Even so, the researchers behind the new preprint study say they hope their theory could eventually help laboratories adapt the AstraZeneca-Oxford and Johnson & Johnson vaccines to increase safety and potentially boost global vaccination efforts.
Though uncommon, vaccine-induced immune thrombotic thrombocytopenia (VITT) is much more severe than a typical blood clot because it can cause cerebral venous sinus thrombosis (CVST), where veins that drain blood from the brain are obstructed and can potentially cause fatal bleeding.
The German researchers suggest the problem lies within the delivery system of these two similar vaccines, both of which use adenovirus vector technology to send genetic instructions into cells to produce the spike protein of the coronavirus.
The findings, which were published online on Wednesday and have not yet been peer reviewed, note this type of vaccine sends the DNA gene sequence of the spike protein directly into the nucleus of the cell, at which point certain parts of the spike protein DNA may become spliced, or broken apart.
The study, based on the team's own lab work involving experiments with the commonly-used HeLa human cell line, suggests these "undesirable" breakdowns can cause mutations to occur within the spike protein DNA, which could make it tougher for those proteins to bond to the cell, allowing them to secrete into the body and potentially trigger "inflammatory reactions" that can result in the rare blood clots.
The researchers suspect three steps are at play: The rogue spike proteins flowing through the bloodstream, combined with the newly built antibodies designed to attack them, plus the highly specific blood flow conditions in veins that drain from the brain, "may result in the rare but severe events after vaccination," the team wrote.
The Public Health Agency of Canada (PHAC) now estimates the rate of VITT in Canadians who have received the AstraZeneca vaccine is between 1 in 83,000 and 1 in 55,000, with a fatality rate of between 20 and 50 per cent, but that is subject to change as more data emerges.
PHAC said in a statement to CBC News Thursday there have been 27 confirmed cases of VITT to date in Canada out of two million doses administered, with five deaths among those cases.
Problem 'absent' in mRNA vaccines
The researchers say their study offers the "first molecular evidence" that adenovirus vector-based vaccines that encode the spike protein "exhibit a problem that is completely absent in mRNA-based vaccines," such as Pfizer-BioNTech and Moderna.
"The adenoviral vaccines are delivering their complete DNA (including the gene for the antigen) to the nucleus, where transcription is taking place," Prof. Rolf Marschalek, a professor of pharmaceutical biology at Goethe University in Frankfurt and lead author of the study, said in an email to CBC News. "Transcription means to make RNA copies from the DNA."
Marschalek says the RNA is then spliced into pieces that encode smaller protein variants when derived outside of the nucleus to the cytosol of the cell. He says his team has identified the "splice products" in experiments in "relevant amounts," so they are significant.
