Co-author Rongxiu Li, PhD, professor of bioengineering at the Shanghai Jiao Tong University Biology Manufacturing Research Center: “Therapeutic vaccines for thrombotic diseases are an obvious option. We designed the factor XI (FXI)-targeting vaccine hoping for long-term protection for people at high risk for thrombosis by reducing the blood clot formation. The FXI vaccine has been demonstrated to be an effective strategy for inhibiting plasma FXI activity in vivo and protecting against thrombosis in mice models. Compared with other inhibitors, FXI vaccine provides several benefits for patients requiring long-term anticoagulation therapy, including a lower therapeutic burden. The sustained efficacy of vaccination reduces administration frequency to a few times per year, which permits reasonable patient convenience and compliance.”
Anticoagulation is a mainstay of treatment for patients with thromboembolic diseases; however, these agents increase bleeding risk. Results from a mouse study published in the Journal of Thrombosis and Haemostasis suggest that coagulation factor XI (FXI) could serve as a safer target for antithrombotic therapies.
Because coagulation FXI serves as a signal amplifier in the intrinsic coagulation pathway, Conghao Zhong, PhD graduate at School of Life Sciences and Biotechnology at the Shanghai Jiao Tong University in China, and co-authors explained, they developed a FXI vaccination (consisting of an antigen comprising the human FXI catalytic domain and diphtheria toxin T domain) that inhibited FXI and prevented thrombosis.
Male mice received the vaccine via subcutaneous injection of 60 μg of antigen delivered in 200 μL of the antigen-adjuvant preparation, and two boosters administered at 2-week intervals. A control group received T domain of diphtheria toxin alone.
Blood samples were collected 1 week after the final booster, and the researchers evaluated anti-FXI antibody response, plasma FXI activity, and antithrombotic efficacy (measured by activated partial thromboplastin time [aPTT]).
In mouse models of inferior vena cava stenosis and pulmonary embolism, the antigen elicited a significant antibody response and reduced plasma FXI activity by 54 percent. The aPTT ratio also increased by 22.4 percent in those receiving the vaccination, compared with controls, “indicating down-regulation of the intrinsic coagulation pathway,” the authors wrote. “Our data demonstrate that [an] FXI vaccine can be used as an effective prophylactic agent against thrombosis.”
The study is limited in that it has not yet been assessed in humans. In addition, the authors noted, a vaccine is not suitable for all patient cases, particularly those in need of emergency treatment. “The vaccination against FXI is a promising strategy for thrombosis prevention,” co-author Rongxiu Li, PhD, told ASH Clinical News, “and it is better suited for chronic indications such as stroke prevention in atrial fibrillation patients and secondary prevention in patients with unprovoked venous thromboembolism.”
Source: Zhong C, Zhang L, Chen L, et al. Coagulation factor XI vaccination: an alternative strategy to prevent thrombosis. J Thromb Haemost. 2017;15:122-30.