A covid vaccine has been one of the greatest medical discoveries of the last decade and it now has

been found to provide long-term protection against anaphylaxis in humanized mice. Further study is

needed to allow for human long-term protection against anaphylaxis!

HomeScience Translational MedicineVol. 17, No. 827A vaccine targeting human IgE induces long-term protection against anaphylaxis in humanized mice

A vaccine targeting human IgE induces long-term protection against anaphylaxis in humanized mice

Editor’s summary

Monoclonal antibodies targeting IgE have been approved to treat IgE-mediated diseases, including allergic asthma and food allergy. However, repeated, and costly, administration of the monoclonal antibodies is required. Here, Conde et al. opted for another source of IgE-targeting antibodies, one’s own B cells. The authors developed a vaccine against IgE by coupling a fragment of the IgE constant region to an immunogenic carrier protein. When given to humanized mice, the vaccine elicited potent and durable antibodies against IgE. These antibodies were sufficient to protect mice against anaphylaxis but did not impair the immune response to a helminth infection. These data suggest that IgE vaccines may yet be a tool in the allergy therapy toolbox. —Courtney Malo

Abstract

Immunoglobulin E (IgE) antibodies play a key role in allergy and its most dangerous and life-threatening manifestation, anaphylaxis. Anti-IgE monoclonal antibodies (mAbs) have been developed to treat IgE-dependent diseases such as allergic asthma, food allergy, and chronic spontaneous urticaria. However, their use is still restricted to a minority of patients suffering from the most severe symptoms because treatment is costly and requires repeated administration. Therefore, we developed a conjugate vaccine against human IgE as a potential alternative therapy for long-term protection from IgE-dependent diseases. The IgE conjugate vaccine was generated by coupling a mutated fragment containing the Cε3-4 domains of human IgE with the carrier protein diphtheria cross-reactive material 197 (CRM197) using kinoid technology to raise autoantibodies against a self-antigen by engrafting it onto the highly immunogenic CRM197 carrier. To assess the efficacy of IgE-kinoid (IgE-K) vaccination, we generated a mouse model humanized for IgE and its high-affinity receptor FcεRI. IgE-K vaccination induced long-term production of anti–human IgE neutralizing antibodies without any detectable adverse effect. Anti-IgE antibodies were detected in the sera of IgE-K–immunized mice for up to 12 months postvaccination with a similar avidity as the approved anti-IgE mAb omalizumab. Furthermore, IgE-K vaccination protected against both IgE-mediated cutaneous and severe systemic anaphylaxis in IgE/FcεRI-humanized mice. Our results demonstrate that long-term reduction in IgE activity can be achieved through vaccination with human kinoids and can protect against anaphylaxis in humanized mice. This may represent a cost-effective, long-term therapeutic strategy for the treatment of IgE-mediated diseases.