title: Induction of interleukin-6 (IL-6) autoantibodies through vaccination with an engineered IL-6 receptor antagonist.
abstract: Neutralization of cytokine activity by monoclonal antibodies or receptor antagonists is beneficial in the treatment of immune and neoplastic diseases, but the necessity for continuous parenteral delivery of these anticytokine agents poses considerable practical limitations. A viable alternative is to induce a neutralizing antibody response. Using transgenic mice with high circulating levels of human interleukin-6 (hIL-6), we show that injection of the hIL-6 receptor antagonist Sant1 (an IL-6 variant with seven amino-acid substitutions) induces a strong anti-hIL-6 antibody response. The elicited antibodies bind circulating hIL-6 with very high affinity, totally masking it, and neutralize hIL-6 bioactivity both in vitro and in vivo.
authors.affiliation: I.R.B.M. P.Angeletti, Pomezia, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Ciapponi
authors.forename: D
authors.initials: D
authors.lastname: Maione
authors.forename: A
authors.initials: A
authors.lastname: Scoumanne
authors.forename: P
authors.initials: P
authors.lastname: Costa
authors.forename: M B
authors.initials: MB
authors.lastname: Hansen
authors.forename: M
authors.initials: M
authors.lastname: Svenson
authors.forename: K
authors.initials: K
authors.lastname: Bendtzen
authors.forename: T
authors.initials: T
authors.lastname: Alonzi
authors.forename: G
authors.initials: G
authors.lastname: Paonessa
authors.forename: R
authors.initials: R
authors.lastname: Cortese
authors.forename: G
authors.initials: G
authors.lastname: Ciliberto
authors.forename: R
authors.initials: R
authors.lastname: Savino
mesh_terms: D000536:Aluminum Hydroxide / Q000737:chemistry; D000818:Animals; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000096:biosynthesis* / Q000276:immunology; D001665:Binding Sites; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology; D005818:Genetic Engineering; D006801:Humans; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic / Q000276:immunology; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000276:immunology; D014611:Vaccination
chemical_list: D001323:Autoantibodies; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D000536:Aluminum Hydroxide