Mimotope vaccination for therapy of allergic asthma: anti-inflammatory effects in a mouse model

Clin Exp Allergy. 2010 Apr;40(4):650-8. doi: 10.1111/j.1365-2222.2009.03392.x. Epub 2009 Dec 2.

Abstract

Background: One of the concerns of allergen-specific immunotherapy is the possible boost of inflammatory allergen-specific T lymphocytes. To address this problem, treatment with B cell epitopes devoid of allergen-specific T cell epitopes would be a promising alternative.

Objective: In this study, we examined the therapeutic potency of a single mimotope, mimicking a structural IgE epitope of grass pollen allergen Phl p 5 in an established memory mouse model of acute allergic asthma.

Methods: In the experimental set-up, BALB/c mice were primed with intraperitoneal injections of recombinant Phl p 5a (rPhl p 5a) and subsequently aerosol challenged with the nebulized allergen. Mice developed signs of bronchial asthma including hypereosinophilia around bronchi, goblet cell hyperplasia and enhanced mucus production.

Results: When the mice were subsequently treated with the grass pollen mimotope coupled to keyhole limpet haemocyanin, bronchial eosinophilic inflammation and mucus hypersecretion decreased. Further, a decrease of Th2 cytokines IL-4 and IL-5 could be observed in the bronchoalveolar lavage (BAL). In contrast to rPhl p 5a, the mimotope was in vitro not able to stimulate splenocytes to proliferation or IL-5 production. Despite not affecting the levels of pre-existing IgE, vaccination with the single mimotope thus rendered anti-inflammatory effects in a mouse model of acute asthma.

Conclusion: From our data, we conclude that vaccination with a mimotope peptide representing a single IgE epitope of the allergen Phl p 5a and being devoid of allergen-specific T cell epitopes is able to down-regulate inflammation in acute asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma* / immunology
  • Asthma* / therapy
  • Disease Models, Animal
  • Epitopes, T-Lymphocyte* / administration & dosage
  • Epitopes, T-Lymphocyte* / chemistry
  • Epitopes, T-Lymphocyte* / immunology
  • Female
  • Humans
  • Immunoglobulin E / immunology*
  • Inflammation / immunology
  • Inflammation / therapy
  • Mice
  • Mice, Inbred BALB C
  • Molecular Mimicry*
  • Plant Proteins* / administration & dosage
  • Plant Proteins* / chemistry
  • Plant Proteins* / genetics
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / immunology
  • Respiratory Hypersensitivity* / immunology
  • Respiratory Hypersensitivity* / therapy
  • Treatment Outcome
  • Vaccination

Substances

  • Epitopes, T-Lymphocyte
  • Phl p V protein, Phleum pratense
  • Plant Proteins
  • Recombinant Proteins
  • Immunoglobulin E