ChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndrome
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.
Date
2021-12-01Journal
Science AdvancesPublisher
American Association for the Advancement of ScienceType
Article
Metadata
Show full item recordAbstract
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
ChAdOx1HAdV-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/10713/17364ae974a485f413a2113503eed53cd6c53
10.1126/sciadv.abl8213