Study Finds Key Link In Rare Blood Disease

New research led by Flinders University and international experts is expanding understanding of vaccine-induced immune thrombocytopenia and thrombosis (known as VITT).At the height of the COVID-19 pandemic in 2021,VITT emerged as a new disease following adenovirus vector-based vaccines – notably the Oxford-AstraZeneca vaccine, used in Australia.

VITT was found to be caused by an unusually dangerous blood autoantibody directed against a protein termed platelet factor 4 (or PF4).

Flinders University researchers Dr Jing Jing Wang and Professor Tom Gordon, Head of Immunology at SA Pathology.

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 which cracked the molecular code of the PF4 antibody and identified a genetic risk factor related to an antibody gene termed IGLV3.21*02.

Now, the Flinders group has collaborated with this international group of researchers to find that the PF4 antibodies in both adenovirus 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, first author on the new article just 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.

Key points:

  • The anti-PF4 antibodies found in vaccine-induced immune thrombocytopenia and thrombosis (VITT) and in the adenovirus VITT-like disorder share essentially identical molecular signatures (or ‘fingerprints’).
  • The findings have important clinical implication that the lessons learned from VITT are applicable to adenovirus anti-PF4 disorders.
  • The findings also have important implications for improving vaccine safety.
The original research letter, Correspondence entitled ‘Antibody Fingerprints Linking Adenoviral Anti-PF4 Disorders‘ (2024), by Jing Jing Wang (Flinders University), Linda Schönborn (Greifswald University Hospital, Germany), Theodore E Warkentin (McMaster University, Canada), Tim Chataway (Flinders University), Leonie Grosse (Ludwig Maximilians University, Germany), Paolo Simioni (Padova University Hospital, Italy), Stephan Moll (University of North Carolina School of Medicine, US), Andreas Greinacher (Greifswald University Hospital) and Tom P Gordon (SA Pathology, South Australia) will be published in the New England Journal of Medicine. DOI: 10.1056/NEJMc2402592
Acknowledgements: 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.
Disclaimer: The views expressed in this letter are those of the authors and do not necessarily represent the position of the European Medicines Agency.

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