Ixodes scapularis Tissue Factor Pathway Inhibitor

Ixodes scapularis is a blood-sucking tick and the principal vector of Lyme disease, a spirochetal illness caused by Borrelia burgdorferi and now the most common vector-borne infection in the United States; more than 50,000 cases have been reported during the last ten years. The salivary gland of I. scapularis has a number of pharmacologically active molecules that help the tick to successfully feed on blood, such as inhibitors of complement system, in addition to coagulation and platelet aggregation inhibitors. This invention describes Ixolaris, a protein that inhibits the initiation of blood coagulation by inhibition of components of the extrinsic pathway. Accordingly, Ixolaris blocks Factor X activation by Factor VIIa/TissueFactor, it attenuates Factor Xa production by the prothrombinase, and inhibits fibrin formation in a diluted prothrombin time. Ixolaris is highly specific since it does not inhibit other serine proteases. Because Ixolaris has anticoagulant properties, it could be used to ameliorate a number of clinical conditions such as disseminated intravascular coagulation, and hypercoagulation states. In addition, Ixolaris may be useful as a vaccine candidate for Lyme disease because inactivation of Ixolaris by antibodies may make transmission of Borrelia burgdorferi more difficult. In addition to the composition of Ixolaris, the invention claims vaccines utilizing Ixolaris, methods of stimulating an immune response, and methods of treatment of restenosis, arterial thrombosis, and stroke.