Abstract
Background Coagulation factor XI serves as a signal amplifier in the intrinsic coagulation pathway. Blockade of FXI by mAbs or small-molecule inhibitors inhibits thrombosis without causing severe bleeding, which is an inherent risk of currently available antithrombotic agents. Objectives To design an FXI vaccine and assess its efficacy in inhibiting FXI activity and preventing thrombosis. Methods An FXI antigen was generated by fusing the catalytic domain of human FXI to the C-terminus of the transmembrane domain of diphtheria toxin. The anti-FXI antibody response, plasma FXI activity and antithrombotic efficacy in mice immunized with the FXI antigen were examined. Results The antigen elicited a significant antibody response against mouse FXI, and reduced the plasma FXI activity by 54.0% in mice. FXI vaccination markedly reduced the levels of coagulation and inflammation in a mouse model of inferior vena cava stenosis. Significant protective effects were also observed in mouse models of venous thrombosis and pulmonary embolism. Conclusions Our data demonstrate that FXI vaccination can serve as an effective strategy for thrombosis prevention.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.