Epicutaneous immune modulation with Bet v 1 plus R848 suppresses allergic asthma in a murine model

S. Siebeneicher, S. Reuter, M. Krause, A. Wangorsch, J. Maxeiner, S. Wolfheimer, S. Schülke, S. Naito, A. Heinz, C. Taube, S. Vieths, S. Scheurer, M. Toda

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

Background: Combining allergen(s) with an adjuvant is a strategy to improve the efficacy and safety of allergen-specific immunotherapy. Here, we aimed at investigating the adjuvant effects of polyadenylic-polyuridylic acid (poly(A:U)), a TLR3 agonist, and R848 (resiquimod), a TLR7 agonist, in epicutaneous immunotherapy with Bet v 1, the major birch pollen allergen, to intervene in birch pollen allergy. Methods and Results: BALB/c mice received epicutaneous immunization (EPI) with recombinant Bet v 1 (rBet v 1) alone, or plus poly(A:U), or R848 on their depilated back using patches. Among the groups, EPI with rBet v 1 and R848 induced detectable levels of IFN-γ-producing CD4+ T cells in lymph nodes and Bet v 1-specific IgG2a antibodies in the sera of mice. Before or after EPI, mice were sensitized with rBet v 1 plus aluminium hydroxide adjuvant and intranasally challenged with birch pollen extract. Prophylactic EPI with rBet v 1 plus R848 inhibited the production of biologically active Bet v 1-specific IgE antibodies in sensitization. Prophylactic and therapeutic EPI with rBet v 1 plus R848 suppressed lung inflammation upon challenges. Remarkably, only rBet v 1 plus R848 reduced the development of enhanced pause (PenH), a substituted parameter for airway hyper-reactivity, in challenged mice. In contrast to R848, poly(A:U) did not present adjuvant effect on the suppression of asthmatic features. Conclusion: Epicutaneous immunization with rBet v 1 plus R848 induced predominant Bet v 1-specific Th1 responses and efficiently suppressed asthmatic features elicited by birch pollen. R848 could be a promising adjuvant in epicutaneous immunotherapy for birch pollen-induced allergic asthma.

Original languageEnglish
Pages (from-to)328-337
Number of pages10
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume69
Issue number3
DOIs
Publication statusPublished - 2014 Mar 1
Externally publishedYes

Keywords

  • R848
  • TLR7 agonist
  • adjuvant
  • birch pollen allergy
  • epicutaneous immunization

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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