Hybrid Antigenic Peptides as a Potential Trigger of Autoimmunity in Vaccine-Induced Immune Thrombotic Thrombocytopenia

My research looks into a rare condition known as Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT). VITT occurs when the immune system mistakenly attacks the body's own platelets, leading to dangerous blood clot formation. VITT has been observed at a very low frequency in the general population, particularly following immunization with adenoviral vector-based vaccines against COVID-19. A key player in VITT is PF4, a blood clotting-associated host protein, which can form complexes with a vaccine protein called hexon. In a very small proportion of the population, vaccination can trigger the formation of antibodies against PF4, leading to blood clot formation. However, the immune mechanisms that allow the production of these antibodies have currently not been elucidated. My research hypothesis proposes that immune cells process PF4 and hexon together, creating hybrid protein fragments. In a subset of the population, these fragments might confuse the immune system and induce an undesired immune response against host PF4, leading to VITT. This concept has precedence in other autoimmune disease models like Type 1 diabetes. My research involves in vitro experiments and mouse studies. Initially, we aim to identify hybrid fragments between hexon and PF4 in test tube reactions and human immune cells. Subsequently, we want to determine if synthetic hybrid fragments can induce a VITT-like reaction in mice. These experiments aim to elucidate VITT's origins and shed light on other autoimmune diseases. Future work may expand this to other viral components, broadening our understanding of autoimmune diseases arising from infections. Ultimately, this research might offer a new perspective on autoimmunity, showcasing how the immune system can confuse self and foreign proteins.