Liposomal peanut extract and CpG co-delivery suppresses peanut allergy in mice

Effective therapies for peanut allergy (PA) remain limited, posing a significant public health challenge. Current approaches often involve allergen avoidance or desensitization, which can be burdensome and carry risks. Cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN) have emerged as promising adjuvants for allergen-specific immunotherapy (AIT) due to their ability to modulate immune responses. This study investigates whether a liposomal delivery system, co-encapsulating peanut extract and CpG, can enhance therapeutic efficacy and restore immune tolerance in a murine model of PA.

Researchers established a murine PA model using peanut extract. Liposomes were formulated to carry peanut extract alone (LipP), CpG alone (LipC), both (LipCP), or were empty (LipE). PA mice received daily gavage of these formulations for two weeks. The primary endpoints included assessment of clinical symptoms (anaphylaxis, diarrhea, core temperature), antibody profiles (serum IgE, IgG2a/IgG2c), intestinal mediator release, and regulatory immune cell populations (B10 cells, Tr1 cells) via flow cytometry and ELISA.

PA mice exhibited severe anaphylaxis, including a 6.0-fold increase in diarrhea incidence (Cohen's d = 8.21) and a 2.3 °C median core temperature decrease (Cohen's d = 7.94) compared to naive controls. Treatment with LipCP substantially reduced PA severity: > Diarrhea incidence decreased by 89% (Cohen's d = 7.86), and the core temperature reduction was abolished. Serum IgE levels decreased by 78% (Cohen's d = 6.58), while IgG2a/IgG2c levels were restored. Furthermore, LipCP suppressed intestinal mast cell and eosinophil activation. Immunologically, LipCP treatment increased intestinal B10 cell frequency by 3.1-fold (Cohen's d = 6.27) and Tr1 cell frequency by 4.2-fold (Cohen's d = 7.15), indicating a restoration of immune tolerance. In contrast, LipP, LipC, or LipE showed only modest, non-significant effects.