No medical intervention is without risk, and vaccination is no exception. The AstraZeneca adenovirus vaccine was prominently in the news earlier this year after being linked to extremely rare cases of blood clots. The company, together with researchers in Wales and the US, believe they have now discovered part of the reason why.
As reported in Science Advances, the scientists looked at how the viral vector – adapted from a chimpanzee adenovirus similar to the cold virus – interacts with the human body. They found that in some rare cases, the virus interacts and binds to a protein in the blood, platelet factor 4 (PF4), as was originally suspected. The interaction is seen as a foreign body by our immune system, which then releases antibodies against PF4.
The antibodies, in turn, can bind to platelets, causing them to clump together. This might lead to the formation of blood clots in very few cases.
This series of events could explain the few hundred cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), among the tens of millions of people vaccinated with an adenovirus COVID-19 vaccine, such as AstraZeneca or Johnson & Johnson.
“VITT only happens in extremely rare cases because a chain of complex events needs to take place to trigger this ultra-rare side effect. Our data confirms PF4 can bind to adenoviruses, an important step in unravelling the mechanism underlying VITT,” senior author Professor Alan Parker, from the University of Cardiff, said in a statement.
“Although very rare, it is critical we fully investigate vector-host interactions of the vaccine at a mechanistic level to help us understand both how the vaccine generates immunity – and how it may lead to any rare adverse events, such as VITT. Establishing a mechanism could help to prevent and treat this disorder.”
The team discovered that the adenovirus, technically known as ChAdOx1, has a strong negative charge that attracts the positively charged PF4, which unfortunately can bind to the virus surface leading to these ultra-rare events.
“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,” lead author Dr Alexander Baker explained.
The risk from COVID-19 in terms of short and long-term illness, as well as death, far outweigh the risk from the vaccines. Also, COVID is far more likely to cause blood clots than these vaccines. That said, studies such as these show how we can minimize the risk of the vaccines even further.