Vaccines derived from chimpanzee adenovirus Y25 (ChAdOx1), human adenovirus type 26 (HAdV-D26) and human adenovirus type 5 (HAdV-C5) are critical in combating the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic.
A new study published in the journal Science Advances by an international team of scientists believe they may have found the molecular mechanism that causes extremely rare blood clots linked to these types of vector vaccines.
The scientists from Cardiff University and Arizona State University worked with AstraZeneca to investigate vaccine-induced immune thrombotic thrombocytopenia (VITT), also known as thrombosis with thrombocytopenia syndrome (TTS), which is a life-threatening condition seen in a very small number of people after receiving the Oxford-AstraZeneca or Janssen vaccines.
They found that it is the viral vector (adenovirus in this case) that binds to platelet factor 4 (PF4) once injected that could be the potential mechanism behind the thrombosis with thrombocytopenia syndrome.
They said that in very rare cases, the viral vector could enter the bloodstream and bind to PF4, forming a complex, which is then recognized as foreign by the immune system. They believe that this could result in the release of antibodies against PF4 that binds to and activate platelets, triggering blood clots in a very small number of people.
The team used computational models to show that one of the ways the two molecules tightly bind is via electrostatic interactions.
The researchers hope their findings can be used to better understand the rare side effects of these new vaccines, and potentially design new and improved vaccines in the future.
“With a better understanding of the mechanism by which PF4 and adenoviruses interact there is an opportunity to engineer the capsid, or outer shell of the vaccine, to prevent this interaction occurring. Modifying ChAdOx1 to reduce electronegativity may reduce the chance of causing thrombosis with thrombocytopenia syndrome,” said Dr Baker, one of the authors of the article.
Alexander T. Baker, et al. ChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndrome. Science Advances. Dec 2021• Vol 7, Issue 49. DOI: 10.1126/sciadv.abl8213