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

Journal Article · · Science Advances
 [1];  [2];  [3];  [4];  [5];  [4];  [6];  [2];  [2];  [2];  [4];  [2];  [7];  [2];  [8];  [4];  [9];  [10];  [8];  [2] more »;  [4];  [8];  [4];  [2];  [11] « less
  1. Mayo Clinic, Scottsdale, AZ (United States); Mayo Clinic, Rochester, MN (United States); Mayo Clinic Cancer Center, Phoenix, AZ (United States); Arizona State Univ., Tempe, AZ (United States); Cardiff Univ. (United Kingdom); Mayo Clinic - Center for Individualized Medicine
  2. Arizona State Univ., Tempe, AZ (United States)
  3. Arizona State Univ., Tempe, AZ (United States); Michigan State Univ., East Lansing, MI (United States)
  4. Cardiff Univ. (United Kingdom)
  5. Univ. of Illinois, IL (United States)
  6. MRC-Univ. of Glasgow Centre for Virus Research (United Kingdom)
  7. Michigan State Univ., East Lansing, MI (United States)
  8. AstraZeneca, Gaithersburg, MD (United States)
  9. Mayo Clinic, Scottsdale, AZ (United States); Mayo Clinic, Rochester, MN (United States); Univ. of Arkansas for Medical Sciences, Little Rock, AR (United States)
  10. Univ. of Maryland School of Medicine, MD (United States)
  11. Mayo Clinic, Scottsdale, AZ (United States); Mayo Clinic, Rochester, MN (United States); Mayo Clinic Cancer Center, Phoenix, AZ (United States)
+ Show Author Affiliations

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.

Research Organization:
Michigan State Univ., East Lansing, MI (United States). MSU-DOE Plant Research Laboratory
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences & Biosciences Division
Grant/Contract Number:
FG02-91ER20021
OSTI ID:
1835546
Journal Information:
Science Advances, Journal Name: Science Advances Journal Issue: 49 Vol. 7; ISSN 2375-2548
Publisher:
AAASCopyright Statement
Country of Publication:
United States
Language:
English

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