An autoimmune reaction, to which some people are predisposed, was responsible for the rare but deadly blood clots associated with the Johnson & Johnson and AstraZeneca Covid-19 vaccines, suggest scientists in a discovery they believe will shape the development of future research.
Adenovirus-based vaccines, like the J&J and AstraZeneca shots that were later withdrawn, contain a component that in genetically susceptible people, can be the catalyst for the production of unusually structured antibodies against a protein involved in blood clotting, the scientists wrote in a letter to the New England Journal of Medicine.
They plan to identify the culprit and then try to remove it using genetic engineering, reports TIME.
An extremely similar deleterious antibody response occurs in susceptible patients after infection with adenoviruses, which often infect the airways and lead to cold-like symptoms, they found.
It’s not known how many people may be susceptible to the complication, said Tom Gordon, head of immunology at Flinders University in South Australia, whose molecular sleuthing led to the finding.
The immune reaction linked to the shot is “a new disease”, he said, adding that haematologists and intensive care specialists are likely to spot more cases as they become familiar with it.
“It’s a kind of autoimmunity where we know the trigger,” said immunologist James McCluskey, assistant vice-chancellor of the University of Melbourne, who wasn’t involved in the research. “That’s unusual. In most cases we never get a handle on the trigger.”
Vaccines withdrawn
Out of more than 18m people who received the single-dose J&J vaccine, 60 cases of the clotting disorder were reported and nine people died, according to the Yale School of Medicine.
A small number of clot-related deaths tied to the AstraZeneca vaccine led to its withdrawal or restriction in Denmark, Norway and other countries in 2021. The complication occurred in about two or three people per 100 000 vaccinated with the Astra shot under the age of 60 in Australia, where it hasn’t been available since March 2023.
The European Commission withdrew the marketing authorisation for the immunisation in March 2024, with AstraZeneca announcing at the beginning of May that it had ended production of the vaccine.
Both shots played an important role in vaccine programmes during the early stages of the pandemic. One analysis found the AstraZeneca vaccine saved an estimated 6.3m lives in 2021.
The mRNA vaccines made by the Pfizer-BioNTech partnership and Moderna were later found to be more effective at protecting against Covid and have been updated to tackle more recent virus variants.
NEJM article – Antibody Fingerprints Linking Adenoviral Anti-PF4 Disorders (Open access
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