Immunization with Virus-Like Particles Displaying Ara h 2‑Derived Peptides to Mitigate Peanut Allergy

Peanut allergy is caused by aberrant IgE-driven immune responses to a well-defined set of peptide sequences within allergenic proteins. Oral and sublingual desensitization therapies are associated with the elicitation of IgG antibodies against allergenic proteins that interfere with IgE-induced effects. We tested whether inducing peptide-specific IgG responses by displaying key epitopes on immunogenic protein nanoparticle platforms protected against peanut allergy. A panel of 10 IgE epitopes from Ara h 2, the major degranulation-inducing peanut allergen, were displayed on two virus-like particles (VLPs): modified versions of both the bacteriophage PP7 coat protein and the iron-regulating encapsulin nanocompartment of the soil bacterium Myxococcus xanthus. Two peptide epitopes (Ah2-1, DPYSPS-QDPYSP-SPYDR-RGAGSSQ, and Ah2-6, HASAR-QQWEL-QGDRR-CQSQL-ERAN) were found to elicit strong and selective serum antibody responses against the full-length Ara h 2 protein. Immunization with a heterologous schedule (priming with PP7-displayed peptides, boosting with the corresponding encapsulin, and adjuvanting with the laboratory analogue of the clinical squalene-based adjuvant AS03) protected BALB/cJ mice against anaphylaxis in challenges with full-length Ara h 2 and whole peanut extract. These results suggest that focusing IgG-generating immune responses against specific peptide epitopes may be an effective prophylactic strategy against food allergies for which dominant epitopes are known.