Mary Wilson
Well-known member
Published December 1 2021
Baker et al., Sci. Adv. 7, eabl8213 (2021) 1
Alexander T. Baker1,2,3,4,5,6*†, Ryan J. Boyd5,7†, Daipayan Sarkar7,8,9‡, Alicia Teijeira-Crespo6‡,Chun Kit Chan10‡, Emily Bates6, Kasim Waraich11, John Vant5,7, Eric Wilson5,7, Chloe D. Truong5,7,Magdalena Lipka-Lloyd12, Petra Fromme5,7, Josh Vermaas8,9, Dewight Williams13,LeeAnn Machiesky14, Meike Heurich15, Bolni M. Nagalo1,2,4§, Lynda Coughlan16,17,Scott Umlauf14, Po-Lin Chiu5,7, Pierre J. Rizkallah18, Taylor S. Cohen19*, Alan L. Parker6*,Abhishek Singharoy5,7*, Mitesh J. Borad1,2,3,4*
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.
https://www.science.org/doi/epdf/10...6472541199F70A4C98A6%40AdobeOrg|TS=1638455380
Baker et al., Sci. Adv. 7, eabl8213 (2021) 1
Alexander T. Baker1,2,3,4,5,6*†, Ryan J. Boyd5,7†, Daipayan Sarkar7,8,9‡, Alicia Teijeira-Crespo6‡,Chun Kit Chan10‡, Emily Bates6, Kasim Waraich11, John Vant5,7, Eric Wilson5,7, Chloe D. Truong5,7,Magdalena Lipka-Lloyd12, Petra Fromme5,7, Josh Vermaas8,9, Dewight Williams13,LeeAnn Machiesky14, Meike Heurich15, Bolni M. Nagalo1,2,4§, Lynda Coughlan16,17,Scott Umlauf14, Po-Lin Chiu5,7, Pierre J. Rizkallah18, Taylor S. Cohen19*, Alan L. Parker6*,Abhishek Singharoy5,7*, Mitesh J. Borad1,2,3,4*
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.
https://www.science.org/doi/epdf/10...6472541199F70A4C98A6%40AdobeOrg|TS=1638455380
