Siglec-Engaging Tolerance-Inducing Antigenic Liposomes (STALs) in the Prevention of Peanut Allergy

Rationale: Peanut-specific B cells are the ultimate source of anti-peanut antibodies that drive peanut allergy.  Sialic acid-binding immunoglobulin-like lectins (siglecs) such as CD22 have been targeted to successfully induce apoptosis of antigen-specific B cells for induction of B cell tolerance.  We hypothesized that treatment with STALs displaying the CD22 ligand (BPA-NeuAc) and the major peanut allergen, Ara h 2 (Ah2) prior to sensitization would mitigate Ah2-induced anaphylaxis.

Methods: BALB/cJ mice received intravenous injections of either PBS (n=6), 100 uM antigenic liposome displaying Ah2 only (n=8), 20 uM Ah2 STALs (n=6), or 100 uM Ah2 STALs (n=7).  After two weeks, mice were sensitized by gavage with crude peanut extract and cholera toxin once weekly for 4 weeks.   Mice were bled and challenged with intraperitoneal Ah2.  Serology and challenge results were compared between groups. 

Results: Compared to PBS controls, injection with 100 uM STALs led to lower Ah2-specific IgG1 (p=0.002) and IgE (p=0.008).  Ah1-specific IgE (p=0.008) and IgG2a (p=0.006) were also lower in mice treated with 100 uM STALs compared to placebo.  Treatment with 20 uM Ah2 STALs had no significant effect on Ah2- or Ah1-specific IgG1, IgG2a, or IgE, suggesting a dose effect.  Upon challenge, the group pre-treated with 100 uM Ah2 STALs maintained a stable body temperature (slope parameter [±SD] -0.040±0.025; p=0.122 for a non-zero slope) unlike mice treated with PBS, that displayed the expected anaphylactic response (-0.099±0.031; p=0.006).

Conclusions: Pre-treatment with 100 uM tolerogenic Ara h 2-loaded STALs leads to lower Ah2- and Ah1-specific IgE and protects from experimental peanut anaphylaxis.