Using Siglec-engaging Tolerance-inducing Antigenic Liposomes (STALs) to reduce memory B cell responses to the major peanut allergen Ara h 2

RATIONALE: CD22 is a Siglec expressed on the surface of B-cells and simultaneous ligation of CD22 with the B-cell receptor leads to suppression of cellular activation. Ara h 2 (Ah2) STALS are nanoparticles that co-display Ah2 and high affinity CD22 ligands, which we have previously shown can prevent sensitization to Ah2 in naïve mice. Here, we aimed to determine whether STALs can abrogate memory B-cell responses.

METHODS: BALB/cJ mice were sensitized to peanut for four weeks, then challenged with peanut to confirm allergic status. Allergic mice were sacrificed within four weeks of challenge, splenocytes isolated and adoptively transferred into naïve BALB/cJ mice. After transfer, STALs or immunogenic Ah2 liposomes without the CD22 ligand were administered. Two weeks later, mice were boosted with purified Ah2 then bled one week later. Finally, mice were challenged with a high dose of Ah2.

RESULTS: Mice that received Ah2 STALs after transfer of splenocytes from peanut allergic mice had only mild decreases in body temperature on the final Ah2 challenge, which were significantly less than the body temperature decreases measured in mice that received the immunogenic Ah2 liposomes (p<0.05). Serum Ah2-specific IgE and IgG1 supports the rectal thermometry data from the final challenge with Ah2, in that STALs treated mice had lower sIgE and sIgG1 than mice given immunogenic Ah2 liposomes.

CONCLUSIONS: A single dose of Ah2 STALs suppressed the memory B-cell response to Ah2, demonstrating viability of a novel approach to targeted deletion of allergen-specific memory B-cells that is considered to be an ultimate source for long-term allergies