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    ChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndrome

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    Author
    Baker, Alexander T.
    Boyd, Ryan J.
    Sarkar, Daipayan
    Teijeira-Crespo, Alicia
    Chan, Chun Kit
    Bates, Emily
    Waraich, Kasim
    Vant, John
    Wilson, Eric
    Truong, Chloe D.
    Lipka-Lloyd, Magdalena
    Fromme, Petra
    Vermaas, Josh
    Williams, Dewight
    Machiesky, Lee Ann
    Heurich, Meike
    Nagalo, Bolni M.
    Coughlan, Lynda
    Umlauf, Scott
    Chiu, Po Lin
    Rizkallah, Pierre J.
    Cohen, Taylor S.
    Parker, Alan L.
    Singharoy, Abhishek
    Borad, Mitesh J.
    Show allShow less

    Date
    2021-12-01
    Journal
    Science Advances
    Publisher
    American Association for the Advancement of Science
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1126/sciadv.abl8213
    Abstract
    Vaccines 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;
    Keyword
    ChAdOx1
    HAdV-D26
    HAdV-C5
    thrombosis with thrombocytopenia syndrome (TTS)
    Platelet Factor 4--adverse effects
    SARS-CoV-2
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/17364
    ae974a485f413a2113503eed53cd6c53
    10.1126/sciadv.abl8213
    Scopus Count
    Collections
    UMB Coronavirus Publications
    UMB Open Access Articles

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