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dc.contributor.authorBaker, Alexander T.
dc.contributor.authorBoyd, Ryan J.
dc.contributor.authorSarkar, Daipayan
dc.contributor.authorTeijeira-Crespo, Alicia
dc.contributor.authorChan, Chun Kit
dc.contributor.authorBates, Emily
dc.contributor.authorWaraich, Kasim
dc.contributor.authorVant, John
dc.contributor.authorWilson, Eric
dc.contributor.authorTruong, Chloe D.
dc.contributor.authorLipka-Lloyd, Magdalena
dc.contributor.authorFromme, Petra
dc.contributor.authorVermaas, Josh
dc.contributor.authorWilliams, Dewight
dc.contributor.authorMachiesky, Lee Ann
dc.contributor.authorHeurich, Meike
dc.contributor.authorNagalo, Bolni M.
dc.contributor.authorCoughlan, Lynda
dc.contributor.authorUmlauf, Scott
dc.contributor.authorChiu, Po Lin
dc.contributor.authorRizkallah, Pierre J.
dc.contributor.authorCohen, Taylor S.
dc.contributor.authorParker, Alan L.
dc.contributor.authorSingharoy, Abhishek
dc.contributor.authorBorad, Mitesh J.
dc.date.accessioned2021-12-13T17:59:02Z
dc.date.available2021-12-13T17:59:02Z
dc.date.issued2021-12-01
dc.identifier.urihttp://hdl.handle.net/10713/17364
dc.description.abstractVaccines derived from chimpanzee adenovirus Y25 (ChAdOx1), human adenovirus type 26 (HAdV-D26), and human adenovirus type 5 (HAdV-C5) are critical in combatting the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic. As part of the largest vaccination campaign in history, ultrarare side effects not seen in phase 3 trials, including thrombosis with thrombocytopenia syndrome (TTS), a rare condition resembling heparin-induced thrombocytopenia (HIT), have been observed. This study demonstrates that all three adenoviruses deployed as vaccination vectors versus SARS-CoV-2 bind to platelet factor 4 (PF4), a protein implicated in the pathogenesis of HIT. We have determined the structure of the ChAdOx1 viral vector and used it in state-of-the-art computational simulations to demonstrate an electrostatic interaction mechanism with PF4, which was confirmed experimentally by surface plasmon resonance. These data confirm that PF4 is capable of forming stable complexes with clinically relevant adenoviruses, an important step in unraveling the mechanisms underlying TTS. Copyright © 2021 The Authors, some rights reserved;en_US
dc.description.urihttps://doi.org/10.1126/sciadv.abl8213en_US
dc.language.isoenen_US
dc.publisherAmerican Association for the Advancement of Scienceen_US
dc.relation.ispartofScience Advancesen_US
dc.subjectChAdOx1en_US
dc.subjectHAdV-D26en_US
dc.subjectHAdV-C5en_US
dc.subjectthrombosis with thrombocytopenia syndrome (TTS)en_US
dc.subject.meshPlatelet Factor 4--adverse effectsen_US
dc.subject.meshSARS-CoV-2en_US
dc.titleChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndromeen_US
dc.typeArticleen_US
dc.identifier.doi10.1126/sciadv.abl8213
dc.source.volume7
dc.source.issue49


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