Rationally Engineered Self-Assembling Protein Nanoparticles for Allergen-Specific Peanut Allergy Immunotherapy

Peanut allergy, an immunoglobulin E (IgE)-mediated food allergy, can lead to life-threatening anaphylaxis. Existing treatments offer limited efficacy and temporary protection. Allergen-displaying virus-like particles (VLPs) have shown potential, but their development is limited by design flexibility and manufacturing complexity.

Researchers have now developed self-assembling protein nanoparticles (SApNPs) to address these issues as a modular platform for peanut allergy immunotherapy. The nanoparticles display the major allergens Ara h 2 and Ara h 6, using the 60-mer TIP60 scaffold. They are engineered by expanding particle size through -helical insertion, replacing a human myosin-X segment with a catfish homolog, and optimizing their structure.

Formulated with a Toll-like receptor 9 (TLR9) agonist, these SApNPs provide robust protection against peanut-induced anaphylaxis, both preventatively and therapeutically. Mechanistically, the SApNPs remain longer in lymph nodes, present longer on follicular dendritic cells, and enhance germinal center responses compared to soluble allergens.

This promotes allergen-specific IgG and functional T cell responses while limiting IgE escalation. The findings demonstrate allergen-displaying SApNPs as a rationally engineered, scalable, and modular platform for peanut allergy treatment, with potential applications to other allergic diseases.