{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T10:26:37Z","timestamp":1782210397668,"version":"3.54.5"},"reference-count":20,"publisher":"Georg Thieme Verlag KG","funder":[{"name":"Forschungsverbund Molekulare Medizin"},{"name":"DFG, German Research Foundation","award":["493623784"],"award-info":[{"award-number":["493623784"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["514598754"],"award-info":[{"award-number":["514598754"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["374031971-TRR240"],"award-info":[{"award-number":["374031971-TRR240"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["GR 2232\/9-1"],"award-info":[{"award-number":["GR 2232\/9-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SCHO 2052\/1-1"],"award-info":[{"award-number":["SCHO 2052\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["TH 2320\/3-1"],"award-info":[{"award-number":["TH 2320\/3-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Universit\u00e4tsmedizin Greifswald"},{"DOI":"10.13039\/100001422","name":"American Society of Hematology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001422","id-type":"DOI","asserted-by":"crossref"}]},{"name":"EMA service","award":["EMA\/2021\/17\/TDA"],"award-info":[{"award-number":["EMA\/2021\/17\/TDA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Vaccination against SARS-CoV-2 was instrumental in controlling the COVID-19 pandemic. Rare cases of vaccine-induced immune thrombocytopenia and thrombosis (VITT) emerged following vaccination with the adenovirus vector-based vaccines ChAdOx1 nCov-19-S and Ad26.COV2.S. VITT is mediated by high-titer IgG anti-platelet factor 4 (PF4) antibodies that activate platelets, leading to thrombosis and thrombocytopenia. Similar antibodies have been detected following natural adenovirus infections, suggesting a common immunological trigger. This indicates that a constituent of adenovirus is relevant. Adenovirus is a DNA virus. Virion-unbound viral DNA is present in natural adenovirus infections.<\/jats:p>\n                  <jats:p>To identify whether free virion-unbound DNA is present in ChAdOx1-nCoV19 vaccine and whether adenoviral DNA enhances the immune response to PF4 in mice.<\/jats:p>\n                  <jats:p>We assessed ChAdOx1 nCov-19-S for virion-unbound DNA and differentiated free human and free adenovirus DNA by sequencing. We immunized mice with ChAdOx1 nCov-19-S and its fractions, in which we removed proteins by proteinase K and\/or DNA by DENERASE.<\/jats:p>\n                  <jats:p>Using ultracentrifugation and proteinase K digestion, we isolated and characterized free nucleic acids, confirming the presence of both adenoviral and host cell-derived DNA in ChAdOx1 nCov-19-S. Mice immunized with PF4 in combination with ChAdOx1 nCov-19-S or its virion-free supernatant\u2014but not with PF4 alone\u2014developed a strong anti-PF4 IgG response, an effect completely abolished by nuclease (DENARASE) treatment.<\/jats:p>\n                  <jats:p>Virion-unbound DNA in ChAdOx1 nCov-19-S contributes to anti-PF4 antibody formation. This highlights the potential of reducing virion-unbound DNA in vaccine formulations to mitigate unintended immune responses to PF4.<\/jats:p>","DOI":"10.1055\/a-2736-5418","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T23:50:43Z","timestamp":1762213843000},"source":"Crossref","is-referenced-by-count":1,"title":["Free Nucleic Acids in the ChAdOx1 nCov-19-S Adenovirus Vector Vaccine Contribute to an Anti-platelet Factor 4 Antibody Response"],"prefix":"10.1055","author":[{"given":"Florian","family":"Siegerist","sequence":"additional","affiliation":[{"name":"Institute for Anatomy and Cell Biology, Universit\u00e4tsmedizin Greifswald, Greifswald, Germany"},{"name":"Neonatology and Pediatric Intensive Care Medicine, Universit\u00e4tsmedizin Greifswald, Greifswald, Greifswald, Germany"},{"name":"German Center for Child and Adolescent Health (DZKJ), partner site Greifswald\/Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Reder","sequence":"additional","affiliation":[{"name":"Neonatology and Pediatric Intensive Care Medicine, Universit\u00e4tsmedizin Greifswald, Greifswald, Greifswald, Germany"},{"name":"Interfaculty Institute for Genetics and Functional Genomics, Department Functional Genomics, Universit\u00e4tsmedizin Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghavendra","family":"Palankar","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine, Universit\u00e4tsmedizin Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Wesche","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine, Universit\u00e4tsmedizin Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine, Universit\u00e4tsmedizin Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Michalik","sequence":"additional","affiliation":[{"name":"Interfaculty Institute for Genetics and Functional Genomics, Department Functional Genomics, Universit\u00e4tsmedizin Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens van den","family":"Brandt","sequence":"additional","affiliation":[{"name":"Central