Related Experiment Video
Updated: Aug 7, 2026
Murine Model of Epicutaneously-Induced Immunomodulation
Published on: June 24, 2025
Induction of partial immune tolerance to factor VIII through prior mucosal exposure to the factor VIII C2 domain
F E Rawle1, K P Pratt, A Labelle
1Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
Background:
The development of anti-factor VIII (FVIII) neutralizing antibodies (inhibitors) is a significant obstacle to FVIII replacement therapy.
Objective:
As mucosal administration of an antigen may induce immune tolerance we have evaluated the efficacy of mucosal antigen exposure to achieve tolerance to FVIII.
Methods:
We investigated the effects of oral and nasal administration of the purified FVIII C2 domain (FVIII-C2) to FVIII-deficient BALB/c mice prior to FVIII protein challenge. Mice received oral or nasal doses of FVIII-C2, followed by a subcutaneous challenge of either FVIII-C2 or FVIII. The development of anti-FVIII inhibitors, cytokine production by splenocytes in vitro, and adoptive transfer assays were analyzed.
Results And Conclusions:
Mucosal administration of FVIII-C2 decreases the titer of anti-FVIII-C2 inhibitors after FVIII-C2 challenge, and decreases the percentage of FVIII-C2 specific antibodies after challenge with full-length FVIII. Tolerance induction to FVIII-C2 is associated with increased IL-10 production by splenocytes in vitro, and can be adoptively transferred to naïve mice. This study is the first to demonstrate that tolerance to the FVIII-C2 domain can be induced via the mucosal route. Based on these results, the potential use of FVIII-specific mucosal tolerance induction as an immunotherapy treatment for anti-FVIII inhibitor development warrants further investigation.
