Camilla Jessen
Scientists say they have uncovered why a small number of people developed a rare blood clotting condition after receiving certain COVID-19 vaccines.
Researchers say they have uncovered the likely mechanism behind a rare blood clotting condition linked to certain COVID-19 vaccines used earlier in the pandemic.
The condition, known as vaccine-induced immune thrombocytopenia and thrombosis (VITT), was reported in a small number of people who received adenoviral vector vaccines.
What is VITT?
VITT is a rare disorder in which the immune system produces antibodies that activate platelets, leading to potentially dangerous blood clots.
These antibodies mistakenly target a protein called platelet factor 4 (PF4), triggering clot formation. While doctors identified the condition during the vaccine rollout, the precise biological trigger had remained unclear.
New findings
A team at Flinders University in Australia says it has identified a possible explanation.
In a study published in the New England Journal of Medicine, researchers found that VITT may occur in people who carry a specific antibody gene variant known as IGLV3-2102 (also referred to as IGLV3-21*02 or 03).
According to the researchers, individuals with this genetic variant may produce antibodies that react to a protein in the adenovirus vector used in some vaccines. In rare cases, this immune response may “misfire” and also target PF4.
“By modifying or removing this specific adenovirus protein, future vaccines can avoid this extremely rare reaction while continuing to provide strong protection against disease,” said Dr Jing Jing Wang of Flinders University.
“A novel aspect of the paper was our use of powerful mass spectrometry sequencing to identify molecular mimicry between the adenovirus vector protein and the PF4 culprit target,” she added. “This was the missing link that explains how a normal immune response can, in very rare cases, become harmful.”
Expert reaction
Immunologist Professor James McCluskey from the University of Melbourne described the findings as “a brilliant piece of molecular sleuthing.”
“The culmination of a body of work that unravels the genetic and structural basis for how a normal immune response to a virus protein leads to pathogenic autoimmunity,” he said.
Professor Tom Gordon said the research marked “a fascinating journey with an outstanding international team of collaborators to complete a trilogy of publications in the New England Journal of Medicine to solve the mystery of this new group of blood clotting disorders, and potentially translate our discoveries into safer vaccines.”
What remains unclear
Researchers caution that the findings do not prove this is the only pathway that can lead to VITT. The study also does not provide a way to fully predict who might develop the condition.
Health authorities have consistently emphasised that VITT is extremely rare, and that the benefits of COVID-19 vaccination in preventing severe illness and death far outweighed the risks.
The new findings may help guide the design of future vaccines to further reduce the likelihood of such rare adverse reactions.
Source: Flinders University; New England Journal of Medicine
