{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:39:31Z","timestamp":1791214771556,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T00:00:00Z","timestamp":1697068800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>There is still great need to develop new strategies to improve the efficacy of allergen immunotherapies with optimal safety standards for patients. A new promising approach is to couple allergoids to mannan. The objective of this phase IIa\/IIb study was to identify the optimal dose of mannan\u2010conjugated birch pollen allergoids for the short\u2010course treatment of birch pollen\u2013induced allergic rhinoconjunctivitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>For this prospective, randomized, double\u2010blind, placebo\u2010controlled, dose\u2010finding study, 246 birch pollen\u2013allergic adults received 0.5\u2009mL placebo or 1000, 3000 or 10,000 mTU\/mL of mannan\u2010conjugated birch pollen allergoids at five pre\u2010seasonal visits. Efficacy was assessed by comparing allergic rhinoconjunctivitis symptoms and use of anti\u2010allergic medication during the peak of the birch pollen season 2020. Immunologic, tolerability and safety effects were also analysed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The highest dose of mannan\u2010conjugated birch pollen allergoids reduced the combined symptom and medication score during the peak birch pollen season by a median of 24.7% compared to placebo. The production of <jats:italic>Bet v 1<\/jats:italic> specific IgG4 significantly increased in a dose\u2010dependent manner (3.6\u2010 and 4.5\u2010fold) in the 3000 and 10,000\u2009mTU\/mL groups. The <jats:italic>Bet v 1<\/jats:italic> specific IgE\/IgG4 ratio was also strongly reduced (up to \u221270%). No fatalities nor serious adverse events were reported, and no adrenaline was used. In total, four systemic reactions occurred (two grade I and two grade II).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>All doses of mannan\u2010conjugated birch pollen allergoids can be considered as safe. Since the application of 10,000\u2009mTU\/mL resulted in the highest efficacy, this dose qualifies for further investigation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.15910","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T07:20:49Z","timestamp":1697095249000},"page":"990-1000","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["A randomized, double\u2010blind, placebo\u2010controlled trial with mannan\u2010conjugated birch pollen allergoids"],"prefix":"10.1111","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1928-810X","authenticated-orcid":false,"given":"Ralph","family":"M\u00f6sges","sequence":"first","affiliation":[{"name":"ClinCompetence Cologne GmbH  Cologne Germany"},{"name":"Faculty of Medicine, Institute of Medical Statistics and Computational Biology University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3355-8663","authenticated-orcid":false,"given":"Christoph","family":"Zeyen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Medical Statistics and Computational Biology University of Cologne  Cologne Germany"},{"name":"Department of Dermatology, Venereology and Allergology, Division of Evidence\u2010Based Medicine (dEBM), Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6461-8593","authenticated-orcid":false,"given":"Esther","family":"Raskopf","sequence":"additional","affiliation":[{"name":"ClinCompetence Cologne GmbH  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5699-4305","authenticated-orcid":false,"given":"Cengizhan","family":"Acikel","sequence":"additional","affiliation":[{"name":"ClinCompetence Cologne GmbH  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5516-2013","authenticated-orcid":false,"given":"Hacer","family":"Sahin","sequence":"additional","affiliation":[{"name":"ClinCompetence Cologne GmbH  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0222-5954","authenticated-orcid":false,"given":"Silke","family":"Allekotte","sequence":"additional","affiliation":[{"name":"ClinCompetence Cologne GmbH  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandy","family":"Cuevas","sequence":"additional","affiliation":[{"name":"Carl Gustav Carus Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine (and University Hospital) Technische Universit\u00e4t Dresden  Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3425-3463","authenticated-orcid":false,"given":"Mohamed H.","family":"Shamji","sequence":"additional","affiliation":[{"name":"Allergy and Clinical Immunology Section Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0134-5321","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Subiza","sequence":"additional","affiliation":[{"name":"Inmunotek S.L.  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2330-3963","authenticated-orcid":false,"given":"Miguel","family":"Casanovas","sequence":"additional","affiliation":[{"name":"Inmunotek S.L.  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,12]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2007.01393.x"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.2003.01773.x"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2015.07.010"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1934"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.157.2.956"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000513445"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-6749(85)90661-x"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-199410010-00002"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2012.03571.x"},{"key":"e_1_2_12_11_1","first-page":"30","article-title":"Skin tests with native, depigmented and glutaraldehyde polymerized allergen extracts","volume":"15","author":"Casanovas M","year":"2005","journal-title":"J Investig Allergol Clin Immunol"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2020.12.008"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2017.07.004"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10719-015-9640-4"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00726-4"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202249980"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.08.042"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.02.029"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13396"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.06.012"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40629-018-0069-8"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.12383"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2007.01469.x"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13092"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2011.02745.x"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.1991.tb00807.x"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40629-014-0009-1"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13358"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13240"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13433"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.11.018"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/clt2.12185"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.12.1001"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjoto.2021.103206"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15550"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-021-06752-2"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.all.0000191237.43502.d7"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2011.03794.x"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15374"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.12236"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD001936.pub2"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.14453"}],"container-title":["Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.15910","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T17:50:01Z","timestamp":1719510601000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/all.15910"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,12]]},"references-count":41,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1111\/all.15910"],"URL":"https:\/\/doi.org\/10.1111\/all.15910","archive":["Portico"],"relation":{},"ISSN":["0105-4538","1398-9995"],"issn-type":[{"value":"0105-4538","type":"print"},{"value":"1398-9995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,12]]},"assertion":[{"value":"2023-05-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}