title: Identification of potent biodegradable adjuvants that efficiently break self-tolerance--a key issue in the development of therapeutic vaccines.
abstract: Monoclonal antibodies are used successfully in the treatment of many human disorders. However, these antibodies are expensive and have in many countries put a major strain on the health care economy. Therapeutic vaccines, directed against the same target molecules, may offer a solution to this problem. Vaccines usually involve lower amount of recombinant protein, approximately 10,000-20,000 times less, which is significantly more cost effective. Attempts to develop such therapeutic vaccines have also been made. However, their efficacy has been limited by the lack of potent immunostimulatory compounds, adjuvants, for human use. To address this problem we have conducted a broad screening for adjuvants that can enhance the efficacy of therapeutic vaccines, whilst at the same time being non-toxic and biodegradable. We have now identified adjuvants that show these desired characteristics. A combination of Montanide ISA720 and phosphorothioate stabilized CpG stimulatory DNA, induced similar or even higher anti-self-antibody titers compared to Freund's adjuvant, currently the most potent, but also toxic, adjuvant available. This finding removes one of the major limiting factors in the field and facilitates the development of a broad range of novel therapeutic vaccines.
authors.affiliation: Dept of Medical Biochemistry and Microbiology, BMC, Box 589, 751 23 Uppsala, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Ringvall
authors.forename: Elisabeth J M
authors.initials: EJ
authors.lastname: Huijbers
authors.forename: Parvin
authors.initials: P
authors.lastname: Ahooghalandari
authors.forename: Ludmila
authors.initials: L
authors.lastname: Alekseeva
authors.forename: Tatyana
authors.initials: T
authors.lastname: Andronova
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Olsson
authors.forename: Lars
authors.initials: L
authors.lastname: Hellman
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D004247:DNA / Q000276:immunology / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005620:Freund's Adjuvant / Q000276:immunology / Q000494:pharmacology; D007073:Immunoglobulin E / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D008353:Mannitol / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology; D009829:Oleic Acids / Q000276:immunology / Q000494:pharmacology*; D009838:Oligodeoxyribonucleotides; D012330:RNA, Double-Stranded / Q000276:immunology / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017634:Self Tolerance / Q000276:immunology*; D014612:Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D001323:Autoantibodies; C423449:CpG ODN 1826; D007143:Immunoglobulin Heavy Chains; D009829:Oleic Acids; D009838:Oligodeoxyribonucleotides; D012330:RNA, Double-Stranded; D014612:Vaccines; C001681:mannide monooleate; D007073:Immunoglobulin E; D008353:Mannitol; D004247:DNA; D005620:Freund's Adjuvant