{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T12:53:46Z","timestamp":1772628826525,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["4708373"],"award-info":[{"award-number":["4708373"]}],"id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008376","name":"Helsingin ja Uudenmaan Sairaanhoitopiiri","doi-asserted-by":"publisher","award":["TYH2023322"],"award-info":[{"award-number":["TYH2023322"]}],"id":[{"id":"10.13039\/100008376","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Research Council of Finland","doi-asserted-by":"publisher","award":["336411"],"award-info":[{"award-number":["336411"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Research Council of Finland","doi-asserted-by":"publisher","award":["336410"],"award-info":[{"award-number":["336410"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Scand J Immunol"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The ChAdOx1 nCoV\u201019 vaccine has been in large\u2010scale use during the COVID\u201019 pandemic. Limited efficacy compared to mRNA vaccines and certain potential side effects raise the question of whether anti\u2010adenoviral vector antibodies influence immune responses against the vaccine. Complement activation by ChAdOx1 and leukocyte phagocytosis of ChAdOx1 in\u00a0vitro were studied. Plasma IgG levels against ChAdOx1 and human adenovirus 2 (hAdV2) hexon protein were determined (<jats:italic>n<\/jats:italic>\u2009=\u200920) and IgGs from high\u2010 and low\u2010titre plasmas were isolated (<jats:italic>n<\/jats:italic>\u2009=\u20093). Complement activation was measured as cleavage of C3 by immunoblotting and generation of C3a and sC5b\u20109 by ELISA. pHrodo\u2010labelled ChAdOx1 was opsonized with complement and IgG, and phagocytosis by isolated blood PMNs in\u00a0vitro was studied by flow cytometry. The transcriptomic profile of PMN cells exposed to ChAdOx1 was analysed by RNA\u2010seq. ChAdOx1 activated the classical complement pathway in an anti\u2010adenovirus antibody\u2010dependent manner. Generation of the terminal complement complex sC5b\u20109 in individual sera correlated with anti\u2010hAdV2 hexon and anti\u2010ChAdOx1 IgG levels. Phagocytosis of ChAdOx1 also correlated significantly with anti\u2010hAdV2 hexon IgG, anti\u2010ChAdOx1 IgG and serum sC5b\u20109 levels. High\u2010titre anti\u2010hAdv2 hexon IgG increased phagocytosis in the presence of normal serum. Anti\u2010vector antibodies induced rapid complement activation and promoted phagocytosis of the ChAdOx1 vaccine by neutrophils. Moreover, transcriptomic analysis revealed upregulation of complement\u2010related genes induced by the ChAdOx1 vaccine in\u00a0vitro. Anti\u2010adenovirus vector antibodies and complement activation may thus influence the efficacy of the ChAdOx1 vaccine against SARS\u2010CoV\u20102 and be also involved in vaccine\u2010related side effects.<\/jats:p>","DOI":"10.1111\/sji.70000","type":"journal-article","created":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T04:24:45Z","timestamp":1738383885000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The COVID\u201019 vaccine ChAdOx1 is opsonized by anti\u2010vector antibodies that activate complement and promote viral vector phagocytosis"],"prefix":"10.1111","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8089-1266","authenticated-orcid":false,"given":"Eija","family":"Nissil\u00e4","sequence":"first","affiliation":[{"name":"Department of Bacteriology and Immunology, Medicum University of Helsinki  Helsinki Finland"},{"name":"Human Microbiome Research Program University of Helsinki  Helsinki Finland"},{"name":"Translational Immunology Research Program University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1021-5449","authenticated-orcid":false,"given":"Leo","family":"Starck","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology, Medicum University of Helsinki  Helsinki Finland"},{"name":"Translational Immunology Research Program University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elias","family":"Aho","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology, Medicum University of Helsinki  Helsinki Finland"},{"name":"Translational Immunology Research Program University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika","family":"Venerandi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Humanitas University  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pinja","family":"Jalkanen","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine University of Turku  Turku Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Leskinen","sequence":"additional","affiliation":[{"name":"Translational Immunology Research Program University of Helsinki  Helsinki Finland"},{"name":"Institute of Biomedicine University of Turku  Turku Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavel","family":"Uvarov","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology, Medicum University of Helsinki  Helsinki Finland"},{"name":"Human Microbiome Research Program University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e4ivi","family":"Saavalainen","sequence":"additional","affiliation":[{"name":"Translational Immunology Research Program University of Helsinki  Helsinki Finland"},{"name":"Folkh\u00e4lsan Research Center  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilkka","family":"Julkunen","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine University of Turku  Turku Finland"},{"name":"Clinical Microbiology Turku University Hospital  Turku Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juha","family":"Kotimaa","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology, Medicum University of Helsinki  Helsinki Finland"},{"name":"Translational Immunology Research Program University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karita","family":"Haapasalo","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology, Medicum University of Helsinki  Helsinki Finland"},{"name":"Human Microbiome Research Program University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seppo","family":"Meri","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology, Medicum University of Helsinki  Helsinki Finland"},{"name":"Translational Immunology Research Program University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32661-1"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2034577"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035389"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2021.10.027"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5247.348"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-019-0132-6"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2021.102728"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03744-4"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab506"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021013231"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021014214"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI151092"},{"key":"e_1_2_10_14_1","first-page":"2875","article-title":"Pre\u2010existing immunity against ad vectors: humoral, cellular, and innate response, what's important?","volume":"10","author":"Fausther\u2010Bovendo H","year":"2014","journal-title":"Landes Bioscience"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13649"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00082-09"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-01179-4"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32466-1"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15620"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2022.06.008"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31604-4"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.2217\/fvl-2016-0070"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2010.03.003"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.61.2.173"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.01.045"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-018-2486-6"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00085"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.10.018"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01641-y"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094496"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-023-00974-6"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2210813"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2105869"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2104840"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2104882"},{"key":"e_1_2_10_38_1","unstructured":"Thrombosis with Thrombocytopenia Syndrome. [Internet]. [cited 2022 Dec 19]. Available from:https:\/\/www.hematology.org\/covid\u201019\/vaccine\u2010induced\u2010immune\u2010thrombotic\u2010thrombocytopenia"},{"issue":"2","key":"e_1_2_10_39_1","first-page":"351","article-title":"Prevalence of neutralizing antibodies to adenoviral serotypes 5 and 35 in the adult populations of The Gambia, South Africa, and the United States","volume":"11","author":"Nwanegbo E","year":"2004","journal-title":"Clin Diagn Lab Immunol"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.10.145"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00450-10"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0040385"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1080\/14760584.2024.2315089"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3301611"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0804269"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2020732118"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.100971"},{"key":"e_1_2_10_48_1","first-page":"53","article-title":"Adenoviral vector\u2010based vaccines and gene therapies: current status and future prospects","volume":"4","author":"Singh S","year":"2018","journal-title":"Adenoviruses"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302037"}],"container-title":["Scandinavian Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/sji.70000","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T08:30:58Z","timestamp":1740126658000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/sji.70000"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,31]]},"references-count":48,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1111\/sji.70000"],"URL":"https:\/\/doi.org\/10.1111\/sji.70000","archive":["Portico"],"relation":{},"ISSN":["0300-9475","1365-3083"],"issn-type":[{"value":"0300-9475","type":"print"},{"value":"1365-3083","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,31]]},"assertion":[{"value":"2024-06-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70000"}}