Flinders University researchers, in collaboration with international experts, have discovered that the PF4 antibodies that cause VITT after adenovirus vector-based COVID-19 vaccination share an identical molecular signature to those seen in similar cases after natural adenovirus infection. Using a novel approach developed at Flinders University, the findings have important implications for understanding genetic risk factors and improving future vaccine development.
A new study shows that the dangerous PF4 antibodies involved in vaccine-induced thrombosis (VITT) and a similar disease caused by common cold infection share an identical molecular structure, highlighting implications for future vaccine development and disease management.
New research conducted by Flinders University and international experts is adding to our knowledge of Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT). COVID-19 In the 2021 pandemic, VITT was recognized as a new symptom associated with adenovirus vector-based vaccines, particularly the Oxford-AstraZeneca vaccine.
VITT was found to be caused by a highly dangerous blood autoantibody that targets a protein called platelet factor 4 (PF4). In another study in 2023, researchers from Canada, North America, Germany and Italy described a virtually identical disease caused by the same PF4 antibodies, which in some cases was fatal after a natural adenovirus (common cold) infection.
Flinders University Researcher Dr Jing-Jing Wang and Professor Tom Gordon of Flinders University, head of immunology at SA Pathology in South Australia, said: led previous research In 2022, we decoded the molecular code for the PF4 antibody and identified a genetic risk factor associated with the antibody gene called IGLV3.21*02.
Flinders University immunology researchers Dr Jing-Jing Wang and Professor Tom Gordon. Photo courtesy of the Flinders Foundation.
Joint efforts and future implications
Now, the Flinders research group has collaborated with this international group of researchers and discovered that the PF4 antibodies for both adenovirus infection-associated VITT and traditional adenovirus-vectored VITT share the same molecular fingerprint, or signature.
The research may also have implications for improving vaccine development, says Dr Wang, a Flinders University researcher who is first author of the new paper published in a leading journal. New England Journal of Medicine.
“These discoveries, using an entirely new approach to target blood antibodies developed at Flinders University, virus Professor Gordon will explain the “vaccine construct that activates pathological pF4 antibodies.”
“Indeed, the pathways leading to lethal antibody production in these diseases are virtually identical, and the genetic risk factors should be similar. Our findings have important clinical implications in that lessons learned from VITT can be applied to rare cases of blood clotting after adenovirus (common cold) infection, with implications for vaccine development,” he says.
Reference: “Antibody Fingerprint Links Adenovirus Anti-PF4 Disease” by Jing-Jing Wang, Linda Schonborn, Theodore E. Warkentin, Tim Chataway, Leonie Gross, Paolo Simioni, Stefan Mol, Andreas Greinacher, and Tom P. Gordon, May 15, 2024; New England Journal of Medicine.
Publication date: 10.1056/NEJMc2402592
This research was supported by a service contract from the Deutsche Forschungsgemeinschaft and the European Medicines Agency. Dr. Schönborn was supported by an ASH Global Research Award from the American Society of Hematology and the Gerhard Domagk Research Program at the Medical University of Greifswald. Dr. Wang was supported by a Health Seed Grant from the Flinders Foundation.
