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- Title
Epicutaneous immune modulation with Bet v 1 plus R848 suppresses allergic asthma in a murine model.
- Authors
Siebeneicher, S.; Reuter, S.; Krause, M.; Wangorsch, A.; Maxeiner, J.; Wolfheimer, S.; Schülke, S.; Naito, S.; Heinz, A.; Taube, C.; Vieths, S.; Scheurer, S.; Toda, M.
- 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.
- Subjects
IMMUNOREGULATION; ALLERGENS; IMMUNOTHERAPY; IMMUNOLOGICAL adjuvants; POLLEN extract
- Publication
Allergy, 2014, Vol 69, Issue 3, p328
- ISSN
0105-4538
- Publication type
Article
- DOI
10.1111/all.12326