D000276:Adjuvants, Immunologic; D002352:Carrier Proteins; D007074:Immunoglobulin G; D007375:Interleukin-1; D058619:Maltose-Binding Proteins; D010446:Peptide Fragments; D005408:Flagellin