title: A novel mannoside-glycocluster adjuvant: Compared in vitro to CpG ODN and MPL and tested in vivo in mouse asthma model.
abstract: BACKGROUND
  Allergen-specific immunotherapy balances the Th2-biased immunity towards Th1 and Treg responses. Adjuvants are used in allergen preparations to intensify the immune responses. The increased prevalence of allergies in developed societies has been associated with decreased microbial load during childhood. This has initiated a search for microbial structures to be used as adjuvants. Our study has shown that a synthetic triacedimannose (TADM) may suppress the Th2-type allergic inflammatory response. The aim of this study was to compare the properties of TADM with capacities of other adjuvants, CpG ODN and MPL, to modulate cytokine production in PBMC and regulate sensitisation in an OVA-sensitised mouse asthma model.
  
  
  METHODS
  The effects of TADM were studied in vitro on birch stimulated PBMC cultures of birch allergic rhinitis patients with other known adjuvants. Cytokines in supernatants were measured by Luminex. Effects of TADM were analysed in vivo in a mouse model of OVA-induced allergic asthma by analysing BAL, cytokine mRNA and serum antibodies.
  
  
  RESULTS
  TADM was the only adjuvant that significantly suppressed the production of all birch induced Th2-type cytokines. In a murine model, TADM significantly suppressed the specific IgE production and enhanced IFN-γ production.
  
  
  CONCLUSIONS
  TADM suppresses the birch allergen induced Th2-type cytokine responses in allergic subjects more efficiently than the two other adjuvants, MPL and CpG ODN. TADM is immunomodulatory also in vivo and decreases the IgE levels and increases the IFN-γ responses in a murine model. These results suggest that TADM may be a promising candidate for novel adjuvants in immunotherapy.
authors.affiliation: Department of Pulmonary Diseases and Clinical Allergology, University of Turku, Turku University Hospital, Finland. Electronic address: kkrant@utu.fi.
authors.forename: K
authors.initials: K
authors.lastname: Mäkinen
authors.affiliation: Laboratory of Organic Chemistry, Åbo Akademi University, Finland.
authors.forename: C
authors.initials: C
authors.lastname: Mukherjee
authors.affiliation: Unit of Systems Toxicology, Centre of Expertise for Health and Work Ability, Finnish Institute of Occupational Health, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Leino
authors.affiliation: Laboratory of Organic Chemistry, Åbo Akademi University, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Panchadhayee
authors.affiliation: Unit of Systems Toxicology, Centre of Expertise for Health and Work Ability, Finnish Institute of Occupational Health, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Lehto
authors.affiliation: Unit of Systems Toxicology, Centre of Expertise for Health and Work Ability, Finnish Institute of Occupational Health, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Wolff
authors.affiliation: Unit of Systems Toxicology, Centre of Expertise for Health and Work Ability, Finnish Institute of Occupational Health, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Alenius
authors.affiliation: Laboratory of Organic Chemistry, Åbo Akademi University, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Leino
authors.affiliation: Department of Pulmonary Diseases and Clinical Allergology, University of Turku, Turku University Hospital, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Savolainen
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000628:therapy*; D029662:Betula / Q000276:immunology; D002478:Cells, Cultured; D003231:Conjunctivitis / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000378:metabolism; D003888:Desensitization, Immunologic; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives; D008297:Male; D008362:Mannosides / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D010047:Ovalbumin / Q000276:immunology; D065631:Rhinitis, Allergic / Q000276:immunology / Q000628:therapy*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000485:Allergens; C408982:CPG-oligonucleotide; D016207:Cytokines; D008050:Lipid A; D008362:Mannosides; D009838:Oligodeoxyribonucleotides; D010047:Ovalbumin; C048436:monophosphoryl lipid A
keywords: Adjuvant; Glycocluster; Murine model; Specific Immunotherapy; Triacedimannose