Department of Rheumatology and Immunology

Vaccine-Induced Anti-IgE Antibodies Neutralize Free IgE but Fail to Bind and Activate Mast Cell-Displayed IgE

Type I hypersensitivity, IgE is the antibody that contributes to the onset of anaphylaxis through the activation of effector cells, causing the release of allergic mediators. Blocking IgE activity with anti-IgE autoantibodies induced by active immunization could potentially offer an efficient and cost-effective method to treat allergic disorders. We recently developed an effective and safe anti-IgE vaccine in mice. Here, our objective was to better understand themechanism of action and the safety of the vaccine.Immunized mice generated high titers of IgG antibodies specific for IgE that conferred protection against allergic responses, independently of FcγRIIb and CD23. Sera of immunized mice blocked IgE binding to BMMC FcεRI and suppressed degranulation, independent of FcγRIIb. Purified anti-IgE antibodies did not provoke an anaphylactic response when transferred into allergic mice but protected against subsequent allergen challenge. Interestingly, the purified IgG antibodies were unable to recognize receptor-bound IgE in BMMCs, explained by the finding that recognition by these anti-IgEs depends on the same mannose moieties on IgE that are essential for FcεRI binding and thus hidden when receptor-bound.

In conclusion, the CuMVTT-Cε3-Cε4 vaccine induces high titers of anti-IgE IgGs that confer protection by neutralizing IgE through its glycan epitopes, without causing FcεRI cross-linking. Our results imply that an anti-IgE vaccine may represent a promising therapeutic strategy, offering effective protection while minimizing the risk of adverse reactions similar to the monoclonal antibody omalizumab.

Gharailoo et al., Allergy. 2025

Publication: Optimized Omalizumab Variants Prevent Severe Allergic Reactions

Immunoglobulin E (IgE) is a central driver of allergic reactions, binding to mast cells and basophils through its high-affinity receptor FcεRI and triggering inflammation when allergens are encountered. Omalizumab the only approved anti-IgE antibody therapy, has transformed treatment for various allergic conditions including asthma and chronic urticaria but has limitations due to its moderate affinity and need for frequent dosing. Researchers have long sought next-generation anti-IgE approaches that offer stronger, faster, and safer blockade of the allergic cascade. In this study, Brigger et al. engineered and functionally characterized new omalizumab variants with higher binding affinity and enhanced ability to actively displace IgE from the surface of mast cells and basophils. The optimized anti-IgE antibodies, called C03 variants, were tested on human basophils and mast cells in vitro as well as in an in vivo mouse model of systemic anaphylaxis.

Key findings included:

• The C03 variants demonstrated 10-fold higher affinity for IgE than omalizumab, leading to superior blockade of IgE binding to FcεRI.
• Importantly, C03 variants were able to actively displace receptor-bound IgE at physiologically relevant concentrations without activating the cells themselves.
• IgE sensitized mice given a single dose of the C03 variants were fully protected from antigen-induced anaphylaxis within 36 hours, unlike those treated with omalizumab.

These findings highlight the potential of high-affinity, disruptive anti-IgE antibodies to improve on current therapy by not only neutralizing free IgE but also removing IgE already attached to effector cells. Such dual action may allow for more complete protection from allergic reactions, including life-threatening anaphylaxis. While these results are preclinical, they underscore the promise of optimized anti-IgE antibodies in advancing the treatment of allergic disease.

Brigger et al., J Allergy Clin Immunol. 2025

Pro-inflammatory properties of salivary gland-derived fibroblasts – implications into Sjögren’s disease

This study points to the pro-inflammatory role of salivary gland-derived fibroblasts (SGF) in Sjögren’s disease (SjD). They are expanded in salivary glands of patients with SjD compared to non-SjD patients with sicca symptoms. Even in culture, SGF from patients with SjD exhibit increased proliferation rates compared to control SGF. Upon stimulation with pro-inflammatory stimuli, SGF secrete pro-inflammatory cytokines and chemokines and show similarities to synovial fibroblasts from patients with rheumatoid arthritis. This becomes not only evident in the transcriptomes of SGF but is additionally reflected by a similar enhancer activation, indicated by the expression of transcribed enhancer-RNAs. Treatment of SGF with the bromodomain inhibitor I-BET suppressed the expression of pro-inflammatory cytokines and chemokines and the activation of associated enhancer-RNAs.

Brunner et al, Cells 2025