A preservative, present in large amounts in the AstraZeneca vaccine, could cause the rare autoimmune reaction seen in cases of atypical thrombosis in some patients. But is the adenovirus used as the viral vector involved?
The AstraZeneca vaccine is suspected of causing severe thrombosis in very rare cases. But it is not yet clear what causes these atypical events. From what we know now, patients could have an autoimmune reaction against a platelet factor called PF4. There could be an aggregation of platelets at the level of capillaries, particularly in the brain, which would cause these atypical thromboses.
Adenoviruses which are used as viral vectors in the vaccines from AstraZeneca and Janssen carry a gene in the form of DNA that, from a chemical point of view, is very close to heparin. Heparin is known to bind to platelet factor PF4, which is then seen as a foreign object and triggers the autoimmune response.
The EDTA, Hypothesis
Paradoxically, other adenovirus vaccines, such as those for Ebola, do not seem to cause such effects. A team of researchers from the Medical University of Greifswald, Germany, has come up with a new hypothesis, outlined in a pre-published paper in Research Square.
The autoimmune reaction may not be due to the adenovirus itself, but to a commonly used substance called ethylenediaminetetraacetic acid (EDTA). The latter, which is used as a preservative in certain vaccines, is known to make blood vessels a bit leaky, says Andreas Greinacher, the study’s lead author. The AstraZeneca vaccine appears to contain much higher concentrations of this ingredient than other vaccines, Greinacher said. The researchers also found large doses of human cell proteins in the vaccine, probably from the human cell line used to make the virus.
The combination of these two factors may cause thrombosis. The EDTA-induced increase in vascular permeability promotes the proliferation of these proteins in the blood. “Any remaining proteins are likely to encounter platelets [thrombocytes] in the recipient’s bloodstream, with which they will form complexes in the presence of the PF4 factor,” describes Greinacher. In a very small minority of people, these PF4 complexes, combined with strong inflammation caused by the vaccine, could trigger the autoimmune reaction.
Higher levels of PF4 in some people
However, not everyone is convinced by this hypothesis. First of all, other vaccines contain cellular residues and it is not known whether AstraZeneca’s vaccine contains more or less of them. Also, the Janssen vaccine does not contain EDTA, but this too has been shown to be the cause of rare cases of thrombosis. “The adenovirus itself, given in large amounts, is probably enough on its own to cause an inflammatory response,” says Gowthami Arepally, a hematologist at Duke University School of Medicine who works as an outside consultant for AstraZeneca on this issue. “Some unlucky people have higher levels of PF4 for some unknown reason, and that’s why they form these complexes when they get the vaccine.”