This article is more than 5 years old. Information may no longer be current.
Factor XI vaccination may help prevent thrombosis
Click Here to Manage Email Alerts
A novel coagulation Factor XI vaccine may serve as a promising strategy in the prevention of thromboembolic diseases, according to a report published in Journal of Thrombosis and Haemostasis.
“We have demonstrated that vaccination against Factor XI is an effective strategy for inhibiting plasma Factor XI activity in vivo,” C. H. Zhong, researcher at Shanghai Jiao Tong University, and colleagues wrote. “Our data suggest that a modest reduction in plasma Factor XI activity is sufficient to inhibit coagulation initiated both in vitro and in vivo, which is consistent with the result from the cynomolgus monkey study.”
Thromboembolic diseases, such as myocardial infarction, stroke and venous thromboembolism, are the leading causes of morbidity and mortality in high-income and middle-income countries. For years, anticoagulants such as molecular-weight heparin, vitamin K antagonists, and activated Factor X and thrombin inhibitors have been a mainstay for the treatment of thromboembolic diseases. However, those drugs carry a high risk for substantial bleeding, including intracranial hemorrhage and gastrointestinal bleeding.
Researchers hoped that by blocking Factor XI with monoclonal antibodies or small-molecule inhibitors, they could design a Factor XI vaccine and assess its efficacy in inhibiting Factor XI activity and preventing thrombosis.
Zhong and colleagues generated a Factor XI antigen by fusing the catalytic domain of human Factor XI to the C-terminus of the transmembrane domain of diphtheria toxin. They then examined the anti–Factor XI antibody response, plasma Factor XI activity and antithrombotic efficacy in models immunized with the Factor XI antigen.
The antigen elicited a significant antibody response against Factor XI, and reduced the plasma Factor XI activity by 54%. Factor XI vaccination markedly reduced the levels of coagulation and inflammation in a model of inferior vena cava stenosis.
Researchers also observed significant protective effects in models of VTE and pulmonary embolism.
Researchers noted that a Factor XI vaccine in humans could serve as long-term anticoagulation therapy because the administration frequency may be lower than a few times per year, which permits “reasonable patient convenience and compliance.” However, because the vaccine requires a week before immune onset, it would not be suitable for emergency treatment.
“[The] vaccine is better suited for chronic indications, such as stroke prevention, in atrial fibrillation patients, and secondary prevention in patients with unprovoked venous thromboembolism,” Zhong and colleagues wrote. – by Chuck Gormley
Disclosure: Researchers report no relevant financial disclosures.
Click Here to Manage Email Alerts