title: Allergen-specific immunotherapy with a monophosphoryl lipid A-adjuvanted vaccine: reduced seasonally boosted immunoglobulin E production and inhibition of basophil histamine release by therapy-induced blocking antibodies.
abstract: BACKGROUND
  Allergen-specific immunotherapy represents a causal form of treatment for IgE-mediated allergies. The allergen extract-based analyses of immunotherapy-induced effects yielded highly controversial results regarding a beneficial role of therapy-induced IgG antibodies.
  
  
  OBJECTIVE
  We analysed allergen-specific IgE, IgG subclass, and IgM responses in patients treated with a grass pollen allergy vaccine adjuvanted with monophosphoryl lipid A (MPL), a Th1-inducing agent, and in a placebo group using recombinant timothy grass pollen allergen molecules (rPhl p 1, rPhl p 2, rPhl p 5).
  
  
  RESULTS
  The strong induction of allergen-specific IgG1 and IgG4 antibodies observed only in the actively treated group was associated with significant clinical improvement. Therapy-induced allergen-specific IgM and IgG2 responses were also noted in several actively treated patients. An inhibition of allergen-dependent basophil histamine release was only obtained with sera containing therapy-induced allergen-specific IgG, but not with sera obtained before therapy or from placebo-treated patients. Moreover, patients with therapy-induced allergen-specific IgG antibodies showed a reduced induction of allergen-specific IgE responses during seasonal grass pollen exposure.
  
  
  CONCLUSIONS
  Successful immunotherapy with the MPL-adjuvanted grass pollen allergy vaccine is associated with the production of allergen-specific IgG antibodies. These blocking antibodies may have protective effects by inhibiting immediate-type reactions and systemic increases of IgE responses caused by seasonal allergen exposure.
authors.affiliation: Department of Pathophysiology, Vienna General Hospital, University of Vienna, Vienna, Austria.
authors.forename: N
authors.initials: N
authors.lastname: Mothes
authors.forename: M
authors.initials: M
authors.lastname: Heinzkill
authors.forename: K J
authors.initials: KJ
authors.lastname: Drachenberg
authors.forename: W R
authors.initials: WR
authors.lastname: Sperr
authors.forename: M T
authors.initials: MT
authors.lastname: Krauth
authors.forename: Y
authors.initials: Y
authors.lastname: Majlesi
authors.forename: H
authors.initials: H
authors.lastname: Semper
authors.forename: P
authors.initials: P
authors.lastname: Valent
authors.forename: V
authors.initials: V
authors.lastname: Niederberger
authors.forename: D
authors.initials: D
authors.lastname: Kraft
authors.forename: R
authors.initials: R
authors.lastname: Valenta
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000485:Allergens / Q000276:immunology*; D001491:Basophils / Q000276:immunology; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006636:Histamine Release / Q000276:immunology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000517:prevention & control; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D008050:Lipid A / Q000031:analogs & derivatives* / Q000276:immunology / Q000627:therapeutic use*; D031784:Phleum / Q000276:immunology; D011058:Pollen / Q000276:immunology; D012621:Seasons; D014612:Vaccines / Q000627:therapeutic use
chemical_list: D000276:Adjuvants, Immunologic; D000485:Allergens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008050:Lipid A; D014612:Vaccines; D007073:Immunoglobulin E; C048436:monophosphoryl lipid A