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

Clin Exp Allergy. 2003 Sep;33(9):1198-208. doi: 10.1046/j.1365-2222.2003.01699.x.

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.

Conclusion: 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Allergens / immunology*
  • Basophils / immunology
  • Double-Blind Method
  • Enzyme-Linked Immunosorbent Assay / methods
  • Histamine Release / immunology
  • Humans
  • Hypersensitivity, Immediate / immunology
  • Hypersensitivity, Immediate / prevention & control
  • Immunoglobulin E / biosynthesis*
  • Immunoglobulin E / immunology
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / immunology
  • Immunoglobulin M / biosynthesis
  • Immunoglobulin M / immunology
  • Immunotherapy / methods*
  • Lipid A / analogs & derivatives*
  • Lipid A / immunology
  • Lipid A / therapeutic use*
  • Phleum / immunology
  • Pollen / immunology
  • Seasons
  • Vaccines / therapeutic use

Substances

  • Adjuvants, Immunologic
  • Allergens
  • Immunoglobulin G
  • Immunoglobulin M
  • Lipid A
  • Vaccines
  • Immunoglobulin E
  • monophosphoryl lipid A