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Scientists explain the AstraZeneca vaccine’s rare clotting issue, and they might just have a remedy

Staff at CSL in Melbourne where the AstraZeneca vaccine is manufactured.

Staff at CSL in Melbourne where the AstraZeneca vaccine is manufactured. Photo: Getty

German scientists have reportedly discovered the cause of the rare blood clot syndrome that has bedevilled the AstraZeneca and Johnson & Johnson vaccine rollouts.

The vaccines have been linked to a small number of cases of ‘clotting with small platelets’ syndrome – known formally as ‘thrombosis with thrombocytopenia’.

The researchers believe their discovery opens up a path for tweaking the vaccine at the manufacturing stage and eliminating the problem.

This is the claim made by Dr Rolf Marschalekled, a professor of pharmaceutical biology at Goethe University in Frankfurt.

He told the Financial Times that Johnson & Johnson “had already contacted Marschalekled’s lab to ask for guidance”.

The reaction from the broader science world? Typical is this shrug from a Canadian virologist: “An interesting observation that should be explored but, at this time, nothing to hang my hat on”.

One sceptic said the research might have thrown up “a red herring”.

The new study is published as a pre-print and has not yet been peer reviewed.

So what’s the discovery?

The AstraZeneca and Johnson & Johnson vaccines use adenovirus vectors – made from the common cold virus – to deliver the genetic instructions for the spike protein of the Sars-Cov-2 virus into our cells.

It’s the delivery mechanism causing the problem.

The authors write: “The adenovirus life cycle includes the infection of cells.”

During this infection, some of the DNA gene sequences of the coronavirus spike protein enter the cell nucleus.

What happens there is the process of transcription, where the DNA of the vaccine is copied to RNA.

The RNA, in a process called translation, then copies the new proteins that are designed to protect us against the virus.

All of this works better in the cytosol fluid found inside the cell (and surrounds the nucleus the way the white of an egg surrounds the yolk).

Indeed, as the authors write, the vaccine DNA “is not optimised to be transcribed inside of the nucleus.”

The result are substandard proteins. Some of these split apart and float off as mutant fragments. It is these fragments that cause the clotting in about one in 100,000 people.

What does it mean for vaccine hesitancy?

The research gives hope that the risk of the clotting syndrome might be vanquished. That’s not going to happen overnight, but it’s certainly a step forward.

Until now, there’s only been an association between the vaccines and the clotting syndrome.

Initially, it was thought that the clotting was a coincidence.

That was ruled out when the syndrome wasn’t reported in vaccines using mRNA technology: the Pfizer and Moderna jabs.

This what’s called observational evidence.

Professor Marschalekled’s study at least takes the question forward because it provides the “first molecular evidence that adenovirus vector-based vaccines … exhibit a problem that is completely absent in mRNA-based vaccines.”

Meanwhile, following the clotting death of a 52-year-old woman, the Australian Technical Advisory Group on Immunisation changed its advice on the locally-made AstraZeneca vaccine.

It’s now recommended only for people 60 and older.

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