Researchers from Flinders University, along with international experts, have discovered that the PF4 antibodies causing VITT after adenovirus vector-based COVID-19 vaccination share identical molecular signatures with those found in similar cases following natural adenovirus infection. This finding, using a new approach developed at Flinders, has significant implications for understanding the genetic risk factors and improving future vaccine development.
New research has shown that the dangerous PF4 antibodies involved in vaccine-induced thrombosis (VITT) and similar disorders from common cold infections share identical molecular structures, highlighting implications for future vaccine development and disease management.
New research conducted by Flinders University and global specialists is deepening our knowledge of vaccine-induced immune thrombocytopenia and thrombosis (VITT). During the peak of the COVID-19 pandemic in 2021, VITT was recognized as a new condition linked to adenovirus vector-based vaccines, particularly the Oxford-AstraZeneca vaccine.
VITT was found to be caused by an unusually dangerous blood autoantibody directed against a protein termed platelet factor 4 (or PF4). In separate research in 2023, researchers from Canada, North America, Germany, and Italy described a virtually identical disorder with the same PF4 antibody that was fatal in some cases after natural adenovirus (common cold) infection.
Flinders University researchers Dr. Jing Jing Wang and Flinders Professor Tom Gordon, Head of Immunology at SA Pathology in South Australia, led a previous study in 2022 that cracked the molecular code of the PF4 antibody and identified a genetic risk factor related to an antibody gene termed IGLV3.21*02.
Flinders University immunology researchers Dr. Jing Jing Wang and Professor Tom Gordon. Credit: Flinders Foundation
Collaborative Efforts and Future Implications
Now, the Flinders group has collaborated with this international group of researchers to find that the PF4 antibodies in both adenoviruses infection-associated VITT and classic adenoviral vectored VITT share identical molecular fingerprints or signatures.
The research will also have implications for improving vaccine development, says Flinders University researcher Dr. Wang, the first author on the new article that was published in the eminent New England Journal of Medicine.
“These findings, using a completely new approach for targeting blood antibodies developed at Flinders University, indicate a common triggering factor on virus and vaccine structures that initiates the pathological pF4 antibodies,” explains Professor Gordon.
“Indeed, the pathways of lethal antibody production in these disorders must be virtually identical and have similar genetic risk factors. Our findings have the important clinical implication that lessons learned from VITT are applicable to rare cases of blood clotting after adenovirus (a common cold) infections, as well as having implications for vaccine development,” he says.
Reference: “Antibody Fingerprints Linking Adenoviral Anti-PF4 Disorders” by Jing Jing Wang, Linda Schönborn, Theodore E. Warkentin, Tim Chataway, Leonie Grosse, Paolo Simioni, Stephan Moll, Andreas Greinacher and Tom P. Gordon, 15 May 2024, New England Journal of Medicine.
DOI: 10.1056/NEJMc2402592
The research was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft) and a European Medicines Agency service contract. Dr. Schönborn was supported by the ASH Global Research Award from the American Society of Hematology and by the Gerhard Domagk Research Program through the Medical University of Greifswald. Dr. Wang was supported by a Flinders Foundation Health Seed Grant.
