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Immunization against peanut allergy with a safe and protective vaccine holds a promise to induce durable protection against anaphylaxis caused by exposure to peanut. A novel vaccine candidate (VLP Peanut), based on virus\u2010like particles (VLPs), is described here for the treatment of peanut allergy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>VLP Peanut consists of two proteins: a capsid subunit derived from <jats:italic>Cucumber mosaic virus<\/jats:italic> engineered with a universal T\u2010cell epitope (CuMV<jats:sub>TT<\/jats:sub>) and a CuMV<jats:sub>TT<\/jats:sub> subunit fused with peanut allergen Ara h 2 (CuMV<jats:sub>TT<\/jats:sub>\u2010Ara h 2), forming mosaic VLPs. Immunizations with VLP Peanut in both na\u00efve and peanut\u2010sensitized mice resulted in a significant anti\u2010Ara h 2 IgG response. Local and systemic protection induced by VLP Peanut were established in mouse models for peanut allergy following prophylactic, therapeutic, and passive immunizations. Inhibition of Fc\u03b3RIIb function resulted in a loss of protection, confirming the crucial role of the receptor in conferring cross protection against peanut allergens other than Ara h 2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>VLP Peanut can be delivered to peanut\u2010sensitized mice without triggering allergic reactions, while remaining highly immunogenic and offering protection against all peanut allergens. In addition, vaccination ablates allergic symptoms upon allergen challenge. Moreover, the prophylactic immunization setting conferred the protection against subsequent peanut\u2010induced anaphylaxis, showing the potential for preventive vaccination. This highlights the effectiveness of VLP Peanut as a prospective break\u2010through immunotherapy vaccine candidate toward peanut allergy. VLP Peanut has now entered clinical development with the study PROTECT.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.15704","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T10:08:41Z","timestamp":1678270121000},"page":"1980-1996","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["The next generation virus\u2010like particle platform for the treatment of peanut allergy"],"prefix":"10.1111","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5271-7826","authenticated-orcid":false,"given":"Jan M.","family":"Sobczak","sequence":"first","affiliation":[{"name":"Department of Immunology University Clinic of Rheumatology and Immunology, Inselspital  Bern Switzerland"},{"name":"Department of BioMedical Research University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal S.","family":"Krenger","sequence":"additional","affiliation":[{"name":"Department of Immunology University Clinic of Rheumatology and Immunology, Inselspital  Bern Switzerland"},{"name":"Department of BioMedical Research University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5570-4281","authenticated-orcid":false,"given":"Federico","family":"Storni","sequence":"additional","affiliation":[{"name":"Department of Immunology University Clinic of Rheumatology and Immunology, Inselspital  Bern Switzerland"},{"name":"Department of BioMedical Research University of Bern  Bern Switzerland"},{"name":"Department of Visceral Surgery and Medicine Inselspital, University Hospital Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona O.","family":"Mohsen","sequence":"additional","affiliation":[{"name":"Department of Immunology University Clinic of Rheumatology and Immunology, Inselspital  Bern Switzerland"},{"name":"Department of BioMedical Research University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5171-7744","authenticated-orcid":false,"given":"Ina","family":"Balke","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre  Riga Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunta","family":"Resevi\u010da","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre  Riga Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6095-4098","authenticated-orcid":false,"given":"Matthew D.","family":"Heath","sequence":"additional","affiliation":[{"name":"Allergy Therapeutics (UK) Ltd.  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