Core and Research Facility of Laboratory Animals (ZSFV), University Medicine Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Hoppen","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Department of Synthetic and Structural Biochemistry, University of Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6660-9949","authenticated-orcid":false,"given":"Linda","family":"Sch\u00f6nborn","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine, Universit\u00e4tsmedizin Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Thiele","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine, Universit\u00e4tsmedizin Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"V\u00f6lker","sequence":"additional","affiliation":[{"name":"Interfaculty Institute for Genetics and Functional Genomics, Department Functional Genomics, Universit\u00e4tsmedizin Greifswald, Greifswald, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), partner site Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Endlich","sequence":"additional","affiliation":[{"name":"Institute for Anatomy and Cell Biology, Universit\u00e4tsmedizin Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8343-7336","authenticated-orcid":false,"given":"Andreas","family":"Greinacher","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine, Universit\u00e4tsmedizin Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"issue":"22","key":"ref1","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1056\/NEJMoa2104840","article-title":"Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination","volume":"384","author":"A Greinacher","year":"2021","journal-title":"N Engl J 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features of vaccine-induced immune thrombocytopenia and thrombosis","volume":"385","author":"S Pavord","year":"2021","journal-title":"N Engl J Med"},{"issue":"02","key":"ref6","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1182\/blood-2013-01-478966","article-title":"Complex formation with nucleic acids and aptamers alters the antigenic properties of platelet factor 4","volume":"122","author":"M E Jaax","year":"2013","journal-title":"Blood"},{"issue":"05","key":"ref7","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.jmoldx.2022.01.007","article-title":"Fragment size-based enrichment of viral sequences in plasma cell-free DNA","volume":"24","author":"Q Phung","year":"2022","journal-title":"J Mol Diagn"},{"issue":"11","key":"ref8","doi-asserted-by":"crossref","first-page":"2560","DOI":"10.1111\/ajt.17125","article-title":"Elevated cell-free DNA in respiratory viral infection and associated lung allograft dysfunction","volume":"22","author":"K Bazemore","year":"2022","journal-title":"Am J Transplant"},{"issue":"22","key":"ref9","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1182\/blood.2021013231","article-title":"Insights in ChAdOx1 nCoV-19 vaccine-induced immune thrombotic thrombocytopenia","volume":"138","author":"A Greinacher","year":"2021","journal-title":"Blood"},{"issue":"04","key":"ref10","doi-asserted-by":"crossref","first-page":"947","DOI":"10.3324\/haematol.2021.280154","article-title":"Comparative analysis of ChAdOx1 nCoV-19 and Ad26.COV2.S SARS-CoV-2 vector vaccines","volume":"107","author":"S Michalik","year":"2022","journal-title":"Haematologica"},{"issue":"06","key":"ref11","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1055\/s-0042-1758818","article-title":"Laboratory testing for heparin-induced thrombocytopenia and vaccine-induced immune thrombotic thrombocytopenia antibodies: a narrative review","volume":"49","author":"T E Warkentin","year":"2023","journal-title":"Semin Thromb 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Rep"},{"issue":"12","key":"ref18","doi-asserted-by":"crossref","first-page":"3532","DOI":"10.1016\/j.jtha.2024.08.019","article-title":"Assessment of antibodies against platelet factor 4 following vaccination with adenovirus type 26-vectored vaccines","volume":"22","author":"H Kristyanto","year":"2024","journal-title":"J Thromb Haemost"},{"issue":"04","key":"ref19","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1182\/blood.2023021307","article-title":"Characterization of reverse-engineered anti-PF4 stereotypic antibodies derived from serum of patients with VITT","volume":"143","author":"J J Wang","year":"2024","journal-title":"Blood"},{"issue":"09","key":"ref20","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1056\/NEJMoa2507175","article-title":"Monoclonal antibodies in the pathogenesis of heparin-induced thrombocytopenia","volume":"393","author":"J Treverton","year":"2025","journal-title":"N Engl J Med"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2736-5418.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T23:52:57Z","timestamp":1763077977000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2736-5418"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,3]]},"references-count":20,"URL":"https:\/\/doi.org\/10.1055\/a-2736-5418","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,11,3]]},"published":{"date-parts":[[2025,11,3]]}}}