Sci Transl Med. 2025 Dec 03. 17(827): eads0982
Eva Conde,
Emma Lamanna,
Aurélie Mougel,
Jasper B J Kamphuis,
Alexia Loste,
Julien Stackowicz,
Ophélie Godon,
Emilie Mauré,
Cyprien Pecalvel,
William P M Worrall,
Léna Andrieux,
Edouard Leveque,
Zohra Benmessaoud,
Pol-André Apoil,
Marija Backovic,
Bruno Iannascoli,
Jonathan Bonnefoy,
Samir Hamdi,
Fabien Colaone,
Friederike Jönsson,
Patrick England,
Laurent Guilleminault,
Bernard Malissen,
Frédéric Fiore,
Lara Linnemann,
Minka Breloer,
Nicolas Gaudenzio,
Béatrice Drouet,
Katia Lemdani,
Vincent Serra,
Pierre Bruhns,
Laurent L Reber.
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.