Generation of a virus‐like particles based vaccine against IgE

• Published in: Allergy (Copenhagen) 2024-08, Vol.79 (8), p.2207-2221
• Main Authors: Gharailoo, Zahra, Plattner, Kevin, Augusto, Gilles, Engeroff, Paul, Vogel, Monique, Bachmann, Martin F.
• Format: Article
• Language: English
• Subjects: Allergens; Allergens - immunology; Allergic diseases; Allergies; allergy; Animals; Antibodies; Antibodies, Anti-Idiotypic - immunology; Cell activation; Disease Models, Animal; Effector cells; Female; Hypersensitivity - immunology; IgE; Immunogenicity; Immunoglobulin E; Immunoglobulin E - immunology; Immunoglobulin G; Immunotherapy; Leukocytes (basophilic); Mice; Mice, Inbred BALB C; Monoclonal antibodies; Plasma cells; vaccination; Vaccines; Vaccines, Virus-Like Particle - immunology; VLPs
• ISSN: 0105-4538; 1398-9995; 1398-9995
• DOI: 10.1111/all.16090

Background Anti‐IgE immunotherapy with monoclonal antibodies represents a breakthrough in treatment of severe allergic diseases. However, drawbacks such as short half‐life and high price are not negligible. Our objective is to develop an anti‐IgE vaccine based on virus‐like particles (VLPs) which can induce long‐lasting neutralizing IgG anti‐IgE antibodies reducing allergic responses without causing intrinsic mast cell activation due to IgE cross‐linking. Methods The vaccines were made by chemically coupling three synthetic mouse IgE‐Fc fragments to plant‐derived immunologically optimized CuMVTT VLPs. The immunogenicity of the vaccines was tested by immunizing naive or allergic mice either with the coupled vaccines or the VLP control followed by systemic or local allergen challenge. Results Mice immunized with the vaccines exhibited high titers of anti‐IgE antibodies in the sera and high levels of anti‐IgE secreting plasma cells in lymphoid organs. Moreover, free IgE in serum were reduced by the induced anti‐IgE antibodies; therefore, less IgE was bound to FcεRI on the surface of basophils. In line with these reduced IgE levels on effector cells after vaccination, immunized mice were protected from challenge with allergens. Importantly, despite presence of anti‐IgE antibodies, no signs of acute or chronic allergic response were seen in immunized allergic mice. Conclusion The generated vaccines can effectively induce anti‐IgE antibodies that did not cause allergic responses in sensitized mice but were able to decrease the level of free and cell bound IgE and protected sensitized animals from allergic responses upon allergen challenge. This study aimed to develop an anti‐IgE vaccine based on VLPs which can induce long‐lasting neutralizing IgG anti‐IgE antibodies reducing allergic responses without causing intrinsic mast cell activation due to IgE cross‐linking. VLP‐based anti‐IgE vaccine candidates were produced by chemically coupling synthetic mouse IgE‐Fc fragments to plant‐virus derived CuMVTT VLPs. These vaccine candidates were highly immunogenic and induced protection upon allergen challenge by decreasing the level of free and cell bound IgE. Abbreviations: CuMVTT, Cucumber mosaic virus engineered with a universal T cell epitope; Ig, immunoglobulin; VLPs, virus‐like particles.