<scp>SpaCBA</scp> ‐ <scp>OVA</scp> Liposome Reprograms Immune Tolerance to Ameliorate Allergic Rhinitis via <scp>DC</scp> ‐T Cell Crosstalk

Allergic rhinitis (AR) is a prevalent immune disorder driven by Th2-polarised inflammation, with current therapies primarily providing symptomatic relief rather than addressing the underlying immune dysfunction. Allergen-specific immunotherapy (AIT) holds promise for inducing long-term tolerance but is limited by poor mucosal delivery, enzymatic degradation of antigens, and inconsistent efficacy. A liposomal formulation co-encapsulating SpaCBA (probiotic protein) and ovalbumin (OVA) was engineered. Characterisation included in vitro/in vivo evaluations of immune modulation and therapeutic efficacy in a murine AR model. The SpaCBA-OVA liposome exhibited stable characteristics (size: 100 ± 25 nm; zeta potential: -22 ± 3 mV; 85% entrapment efficiency) and enhanced proteolytic resistance (> 70% protein integrity after 48-h trypsin exposure vs. > 90% degradation of free proteins). Bone marrow-derived DCs (BMDCs) internalised the liposome 3-3.5× more efficiently via CD206/TLR2, adopting a semi-mature (CD86low/MHC-II^high) phenotype and secreting IL-10 (320 ± 30 pg/mL) and TGF-β (280 ± 25 pg/mL). RNA-seq identified 980 differentially expressed genes in T cells, with upregulation of Treg markers (FOXP3, IL-10) and downregulation of Th2 factors (GATA3, IL4). Epigenetic analysis confirmed 55% demethylation of the FOXP3 promoter. In AR mice, the liposome reduced sneezing and nasal rubbing by 60%-65% (p < 0.001), decreased nasal eosinophils by 55%, normalised ZO-1/occludin expression (90% of controls), and reduced epithelial permeability (FITC-dextran flux). The SpaCBA-OVA liposome enhances mucosal delivery and stability of antigens, reprograms DCs to induce Treg-mediated tolerance via metabolic and epigenetic mechanisms, and effectively ameliorates AR pathology in mice. This formulation represents a promising targeted therapy for AR, addressing key limitations of current AIT.