The concept of idiotypic vaccination against factor VIII inhibitors in haemophilia A

Abstract

Idiotypic vaccination has proven successful in several animal models and human trials. Here we suggest that the expression of cross-reactive idiotypes on factor VIII (FVIII) inhibitors of patients with haemophilia A, patients with anti-FVIII autoimmune disease and natural anti-FVIII antibodies of healthy individuals, together with the ability of anti-idiotypic reagents to neutralize anti-FVIII antibodies, provides a rationale for designing a vaccine strategy aimed at preventing the occurrence of or suppressing inhibitors, based on the induction of protective anti-idiotypes. Here we discuss the rationale supporting the concept of using idiotypic vaccination to prevent the occurrence of FVIII inhibitors in patients with haemophilia A.

Combinatorial peptides directed to inhibitory antibodies against human blood clotting factor VIII

“…It has been proposed thatanti-idiotypic antibodies compensate existing anti-FVIII antibodiesinhealthypersons, thus maintaining anormal coagulation status (32).Apromising approach for the treatment of inhibitor patient therefore is the application of anti-idiotypic antibodies (33,34). Desensitization of patients with high levels of FVIII can lead to an increased levelofantiidiotypes, restoring the procoagulant activity of FVIII (35).Peptide decoys mimicking the propertieso fF VIII epitopes could also be usedasv accines foractiveimmunization to induce the production of anti-idiotypic antibodiesasproposed before (36).…”

Using Factor VII in Hemophilia Gene Therapy

“…Specific thrombin anticoagulant Bivalirudin (Krolick, 2005) and monoclonal antibody Retoximab (Franchini, 2007;Wiestner et al, 2002) are also used for hemophilia treatment and patients with FVIII autoantibody, respectively. Idiotype vaccines will neutralize anti human FVIII antibody in hemophilia A patients (Lacroix-Desmazes et al, 2002). Production and characterization of recombinant FVIII for the treatment of hemophilia was conducted in 1984 for the first time (Toole et al, 1984;Wood et al, 1984).…”