Low-dose allergen targeting to cDC2 induces long-term protection associated with IL-10+ Foxp3- CD8+ regulatory T cells in mice

Desensitizing immunotherapy is currently the only available treatment, but it is often ineffective for certain allergies, underscoring the need for new treatments. This study tested whether direct allergen targeting to DC subsets can improve desensitization.

An Ovalbumin (OVA)-mediated allergy mouse model was used to compare a Standard desensitization protocol, which is also used in humans, with a novel antibody-OVA fusion protein targeting the conventional cDC1 and cDC2 subsets via their respective receptors CD205 (CD205-Fp) or DCIR2 (DCIR2-Fp). OVA allergy treatment by cDC2 targeting provided long-lasting protection for up to 56 days after desensitization with only nanogram doses of allergen, whereas the Standard therapy protected for only 20 days, requiring microgram doses and repeated injections with Alum adjuvant.