German researchers believe cell nuclei misread adenovirus vectors, creating proteins that trigger clotting
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German researchers on Wednesday said that based on laboratory research, they believed they have found the cause of the rare but serious blood clotting events among some people who received COVID-19 vaccines made by AstraZeneca and Johnson & Johnson.
The researchers, in a study not yet reviewed by experts, said COVID-19 vaccines that employ adenovirus vectors — cold viruses used to deliver vaccine material — send some of their payload into the nucleus of cells, where some of the instructions for making coronavirus proteins can be misread. These mutant versions do not bind to the membrane where immunization takes place. Instead, these proteins are secreted into the body, where they can cause blood clots.
Scientists and U.S. and European drug regulators have been searching for an explanation for what is causing the rare but potentially deadly clots accompanied by low blood platelet counts, which have led some countries to halt or limit use of the AstraZeneca and J&J vaccines. Other scientists have suggested competing theories for the clotting condition.
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But Prof. Rolf Marschalek of Frankfurt’s Goethe University claims the issue can be fixed by modifying the spike protein to prevent it splitting.
“With the data we have in our hands we can tell the companies how to mutate these sequences, coding for the spike protein in a way that prevents unintended splice reactions,” he told the Financial Times. He said Johnson & Johnson had already been in contact with his lab about a potential fix but he had not spoken to AstraZeneca.
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Johnson & Johnson, in an emailed statement said: “We are supporting continued research and analysis of this rare event as we work with medical experts and global health authorities. We look forward to reviewing and sharing data as it becomes available.” AstraZeneca declined to comment.
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Researchers at the Goethe-University of Frankfurt and other sites explained in their paper that vaccines using a different technology known as messenger RNA (mRNA), such as those developed by BioNTech with partner Pfizer and Moderna, deliver the genetic material of the coronavirus spike protein only to fluid found inside cells, not to the nucleus of the cells. “All mRNA-based vaccines should represent safe products,” the paper said.
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The paper suggests that vaccine makers using adenovirus vectors could modify the sequence of the spike protein “to avoid unintended splice reactions and to increase the safety of these pharmaceutical products.”
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Another German study, led by Prof. Andreas Greinacher of Greifswald University Hospital, claimed the clots were being caused by EDTA, a chemical used as a preservative in the AstraZeneca vaccine. EDTA can cause cells in blood vessels to become “leaky,” causing platelets and proteins to flood through the body, triggering a massive immune reaction that can cause the blood clots.
“There is, in my opinion, rock-solid evidence,” Greinacher said in April.
EDTA is not listed as an ingredient in the Johnson & Johnson vaccine but Greinacher believes the phenomenon may be common to all vector vaccines.
A third German study, at Ulm University Medical Centre, claims unusually high levels of proteins in the AstraZeneca vaccine could be the problem.
— with additional reporting by The Daily Telegraph
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Cold viruses that are used to deliver COVID-19 vaccine linked to rare blood clot risk - National Post
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