Researchers led by Flinders University have identified the molecular trigger behind a rare blood clotting disorder linked to adenovirus-based COVID-19 vaccines and infections. The immune system mistakes an adenovirus protein for the human blood protein PF4, leading to harmful antibodies in extremely rare cases. The discovery, detailed in the New England Journal of Medicine, paves the way for safer vaccines.
A team from Flinders University in Australia, collaborating with scientists from Greifswald University in Germany and McMaster University in Canada, revealed that the immune system can confuse a specific adenovirus protein with platelet factor 4 (PF4). This mix-up prompts the production of antibodies that trigger clotting, known as vaccine-induced immune thrombocytopenia and thrombosis (VITT). The condition first emerged in 2021 after adenovirus vector vaccines like Oxford-AstraZeneca were deployed widely, including in Australia, and has also appeared following natural adenovirus infections, such as the common cold, with some fatal outcomes reported by Professor Ted Warkentin in 2023. Antibodies from both vaccine and infection cases proved indistinguishable in a 2024 study, pinpointing the adenovirus protein itself as the culprit rather than vaccine additives. Dr. Jing Jing Wang of Flinders University highlighted the breakthrough's potential. > By modifying or removing this specific adenovirus protein, future vaccines can avoid this extremely rare reaction while continuing to provide strong protection against disease. The researchers employed mass spectrometry to confirm molecular mimicry between the adenovirus protein—specifically pVII—and PF4, building on prior work decoding the PF4 antibody structure in 2022 and identifying a genetic risk factor. Professor Tom Gordon, Head of Immunology at SA Pathology, described the effort as a 'fascinating journey' with an international team, culminating in three New England Journal of Medicine publications. Immunologist Professor James McCluskey from the University of Melbourne praised it as 'brilliant molecular sleuthing' that unravels how a normal immune response turns pathogenic. With this insight, developers can tweak the pVII protein to eliminate the risk, enhancing safety for adenovirus-based vaccines crucial in disease prevention worldwide.
