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

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 (CRM<sub>197</sub>) using kinoid technology to raise autoantibodies against a self-antigen by engrafting it onto the highly immunogenic CRM<sub>197</sub> 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.

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Publication Details

Journal
Science Translational Medicine
Published
2025-12-03
DOI
https://doi.org/10.1126/scitranslmed.ads0982
Citations
4
Primary Topic
Urticaria and Related Conditions
Type
article
Field-Weighted Citation Impact
6.67
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article

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

Nicolas Gaudenzio, Béatrice Drouet, P.A. Apoil, Emilie Mauré et al.
4 citations
Science Translational Medicine
Urticaria and Related Conditions
6.67
article

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

Nicolas Gaudenzio, Béatrice Drouet, P.A. Apoil, Emilie Mauré, Frédéric Di Fiore, Emma Lamanna, Katia Lemdani, Pierre Bruhns, Jonathan Bonnefoy, Cyprien Pecalvel, Laurent L. Reber, Minka Breloer, Vincent Serra, Edouard Leveque, Aurélie Mougel, Julien Stackowicz, Laurent Guilleminault, Bruno Iannascoli, Samir Hamdi, Ophélie Godon, Alexia Loste, Lara Linnemann, Jasper Kamphuis, Friederike Jönsson, Marija Backović, Patrick England, E. Condé, William P. M. Worrall, Léna Andrieux, Fabien Colaone, Zohra Benmessaoud
article en
4 citations

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 (CRM<sub>197</sub>) using kinoid technology to raise autoantibodies against a self-antigen by engrafting it onto the highly immunogenic CRM<sub>197</sub> 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.

Science Translational MedicineVol. 17(827)
Centre National de la Recherche Scientifique (FR), Inserm (FR), Institut Pasteur (FR), Universität Hamburg (DE), Université Fédérale de Toulouse Midi-Pyrénées (FR), Université Sorbonne Nouvelle (FR), Université Paris Cité (FR), Aix-Marseille Université (FR), Sorbonne Université (FR), Laboratoire de Génie Chimique (FR), Centre de Recherches en Cancérologie de Toulouse (FR), Toulouse Mathematics Institute (FR), Délégation Paris 6 (FR), Neovacs (France) (FR), Centre d'Immunophénomique, Université Paris 1 Panthéon-Sorbonne (FR), HAW Hamburg (DE), Bernhard Nocht Institute for Tropical Medicine (DE)
Openalex Percentile: Top 3%
Urticaria and Related Conditions
6.67
DOISourceOpenAlex
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