Evaluation of peanut tolerance in sensitized mice through intradermal allergen delivery with adjuvants

Peanut allergy is a significant worldwide health issue and requires innovative approaches to provide safer and more effective treatments. This study explores the potential of intradermal immunotherapy using peanut formulations combined with adjuvants. Six groups of BALB/c mice previously sensitized to peanut received intradermal treatments every other week for three months comprising of: Group 1 (G1) = Peanut extract (PE) + epinephrine (EPN); G2 = PE + EPN + topical Aldara® pretreatment; G3 = PE + EPN + topical imiquimod (IMQ) micellar gel pretreatment; G4 = PE + EPN + monophosphoryl lipid A (MPLA) + IMQ; G5 = PE + EPN + IMQ; G6 = Peanut powder + EPN + hyaluronic acid (HA). Clinical scores of peanut allergy, serological levels of peanut-specific IgE (Pe-IgE), IgG1, IgG2a, and histamine were compared before and after treatment, alongside studies on IMQ permeation and the pharmacokinetics of major peanut allergen ara h 2. Clinical scores improved significantly in all groups except G2 (trend towards improvement without statistical significance). Pe-IgE level decreased in G1, G2, and G3, while Pe-IgG1 increased in G1, G3, and G4. G3 alone showed a significant rise in Pe-IgG2a. No group was statistically superior to G1 after adjusting for differences in cumulative allergen doses received and initial IgE levels. Ex vivo experiments revealed that IMQ micellar gel in G3 enhanced skin permeation compared to Aldara®. Additionally, ara h 2 absorption was significantly reduced in naive mice treated with PE and HA. Baseline treatment of PE and EPN effectively reduced markers of peanut allergy. However, addition of TLR-agonist adjuvants or HA did not yield statistically significant improvements compared to baseline (G1).